5: Infection Flashcards
What is the most common organism overall in surgical wound infections?
Staphylococcus aureus
[Coagulase positive]
[UpToDate: The predominant organisms causing surgical site infections (SSIs) after clean procedures are skin flora, including streptococcal species, Staphylococcus aureus, and coagulase-negative staphylococci. In clean-contaminated procedures, the predominant organisms include gram-negative rods and enterococci in addition to skin flora. When the surgical procedure involves a viscus, the pathogens reflect the endogenous flora of the viscus or nearby mucosal surface; such infections are typically polymicrobial.]
What is the most common source of fever 48 hours - 5 days after surgery?
Urinary tract infection
[UpToDate: There are many causes of fever in the first week after surgery. Nosocomial infections are common during this period. Occasionally, fever or other symptoms predate surgery and are manifestations of community-acquired infection, such as a viral upper respiratory tract infection.
While SSI and intravascular catheter infections can cause acute postoperative fever, other infections are more frequently identified, including pneumonia and urinary tract infection (UTI).
Patients receiving mechanical ventilation during surgery are at risk for ventilator-associated pneumonia (VAP). The risk of VAP increases with the duration of mechanical ventilation. The risk of pneumonia tapers to a stable, lower rate over the first postoperative week and with the discontinuation of mechanical ventilation.
Patients with depressed mental status or gag reflex due to anesthesia and analgesia are more susceptible to aspiration if they vomit after surgery. A nasogastric tube also increases gastroesophageal reflux and the risk for aspiration.
UTI is a frequent cause of postoperative fever in patients with indwelling urethral catheters. The risk of UTI increases with the duration of catheterization. UTI is more common in patients who have undergone a genitourinary procedure and in those who have chronic, indwelling catheters prior to surgery.
SSI most often presents in the subacute period, one week or more after surgery. However, two organisms, group A streptococcus (GAS) and Clostridium perfringens, can cause fulminant SSI within a few hours after surgery.
Catheter exit site infections and bacteremia associated with intravascular catheters also tend to occur subacutely but should be considered as sources of fever in any patient with a catheter in place, especially if insertion was performed under emergent or nonsterile conditions.
Acute fever can also be caused by noninfectious conditions. Pancreatitis, myocardial infarction, pulmonary embolism, thrombophlebitis, alcohol withdrawal, and acute gout can complicate the acute postoperative period.]
Which bacteria usually cause a furuncle (boil)?
Staph epidermidis or staph aureus
[Treat with drainage +/- antibiotics]
What is the risk of someone contracting HIV from mucous membrane exposure to an HIV positive individual?
0.1%
[UpToDate: The risk of transmission of HIV infection following inadvertent exposure varies widely depending upon the type of exposure. The risk is increased when the source has a high viral load, the volume is large, and the exposure is deep. The healthcare personnel (HCP) at highest risk are those who have percutaneously been inoculated with blood from an HIV-infected source. All known seroconversions have occurred with exposure to blood, bloody fluids, or viral cultures.
The risk of becoming infected with HIV after exposure to body fluids from an HIV-infected patient is low. In the United States, there were 58 confirmed and 150 possible cases of occupationally-acquired HIV reported to the Centers for Disease Control from 1985 to 2013; there was only 1 confirmed case from 2000 to 2012.
A review of prospective studies of seroconversion following occupational exposure to an HIV-infected source in the era before the introduction of potent antiretroviral therapy (ART) found the following:
HIV transmission occurred in 20 of 6135 cases (0.33%) following percutaneous exposure
One case of HIV was transmitted out of 1143 exposures (0.09%) on the mucosa of HCP
There were no cases after 2712 intact skin exposures
A similar frequency of HIV seroconversion after needlestick injury (0.36%) was found in a later report from the Centers for Disease Control and Prevention (CDC) Cooperative Needlestick Surveillance Group and in another meta-analysis (0.23%). The risk of HIV infection following an occupational mucosal exposure was subsequently estimated to be 0.03%]
What is the most common gram negative rod in surgical wound infections?
E. coli
What is the treatment for lymphoma in HIV patients?
Usually chemotherapy
[May need surgery with significant bleeding or perforation]
[UpToDate: The optimal initial therapy for lymphomas in the setting of HIV has yet to be defined. Antiretroviral therapy (ART) is started or modified (if already begun) to control the HIV infection and allow for the administration of chemotherapy and/or radiation therapy. As in the HIV-seronegative population, the choice of therapy is principally determined by the subtype of NHL and the stage of disease. Modifications are made based upon the degree of immunosuppression from HIV as measured by the CD4 count.
The following represents our approach for patients with diffuse large B cell lymphoma (DLBCL). A similar approach may be taken for other types of clinically aggressive NHL, although rituximab is not used for NHL that lacks expression of CD20.
For most patients with DLBCL who have a CD4 count >50 cells/microL, we suggest the combination of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus rituximab (R-CHOP) rather than CHOP alone (Grade 2B).
The decision to use rituximab in the setting of a CD4 count <50 cells/microL must be individualized. For most patients with DLBCL who have a CD4 count <50 cells/microL, we suggest CHOP chemotherapy without rituximab rather than the combination (Grade 2B). Caution is advised if rituximab is incorporated into CHOP chemotherapy in the setting of CD4 count <50/microL.
For DLBCL patients with >80% growth fraction, or plasmablastic histology in the setting of CD4 count >50/microL, we suggest the standard dose-adjusted EPOCH (etoposide, vincristine, and doxorubicin plus oral prednisone and IV bolus cyclophosphamide) regimen plus rituximab rather than R-CHOP (Grade 2C). In such cases, we suggest concurrent rather than sequential rituximab (Grade 2B).
If treatment with R-EPOCH is chosen, supportive care should include prophylaxis for Pneumocystis jiroveci pneumonia (PCP, previously Pneumocystis carinii pneumonia), and antibiotic prophylaxis for enteric organisms. Given the high incidence of recurrent Herpes simplex, Herpes zoster, and Candida infections in this population, many clinicians also advise instituting antiviral and antifungal prophylaxis.
Lumbar puncture should be performed at diagnosis in the setting of >2 extranodal sites of disease accompanied by elevated LDH, or specific high-risk sites such as paranasal sinuses, testes, epidural space, and bone marrow. CNS prophylaxis is not routinely administered.]
Should clippers or razors be used preoperatively to shave an area?
Clippers to decrease chance of wound infections
[UpToDate: Shaving hair with razors at the planned operative site should be avoided; if hair removal is absolutely necessary, it may be performed with clippers or depilatory agents.
Preoperative hair removal has been associated with an increased risk for SSI. One meta-analysis including 19 trials concluded no hair removal was associated with a significantly lower risk of SSI compared with hair removal via shaving (relative risk [RR] 0.56; 95% CI, 0.34 to 0.96). Of hair removal methods, shaving was associated with the highest risk of SSI, followed by clipping and depilatory creams. In one study, rates of SSI associated with shaving, clipping, or depilatory creams were 5.6%, 1.7%, and 0.6%, respectively.
Scanning electron micrographs have demonstrated that razors cause gross skin cuts and clippers cause less injury than razors; depilatory agents cause no injury to the skin surface. The timing of hair removal is also important; the lowest rates of SSI have been observed when hair was removed just prior to the surgical incision.]
Cirrhotic patients with ascitic protein concentrations below 1 g/dL are at what risk of developing primary spontaneous bacterial peritonitis (SBP) compared to individuals with higher concentrations?
10 times more likely to develop SBP when ascitic protein concentration is below 1 g/dL
[UpToDate: The vast majority of patients with SBP have advanced cirrhosis. Other risk factors (most of which are associated with cirrhosis) include:
- Ascitic fluid total protein concentration less than 1 g/dL (<10 g/L)
- Prior episode of SBP
- Serum total bilirubin concentration above 2.5 mg/dL
- Variceal hemorrhage
- Possibly malnutrition
- Use of proton pump inhibitors
The combination of certain clinical and laboratory features is also associated with an increased risk of SBP:
- An ascitic fluid total protein <1.5 g/dL (<15 g/L) with
- Child-Pugh score ≥9 points with serum bilirubin ≥3 mg/dL or with
- Plasma creatinine ≥1.2 mg/dL, blood urea nitrogen ≥25 mg/dL or plasma sodium ≤130 mEq/L
Patients who meet the above combination criteria should be considered candidates for antibiotic prophylaxis.]
The microflora of which part of the gastrointestinal tract contains 10^5 bacteria (mostly gram positive cocci)?
Proximal small bowel
What is the risk of Hepatitis C infection with blood transfusion today?
0.0001% per unit of blood
[UpToDate: Blood transfusion was a major risk factor for acute infection in the past, with more than 10% of transfusion recipients acquiring infection in some studies. The screening of blood donors for historical risk factors, serologic evidence of hepatitis B infection (HBsAg and anti-HBc), and elevated serum ALT caused a striking reduction in the rates of non-A, non-B post-transfusion hepatitis, even before HCV was identified. The subsequent initiation of donor screening for anti-HCV antibodies in 1990 has nearly eliminated the risk of posttransfusion acute HCV infection. The estimated risk is now less than one in a million per unit transfused.]
Fungal infection with which organism is most commonly associated with CNS symptoms in AIDS patients?
Cryptococcus
[UpToDate: Disseminated Cryptococcus neoformans infection is a serious opportunistic infection that occurs in patients with untreated AIDS. Although cryptococcal infection begins in the lungs, meningitis is the most frequently encountered manifestation of cryptococcosis among those with advanced immunosuppression. However, the infection is more properly characterized as “meningoencephalitis” rather than meningitis since the brain parenchyma is almost always involved on histologic examination.
Symptoms of cryptococcal meningoencephalitis typically begin indolently over a period of one to two weeks. The most common symptoms are fever, malaise, and headache. Stiff neck, photophobia, and vomiting are seen in one-fourth to one-third of patients. Patients rarely present with coma and fulminant death in days.
Other symptoms suggesting disseminated disease include cough, dyspnea, and skin rash. Visual and hearing loss has also been reported.
The initial physical examination may be notable for lethargy or confusion in association with fever. In one report, 24% of patients had altered mentation on presentation, and 6% presented with focal neurologic deficits. Other manifestations of disseminated disease may be evident, including tachypnea and skin lesions resembling molluscum contagiosum. Increased diastolic hypertension may be reflective of increased intracranial pressure.
General laboratory studies are nonspecific. Patients with advanced immunosuppression may have leukopenia, anemia, hypoalbuminemia, and an increased gamma globulin antibody fraction.
We have a high index of suspicion for cryptococcal meningitis in patients with advanced HIV infection (CD4 cell count <100 cells/microL) who have isolated fever and headache. Initial evaluation includes a careful history, neurologic exam, and serum cryptococcal antigen. Evaluation should also include a lumbar puncture to assess for increased intracranial pressure and culture of cerebrospinal fluid (CSF) to confirm the diagnosis in those with symptoms and/or a positive serum cryptococcal antigen (CrAg).]
What is the most common anaerobe in the colon?
Bacteroides fragilis
[UpToDate: The largest concentrations of anaerobic bacteria are found in the relatively stagnant terminal ileum and colon, where concentrations reach 1011 per gram, and anaerobic bacteria account for approximately 99.9% of the cultivable flora. The most important and frequent anaerobic bacteria are Bacteroides spp (principally members of the B. fragilis group), Prevotella spp, Clostridium spp, and Peptostreptococcus spp.]
The exoslime released by staph species is composed of what?
Exopolysaccharide matrix
What is the treatment for acute septic arthritis?
Drainage, 3rd generation cephalosporin and vancomycin until cultures show which organism is responsible
[Commonly gonococcus, staph, H. influenzae, strep]
[UpToDate: Treatment of acute bacterial arthritis consists of antibiotic therapy and joint drainage. The initial choice of antibiotics for treatment of septic arthritis is based on the Gram stain. The initial regimen should be tailored to culture and susceptibility results when available. The typical duration of therapy is three to four weeks.
If the initial Gram stain of the synovial fluid shows gram-positive cocci, we suggest treatment with vancomycin (Grade 2B). If the initial Gram stain of the synovial fluid shows gram-negative bacilli, we suggest treatment with a third-generation cephalosporin (Grade 2B).
If the initial Gram stain is negative and the patient is immunocompetent, we suggest treatment with vancomycin (Grade 2C). If the initial Gram stain is negative and the patient is immunocompromised, we suggest treatment with vancomycin plus a third-generation cephalosporin (Grade 2C).
In general, we recommend joint drainage in the setting of septic arthritis (Grade 1B), as this condition represents a closed abscess collection. Options for drainage include needle aspiration (single or multiple), arthroscopic drainage, or arthrotomy (open surgical drainage).]
What is the treatment for Nocardia infection?
Drainage and sulfonamides (Bactrim)
[UpToDate: Nocardiosis is an uncommon gram-positive bacterial infection that usually causes infection in immunocompromised hosts. Two characteristics that distinguish nocardiosis are the ability to disseminate to virtually any organ, particularly the central nervous system, and the tendency to relapse or progress despite appropriate therapy.
Patients with systemic disease require antibiotic therapy. We also recommend antibiotic therapy even in patients with limited cutaneous disease (Grade 1C).
Antibiotics that are typically effective against Nocardia spp include trimethoprim-sulfamethoxazole (TMP-SMX), amikacin, imipenem, and third-generation cephalosporins (ceftriaxone and cefotaxime). However, antibiotic susceptibilities vary among isolates. The suggested regimens discussed below are empiric and should be tailored once information on susceptibilities is available. Dosing is presented in the table.
Patients with isolated cutaneous infection can usually be managed with oral monotherapy. We suggest initial therapy with oral TMP-SMX (Grade 2C). Patients who do not respond require intravenous therapy as discussed below for severe disease.
For patients with nonsevere mycetomas, we suggest initial therapy with oral TMP-SMX with or without dapsone (Grade 2C). For patients with severe mycetomas, we suggest initial therapy with imipenem with or without amikacin (Grade 2C).
For patients with mild to moderate pulmonary nocardiosis without involvement of other organs, we suggest monotherapy with oral TMP-SMX (Grade 2C).
Most experts would treat severe infection with two or three intravenous agents while awaiting results of susceptibility testing. In patients without central nervous system (CNS) disease, we suggest treating with TMP-SMX plus amikacin (Grade 2C). In patients with CNS disease, we suggest TMP-SMX plus imipenem (Grade 2C). In patients with CNS disease who have multiorgan involvement, we also add amikacin.
In selected patients with severe disease who have improved after receiving three to six weeks of intravenous therapy and do not have CNS disease, treatment can be switched to an oral regimen. In these patients, we suggest a monotherapy oral regimen to complete the treatment course (Grade 2C). The oral agent is selected based on susceptibility testing; we use TMP-SMX if the isolate is susceptible.
The optimal duration of antimicrobial treatment for severe disease has not been determined, but most recommend a prolonged course because of the relapsing nature of Nocardia infection. We usually treat for a duration of 3 to 6 months for isolated cutaneous infection in immunocompetent patients but for 6 to 12 months in immunocompromised patients with isolated cutaneous infection. For patients with serious pulmonary infection, we treat for 6 to 12 months or longer. All immunocompromised patients (except those with isolated cutaneous infection) as well as patients with CNS involvement should be treated for at least one year. Within these ranges, the duration of therapy is based upon the severity and extent of disease and the clinical and radiographic response to treatment.]
What is/are the oral treatment option(s) for Clostridium Difficile Colitis?
Oral Vancomycin or Flagyl
[Lactobacillus can help]
[UpToDate: For initial treatment of nonsevere CDI, we suggest oral metronidazole (Grade 2B).
For treatment of severe CDI, we recommend vancomycin 125 mg four times daily for 10 to 14 days (Grade 1B). For patients with severe disease who do not demonstrate clinical improvement, we suggest treatment with oral vancomycin 500 mg four times daily (Grade 2C); fidaxomicin may be considered in patients who cannot tolerate vancomycin, although more data are needed. In critically ill patients with fulminant or refractory disease, we suggest oral vancomycin 500 mg four times daily and intravenous metronidazole 500 mg every eight hours (Grade 2C); fidaxomicin may be considered in patients who cannot tolerate vancomycin, although more data are needed.
For treatment of severe disease in patients with profound ileus, we suggest addition of intracolonic vancomycin (Grade 2C), but there is risk of colonic perforation. Therefore, use of intracolonic vancomycin should be restricted to patients who are not responsive to oral therapy, and the procedure should be performed by personnel with expertise in administering enemas.
For treatment of a nonsevere initial recurrence of CDI, we suggest oral metronidazole (Grade 2A). Alternatives include oral vancomycin or fidaxomicin.
For treatment of a second recurrence of CDI, we suggest intermittent and tapering vancomycin therapy or fidaxomicin. For treatment of subsequent recurrences of CDI, we suggest administering either fidaxomicin or vancomycin followed by rifaximin (Grade 2C).
We recommend urgent surgical evaluation for patients with a white blood cell count ≥20,000 cells/microL and/or a plasma lactate between 2.2 and 4.9 mEq/L (Grade 1B). In addition, surgical intervention should be strongly considered in the setting of peritoneal signs, severe ileus, or toxic megacolon.]
What is the treatment for diabetic foot infections?
Broad-spectrum antibiotics such as Unasyn (Ampicillin/Sulbactam)
[Commonly mixed staph, strep, gram negative rods, and anaerobes]
[UpToDate: Management of diabetic foot infections requires attentive wound management, good nutrition, antimicrobial therapy, glycemic control, and fluid and electrolyte balance. Wound management includes attentive local wound care including debridement of callus and necrotic tissue, wound cleansing, and relief of pressure on the ulcer. Consultation with a surgeon with experience in diabetic foot infection is important for cases of severe infections and most cases of moderate infections. Prompt surgical debridement is critical for cure of infections complicated by abscess, extensive bone or joint involvement, crepitus, necrosis, gangrene or necrotizing fasciitis and is important for source control in patients with severe sepsis.
The microbiology of diabetic foot wounds varies with the severity and extent of involvement. Superficial infections are likely due to aerobic gram-positive cocci whereas deep, chronically infected, and/or previously treated ulcers are more likely to be polymicrobial. Anaerobic organisms may also be involved in wounds with extensive local inflammation, necrosis, or gangrene. When there is concern for multidrug-resistant organisms or in cases of moderate or severe infection (including deep infections and osteomyelitis), aerobic and anaerobic cultures of deep tissue or bone biopsies should be obtained at the time of debridement. Organisms cultured from superficial swabs are not reliable for predicting the pathogens responsible for deeper infection.
Empiric antibiotic therapy should be selected based upon the severity of infection and the likelihood of involvement of resistant organisms:
- For patients with mild infections, we suggest an empiric antimicrobial regimen with activity against skin flora including streptococci and Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA] if risk factors are present) (Grade 2C).
- For patients with deep ulcers, we suggest an empiric antimicrobial regimen with activity against streptococci, S. aureus (and MRSA if risk factors are present), aerobic gram-negative bacilli and anaerobes (Grade 2C). Oral antibiotics may be appropriate for ulcers that extend to the fascia, whereas parenteral regimens should be used for deeper infections.
- For patients with limb-threatening diabetic foot infections or evidence of systemic toxicity, we suggest treatment with a broad-spectrum parenteral antibiotic regimen with activity against streptococci, MRSA, aerobic gram-negative bacilli, and anaerobes (Grade 2C).
Antimicrobial therapy should be tailored to culture and susceptibility results when available, and a switch to an oral from parenteral regimen is reasonable following clinical improvement. Antibiotics need not be administered for the entire duration that the wound remains open. Close follow-up is important to ensure continued improvement and to evaluate the need for modification of antimicrobial therapy, further imaging, or additional surgical intervention.
Many patients with osteomyelitis of the foot benefit from surgical resection. However, in certain cases, limited surgical debridement combined with prolonged antibiotic therapy may be appropriate. The duration of antibiotic therapy of osteomyelitis depends on the extent of residual affected tissue.]
What are 2 risk factors for Fournier’s gangrene (a severe infection in the perineal and scrotal region)?
- Diabetes mellitus
- Immunocompromised state
[UpToDate: Necrotizing infection of the male perineum, known as Fournier’s gangrene, can result from a breach in the integrity of the gastrointestinal or urethral mucosa. Infection can occur in all age groups but is most common in older men. Necrotizing infection involving the labia and perineum can also occur in females, particularly in the setting of diabetes. Fournier’s gangrene begins abruptly with severe pain and may spread rapidly to the anterior abdominal wall, the gluteal muscles, and, in males, onto the scrotum and penis. In the setting of Fournier’s gangrene, early aggressive drainage or debridement is essential. Affected patients may require cystostomy, colostomy, or orchiectomy.]
What are 2 causes of surgical infection within 48 hours of a procedure?
- Injury to bowel with a leak
- Invasive soft tissue infection (clostridium perfringens and beta-hemolytic strep can present within hours postoperatively)
[UpToDate: SSI most often presents in the subacute period, one week or more after surgery. However, two organisms, group A streptococcus (GAS) and Clostridium perfringens, can cause fulminant SSI within a few hours after surgery.]
How soon after surgical procedures can necrotizing soft tissue infections occur?
Within hours
What is the line salvage rate with antibiotics?
50%
[Much less likely with yeast line infections]
[UpToDate: Following diagnosis of catheter-related infection, catheter salvage may be attempted in the setting of uncomplicated CRBSI involving long-term catheters due to pathogens other than S. aureus, P. aeruginosa, fungi, or mycobacteria. Salvage is also difficult in the setting of CRBSI due to organisms of relatively low virulence that are difficult to eradicate (eg, Bacillus spp, Micrococcus spp, or Propionibacteria). Catheter salvage in the setting of coagulase-negative staphylococcal infection does not influence resolution of bacteremia but may be a risk factor for recurrence (relative risk 6.6 in a retrospective series of 175 cases).
If salvage is attempted, both systemic and antimicrobial lock therapy may be administered through the colonized catheter for the duration of therapy, depending upon the microorganism. The efficacy of antibiotic lock therapy remains uncertain and concerns have been raised about the emergence of antimicrobial resistance and fungal superinfection. The optimal antimicrobial dosing for lock therapy is also uncertain. Antibiotic lock therapy is not warranted for management of catheter infection for devices in place for <2 weeks; these are usually extraluminal infections.
Two sets of blood cultures should be obtained after 72 hours of appropriate antimicrobial therapy (for neonates, one set is acceptable); positive cultures should prompt catheter removal.
Catheter removal is not necessary for hemodynamically stable patients with unexplained fever in the absence of documented bloodstream infection and without endovascular prosthetic material (such as a prosthetic valve, pacemaker, or vascular graft).]
The microflora of which part of the gastrointestinal tract contains 10^11 bacteria consisting almost entirely of anaerobes, some gram negative rods, and some gram positive cocci?
Colon
Which endotoxin gets released in gram-negative sepsis?
Lipopolysaccharide lipid A
[UpToDate: Anaerobic gram-negative bacteria, like all gram-negative bacteria, contain lipopolysaccharide (LPS) that can be extracted from the envelope, but the biologic activity of this endotoxin (mouse lethality assays, the chick embryo death test, and the Shwartzman reaction) is 100 to 1000 times less than that of LPS from Enterobacteriaceae. The LPS of B. fragilis contains a lipid A moiety (the endotoxin portion of LPS), but there are structural and chemical composition differences that render this LPS less potent than the LPS of Escherichia coli. The inability of B. fragilis LPS to activate TLR 2 may be responsible for this difference.
Lipid A is the biologically active component of lipopolysaccharide (LPS) found in the cell wall of Salmonella and other gram-negative bacteria. Lipid A is toxic to mammalian cells and is a potent immunomodulator. Certain features of the lipid A in Salmonella may correlate with virulence or with activation of host inflammation. Lipid A induces toll-like receptor 4 (TLR4)-mediated responses, which are important for host defense against Salmonella infection, and modifications in lipid A as part of Salmonella’s adaptation to host environments reduce this signaling. Death in mice from Salmonella may be related to the toxic effect of lipid A, which triggers further production of TNF-alpha and IL-1 beta. S. typhimurium mutants with a defective lipid A molecule have greatly attenuated virulence in mice. Structural modifications of lipid A are influenced by the Salmonella virulence regulatory locus (phoP/phoQ) which responds to a variety of host intracellular environmental signals. For example, antimicrobial peptides have been shown to be part of the first step in signal transduction across the bacterial membrane, resulting in activation of phoQ and promotion of bacterial virulence. PhoP has also been found to bind a promoter region of a drug efflux system, thus connecting virulence with possible drug resistance.]
Which 2 locations in the body are the most common sites of lymphoma in HIV patients?
- Stomach
- Rectum
[UpToDate: The GI tract is a frequent presenting site in patients with HIV-associated lymphoma, though the prevalence of GI involvement may have declined in the post-antiretroviral therapy (ART) era. Virtually any area of the GI tract may be involved, but the most common sites are the stomach, duodenum, perianal/anal area, and the oropharynx. The major presenting features are abdominal or perianal pain, fever, diarrhea, and/or weight loss; life-threatening complications such as bleeding, perforation and obstruction are not uncommon. When GI involvement is suspected, the evaluation includes imaging studies, upper and lower endoscopy with evaluation of the small bowel, and biopsy.
Most information regarding gastrointestinal (GI) lymphoma in the HIV-positive population comes from the era before the routine implementation of ART, since this condition is most commonly associated with advanced HIV and low CD4 counts. Based on older series, the gastrointestinal tract is the presenting site of AIDS-related systemic lymphoma in 30% to 50% of patients, and is the most frequent site of extranodal disease. A more recent series indicates the rate of GI involvement to be 14% of AIDS-related lymphoma. The area of gastrointestinal tract involvement is different from that in the non-HIV setting. Virtually any area of the gastrointestinal tract may be involved, including the oral cavity, esophagus, bile duct, pancreas, mesentery, small bowel, perianal area, and anal canal.
In one series of 48 patients with HIV-associated gastrointestinal lymphoma, involvement was multifocal in 23%. Areas of involvement included:
- Stomach – 50%
- Duodenum – 25%
- Perianal/anal – 15%
- Oropharynx – 10%
- Small bowel – 8%
- Esophagus – 6%
- Liver, cecum, and rectum – Each <5%
The major presenting features of these tumors are abdominal or perianal pain, fever, diarrhea, and/or weight loss; life-threatening complications such as bleeding, perforation, and obstruction have been reported in 16% to 55%.]
What percent of abdominal abscesses have anaerobes?
90%
What is the most common source of fever within 48 hours of surgery?
Atelectasis
[UpToDate: The potential causes of fever in the immediate operative and postoperative period are mainly limited to: medications or blood products to which the patient was exposed during preoperative care either in the operating room or in the recovery area; trauma suffered prior to surgery or as part of surgery; infections that were present prior to surgery; and rarely malignant hyperthermia.
Adverse medication reactions that produce immediate fever include immune-mediated reactions, such as reactions to antimicrobials and to transfused blood products. The vasodilation that often accompanies these reactions makes hypotension a common presenting sign; rash may accompany fever in some patients with medication reactions.
The initial clinical signs (ie, hypercarbia) of malignant hyperthermia typically present within 30 minutes following the administration of a triggering agent (eg, inhaled anesthetics, succinylcholine), but have been reported later in the operative course and also following cessation of anesthesia. If the malignant hyperthermia response is not recognized and aborted with dantrolene, high fever may develop as result of hypermetabolism.
Fever due to the trauma of surgery usually resolves within 2 to 3 days. The severity and duration of these self-limited postoperative fevers depends on the type of surgery, but tends to be greater in patients with longer and more extensive surgical procedures. Fever caused by severe head trauma can be persistent and may resolve gradually over days or even weeks.
Atelectasis is often used as an explanation for otherwise unexplained postoperative fever. Both atelectasis and fever occur frequently after surgery, but their concurrence is probably coincidental rather than causal.
- In one study of 270 consecutive patients after abdominal surgery, the sensitivity and negative predictive value of fever as a predictor of atelectasis were both less than 50%, and the specificity and positive predictive value were 68% and 66% respectively.
- In another study, there was also no association between fever and the presence of, or the degree of, atelectasis. Therefore, ascribing a postoperative fever to atelectasis is probably false reassurance and may mislead the clinician from pursuing the true cause of the fever.]
What is the optimal glucose level in a septic patient?
100-120 mg/dL
[UpToDate: For hyperglycemic critically ill adult patients:
- We recommend a blood glucose target of 140 to 180 mg/dL (7.7 to 10 mmol/L), rather than a more stringent target (eg, 80 to 110 mg/dL [4.4 to 6.1 mmol/L]) (Grade 1A).
- We also suggest a blood glucose target of 140 to 180 mg/dL (7.7 to 10 mmol/L), rather than a more liberal target (eg, 180 to 200 mg/dL [10 to 11.1 mmol/L]) (Grade 2C).
The Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP) trial was a multicenter two-by-two factorial trial conducted in medical and surgical ICU patients with severe sepsis. It compared IIT (target blood glucose level of 80 to 110 mg/dL [4.4 to 6.1 mmol/L]) to conventional glucose control (target blood glucose level of 180 to 200 mg/dL [10 to 11.1 mmol/L]), as well as comparing two methods of volume resuscitation. The IIT arm of the trial was stopped after 488 patients were enrolled because IIT significantly increased the rate of hypoglycemia (12.1% vs 2.1%) and serious adverse events (10.9% vs 5.2%). The trial then continued with only patients in the conventional therapy group until 537 patients were enrolled. The following outcomes were detected when IIT was compared to conventional glucose control:
- Mean morning blood glucose was significantly lower in the IIT group (112 vs 151 mg/dL [6.2 vs 8.4 mmol/L])
- Hypoglycemia (blood glucose ≤40 mg/dL [2.2 mmol/L]) was significantly more common in the IIT group (17% vs 4.1%)
- There was no significant difference in 28 day mortality (24.7% vs 26% in the conventional glucose control group), morbidity, or organ failures
- There was a nonstatistically significant increase in 90 day mortality in the IIT group (39.7% vs 35.4%)
The Glucontrol trial was a multicenter trial that randomly assigned 1101 critically ill medical and surgical patients to IIT (target blood glucose of 80 to 110 mg/dL [4.4 to 6.1 mmol/L]) or conventional glucose control (target blood glucose of 140 to 180 mg/dL [7.8 to 10 mmol/L]). The trial was terminated early because of a high rate of unintended protocol violations. IIT significantly increased the rate of hypoglycemia (8.7% vs 2.7%). There was no difference in ICU mortality, although the IIT group had a nonsignificant trend toward increased 28 day mortality and hospital mortality.
Meta-analysis — Meta-analyses have been performed in an effort to consolidate the data from numerous randomized trials. One such meta-analysis of 15 randomized trials (10,140 patients) compared IIT (defined as a target blood glucose level ≤150 mg/dL [8.3 mmol/L]) to less stringent glycemic control in mixed medical and surgical ICU patients. Patients who received IIT had a similar mortality to those who received less stringent glycemic control (26.7% vs 25.6%, relative risk 0.99, 95% CI 0.87-1.12).
Summary - In mixed adult populations of critically ill medical and surgical patients, IIT (target blood glucose of 80 to 110 mg/dL [4.4 to 6.1 mmol/L]) increased the incidence of severe hypoglycemia and either increased mortality or had no effect on mortality, when compared to the more permissive blood glucose ranges of 140 to 180 mg/dL (7.8 to 10 mmol/L) and 180 to 200 mg/dL (10 to 11.1 mmol/L). Similar trends have been noted in children.]
Which are most common in the GI tract: Aerobes or anaerobes?
Anaerobes
What must be ruled out if primary spontaneous bacterial peritonitis is not responding to antibiotics or if cultures are polymicrobial?
Intra-abdominal source (IE bowel perforation)
[UpToDate: Patients with suspected secondary bacterial peritonitis should receive broader coverage with cefotaxime and metronidazole. A similar regimen should be used with polymicrobial bacterascites.]
What is the risk of someone contracting HIV from a needle stick from an HIV positive patient?
0.3%
[UpToDate: The risk of transmission of HIV infection following inadvertent exposure varies widely depending upon the type of exposure. The risk is increased when the source has a high viral load, the volume is large, and the exposure is deep. The healthcare personnel (HCP) at highest risk are those who have percutaneously been inoculated with blood from an HIV-infected source. All known seroconversions have occurred with exposure to blood, bloody fluids, or viral cultures.
The risk of becoming infected with HIV after exposure to body fluids from an HIV-infected patient is low. In the United States, there were 58 confirmed and 150 possible cases of occupationally-acquired HIV reported to the Centers for Disease Control from 1985 to 2013; there was only 1 confirmed case from 2000 to 2012.
A review of prospective studies of seroconversion following occupational exposure to an HIV-infected source in the era before the introduction of potent antiretroviral therapy (ART) found the following:
- HIV transmission occurred in 20 of 6135 cases (0.33%) following percutaneous exposure
- One case of HIV was transmitted out of 1143 exposures (0.09%) on the mucosa of HCP
- There were no cases after 2712 intact skin exposures
A similar frequency of HIV seroconversion after needlestick injury (0.36%) was found in a later report from the Centers for Disease Control and Prevention (CDC) Cooperative Needlestick Surveillance Group and in another meta-analysis (0.23%). The risk of HIV infection following an occupational mucosal exposure was subsequently estimated to be 0.03%]
Which bacteria has alpha toxin that is a membrane-disrupting toxin with phospholipase C activity, directly responsible for gas gangrene and myonecrosis?
Clostridium perfringens
[UpToDate: Many extracellular toxins are produced by C. perfringens; of these, alpha and theta toxins have been implicated in pathogenesis:
Alpha toxin is a hemolytic toxin with both phospholipase C (PLC) and sphingomyelinase activities. Two independent studies have identified alpha toxin as an essential toxin in disease. First, genetic interruption of the alpha toxin gene in C. perfringens rendered the organism avirulent in a mouse myonecrosis model. Complementation of the chromosomal mutation with a recombinant plasmid carrying a wild-type gene fully restored ability to cause disease. Second, vaccination with the C-terminal domain of alpha toxin (amino acids 247 to 370) protected mice from experimental C. perfringens infection in part by improving tissue perfusion and restoring the tissue inflammatory response.
Theta toxin (also known as perfringolysin O) is a member of the cholesterol-dependent cytolysin family that includes streptolysin O, pneumolysin, listeriolysin, septicolysin, and others. These pore-forming toxins contain a conserved amino acid motif. Theta toxin appears to contribute to pathogenesis by its effects on cells of the vascular and immune systems. However, theta toxin is not essential in causing mortality since isogenic mutant strains lacking an intact theta toxin structural gene (pfoA) remained lethal in the mouse myonecrosis model.
Molecular and animal studies have shown that alpha toxin is largely responsible for both the widespread tissue necrosis and the characteristic absence of tissue inflammatory response. Alpha toxin potently stimulates platelet aggregation and upregulates adherence molecules on PMN and endothelial cells. Experimental intramuscular alpha toxin injection causes a rapid, irreversible decline in muscle blood flow and concomitant ischemic necrosis of tissue due to the formation of occlusive intravascular aggregates composed of activated platelets, leukocytes, and fibrin. The perfusion deficits expand the anaerobic environment and contribute to the rapidly advancing margins of tissue destruction characteristic of clostridial gas gangrene.
Shock associated with gas gangrene may be attributable to both direct and indirect effects of alpha and theta toxins. Alpha toxin directly suppresses myocardial contractility and may contribute to profound hypotension via a sudden reduction in cardiac output. In experimental models, theta toxin causes markedly reduced systemic vascular resistance combined with a markedly increased cardiac output (ie, “warm shock”). This likely occurs via induction of endogenous mediators such as prostacyclin, platelet activating factor, and other lipid autocoids that cause vasodilation.]
What is the risk of surgical site infection in a clean contaminated procedure (IE. elective colon resection with prepped bowel)?
3-5%
[UpToDate: A widely accepted wound classification system has been developed by the National Academy of Sciences and the National Research Council based upon the degree of expected microbial contamination during surgery. It stratifies wounds as clean, clean-contaminated, contaminated, or dirty using the following definitions:
Clean wounds are uninfected operative wounds in which no inflammation is encountered and the wound is closed primarily. By definition, a viscus (respiratory, alimentary, genital, or urinary tract) is not entered during a clean procedure.
Clean-contaminated wounds are operative wounds in which a viscus is entered under controlled conditions and without unusual contamination.
Contaminated wounds are open, fresh accidental wounds, operations with major breaks in sterile technique, or gross spillage from a viscus. Wounds in which acute, nonpurulent inflammation was encountered also were included in this category.
Dirty wounds are old traumatic wounds with retained devitalized tissue, foreign bodies, or fecal contamination or wounds that involve existing clinical infection or perforated viscus.
Several studies have found a moderate correlation between the wound classification and the SSI rate. SSI rates according to wound class were:
Clean – 1.3% to 2.9%
Clean-contaminated – 2.4% to 7.7%
Contaminated – 6.4% to 15.2%
Dirty – 7.1% to 40.0%
While widely used, this classification scheme may be a poor predictor of overall risk of SSI. Other factors, such as the operative technique, length of surgery, and health of the surgical patient, may be as important as wound classification in predicting infectious risks for SSI.
Available data suggest that the relative risk reduction of SSI from the use of antimicrobial prophylaxis is the same in clean and in higher-risk procedures. Antimicrobial prophylaxis is justified for most clean-contaminated procedures. The use of antimicrobial agents for dirty procedures or established infection is classified as treatment of presumed infection, not prophylaxis.]
What are the bacterial causes of necrotizing soft tissue infections?
- Beta-hemolytic strep (Group A)
- C. perfringens
- Mixed organisms
[UpToDate: Necrotizing soft tissue infections are comprised of two distinct bacteriologic entities: type I (polymicrobial infection) and type II (group A streptococcal [GAS] infection). There are also case reports of monomicrobial necrotizing soft tissue infections due to other organisms, including Haemophilus influenzae.
In type I infection, at least one anaerobic species (most commonly Bacteroides, Clostridium, or Peptostreptococcus) is isolated in combination with one or more facultative anaerobic streptococci (other than group A) and members of the Enterobacteriaceae (eg, Escherichia coli, Enterobacter, Klebsiella, Proteus). An obligate aerobe, such as P. aeruginosa, is only rarely a component of such a mixed infection. Necrotizing fasciitis of the head and neck is usually caused by mouth anaerobes, such as Fusobacteria, anaerobic streptococci, Bacteroides, and spirochetes. Fournier’s gangrene is caused by facultative organisms (E. coli, Klebsiella, enterococci) along with anaerobes (Bacteroides, Fusobacterium, Clostridium, anaerobic or microaerophilic streptococci).
In type II, necrotizing fasciitis is generally mono-microbic, most commonly caused by group A Streptococcus (also known as hemolytic streptococcal gangrene). Aeromonas hydrophila has been associated with traumatic lesions in fresh water, and Vibrio vulnificus can cause necrotizing fasciitis in association with seawater injuries (Gulf coast and South Atlantic seaboard) or among patients with cirrhosis who ingest raw oysters. Group A streptococci or other beta-hemolytic streptococci are isolated alone or in combination with other species, most commonly Staphylococcus aureus. In communities with relatively high prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA) infection, this organism is also a potential cause of monomicrobial necrotizing infection.
An important virulence determinant of GAS, M protein, is a filamentous protein anchored to the cell membrane. M protein has antiphagocytic properties. Many M types of GAS have been associated with necrotizing fasciitis; types 1 and 3 are most common. These strains can produce one or more of the pyrogenic exotoxins A, B, or C. Necrotizing fasciitis caused by these strains is associated with streptococcal toxic shock syndrome in about 50% of cases.
Group A streptococci may localize to the exact site of muscle injury due to increased surface expression of vimentin, which specifically binds the microbe. In an in vitro model, investigators demonstrated that injured skeletal muscle cells in tissue culture increased adherence of GAS twofold due to specific binding of GAS by vimentin on the surface of these cells.
Pyrogenic exotoxins lead to cytokine production, which may explain some of the clinical findings of necrotizing fasciitis. The exotoxins bind to the MHC class II portion of antigen presenting cells, such as macrophages. This complex can then bind to a specific V beta segment of the T cell receptor in the absence of classical antigen processing by the macrophage. Thus, pyrogenic exotoxins are superantigens and cause rapid proliferation of T cells bearing specific V beta repertoires. Such stimulation of the host’s immune cells is associated with production of both monokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1, and IL-6) and lymphokines (IL-2 and TNF-beta). Expression of these cytokines in vivo probably contributes to shock, tissue destruction, and organ failure.]
When should an infected peritoneal dialysis catheter be removed?
For peritonitis that lasts for 4-5 days (First treat with intraperitoneal Vancomycin and gentamicin)
[Some say need removal of peritoneal dialysis catheter for all fungal, tuberculous, and pseudomonas infections]
[UpToDate: If the exit site remains infected after two weeks of antibiotics, compliance should be ensured and a thorough repeat examination performed. One should also examine the exit site to see if the external cuff is exposed since an exposed cuff may cause infection. Ultrasonography, computed tomography (CT) scanning, or less often gallium scanning may be performed to exclude an abscess. If the cuff is not exposed and there is no evidence of abscess or tunnel infection, additional antibiotic therapy may be attempted or salvage techniques may be employed to rescue the infected catheters.
Catheter removal is required for some exit-site and tunnel infections such as those complicated by a tunnel abscess or peritonitis, or if the infection does not respond or progresses after several weeks of antibiotic therapy. In all cases, perioperative antibiotics should be given and then continued for one to two weeks after catheter removal.
If there is no peritonitis associated with the exit-site infection, the infected catheter can be removed and a new catheter placed simultaneously in the opposite lower quadrant. A new catheter should not be placed at the time the infected catheter is removed if active peritonitis is present.]
What is the most common type of lymphoma in HIV patients?
Non-Hodgkin’s B-cell lymphoma
[UpToDate: AIDS-related non-Hodgkin lymphoma (NHL) can be divided into three general categories based on location:
- Systemic NHL
- Primary central nervous system (CNS) lymphoma
- Primary effusion (or body cavity) lymphoma
Systemic NHL accounts for the great majority of AIDS-related lymphomas, while primary CNS lymphoma accounts for approximately 15%, and primary effusion lymphoma for less than 1%. Systemic NHL can be further divided into common subtypes described in the World Health Organization (WHO) classification system. The most common systemic NHL subtypes seen in HIV-positive persons are:
●Burkitt lymphoma (approximately 25%)
●Diffuse large B cell lymphoma (DLBCL, approximately 75%)
●Plasmablastic lymphoma (less than 5%)
●T cell lymphoma (1% to 3%)
●Indolent B cell lymphoma (less than 10%)
The WHO classification does not order lymphoid neoplasm according to their aggressiveness, in part due to recognition that the natural history of these tumors shows significant patient-to-patient variability. However, some studies have separated histologic subtypes into three general categories (highly aggressive, aggressive, and indolent) according to the usual clinical behavior of each of the lymphoid neoplasms.]
What is the most common anaerobe in surgical wound infections?
Bacteroides fragilis
What is the treatment for Histoplasma infection (Histoplasmosis)?
Liposomal amphotericin for severe infections
[UpToDate: Histoplasmosis is a common endemic mycosis that is usually asymptomatic but occasionally results in severe illness. Histoplasmosis and its causative agent, Histoplasma capsulatum, are found worldwide but particularly in North and Central America. Pulmonary histoplasmosis should be considered in patients with the following clinical presentations, particularly in the appropriate epidemiologic setting:
- Pneumonia with mediastinal or hilar lymphadenopathy
- Mediastinal or hilar masses
- Pulmonary nodule
- Cavitary lung disease
- Pericarditis with mediastinal lymphadenopathy
- Pulmonary manifestations with arthritis or arthralgia plus erythema nodosum
- Dysphagia caused by esophageal narrowing
- Superior vena cava syndrome or obstruction of other mediastinal structures. These manifestations place pulmonary histoplasmosis in the differential diagnosis of sarcoidosis, tuberculosis, and malignancy.
Histopathology using stains for fungi, cultures, antigen detection, and serologic tests for Histoplasma-specific antibodies can all help make a diagnosis of pulmonary histoplasmosis.
The clinical and radiographic findings in pulmonary histoplasmosis and sarcoidosis may be similar. A mistake in diagnosis can be disastrous if the patient is treated with corticosteroids or other immunosuppressive medications. As a result, histoplasmosis must be excluded before treating patients with presumed sarcoidosis with immunosuppressive medications.
The yield of the diagnostic modalities differs depending upon the extent of the infection and timing following exposure. A battery of tests is required to achieve the highest sensitivity for diagnosis. Antigen tests and serology may be negative when first performed but become positive later as the illness progresses.
The optimal treatment for histoplasmosis varies according to the patient’s clinical syndrome. Most infections caused by H. capsulatum are self-limited and require no therapy. However, patients who are exposed to a large inoculum of Histoplasma and those who are immunocompromised usually require antifungal therapy.
Itraconazole is generally preferred for mild to moderate histoplasmosis, and amphotericin B for the treatment of moderately severe to severe infections.
Therapy should be considered in patients with more than four weeks of symptoms but may not be indicated in those with mild symptoms who are already improving. Therapy is indicated without delay in patients with moderately severe or severe disease.
Treatment is indicated in all patients with chronic pulmonary histoplasmosis because the infection results in progressive loss of pulmonary function in most patients and death in as many as 30% of cases.]
What percent of the population is infected with Hepatitis C?
1%-2%
[UpToDate: The prevalence of antibodies to hepatitis C virus (anti-HCV) in the United States is approximately 1.6% (equating to about 4.1 million anti-HCV positive persons), while the prevalence of positive HCV RNA is approximately 1.3% (or about 3.2 million persons who are HCV RNA-positive). The peak prevalence is observed among persons born between 1945 and 1964.
Most patients infected with HCV in the United States and Europe acquired the disease through intravenous drug use or blood transfusion, the latter of which has become rare since routine testing of the blood supply for HCV began in 1990.]
What is the treatment for Coccidiodomycosis infection?
Liposomal amphotericin for severe infections
[UpToDate: Otherwise healthy patients without evidence of extensive coccidioidal infection or risk factors for more serious infection usually do not need antifungal therapy. However, for patients with severe illness, and for those at increased risk of dissemination or complications (eg, immunocompromised hosts or pregnant women), we suggest antifungal therapy (Grade 2C).
When treatment is indicated, we recommend fluconazole or itraconazole for most nonpregnant patients (Grade 1C). Amphotericin B should be used as initial therapy only in the most severe cases due to its toxicity; it is also used for treatment of pregnant women during the first trimester.
We generally treat immunocompetent patients, and those without severe underlying immunocompromise, for three to six months. The duration of treatment for patients with other immunocompromising conditions (eg, malignancy, AIDS, transplant recipients, patients receiving immunosuppressive therapy for autoimmune diseases) and pregnant women is discussed separately.
It is important that patients with coccidioidal infection (regardless of treatment) be followed for a year or longer to monitor for the development of complications (eg, chronic cavitary pneumonia, extrapulmonary disease).
Some patients may develop fatigue and lethargy associated with coccidioidal pneumonia without evidence of complications, and this may persist for many weeks or months. For such patients, developing a structured physical rehabilitation program and referral to a physical therapist for reconditioning training is often very helpful.]
How does a necrotizing C. perfringens infection present on physical exam?
- Pain out of proportion to exam
- Skin signs may not be evident with a deep infection
[UpToDate: Traumatic gas gangrene usually presents with sudden onset of severe pain at the site of surgery or trauma. The mean incubation period is less than 24 hours (range 6 hours to several days), depending on the size of the bacterial inoculum and the extent of vascular compromise. Pain is likely related to toxin-mediated ischemia.
The skin over the infected area initially may appear pale then rapidly develops a bronze appearance, followed by purple or red discoloration. The skin becomes tense and exquisitely tender. Overlying bullae may be clear, red, blue, or purple.
Signs of systemic toxicity develop rapidly including tachycardia and fever, followed by shock and multiorgan failure. In one series, shock was present in 50% of patients at the time of presentation to the hospital.
Bacteremia occurs in about 15% of cases and may be associated with brisk intravascular hemolysis. One case report described a patient whose hematocrit dropped from 37% to 0% over a 24-hour period; despite transfusion with 10 units of packed red blood cells over 4 hours, the hematocrit never exceeded 7%. Both alpha and theta toxins appear to contribute to the marked intravascular hemolysis based upon studies performed with recombinant toxins in the laboratory.
Bacteremia with C. perfringens can occur transiently in patients without gas gangrene, although the majority of C. perfringens and C. septicum blood isolates are associated with clinically significant infection.
Additional complications of clostridial myonecrosis include jaundice, renal failure, hypotension, and liver necrosis. Renal failure is largely due to the combined effects of hypotension, hemoglobinuria, and myoglobinuria. Bacterial toxins may also exert a direct effect on renal tubular cells.]
Which bacteria has alpha toxin that is a membrane-disrupting toxin that creates pores causing hemolysis and tissue damage?
Staphylococcus aureus
[Wikipedia: Alpha-toxin, also known as alpha-hemolysin (Hla), is the major cytotoxic agent released by bacterium Staphylococcus aureus and the first identified member of the pore forming beta-barrel toxin family. This toxin consists mostly of beta-sheets (68%) with only about 10% alpha-helices. The hla gene on the S. aureus chromosome encodes the 293 residue protein monomer, which forms heptameric units on the cellular membrane to form a complete beta-barrel pore. This structure allows the toxin to perform its major function, development of pores in the cellular membrane, eventually causing cell death.]
[UpToDate: Alpha-hemolysin is a well-characterized toxin capable of forming pores in selected host cells, including erythrocytes, macrophages, and lymphocytes; it appears to play a critical role in the pathogenesis of infection in a mouse model. In mice infected with isogenic strains of USA300, alpha-hemolysin was essential for development of pneumonia, but PVL was not. Subsequent studies demonstrated vaccination with the toxin protected mice from infection.]
Fungal infection with which organism is most commonly associated with pulmonary symptoms and can cause tortuous abscesses in cervical, thoracic, and abdominal areas?
Actinomyces
[Not a true fungus]
[UpToDate: Actinomycetes are commensal inhabitants of the oral cavity and intestinal tract but acquire pathogenicity through invasion of breached or necrotic tissue. As the infection progresses, granulomatous tissue, extensive reactive fibrosis and necrosis, abscesses, draining sinuses, and fistulas are formed.
Infection involving the cervicofacial area is most common (50%), followed by abdominal involvement (20%) and thoracic involvement (15% to 20%). In abdominal actinomycosis, the appendix and ileocecal region are usually involved. The disease tends to remain localized as the infection spreads contiguously, disregarding tissue planes. Lymphadenopathy is not a clinical feature. Hematogenous dissemination is also rare.
Actinomycotic abscesses can also present in the abdomen following cholecystectomy complicated by spilled gallstones during gallbladder removal. Because of the slow growth characteristics of the pathogen, such patients may present months to years after cholecystectomy.
Factors that predispose to abdominal actinomycosis include recent abdominal surgery, trauma, neoplasia, or a perforated viscus. In addition, there have been multiple reports of abdominopelvic actinomycosis associated with the use of intrauterine contraceptive devices.
Actinomycosis is a difficult disease to diagnose preoperatively by virtue of its rarity, nonspecific symptoms, and imitation of more common conditions such as malignancy, Crohn’s disease, and tuberculosis. It has been estimated that fewer than 10% of cases are diagnosed preoperatively. As a result, a high index of suspicion is required in patients presenting with constitutional or nonspecific abdominal symptoms and an abdominal mass. The disease is characterized by a chronic, indolent course with symptoms such as fatigue, fever, weight loss, and abdominal pain. Physical findings may include a palpable mass, visible sinus tracts, or fistulas. Laboratory abnormalities may show anemia and leukocytosis.]
What are the 2 most common organisms in ICU pneumonia?
- Staph aureus
- Pseudomonas
[UpToDate: Hospital-acquired (or nosocomial) pneumonia (HAP) and ventilator-associated pneumonia (VAP) may be caused by a wide variety of pathogens and can be polymicrobial. Common pathogens include aerobic gram-negative bacilli (eg, Escherichia coli, Klebsiella pneumoniae, Enterobacter spp, Pseudomonas aeruginosa, Acinetobacter spp) and gram-positive cocci (eg, Staphylococcus aureus, including methicillin-resistant S. aureus [MRSA], Streptococcus spp). Nosocomial pneumonia due to viruses or fungi is significantly less common, except in the immunocompromised patient.
There is a paucity of data regarding whether the pathogens that cause VAP differ from those that cause HAP in patients who are not mechanically ventilated. One prospective observational study evaluated 158,519 patients admitted to a single center over a four-year period. A total of 327 episodes of VAP and 261 episodes of HAP in nonventilated patients were identified:
The infecting flora in patients with VAP included methicillin-susceptible S. aureus (MSSA; 9%), MRSA (18 percent), P. aeruginosa (18%), Stenotrophomonas maltophilia (7%), Acinetobacter spp (8%), and other spp (9%).
The infecting flora in nonventilated patients with HAP was similar, except non-Enterobacteriaceae gram-negative bacilli (P. aeruginosa, Acinetobacter, and S. maltophilia) were less likely. Specifically, it included MSSA (13%), MRSA (20%), P. aeruginosa (9%), S. maltophilia (1%), Acinetobacter spp (3%), and other spp (18%).
These findings are supported by a prospective, multicenter, observational study of 398 intensive care unit (ICU) patients with suspected VAP. In this study, there was a similar distribution of pathogens: MRSA (14.8%), P. aeruginosa (14.3%), and other Staphylococcus species (8.8%).
Of 8474 cases of VAP reported to the United States Centers for Disease Control and Prevention from 2009 to 2010, the distribution of pathogens associated was S. aureus (24.1%), P. aeruginosa (16.6%), Klebsiella species (10.1%), Enterobacter species (8.6%), Acinetobacter baumannii (6.6%), and E. coli (5.9%). Similar findings were observed in another surveillance study.
A frequent criticism of such studies is that they may underestimate the prevalence of certain pathogens (eg, anaerobes) because special culturing techniques are required to identify them. However, a study performed anaerobic cultures using protective brush specimens and bronchoalveolar lavage fluid from 185 patients with possible VAP identified only one anaerobic organism, nonpathogenic Veillonella spp. This suggests that the practice of including anaerobic coverage in the treatment of VAP is unnecessary.]
PMNs greater than what amount in the peritoneal fluid is diagnostic of spontaneous bacterial peritonitis?
PMNs greater than 500 cells/cc fluid
[UpToDate: Spontaneous bacterial peritonitis (SBP) is typically diagnosed if there is an elevated ascitic fluid absolute polymorphonuclear cell (PMN, also referred to as neutrophils) count (≥250 cells/mm3), a positive ascitic fluid bacterial culture, and absence of secondary causes of peritonitis, such as bowel perforation. However, in some cases, additional tests may be needed to support the diagnosis or to differentiate SBP from secondary bacterial peritonitis.
Fungal infection with which organism is most commonly associated with pulmonary and CNS symptoms and can be diagnosed by visualizing partially acid-fast filamentous branching rods in clinical specimens?
Nocardia
[Not a true fungus]
[UpToDate: Nocardiosis is caused by an aerobic actinomycete in the genus Nocardia, an unusual gram-positive bacteria. Nocardial infection most often occurs in immunocompromised patients.
The most common disease sites are the lung, central nervous system (CNS), and skin. There are no pathognomonic signs or symptoms for nocardiosis. It should be suspected in any patient who presents with brain, soft tissue, or cutaneous lesions and a concurrent or recent pulmonary process.
The lungs are the primary site of nocardial infection in more than two-thirds of cases. The onset of pulmonary nocardiosis may be acute, subacute, or chronic and is not distinguished by any specific signs or symptoms.
Radiographic findings of lung involvement are variable and include single or multiple nodules, lung masses (with or without cavitation), reticulonodular infiltrates, interstitial infiltrates, lobar consolidation, subpleural plaques, and pleural effusions.
CNS disease accounts for approximately 20% of Nocardia cases and most commonly results from dissemination of infection from a pulmonary or cutaneous site. The hallmark of CNS nocardiosis is formation of a parenchymal abscess that can occur in any region of the brain.
Four patterns of cutaneous disease occur: primary cutaneous, lymphocutaneous, cutaneous involvement from a disseminated focus, and mycetoma.
Most cutaneous disease results from the direct inoculation of organisms into the skin from trauma.
Disseminated nocardiosis is defined as two or more noncontiguous sites of involvement that may or may not include a pulmonary focus.]
What is the most common immune deficiency?
Malnutrition
[UpToDate: Most studies on nutritionally-determined immunosuppression have focused on protein-energy malnutrition. This is associated with a spectrum of immune defects including cutaneous anergy, diminished T cell mitogen responses, and decreased phagocytic cell function. Additional abnormalities include the following:
- The number of circulating T cells declines, while the percentage of natural killer (NK) cells rises.
- Serum immunoglobulin is normal or increased; however, specific antibody responses are impaired.
- Primary and secondary lymphoid organs are relatively depleted of cells, and lymphoid follicles are sparse.
An acute lowering of food intake may also severely affect immune function. One study, for example, found depression of circulating lymphocytes and IL-2 production following mitogen stimulation after a fast of only seven days.
Malnutrition predisposes to a greater incidence of clinically apparent infection and increased morbidity and mortality due to infection with the pathogens prevalent in a given geographic area. It is estimated that worldwide, for example, malnutrition leads to 10- and 30-fold increased mortality from pneumonia and gastroenteritis, respectively. In Latin America, malnutrition is a contributing factor in approximately 60% of the deaths due to infection. In a study conducted in rural Bangladesh, the severity of malnutrition was linked to the rate of symptomatic upper respiratory infection. Reduced blood levels of the hormone leptin may be an important pathway in the immune, endocrine, and neurologic dysregulation associated with starvation.
A similar spectrum of defects and increased susceptibility to infection has also been linked to restricted nutritional deficiencies of zinc, iron, folate, pyridoxine, and vitamin A.
Immune function returns to normal when proper nutritional balance is restored.]
Are upper or lower GI bleeds more common in HIV patients?
Lower GI bleeds are more common
[Upper GI bleed: Kaposi’s sarcoma, lymphoma. Lower GI bleed: CMV, bacterial, HSV]
What is the risk of a patient contracting HIV from a blood transfusion with HIV positive blood?
70%
[UpToDate: Tremendous progress has been made in understanding and decreasing the risk of human immunodeficiency virus (HIV) transmission from blood transfusion. The major interventions used to minimize this risk include questioning donors concerning HIV risk behaviors, laboratory testing for HIV antibody and minipool nucleic acid testing (MP-NAT), and inactivation of HIV in plasma derivatives (eg, albumin, intravenous immune globulin, and plasma-derived clotting factors). HIV transmission may still occur for the following reasons:
- Donations may be collected during the window period of infection, when the donor is infectious but has not yet developed positive HIV laboratory tests.
- Infection with variant strains of HIV that may escape detection by current assays.
- Testing or clerical errors.
Transfusion of window period units (ie, units from individuals who have been infected but who are in the window during which testing has not yet become positive) accounts for virtually all cases of transfusion-transmitted HIV. The window period is approximately 11 days with combined HIV antibody and MP-NAT testing.
The risk of transfusion-transmitted HIV infection in the US is one in approximately 1.5 to 2 million units.]
What is the treatment for Actinomyces infection?
Drainage and Penicillin G
[UpToDate: We recommend high-dose penicillin as the treatment of choice for actinomycosis. Initial intravenous therapy is required for larger lesions with abdominal abscesses or draining sinus tracts. The recommended dose is penicillin G (10 to 20 million units per day divided every four to six hours) for 4 to 6 weeks, followed by oral penicillin (2 to 4 g/day) or amoxicillin for 6 to 12 months. For penicillin-allergic patients, tetracycline, erythromycin, or clindamycin are acceptable alternatives.
Surgery is usually reserved for patients with extensive lesions with severe necrosis and large abscess formation and for removal of persistent fistulas, recurrent disease, or inability to rule out neoplasm. Patients who undergo resection should also be treated with high-dose antibiotic therapy.
With combined medical and surgical treatment, the outcome is favorable in more than 90% of cases. Mortality is rare.]
What is the ratio of anaerobic bacteria to aerobic bacteria in the colon?
1,000 to 1
Which drug may help prevent the development of cirrhosis in Hepatitis C patients?
Interferon
[UpToDate: The antifibrotic effects of the interferons were anticipated because they downregulate collagen gene transcription. This effect was hypothesized to explain the improvement in fibrosis seen in some studies of patients with hepatitis C virus (HCV) treated with interferon who did not achieve a sustained virologic response. Unfortunately, such a benefit was not confirmed in a large, multicenter clinical trial of maintenance interferon therapy.
Interferon gamma is another interferon that has inhibitory effects on hepatic stellate cell activation. It also reduces the expression of mRNAs of type I and IV collagen as well as fibronectin in activated hepatic stellate cells grown in tissue culture, inhibits stellate cell proliferation, and reduces smooth muscle actin expression. However, a randomized controlled trial was also negative. Efforts to target gamma interferon delivery to stellate cells could resurrect this approach.]
What are the 2 most common causes of impetigo, erysipelas, cellulitis, and folliculitis?
Staph and strep
[UpToDate: Impetigo — The principal pathogen is S. aureus. Beta-hemolytic streptococci (primarily group A, but occasionally other serogroups such as C and G) account for a minority of cases, either alone or in combination with S. aureus. The relative frequency of S. aureus infections has changed with time. It was predominant in the 1940s and 1950s, after which group A streptococci became more prevalent. Since the 1990s, S. aureus has become more common again.
Cellulitis and erysipelas — The most common cause of cellulitis is beta-hemolytic streptococci, most commonly group A Streptococcus or Streptococcus pyogenes; S. aureus (including methicillin-resistant strains) is a notable but less common cause. Gram-negative aerobic bacilli are identified in a minority of cases.
Folliculitis — S. aureus, a gram-positive bacterium, is the most common cause of bacterial folliculitis. “Impetigo of Bockhart” and “Bockhart impetigo” are alternative terms for superficial staphylococcal folliculitis. Both methicillin-sensitive and methicillin-resistant S. aureus (MRSA) can cause folliculitis. Folliculitis is among the infections contributing to the increasing prevalence of community-acquired MRSA infections.
Pseudomonas aeruginosa is a gram-negative bacterium and the cause of “hot tub folliculitis,” a form of folliculitis attributed to contact with water contaminated with Pseudomonas as a result of inadequate chlorine, bromine, or pH levels in whirlpools, hot tubs, or swimming pools. Bathing with contaminated sponges or nylon towels and use of contaminated rubber gloves are additional potential modes of acquisition.
Other organisms responsible for gram-negative folliculitis include Klebsiella, Enterobacter, and Proteus species. These bacteria are common causes of gram-negative folliculitis associated with long-term treatment with oral antibiotics (eg, tetracyclines) for acne vulgaris. Aeromonas hydrophila, another gram-negative organism, can cause folliculitis after recreational water exposure.]
When do abscesses usually occur after an operation?
7-10 days after operation
What is the risk of surgical site infection in a clean procedure (IE. hernia repair)?
2%
[UpToDate: A widely accepted wound classification system has been developed by the National Academy of Sciences and the National Research Council based upon the degree of expected microbial contamination during surgery. It stratifies wounds as clean, clean-contaminated, contaminated, or dirty using the following definitions:
Clean wounds are uninfected operative wounds in which no inflammation is encountered and the wound is closed primarily. By definition, a viscus (respiratory, alimentary, genital, or urinary tract) is not entered during a clean procedure.
Clean-contaminated wounds are operative wounds in which a viscus is entered under controlled conditions and without unusual contamination.
Contaminated wounds are open, fresh accidental wounds, operations with major breaks in sterile technique, or gross spillage from a viscus. Wounds in which acute, nonpurulent inflammation was encountered also were included in this category.
Dirty wounds are old traumatic wounds with retained devitalized tissue, foreign bodies, or fecal contamination or wounds that involve existing clinical infection or perforated viscus.
Several studies have found a moderate correlation between the wound classification and the SSI rate. SSI rates according to wound class were:
Clean – 1.3% to 2.9%
Clean-contaminated – 2.4% to 7.7%
Contaminated – 6.4% to 15.2%
Dirty – 7.1% to 40.0%
While widely used, this classification scheme may be a poor predictor of overall risk of SSI. Other factors, such as the operative technique, length of surgery, and health of the surgical patient, may be as important as wound classification in predicting infectious risks for SSI.
Available data suggest that the relative risk reduction of SSI from the use of antimicrobial prophylaxis is the same in clean and in higher-risk procedures. Antimicrobial prophylaxis is justified for most clean-contaminated procedures. The use of antimicrobial agents for dirty procedures or established infection is classified as treatment of presumed infection, not prophylaxis.]
Secondary spontaneous bacterial peritonitis is polymicrobial and most commonly caused by which 3 bacteria?
- Bacteriodes fragilis
- E. coli
- Enterococcus
What is the most common intestinal manifestation of AIDS?
CMV colitis
[Can present with pain, bleeding, or perforation]
[UpToDate: Cytomegalovirus (CMV) gastrointestinal disease is an uncommon but serious complication of AIDS. Prior to the availability of potent antiretroviral therapy (ART), CMV gastrointestinal disease occurred in up to 5% of patients with AIDS, primarily in those with advanced immunosuppression. However, the incidence of CMV gastrointestinal disease has decreased substantially since ART became available.]
Which bacteria is found in dog and cat bites?
Pasteurella multocida
[UpToDate: The predominant pathogens in animal bite wounds are the oral flora of the biting animal and human skin flora. About 85% of bites harbor potential pathogens, and the average wound yields five types of bacterial isolates; 60% have mixed aerobic and anaerobic bacteria. Skin flora such as staphylococci and streptococci are isolated in about 40% of bites.
Pasteurella species are isolated from 50% of dog bite wounds and 75% of cat bite wounds. Capnocytophaga canimorsus, a fastidious gram-negative rod, can cause bacteremia and fatal sepsis after animal bites, especially in asplenic patients or those with underlying hepatic disease. Anaerobes isolated from dog and cat bite wounds include Bacteroides, fusobacteria, Porphyromonas, Prevotella, propionibacteria, and peptostreptococci.]
With central line cultures, what is the criteria for a line infection?
Greater than 15 colony forming units
[UpToDate: In general, the diagnostic approach to catheter-related bloodstream infection (CRBSI) consists of clinical evaluation and microbiologic confirmation with peripheral blood and catheter cultures. CRBSI should be suspected when bloodstream infection occurs in the setting of a central venous catheter with no other apparent source.
Fever is the most sensitive clinical manifestation. Other clinical manifestations include hemodynamic instability, altered mental status, catheter dysfunction, and clinical signs of sepsis that start abruptly after catheter infusion.
Cultures of blood and catheters should be pursued in the setting of clinical suspicion for CRBSI when the local microbiology laboratory has appropriate resources for such testing. Blood cultures positive for S. aureus, coagulase-negative staphylococci, or Candida species in the absence of other identifiable sources of infection should increase the suspicion for CRBSI.
Paired blood samples drawn from the catheter and a peripheral vein should be obtained for culture prior to initiation of antibiotic therapy. Microbiologic confirmation of CRBSI may be made based on blood culture data meeting one of the following criteria:
- Culture of the same organism from both the catheter tip and at least one percutaneous blood culture.
- Culture of the same organism from at least two blood samples (one from a catheter hub and the other from a peripheral vein or second lumen) meeting criteria for quantitative blood cultures or differential time to positivity.
Most laboratories do not perform quantitative blood cultures, but many laboratories are able to determine differential time to positivity (DTP). DTP refers to growth detected from the catheter hub sample at least two hours before growth detected from the peripheral vein sample.
Catheter cultures should be performed when a catheter is removed for suspected CRBSI; there is no role for routine catheter cultures in the absence of clinical suspicion for infection. Catheter colonization is established by the following quantitative definitions:
- Semiquantitative broth culture growth of >15 colony forming units (CFU) from a 5 cm segment of the catheter tip by roll-plate culture. Short-term catheter tips should be evaluated using this technique.
- Quantitative broth culture of >102 CFU from a catheter by sonication by broth culture.]
What is the leading cause of infectious death after surgery?
Nosocomial pneumonia
[Related to the length of ventilation; aspiration from duodenum thought to have a role]
[UpToDate: Pulmonary complications are a major cause of morbidity and mortality during the postoperative period. The reported incidence of postoperative pulmonary complications ranges from 5% to 80%, depending upon the patient population and the criteria used to define a complication. The incidence also varies across hospitals, with one study reporting lower rates of complications in hospitals with a high volume of patients than in hospitals with a lower volume following esophagectomy, pancreatectomy, and intact abdominal aortic aneurysm repair.
Traditional definitions of postoperative pulmonary complications include atelectasis, bronchospasm, pneumonia, and exacerbation of chronic lung disease. However, the list can be expanded to include acute upper airway obstruction, complications from obstructive sleep apnea, pleural effusions, chemical pneumonitis, pulmonary edema, hypoxemia due to abdominal compartment syndrome, and tracheal laceration or rupture. Recognition and management of these postoperative pulmonary complications are reviewed here.
Postoperative pneumonia tends to occur within five postoperative days. It has clinical manifestations and a diagnostic approach that is nearly identical to other types of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Postoperative pneumonia is frequently caused by resistant organisms, such as Gram-negative bacteria and Staphylococcus aureus, or multiple organisms. The management of postoperative pneumonia involves collection of respiratory specimens for microbiological analysis, followed by the initiation of empiric antimicrobial therapy. Once the microbiological data has been reported and the patient’s response to empiric therapy assessed, the antimicrobial regimen should be tailored.]
Which 2 drugs can help decrease seroconversion after exposure to HIV?
- AZT (Zidovudine, reverse transcriptase inhibitor)
- Ritonavir (Protease inhibitor)
[Seroconversion occurs in 6-12 weeks]
[UpToDate: We offer post-exposure prophylaxis (PEP) using a three-drug regimen to healthcare personnel (HCP) with a percutaneous, mucous membrane, or nonintact skin exposure to body fluids of concern (eg, blood or blood tinged fluids) if the source patient is, or is suspected to be, HIV-infected.
PEP should be discontinued if testing shows that the source patient is HIV-negative, unless there is concern that the source is acutely infected with HIV.
We prefer the following PEP regimens for HCP with an occupational exposure to HIV, provided the source does not have detectable virus with known resistance to these agents. The following regimens include a nucleoside/tide (NRTI) combination plus an integrase inhibitor:
- Tenofovir-emtricitabine (300/200 mg once daily) plus dolutegravir (50 mg once daily)
- Tenofovir-emtricitabine (300/200 mg once daily) plus raltegravir (400 mg twice daily)
Acceptable alternatives include tenofovir-emtricitabine with a boosted protease inhibitor (ritonavir-boosted darunavir or ritonavir-boosted atazanavir). In this situation, we prefer tenofovir-emtricitabine (300/200 mg once daily) plus darunavir (800 mg once daily) and ritonavir (100 mg once daily) since darunavir appears to be better tolerated than atazanavir. However, we do not generally administer darunavir to patients with a sulfa allergy since darunavir contains a sulfonamide moiety.]
Which bacteria is found only in human bites?
Eikenella
[Can cause permanent join injury]
[UpToDate: The pathogens involved in human bite wound infections usually reflect normal human mouth and skin flora. The types of organisms recovered differ from animal bites:
- Pasteurella multocida is a rare isolate.
- Eikenella corrodens, a gram-negative anaerobe, is a common constituent of normal human mouth flora and is recovered from 7% to 29% of human bite wounds but rarely from animal bites.
- Aerobic gram-positive cocci (eg, Group A Streptococcus) and anaerobes are found more frequently in bites from humans than from other animals.
There are no comparative antibiotic trials for treatment of human bite infections. Antibiotic agents should be selected based on their activity against potential flora including S. aureus, E. corrodens, H. influenzae, and beta-lactamase–producing oral anaerobic bacteria.
Agents lacking activity against Eikenella corrodens should be avoided; these include first-generation cephalosporins (such as cephalexin), penicillinase-resistant penicillins (such as dicloxacillin), macrolides (such as erythromycin), clindamycin, and aminoglycosides. However, clindamycin may be used for anaerobic coverage if it is administered in conjunction with an additional agent that is active against E. corrodens.]
What are the percentages of patients infected with Hepatitis C that develop each of the following?
- Chronic infection
- Cirrhosis
- Hepatocellular carcinoma
- Chronic infection: 60%
- Cirrhosis: 15%
- Hepatocellular carcinoma: 1%-5%
[UpToDate: Following infection with the hepatitis C virus (HCV), chronic infection typically occurs, with approximately 50% to 85% of cases developing chronic hepatitis. However, chronic HCV infection is usually slowly progressive and may not result in clinically apparent liver disease in many patients. Approximately 5% to 30% of chronically infected individuals develop cirrhosis over a 20- to 30-year period of time.
HCV-associated mortality is more likely to be due to end stage liver disease rather than hepatocellular carcinoma. Nevertheless, in the United States, HCV accounts for approximately one-third of hepatocellular carcinoma cases. Estimates of the risk of developing hepatocellular carcinoma once cirrhosis has developed have varied from 0% to 3% per year in various reports.
In contrast to hepatitis B virus infection, hepatocellular carcinoma in patients with HCV occurs almost exclusively in those with cirrhosis, suggesting that cirrhosis is the major risk factor. One study found that obesity may also be an independent risk factor. There is also suggestive experimental evidence that HCV infection itself can promote the development of hepatocellular carcinoma. Mice that were made transgenic for the HCV core gene developed adenomas and subsequent carcinoma within the adenomas.]
What are the 3 most common bacteria responsible for line infections?
- Staph epidermidis
- Staph aureus
- Yeast
[UpToDate: Prior to the 1980s, gram-negative aerobes were the predominant organisms associated with nosocomial bloodstream infections. Since then, gram-positive aerobes (eg, coagulase-negative staphylococci, S. aureus, and Enterococcus), and Candida species have increased in relative importance. As an example, the following distribution of pathogens was noted in the prospective analysis from the Surveillance and Control of Pathogens of Epidemiologic Importance (SCOPE) database cited above of 24,179 nosocomial bloodstream infections (BSIs) occurring in 49 hospitals in the United States between 1995 and 2002:
- Coagulase-negative staphylococci – 31%
- Staphylococcus aureus – 20%
- Enterococci – 9%
- Candida species – 9%
- Escherichia coli – 6%
- Klebsiella species – 5%
- Pseudomonas species – 4%
- Enterobacter species – 4%
- Serratia species – 2%
- Acinetobacter baumannii – 1%
Subsequent surveillance reports in the United States and Europe have documented similar microbiological distributions, with coagulase-negative staphylococci, S. aureus, enterococci, and candidal species accounting for the majority of catheter-related bloodstream infections.]
What are the CD4 count ranges for normal individuals, symptomatic HIV patients, and HIV patients prone to opportunistic infections?
- Normal: 800-1200
- Symptomatic: 300-400
- Opportunistic infection: Less than 200
[UpToDate: The normal adult CD4 count for most laboratories falls in a range of 800 to 1050 cells/mm3; furthermore, when considering laboratory variations of two standard deviations, the normal CD4 cell count range falls within 500 to 1400 cells/mm3. This broad range in normal values reflects the fact that the CD4 cell count is the product of three variables: the white blood cell count, the percentage of lymphocytes, and the percentage of lymphocytes that bears the CD4 receptor.
A CD4 count of <200 cells/mm3 indicates the clinical stage of AIDS, which implies a high susceptibility to opportunistic infections, such as Pneumocystis pneumonia.]
What is the most common infection in surgery patients?
Urinary tract infection
[Most commonly E. coli]
The microflora of which part of the gastrointestinal tract is virtually sterile, with some gram positive cocci and some yeast?
Stomach
What will a CT head show in a patient with sinusitis?
Air-fluid levels in the sinus
[UpToDate: Normal imaging can rule out sinusitis; however, abnormal imaging is not useful in the diagnosis of acute rhinosinusitis, as healthy adults often have abnormal sinuses on imaging. Imaging also does not distinguish between viral and bacterial etiology.
Common findings of sinusitis on CT scan include air-fluid levels, mucosal edema, and air bubbles within the sinuses. CT findings are not specific for sinusitis. Mucosal abnormality on CT scan may be observed in as many as 42% of asymptomatic healthy individuals. Abnormalities in the sinuses are also often seen in patients with the common cold.
CT scan without contrast may be used to evaluate for findings of sinusitis and can be used to rule out sinusitis. When concerned about complications of sinusitis, CT scan with contrast or magnetic resonance imaging (MRI) should be used.]
Which bacteria is the most common cause of gram-negative sepsis?
E. coli
[UpToDate: Gram-negative bacilli are the cause of approximately a quarter to a half of all bloodstream infections, depending on geographic region, hospital- or community-onset, and other patient risk factors. Most hospitalized patients with gram-negative bacteremia have at least one comorbid condition, such as diabetes, liver or kidney failure, and immunosuppression.
The frequency of specific gram-negative bacilli responsible for bacteremia differs by whether the onset of the infection is in the hospital or community and by the likely primary source of infection. As an example, Pseudomonas aeruginosa is a frequent pathogen in hospital-onset infections, particularly those that occur in intensive care unit patients. In contrast, community-acquired infections are most often secondary to urinary tract infections, among which Escherichia coli predominate.]
What is the treatment for Cryptococcus infection?
Liposomal amphotericin for severe infections
[UpToDate: Treatment of Cryptococcus neoformans meningoencephalitis consists of antifungal therapy, management of intracranial pressure and reducing immunosuppressive therapy. The choice of the antifungal regimen varies depending on the nature of the host and extent of disease.
Patients with severe pulmonary disease (eg, diffuse pulmonary infiltrates) or disseminated disease (eg, at least two noncontiguous sites or cryptococcal antigen titer ≥1:512) should be managed as for central nervous system disease, even in the setting of normal findings on spinal fluid examination.
We suggest that organ transplant recipients with cryptococcal meningoencephalitis receive induction therapy with amphotericin B plus flucytosine (Grade 2B). We suggest lipid formulation amphotericin agents over amphotericin B deoxycholate (Grade 2B). Dosing is liposomal amphotericin B (3 to 4 mg/kg IV daily) or amphotericin B lipid complex (5 mg/kg IV daily) plus flucytosine (100 mg/kg per day orally in four divided doses, adjusted for renal function) for at least two weeks.
We suggest that non-HIV infected, non-transplant hosts with cryptococcal meningoencephalitis receive induction therapy with amphotericin B deoxycholate plus flucytosine (Grade 2B). Dosing is amphotericin B deoxycholate (0.7 to 1.0 mg/kg IV daily) plus flucytosine (100 mg/kg per day orally in four divided doses) for at least 4 weeks; a 2 week induction period of combination therapy is appropriate for patients with good responses and prognosis. In patients with renal insufficiency, liposomal amphotericin B (3 to 4 mg/kg IV daily) or amphotericin B lipid complex (5 mg/kg IV daily) may be substituted for amphotericin B.
Patients who present with positive baseline CSF cultures, severe symptoms, or significant underlying immunosuppression should undergo repeat lumbar puncture after two weeks of induction therapy; lumbar puncture may be repeated sooner for management of increased intracranial pressure or concern about potential microbiologic failure.
Patients whose cerebrospinal fluid (CSF) cultures remain positive despite two weeks of induction therapy should continue the induction regimen with serial lumbar punctures every two weeks until the CSF becomes sterile.
We recommend consolidation and maintenance therapy following induction therapy (Grade 1A). We suggest that consolidation therapy with fluconazole (400 to 800 mg [6 to 12 mg/kg] per day orally) for eight weeks be administered, followed by maintenance therapy with fluconazole (200 to 400 mg per day orally) for 6 to 12 months (Grade 2C).
We suggest that non-HIV-infected, non-transplant hosts with cerebral cryptococcoma receive induction with amphotericin B deoxycholate, liposomal amphotericin B, or amphotericin B lipid complex plus flucytosine (Grade 2C). Dosing is amphotericin B deoxycholate (0.7 to 1.0 mg/kg IV daily), liposomal amphotericin B (3 to 4 mg/kg IV daily) or amphotericin B lipid complex (5 mg/kg IV daily) plus flucytosine (100 mg/kg per day orally in four divided doses, adjusted for renal function) for at least 6 weeks. We suggest consolidation and maintenance therapy with fluconazole (Grade 2C). Dosing is fluconazole (400 to 800 mg per day orally) for 6 to 18 months.]
When should prophylactic antibiotics to prevent surgical site infections be stopped after surgery?
Within 24 hours of end of operation time
[Antibiotics are stopped within 48 hours of end of operation time in cardiac surgery]
[UpToDate: Antimicrobial therapy should be initiated within the 60 minutes prior to surgical incision to optimize adequate drug tissue levels at the time of initial incision. The half-life of the antibiotic should be considered; administration of vancomycin or a fluoroquinolone should begin within 120 minutes before surgical incision because of the prolonged infusion times required for these drugs. Some studies suggest lower infection risk with initiation of antimicrobial administration within 30 minutes before surgical incision, although thus far data are insufficient to support this approach as a routine practice. If the 60-minute window for prophylaxis has passed, antimicrobial administration 30 to 60 minutes prior to incision appears to be more effective than administration immediately before surgical incision
In general, repeat antimicrobial dosing following wound closure is not necessary and may increase the risk for development of antimicrobial resistance. In a systematic review of randomized trials, there was no difference in the rate of SSI with single dose compared with multiple-dose regimens given for less than or more than 24 hours (combined odds ratio 1.04, 95% CI 0.86-1.25).
For cases in which prophylaxis beyond the period of surgery is warranted, in general, the duration should be less than 24 hours.]
What is a carbuncle?
A multiloculated furuncle (boil)
[UpToDate: A carbuncle is a coalescence of several inflamed follicles into a single inflammatory mass with purulent drainage from multiple follicles.]
What is the treatment for peritoneal dialysis catheter infections?
Intraperitoneal vancomycin and gentamicin
[Increased dwell time and intraperitoneal heparin may help]
[UpToDate: As noted in the 2010 International Society for Peritoneal Dialysis (ISPD) guidelines, oral antibiotic therapy is as effective as intraperitoneal antibiotic therapy, with the exception of the treatment of methicillin-resistant S. aureus.
If the patient has a history of methicillin-resistant S. aureus (MRSA) and there is drainage from the exit site, most centers would obtain a culture and treat with an appropriate antibiotic to cover MRSA. At our center, in these cases, we use oral cephalexin or ciprofloxacin for broad-spectrum coverage and also give intraperitoneal vancomycin to cover possible MRSA.
Mild infection can be treated with topical antimicrobial agents, such as chlorhexidine and dilute hydrogen peroxide. Moderate infection with drainage requires culture of drainage and an oral antibiotic. Gram stain of the drainage or the microbiologic history of a preceding exit-site infection can help to direct therapy. If a gram-negative infection is suspected, the patient should be treated with an antipseudomonal antibiotic such as ciprofloxacin. Empiric therapy may need to be based on local patterns of infection and resistance and also based on the type of exit-site antimicrobial prophylaxis being used.
If the exit site remains infected after two weeks of antibiotics, compliance should be ensured and a thorough repeat examination performed. One should also examine the exit site to see if the external cuff is exposed since an exposed cuff may cause infection. Ultrasonography, computed tomography (CT) scanning, or less often gallium scanning may be performed to exclude an abscess. If the cuff is not exposed and there is no evidence of abscess or tunnel infection, additional antibiotic therapy may be attempted or salvage techniques may be employed to rescue the infected catheters.
Catheter removal is required for some exit-site and tunnel infections such as those complicated by a tunnel abscess or peritonitis, or if the infection does not respond or progresses after several weeks of antibiotic therapy. In all cases, perioperative antibiotics should be given and then continued for one to two weeks after catheter removal.
If there is no peritonitis associated with the exit-site infection, the infected catheter can be removed and a new catheter placed simultaneously in the opposite lower quadrant. A new catheter should not be placed at the time the infected catheter is removed if active peritonitis is present.
The first step in the evaluation of recurrent exit-site infection is to determine if the patient received a complete course of therapy for the first infection and if the organism responsible was sensitive to the antibiotic prescribed. Breaks in the proper maintenance and hygiene of the exit site should be identified and the patient retrained as necessary. Tunnel infection should be excluded by ultrasonography or CT scanning. Mupirocin or gentamicin should be considered.]
When does hyperglycemia often occur in gram-negative sepsis?
Just before the patient becomes clinically septic
What is the treatment for primary spontaneous bacterial peritonitis?
Ceftriaxone or other 3rd generation Cephalosporins
[Liver transplant is not an option with active infection]
[UpToDate: In patients receiving a nonselective beta blocker, we permanently discontinue the medication once SBP has developed because nonselective beta blocker use in this setting has been associated with decreased transplant-free survival, increased rates of hepatorenal syndrome, and more days of hospitalization compared with patients not receiving nonselective beta blockers.
For patients with suspected SBP, while awaiting culture results, we suggest treatment with a third-generation cephalosporin (eg, cefotaxime) rather than narrower coverage (Grade 2C). Antibiotics used for the treatment of SBP should provide good coverage for the organisms commonly associated with SBP (eg, E. coli, Klebsiella) and should achieve good ascitic fluid levels. Cefotaxime (2 g intravenously every eight hours) or a similar third-generation cephalosporin provides appropriate microbial coverage and attains good ascitic fluid levels. A fluoroquinolone (eg, levofloxacin) is an alternative in patients who are allergic to penicillin. The selection of antibiotics for SBP should include consideration of local resistance patterns and recent antibiotic use (eg, a fluoroquinolone should not be used in a patient who has been receiving SBP prophylaxis with a fluoroquinolone). Antibiotic therapy should be tailored once the results of sensitivity testing are available.
We suggest treating most patients with SBP for five days rather than a longer course of therapy (Grade 2B). A longer course of therapy is appropriate for patients who grow an unusual organism (eg, pseudomonas, Enterobacteriaceae), an organism resistant to standard antibiotic therapy, or an organism routinely associated with endocarditis (eg, S. aureus or viridans group streptococci). In addition, a longer course of therapy is required for patients who fail to respond to therapy appropriately.
After five days of treatment, we reassess the patient. Treatment is discontinued if there has been the usual dramatic improvement. However, if fever or pain persists, paracentesis is repeated, and the decision to continue or discontinue treatment is determined by the PMN response:
- If the PMN count is <250 cells/mm3, treatment is stopped
- If the PMN count is greater than the pretreatment value, a search for a surgical source of infection is undertaken
- If the PMN count is elevated but less than the pretreatment value, antibiotics are continued for another 48 hours, and the paracentesis is repeated.]
Is fulminant hepatic failure common or rare in individuals infected with Hepatitis C?
Rare
[UpToDate: Acute liver failure is characterized by acute liver injury, hepatic encephalopathy, and an elevated prothrombin time/international normalized ratio (INR). It has also been referred to as fulminant hepatic failure, acute hepatic necrosis, fulminant hepatic necrosis, and fulminant hepatitis. Untreated, the prognosis is poor, so timely recognition and management of patients with acute liver failure is crucial. Whenever possible, patients with acute liver failure should be managed in an intensive care unit at a facility capable of performing liver transplantation.
Viral and drug-induced hepatitis are the most common causes of acute liver failure in adults. In Australia, Denmark, the United Kingdom, and the United States, acetaminophen is the most common cause of acute liver failure, whereas in Asia and some other parts of Europe, viral hepatitis predominates.
Acute liver failure is estimated to develop in 0.35% of patients with hepatitis A and in 0.1% to 0.5% of patients with acute hepatitis B. However, the incidence of acute liver failure from hepatitis B may be underestimated. Precore or pre-S mutant hepatitis B viruses that are able to produce infection but do not produce hepatitis B e antigen (precore mutants) or surface antigen (pre-S mutants) may be difficult to diagnose by routine serology. Thus, liver failure in such patients may be erroneously attributed to cryptogenic causes. This was illustrated in a study in which evidence of hepatitis B infection was detected by polymerase chain reaction (PCR) in 6 of 17 patients (35%) who underwent liver transplantation for what was initially thought to be non-A, non-B hepatitis.
In addition to acute hepatitis B, acute liver failure may also develop in patients who are receiving chemotherapy or immunosuppression and have reactivation of previously inactive hepatitis B.
Hepatitis C virus alone does not appear to be a significant cause of acute liver failure in the absence of coinfection with hepatitis B. In a study of 109 patients with acute hepatitis C, acute liver failure developed in 11 (10%), 9 of whom had concurrent hepatitis B infection.]
Which antibiotic is effective in prophylaxis of primary spontaneous bacterial peritonitis?
Fluoroquinolones (IE Norfloxacin)
[UpToDate: Antibiotic prophylaxis for patients with risk factors for spontaneous bacterial peritonitis (SBP) (including ascitic fluid protein concentration <1 g/dL, variceal hemorrhage, or a prior episode of SBP) decreases the risk of bacterial infection and mortality. Prophylactic regimens include:
- History of SBP: Prolonged outpatient trimethoprim-sulfamethoxazole therapy (one double-strength tablet once daily) or fluoroquinolone therapy (eg, ciprofloxacin 500 mg/day or norfloxacin 400 mg/day [not available in the United States]).
- Inpatients with an ascitic protein concentration of less than 1 g/dL or <1.5 g/dL (10 or 1.5 g/L) who are hospitalized for a reason other than SBP or gastrointestinal bleeding: Treatment with trimethoprim-sulfamethoxazole (one double-strength tablet once daily) or fluoroquinolone therapy (ciprofloxacin 500 mg/day or norfloxacin 400 mg/day) while hospitalized. In the United States, the 1 g/dL threshold was validated whereas in the EU 1.5 g/dL was studied.
- Patients with cirrhosis and gastrointestinal bleeding: Initial treatment for patients with Child-Pugh class B or C cirrhosis is with intravenous ceftriaxone (1 g intravenously daily) followed by trimethoprim-sulfamethoxazole (one double-strength tablet twice daily), oral ciprofloxacin (500 mg orally every 12 hours), or norfloxacin (400 mg orally twice daily where available) once the patient is able to take medications by mouth. Patients with Child-Pugh class A cirrhosis can be managed with norfloxacin (400 mg orally twice daily; not available in the United States), trimethoprim-sulfamethoxazole (one double-strength tablet twice daily), or ciprofloxacin (500 mg orally every 12 hours or 400 mg IV every 12 hours). The total number of days of antibiotic (parenteral and oral) is seven days.
In addition to decreasing infection rates and lowering mortality, prophylactic antibiotics may have the beneficial effects of increasing blood pressure and systemic vascular resistance. These hemodynamic improvements, if sustained, may delay development of hepatorenal syndrome.]
Which 2 bacteria are the most common cause of peritoneal dialysis catheter infections?
Staph aureus and staph epidermidis
[UpToDate: In a peritoneal dialysis population receiving no antimicrobial prophylaxis, approximately one-half of healthy exit sites are colonized by Staphylococcus aureus, which also accounts for over 50% of exit-site infections. In these cases, other causes of bacterial exit-site infection include Staphylococcus epidermidis (20%), Pseudomonas aeruginosa (8%), and Escherichia coli (4%). Nasal carriage of S. aureus, common among patients undergoing peritoneal dialysis, also increases the risk of recurrent exit-site infections
In most cases, a Staphylococcus species (primarily aureus or epidermidis) will be responsible for the infection. Therefore, empiric therapy can be begun with a first-generation oral cephalosporin or a penicillinase-resistant penicillin. Given the increased incidence of vancomycin-resistant organisms, vancomycin should not be used in routine therapy. As noted in the 2010 International Society for Peritoneal Dialysis (ISPD) guidelines, oral antibiotic therapy is as effective as intraperitoneal antibiotic therapy, with the exception of the treatment of methicillin-resistant S. aureus.]
What is the risk of surgical site infection in a contaminated procedure (IE. gunshot wound to colon with repair)?
5-10%
[UpToDate: A widely accepted wound classification system has been developed by the National Academy of Sciences and the National Research Council based upon the degree of expected microbial contamination during surgery. It stratifies wounds as clean, clean-contaminated, contaminated, or dirty using the following definitions:
- Clean wounds are uninfected operative wounds in which no inflammation is encountered and the wound is closed primarily. By definition, a viscus (respiratory, alimentary, genital, or urinary tract) is not entered during a clean procedure.
- Clean-contaminated wounds are operative wounds in which a viscus is entered under controlled conditions and without unusual contamination.
- Contaminated wounds are open, fresh accidental wounds, operations with major breaks in sterile technique, or gross spillage from a viscus. Wounds in which acute, nonpurulent inflammation was encountered also were included in this category.
- Dirty wounds are old traumatic wounds with retained devitalized tissue, foreign bodies, or fecal contamination or wounds that involve existing clinical infection or perforated viscus.
Several studies have found a moderate correlation between the wound classification and the SSI rate. SSI rates according to wound class were:
- Clean – 1.3% to 2.9%
- Clean-contaminated – 2.4% to 7.7%
- Contaminated – 6.4% to 15.2%
- Dirty – 7.1% to 40.0%
While widely used, this classification scheme may be a poor predictor of overall risk of SSI. Other factors, such as the operative technique, length of surgery, and health of the surgical patient, may be as important as wound classification in predicting infectious risks for SSI.
Available data suggest that the relative risk reduction of SSI from the use of antimicrobial prophylaxis is the same in clean and in higher-risk procedures. Antimicrobial prophylaxis is justified for most clean-contaminated procedures. The use of antimicrobial agents for dirty procedures or established infection is classified as treatment of presumed infection, not prophylaxis.]
What is the treatment for Aspergilla infection (Aspergillosis)?
Voriconazole for severe infections
[UpToDate: Aspergillus species are ubiquitous, but invasive aspergillosis occurs primarily in immunocompromised hosts. Neutropenia and glucocorticoid use are the most common predisposing factors. Invasive aspergillosis is a major cause of death in immunosuppressed patients, particularly following hematopoietic cell transplantation (HCT).
Optimal management involves early diagnosis and early initiation of antifungal therapy. Surgery and reduction of immunosuppression are important adjunctive components of management in selected patients.
For initial therapy of patients with confirmed invasive aspergillosis (ie, diagnosed by culture, galactomannan antigen, or histopathology), we recommend a voriconazole-based regimen rather than an amphotericin B–based regimen (Grade 1A). We also suggest the addition of an echinocandin to voriconazole for the first one to two weeks of therapy, particularly in patients with severe disease (Grade 2B). However, some experts prefer monotherapy with voriconazole. Dosing is discussed above.
In patients who are intolerant of voriconazole due to severe reactions, we suggest switching from voriconazole to either a lipid formulation of amphotericin B (AmBisome or Abelcet [ABLC]) (Grade 2B) or isavuconazole (Grade 2B). The decision of which agent to choose depends on organ dysfunction, toxicities, and tolerability.]
What is the treatment for a Candida infection?
Fluconazole (some candida are resistant)
[Anidulafungin for severe infections]
[UpToDate: For nonneutropenic and neutropenic patients with candidemia, we recommend an echinocandin rather than fluconazole or amphotericin B. The echinocandins are administered intravenously as follows:
- Caspofungin is given at an initial dose of 70 mg on the first day of treatment, followed by 50 mg daily; dose reduction is required with hepatic dysfunction.
- Anidulafungin is given at an initial dose of 200 mg on the first day, followed by 100 mg daily.
- Micafungin is given at a dose of 100 mg daily for candidemia; no loading dose is needed.
Nonneutropenic and neutropenic patients who are clinically stable, who have Candida isolates that are susceptible to fluconazole, and who have negative repeat blood cultures can be transitioned to oral fluconazole after 5 to 7 days. For most Candida species, fluconazole should be given at a dose of 400 mg (6 mg/kg) orally once daily for step-down therapy.
Blood cultures should be checked daily or every other day after initiating antifungal therapy until they become negative.]
What are 6 risk factors for wound infection?
- Long operation
- Hematoma or seroma formation
- Advanced age
- Chronic disease (COPD, renal failure, liver failure, diabetes)
- Malnutrition
- Immunosuppressive drugs
[UpToDate: Factors that may impact the rate of SSIs (apart from antimicrobial prophylaxis) include:
- Attention to basic infection control strategies
- Surgical technique
- Prolonged duration of surgery
- Hospital and operating room environments
- Instrument sterilization
- Preoperative preparation (surgical scrub, skin antisepsis)
- Perioperative management (thermoregulation, glycemic control)
- Underlying medical condition of the patient
Several factors related to the surgical environment and operative practices have been identified as risk factors for SSI. These include:
- Preoperative hair removal (particularly shaving)
- Inordinate personnel traffic during an operation
- Excessive use of electrosurgical cautery units
- Presence of a prosthesis or other foreign body
- Degree of tissue trauma
- Need for blood transfusion
Whether an SSI occurs is dependent upon a complex interaction between numerous factors including the nature and number of organisms contaminating the surgical site, the health of the patient, and the technique of the surgeon. Several other patient characteristics have been identified as risk factors for SSI, including:
- Age
- Diabetes
- Obesity
- Cigarette smoking
- Immunosuppression
- Malnutrition
- Preoperative colonization with potentially pathogenic microorganisms
- Presence of infection at a nonsurgical site
- History of prior skin infection
- Recent surgery
- Duration of preoperative hospitalization
- Severity of underlying illness(es)
A cohort study including more than 1500 patients used telephone follow-up one month after surgery to contact 98% of patients. Predictors of SSI for patients in the immediate postoperative period while still hospitalized were not the same as predictors for patients who developed infection following discharge. Predictors of SSI following discharge included obesity, age, and improperly timed antibiotic prophylaxis.]
What causes primary spontaneous bacterial peritonitis?
Decreased host defenses (intrahepatic shunting, impaired bacteriocidal activity in ascities)
[Not due to transmucosal migration]
[UpToDate: One of the early steps in the development of SBP is a disturbance in gut flora with overgrowth and extraintestinal dissemination of a specific organism, most commonly Escherichia coli. Cirrhosis predisposes to the development of bacterial overgrowth, possibly because of altered small intestinal motility, and the presence of hypochlorhydria due to use of proton pump inhibitors. In addition, patients with cirrhosis may have increased intestinal permeability.
However, the role of bacterial overgrowth in the pathogenesis of SBP remains unsettled. In one study, small bowel motility and bacterial overgrowth were compared in 20 patients with cirrhosis and a history of SBP and 20 patients with cirrhosis without a history of SBP. The prevalence of bacterial overgrowth was higher in the patients with a history of SBP (70% vs 20%); these patients also exhibited more severe small intestinal motility disturbances. In contrast, in another study, the presence of bacterial overgrowth was not associated with the development of SBP.
Whether or not they are present in increased numbers, bacteria within the gut lumen can traverse the intestinal wall, and colonize mesenteric lymph nodes. This phenomenon is called translocation and has been documented to occur in animal models of cirrhosis and SBP. Bacterascites can occur if the lymphatic carrying the contaminated lymph ruptures because of the high flow and high pressure associated with portal hypertension. Alternatively, the organism can move from the mesenteric lymphatics to the systemic circulation and then percolate through the liver and weep across Glisson’s capsule to enter the ascitic fluid.
Several studies have demonstrated that bacterial translocation is also increased in patients with advanced cirrhosis. In an illustrative study, mesenteric lymph nodes were obtained from 101 patients with cirrhosis and from 35 non-cirrhotic controls. Enteric organisms were grown from culture in only 8.6% of controls compared to 3.4%, 8.1%, and 30.8% of patients with Child class A, B, and C cirrhosis, respectively. Selective intestinal decontamination reduced the rate of positive cultures to that of non-cirrhotic patients.
Other studies have shown molecular evidence of bacterial translocation and suggested that it occurs prior to the development of clinical SBP. Patients with cirrhosis and ascites can have bacterial DNA in their serum and ascitic fluid even when viable organisms cannot be cultured. Low levels of translocation of intact bacteria or pieces of bacteria may lead to activation of tumor necrosis factor (TNF), which may explain the higher levels of TNF that have been observed in patients who ultimately develop SBP compared with controls. The presence of bacterial DNA in serum and ascitic fluid is a risk factor for death in patients with cirrhosis. Proton pump inhibitors increased bacterial translocation in an animal model of SBP and also increase the risk of SBP in humans. Proton pump inhibitors have also been shown in humans to decrease phagocyte oxidative burst; this could further handicap defenses against resident bacteria.
Bacteria that eventually cause SBP can also originate in sites other than the gut via bacteremic seeding. These include urinary tract infections, pneumococcal sepsis, cellulitis, pharyngitis, and dental infections. These infections are labeled “spontaneous” because they are not amenable to surgical therapy. Surgically treatable infections, eg, perforated duodenal ulcer, that lead to ascitic fluid infection are called secondary bacterial peritonitis. The pathogenesis of this form of peritonitis is quite different than that of SBP; millions of bacteria flood into the peritoneum through the rent in the gut wall.
Host defenses — Once the organism enters ascitic fluid, a battle ensues between the virulence of the bacteria and the host’s resistance to infection. Microbes that cause SBP are usually serum-resistant, ie, they cannot be killed by serum alone but also require functional phagocytes. Foreign matter is first “opsonized” with complement and/or globulin so that it is more identifiable by and digestible to phagocytes.
The resident macrophages represent the first line of defense of the peritoneal cavity. If these phagocytes fail to eradicate the colonizing microbes, complement is activated and cytokines are released. PMNs enter the peritoneum to seek and destroy the invading organisms. If, however, complement levels are inadequate or the PMNs are dysfunctional, then colonization may not be contained and a potentially fatal infection may ensue.
Cirrhosis is actually one of the most common forms of acquired immune deficiency, creating an environment that facilitates the persistence of peritoneal infection.
Serum complement deficiency is quite common in patients with liver disease that is advanced enough to produce ascites. Furthermore, ascitic fluid is frequently a fivefold or even 10-fold dilution of serum in patients with cirrhosis; thus, ascitic fluid complement concentrations may drop to levels similar to those of the serum of patients with congenital complement deficiency.
The function of both motile (eg, PMNs) and stationary phagocytes (eg, Kupffer cells) is reduced in patients with advanced liver disease.]
What is the risk of surgical site infection in a gross contaminated procedure (IE. abscess)?
30%
[UpToDate: A widely accepted wound classification system has been developed by the National Academy of Sciences and the National Research Council based upon the degree of expected microbial contamination during surgery. It stratifies wounds as clean, clean-contaminated, contaminated, or dirty using the following definitions:
Clean wounds are uninfected operative wounds in which no inflammation is encountered and the wound is closed primarily. By definition, a viscus (respiratory, alimentary, genital, or urinary tract) is not entered during a clean procedure.
Clean-contaminated wounds are operative wounds in which a viscus is entered under controlled conditions and without unusual contamination.
Contaminated wounds are open, fresh accidental wounds, operations with major breaks in sterile technique, or gross spillage from a viscus. Wounds in which acute, nonpurulent inflammation was encountered also were included in this category.
Dirty wounds are old traumatic wounds with retained devitalized tissue, foreign bodies, or fecal contamination or wounds that involve existing clinical infection or perforated viscus.
Several studies have found a moderate correlation between the wound classification and the SSI rate. SSI rates according to wound class were:
Clean – 1.3% to 2.9%
Clean-contaminated – 2.4% to 7.7%
Contaminated – 6.4% to 15.2%
Dirty – 7.1% to 40.0%
While widely used, this classification scheme may be a poor predictor of overall risk of SSI. Other factors, such as the operative technique, length of surgery, and health of the surgical patient, may be as important as wound classification in predicting infectious risks for SSI.
Available data suggest that the relative risk reduction of SSI from the use of antimicrobial prophylaxis is the same in clean and in higher-risk procedures. Antimicrobial prophylaxis is justified for most clean-contaminated procedures. The use of antimicrobial agents for dirty procedures or established infection is classified as treatment of presumed infection, not prophylaxis.]
What causes secondary bacterial peritonitis?
Intra-abdominal source such as perforated viscus
[UpToDate: Spontaneous bacterial peritonitis (SBP) must be differentiated from secondary bacterial peritonitis. Secondary bacterial peritonitis is an ascitic fluid infection in which there is a positive ascitic fluid bacterial culture and an ascitic fluid PMN count ≥250 cells/mm3 in the setting of a surgically treatable intra-abdominal source of infection. The distinction of SBP from secondary bacterial peritonitis is based largely upon ascitic fluid analysis, imaging studies, and the response to treatment.
Two varieties of secondary bacterial peritonitis have been reported: perforation peritonitis (eg, perforated peptic ulcer into ascites) and nonperforation peritonitis (eg, perinephric abscess).]
What percent of abdominal abscesses have both anaerobic and aerobic bacteria?
80%
What is the most common neoplasm in AIDS patients?
Kaposi sarcoma
[Surgery is rarely needed]
[UpToDate: AIDS-related or epidemic KS is the most common tumor arising in HIV-infected persons. KS is considered an AIDS-defining illness in the Centers for Disease Control and Prevention (CDC) guidelines. In the United States, KS was over 20,000 times more common in persons with AIDS than in the general population prior to the widespread use of potent antiretroviral therapy (ART), although its incidence has declined substantially since that time.
Although KS has been reported among all risk groups for HIV infection, it is most common in homosexual or bisexual men. AIDS-related KS is much less common in heterosexual injection drug users, transfusion recipients, women or children, and hemophiliacs.
In patients with AIDS-related KS, the CD4 count appears to be an important factor associated with the development of KS. In a series of 70 patients who presented with a new diagnosis of KS while on treatment with combined antiretroviral therapy (ART), the rate ratios for developing KS for patients with CD4 counts <200, 200-349, and 350-499 cells/mm3 were 18.9, 3.6, and 4.1, compared to those with ≥500 cells/mm3.
However, trends in earlier initiation of antiretroviral therapy (ART) and improved health care continuity have altered the epidemiology of AIDS-related malignancies. In a study including 466 patients with AIDS-related KS, less than half of KS cases diagnosed between 2007 and 2011 were in patients with CD4 counts <200, with 29% having a viral load <500 copies/mL. This reflects the growing proportion of the HIV population that, due to ART, has higher CD4 counts and suppressed viral loads, rather than an increased risk of cancer among such patients. In resource-rich areas, AIDS-related KS is predominantly a disease of men. In contrast, in resource poor areas such as sub-Saharan Africa, AIDS-related KS is also more frequent in males, although the difference is less pronounced.]
What is the treatment for Brown recluse spider bites?
Dapsone initially
[May need resection of area and skin graft for large ulcers later]
[UpToDate: For patients with ulceration or systemic complaints, the evidence supporting the use of Loxoscelism specific treatments (eg, dapsone, antivenom) is lacking. Care providers should weigh the relative risks versus potential benefits with the understanding of the controversies surrounding effectiveness.
The treatment of acute local findings following a recluse spider bite involves local wound care, pain management, and, if indicated, tetanus prophylaxis. Initial treatment measures following any spider bite include:
- Clean the bite with mild soap and water.
- Apply cold packs, taking care not to freeze the tissue.
- Maintain the affected body part in an elevated or neutral position (if possible).
- Administer pain medication as needed. Some patients will respond to nonsteroidal antiinflammatory medications, while others may require opioids.
- Administer tetanus prophylaxis if indicated.
Most bites can be managed with minimal intervention and heal without scarring. Resolving bites should be monitored for the development of secondary bacterial infection.
Antibiotics are prescribed only if there are signs of infection such as increased erythema, fluctuation, and suppuration. If infection is suspected, it should be treated with antibiotics for cellulitis.]
What is characterized by a severe infection in the perineal and scrotal region caused by mixed organisms including gram positive cocci, gram negative rods, and anaerobes?
Fournier’s gangrene
[UpToDate: Necrotizing infection of the male perineum, known as Fournier’s gangrene, can result from a breach in the integrity of the gastrointestinal or urethral mucosa. Infection can occur in all age groups but is most common in older men. Necrotizing infection involving the labia and perineum can also occur in females, particularly in the setting of diabetes. Fournier’s gangrene begins abruptly with severe pain and may spread rapidly to the anterior abdominal wall, the gluteal muscles, and, in males, onto the scrotum and penis. In the setting of Fournier’s gangrene, early aggressive drainage or debridement is essential. Affected patients may require cystostomy, colostomy, or orchiectomy.]
What is the treatment for Fournier’s gangrene?
Early debridement and antibiotics
[Try to preserve testicles if possible]
[UpToDate: Necrotizing infection of the male perineum, known as Fournier’s gangrene, can result from a breach in the integrity of the gastrointestinal or urethral mucosa. Infection can occur in all age groups but is most common in older men. Necrotizing infection involving the labia and perineum can also occur in females, particularly in the setting of diabetes. Fournier’s gangrene begins abruptly with severe pain and may spread rapidly to the anterior abdominal wall, the gluteal muscles, and, in males, onto the scrotum and penis. In the setting of Fournier’s gangrene, early aggressive drainage or debridement is essential. Affected patients may require cystostomy, colostomy, or orchiectomy.]
Fungal infection with which organism is most commonly associated with pulmonary symptoms and is common in the Southwest United States?
Coccidiodes
[UpToDate: Coccidioidomycosis is the infection caused by the dimorphic fungi of the genus Coccidioides (Coccidioides immitis and Coccidioides posadasii). Most infections are caused by inhalation of spores. The clinical expression of disease ranges from self-limited acute pneumonia (Valley Fever) to disseminated disease, especially in immunosuppressed patients.
For those who develop symptoms, a wide spectrum of manifestations are possible. Primary infection due to Coccidioides species most frequently manifests as a community-acquired pneumonia (CAP) approximately 7 to 21 days after exposure. The most common presenting symptoms are chest pain, cough, and fever. In a study from Pima County, Arizona, 29% of patients diagnosed with CAP were serologically positive for coccidioidal infection. If hemoptysis occurs, it suggests the development of a pulmonary cavity.
Some patients also develop systemic complaints, often lasting for weeks to months. Patients can experience constitutional symptoms, such as fever, drenching night sweats, and weight loss. Patients can also develop extreme fatigue that can interfere with activities of daily living, and may last for many months.
Patients with early coccidioidal infection can also present with dermatologic or rheumatologic complaints. The frequent complaint of arthralgias has contributed to the alternate name of “desert rheumatism” for this illness. Cutaneous manifestations of primary coccidioidal infection include erythema nodosum and erythema multiforme. Erythema nodosum is much more common in women than in men, and often is the symptom prompting evaluation for Valley Fever.
Cases of coccidioidomycosis in the United States are concentrated in the southwestern part of the country. Coccidioides spp are endemic to certain lower deserts of the western hemisphere, including southern Arizona, the southern and central valleys of California, southwestern New Mexico, and west Texas in the United States. They are also found in parts of Mexico and Central and South America.]
What is the 2nd most common cause for laparotomy in HIV patients?
Neoplastic disease
[Opportunistic infections are the most common reason. CMV infection is most commonopportunistic infection.]
What is the treatment for sinusitis?
Broad-spectrum antibiotics
[Rare to have to tap sinus percutaneously for systemic illness]
[UpToDate: Acute viral rhinosinusitis (AVRS) is expected to improve or resolve within 10 days. Patients with AVRS should be managed with supportive care. Patients who fail to improve after ≥10 days of symptomatic management are more likely to have acute bacterial rhinosinusitis (ABRS) and should be managed as ABRS.
Symptomatic management of acute rhinosinusitis (ARS) aims to relieve symptoms of nasal obstruction and rhinorrhea. We suggest over-the-counter (OTC) analgesics and saline nasal irrigation (Grade 2C). We suggest treatment with intranasal glucocorticoids (Grade 2B). Decongestants may be useful when eustachian tube dysfunction is a factor for patients with AVRS but are not likely to be helpful for patients with ABRS and have adverse side effects.
ABRS may also be a self-limited disease. Systematic reviews and meta-analyses have found that 70% to 80% of immunocompetent patients improve within two weeks without antibiotic therapy. We suggest symptomatic management and observation (watchful waiting) for immunocompetent patients with ABRS who have good follow-up (Grade 2B). We start antibiotic therapy after diagnosis for patients who do not have good follow-up.
Antibiotics should be started in patients who have been managed with observation who have worsening symptoms. Patients with stable symptoms (no worsening or improvement) after 7 days may be managed either with an additional 10 days of observation and symptomatic management or antibiotic therapy depending on patient presentation, comorbidities, and social factors. Patients with worsening symptoms or who fail to improve with an additional 10 days of watchful waiting should be started on antibiotics.
There are also a variety of reasons for patients to have a suppressed immune system, and treatment decisions for immunocompromised patients should be made on a case-by-case basis. They may warrant immediate antibiotic treatment and/or specialist referral. Treatment decisions for patients with other comorbidities that can affect immune function (eg, diabetes) should also be individualized.
In light of increasing microbial resistance to antibiotics, we suggest initial empiric treatment with amoxicillin-clavulanate rather than macrolides (clarithromycin or azithromycin), trimethoprim-sulfamethoxazole, or oral second- or third-generation cephalosporins (Grade 2B).]
Fungal infection with which organism is most commonly associated with pulmonary symptoms and is common along the Mississippi and Ohio river valleys?
Histoplasma
[UpToDate: Histoplasmosis is the most prevalent endemic mycosis in the United States. Histoplasmosis and its causative agent, Histoplasma capsulatum, are found worldwide but particularly in North and Central America. Within the United States, infection is most common in the midwestern states located in the Ohio and Mississippi River valleys.
While most infections are asymptomatic or self-limited, some individuals develop acute pulmonary infections or severe and progressive disseminated infection. Progressive disseminated histoplasmosis occurs in about one in 2000 patients with acute infection. Among the endemic mycoses, it is the most common cause for hospitalization.
Although hematogenous dissemination probably occurs in most patients during the acute infection before cellular immunity develops, progressive illness is unusual except in the host with altered immunity and those at the extremes of age. The diagnosis of disseminated histoplasmosis requires a high index of suspicion, recognition of the common modes of presentation, and familiarity with the appropriate diagnostic tests.
The clinical manifestations of disseminated histoplasmosis as well as the timing of presentation vary based on host immunodeficiency and the degree of exposure to the fungus. Patients may present shortly after the exposure or years later and may experience asymptomatic periods interrupted by symptomatic relapses. Progressive disseminated histoplasmosis occurs in two forms, partly based upon the time course of the illness and partly upon the extent of infection:
- Acute infection, which is mostly seen in infants and heavily immunocompromised hosts
- Chronic infection is noted mostly in older adults and in men more often than women
Patients with chronic infection often present with pancytopenia, hepatosplenomegaly, hepatic enzyme elevation, and oropharyngeal or gastrointestinal lesions. Other sites include the skin, brain, and adrenal glands.
Patients with acute infection present with fever, fatigue, hepatosplenomegaly, and pancytopenia. Diarrhea and dyspnea occur less commonly. Severely immunodeficient patients, such as those with AIDS or those receiving treatment with immunosuppressive medications, can present with overwhelming infection manifested by shock, respiratory distress, hepatic and renal failure, obtundation, and coagulopathy. The mortality in spite of amphotericin B treatment approaches 50% in such cases.
These manifestations were more common early in the course of the AIDS epidemic, prior to the wide recognition of the importance of histoplasmosis as a complication of AIDS and AIDS as a risk factor for histoplasmosis. Since the introduction of potent antiretroviral therapy, unusual manifestations of disseminated disease have been reported in severely immunosuppressed patients within three months of initiating antiretroviral therapy. Atypical signs (eg, splenic infarction, ulcerative skin lesions) were attributed to the immune reconstitution inflammatory syndrome.]
Which fungus is the most common inhabitant of the respiratory tract?
Candida
What is the most common aerobe in the colon?
Escherichia coli
[UpToDate: The largest concentrations of anaerobic bacteria are found in the relatively stagnant terminal ileum and colon, where concentrations reach 1011 per gram, and anaerobic bacteria account for approximately 99.9% of the cultivable flora. The most important and frequent anaerobic bacteria are Bacteroides spp (principally members of the B. fragilis group), Prevotella spp, Clostridium spp, and Peptostreptococcus spp. It should be noted that most of the bacteria in the human colon cannot be cultivated. This has been studied by analysis of 16S rRNA gene sequences, which show substantial individual variation that appears strongly influenced by host phylogeny and diet. The totality is referred to as “the gut microbiome.” Studies in animals suggest a possible role for this microbiome in important conditions, such as obesity and the metabolic syndrome.
The colon flora becomes established after weaning and is thought to remain relatively stable throughout life unless it is disrupted by antibiotic treatment. Its role in maintaining health is believed to be in establishing ecologic balance by preventing colonization with exogenous organisms.]
Myonecrosis and gas gangrene are common presentations of necrotizing infection by which bacteria?
Clostridium perfringens
[Can occur with farming injuries]
[UpToDate: Clostridial myonecrosis (gas gangrene) is a life-threatening muscle infection that develops either contiguously from an area of trauma or hematogenously from the gastrointestinal tract with muscle seeding. Early recognition and aggressive treatment are essential.
There are two major presentations of clostridial gas gangrene: traumatic and spontaneous. Traumatic gas gangrene is most commonly caused by Clostridium perfringens; spontaneous gangrene is most commonly caused by Clostridium septicum.
Clostridium species are widespread in nature due to their ability to form endospores. They are commonly found in soil and marine sediments as well as human and animal intestinal tracts. Categories of clostridial soft tissue infections include wound contamination, anaerobic cellulitis, myonecrosis (gas gangrene), and necrotizing fasciitis.
- Wound contamination with soil containing clostridial spores or vegetative organisms may occur, although contamination with clostridial species in the absence of devitalized tissue does not necessarily lead to infection. In one study, for example, 30% to 80% of open traumatic wounds were contaminated with clostridial species.
- Anaerobic cellulitis occurs in the setting of modest quantities of devitalized tissue that support the growth of C. perfringens or other clostridial strains. Gas is produced locally and extends along fascial planes; bacteremia and invasion of healthy tissue (including muscle) does not occur. Mortality is low in the setting of appropriate management, including prompt removal of the devitalized tissue.
- Myonecrosis (clostridial gas gangrene) may be distinguished from the above infections by the progressive invasion and destruction of healthy muscle tissue. There are two major presentations of clostridial gas gangrene: traumatic and spontaneous.
Myonecrosis (clostridial gas gangrene) consists of progressive invasion and destruction of healthy muscle tissue. Traumatic gas gangrene is most commonly caused by C. perfringens; spontaneous gangrene is most commonly caused by C. septicum.]
What is the treatment for cat/dog/human bites?
Broad-spectrum antibiotics like amoxicillin/clavulanic acid (Augmentin)
[Alternatives include combinations of an anti pseudomonas antibiotic like Doxycycline or TMP-SMX plus an antianaerobic antibiotic like Metronidazole or Clindamycin. Cephalexin, Dicloxacillin, and Erythromycin have poor activity against Pseudomonas and should be avoided.]
[UpToDate: Prophylactic amoxicillin-clavulanate has been shown to reduce the rate of infection due to animal bite wounds. This was illustrated in a prospective trial of 185 patients with full-thickness animal bite wounds; prophylactic antibiotics significantly reduced the infection rate among patients presenting 9 to 24 hours after injury. No significant benefit was observed in patients presenting less than nine hours following bite injury. These findings suggest that patients with more than just superficial wounds who present greater than eight hours after a bite should receive prophylactic antibiotics. In addition, antibiotic prophylaxis should be administered for animal bites that are less than eight hours old in the following circumstances:
- Deep puncture wounds (especially due to cat bites)
- Moderate to severe wounds with associated crush injury
- Wounds in areas of underlying venous and/or lymphatic compromise
- Wounds on the hand(s) or in close proximity to a bone or joint (particularly the hand, as well as prosthetic joints)
- Wounds on the face or in the genital area
- Wounds requiring surgical repair
- Wounds in immunocompromised hosts
Prophylactic oral antibiotics should be administered for three to five days, with close follow-up. On follow-up evaluation, signs of infection should prompt further evaluation (with radiographic imaging and/or surgical consultation, if needed) and an extension of the antibiotic course.]
What bacterial load is needed to cause a wound infection?
Greater than 10^5 bacteria
[Less in the presence of a foreign body]
Necrotizing fasciitis is usually caused by which bacteria?
Beta-hemolytic group A strep
[UpToDate: There are an estimated 3.5 cases of invasive group A Streptococcus infections per 100,000 persons in the United States; necrotizing infections make up approximately 6% of these cases. Conditions associated with necrotizing soft tissue infection include diabetes, drug use, obesity, immunosuppression, recent surgery, and traumatic wounds. In the United States, there are no convincing data that suggest an increase incidence of necrotizing fasciitis; in New Zealand, the incidence increased from 0.18 to 1.68 per 100,000 per year between 1990 and 2006. In New Zealand, the prevalence was similar among different ethnic groups, but the mortality was greater among older adults and native Pacific Islanders. In addition, in the United States and Scotland, mini-epidemics of necrotizing fasciitis and gas gangrene, caused by Clostridium sordellii and C. novyii, respectively, have been reported among drug abusers injecting black tar heroin subcutaneously.
Diabetes is a particularly important risk factor; several forms of necrotizing infection have been described more frequently among diabetics. These include nonclostridial anaerobic cellulitis, synergistic necrotizing cellulitis, and type I necrotizing fasciitis. These infections occur most frequently in the lower extremities. In addition, diabetic patients are also predisposed to developing necrotizing fasciitis in the head and neck region and the perineum.
There are two bacterial forms of necrotizing fasciitis: type I and type II.
Type I necrotizing fasciitis is a mixed infection caused by aerobic and anaerobic bacteria. Risk factors include diabetes, peripheral vascular disease (PVD), immune compromise, and recent surgery, including minor procedures such as circumcision in newborn infants. Patients with diabetes and/or PVD frequently have lower extremity involvement. Neonates usually have abdominal or perineal involvement.
Type II necrotizing fasciitis due to group A Streptococcus (GAS) or other beta-hemolytic streptococci, either alone or in combination with other species, most commonly S. aureus. It can occur among healthy individuals with no past medical history, in any age group. Predisposing factors include a history of skin injury, such as laceration or burn, blunt trauma, recent surgery, childbirth, injection drug use, and varicella infection (chickenpox). In cases with no clear portal of entry, the pathogenesis of infection likely consists of hematogenous translocation of GAS from the throat (asymptomatic or symptomatic pharyngitis) to a site of blunt trauma or muscle strain. Traumatic injuries in the setting of fresh or seawater can predispose to necrotizing infection due to A. hydrophila or V. vulnificus, respectively; the latter can also cause necrotizing infection in patients with underlying cirrhosis who ingest contaminated oysters.
During the 1990s, there was a dramatic increase in the number of invasive infections caused by GAS. In one Canadian report, the incidence of GAS necrotizing fasciitis increased from 0.085 to 0.4 per 100,000 between 1991 and 1995. Most cases were community acquired; 20% were nosocomial or acquired in a nursing home. Almost one-half of patients had streptococcal toxic shock syndrome; this rate is similarly noted in other studies.
In a retrospective review of 14 adults with necrotizing fasciitis due to community-associated methicillin-resistant S. aureus (MRSA), risk factors for infection included injection drug use (43%), diabetes (21%), hepatitis C infection (21%), malignancy (7%), and HIV infection (7%).]
What is the body’s response to lipopolysaccharide lipid A that gets released during gram-negative sepsis?
- Endotoxin triggers release of TNF-alpha from macrophages
- Activation of complement
- Activation of coagulation cascade
[UpToDate: Anaerobic gram-negative bacteria, like all gram-negative bacteria, contain lipopolysaccharide (LPS) that can be extracted from the envelope, but the biologic activity of this endotoxin (mouse lethality assays, the chick embryo death test, and the Shwartzman reaction) is 100 to 1000 times less than that of LPS from Enterobacteriaceae. The LPS of B. fragilis contains a lipid A moiety (the endotoxin portion of LPS), but there are structural and chemical composition differences that render this LPS less potent than the LPS of Escherichia coli. The inability of B. fragilis LPS to activate TLR 2 may be responsible for this difference.
Lipid A is the biologically active component of lipopolysaccharide (LPS) found in the cell wall of Salmonella and other gram-negative bacteria. Lipid A is toxic to mammalian cells and is a potent immunomodulator. Certain features of the lipid A in Salmonella may correlate with virulence or with activation of host inflammation. Lipid A induces toll-like receptor 4 (TLR4)-mediated responses, which are important for host defense against Salmonella infection, and modifications in lipid A as part of Salmonella’s adaptation to host environments reduce this signaling. Death in mice from Salmonella may be related to the toxic effect of lipid A, which triggers further production of TNF-alpha and IL-1 beta. S. typhimurium mutants with a defective lipid A molecule have greatly attenuated virulence in mice. Structural modifications of lipid A are influenced by the Salmonella virulence regulatory locus (phoP/phoQ) which responds to a variety of host intracellular environmental signals. For example, antimicrobial peptides have been shown to be part of the first step in signal transduction across the bacterial membrane, resulting in activation of phoQ and promotion of bacterial virulence. PhoP has also been found to bind a promoter region of a drug efflux system, thus connecting virulence with possible drug resistance.]
When should antivirals be given to an individual exposed to HIV?
Within 1-2 hours of exposure
[UpToDate: PEP should be initiated as soon as possible. The goal is to start within one to two hours (or earlier) after exposure, often using a “starter pack” with appropriate drugs that are immediately available. It is likely that a delay in initiating PEP can reduce efficacy. This concept is supported in primate models of PEP.
For most HCP, we do not initiate PEP if more than 72 hours have elapsed after the initial exposure; PEP is likely to be less effective when administered after that period of time. However, we offer three-drug PEP after a longer interval to patients with a very high-risk exposure (eg, sharps injuries from a needle that was in an artery or vein of an HIV-infected source patient). For such HCP, The United States Public Health Services suggests that PEP can be offered up to one week after the exposure.]
What is/are the IV treatment option(s) for Clostridium Difficile Colitis?
IV Flagyl
[Lactobacillus can help]
[UpToDate: Metronidazole can be used for initial treatment of nonsevere CDI. The recommended regimen is 500 mg three times daily or 250 mg four times daily for 10 to 14 days. Intravenous metronidazole at a dose of 500 mg every eight hours may also be used for treatment of CDI in patients in whom oral therapy is not feasible. Fecal concentrations in the therapeutic range are achievable with this regimen because of the drug’s biliary excretion and increased exudation across the intestinal mucosa during CDI.
If oral vancomycin is used, dosing consists of 125 mg four times daily. Oral vancomycin is not absorbed systemically and achieves predictably high levels in the colon. Dosing regimens of 125 mg four times daily and 500 mg four times daily are equally effective for the treatment of nonsevere CDI. Intravenous vancomycin has no effect on C. difficile colitis since the antibiotic is not excreted appreciably into the colon.
For initial treatment of nonsevere CDI, we suggest oral metronidazole (Grade 2B).
For treatment of severe CDI, we recommend vancomycin 125 mg four times daily for 10 to 14 days (Grade 1B). For patients with severe disease who do not demonstrate clinical improvement, we suggest treatment with oral vancomycin 500 mg four times daily (Grade 2C); fidaxomicin may be considered in patients who cannot tolerate vancomycin, although more data are needed. In critically ill patients with fulminant or refractory disease, we suggest oral vancomycin 500 mg four times daily and intravenous metronidazole 500 mg every eight hours (Grade 2C); fidaxomicin may be considered in patients who cannot tolerate vancomycin, although more data are needed.
For treatment of severe disease in patients with profound ileus, we suggest addition of intracolonic vancomycin (Grade 2C), but there is risk of colonic perforation. Therefore, use of intracolonic vancomycin should be restricted to patients who are not responsive to oral therapy, and the procedure should be performed by personnel with expertise in administering enemas.
For treatment of a nonsevere initial recurrence of CDI, we suggest oral metronidazole (Grade 2A). Alternatives include oral vancomycin or fidaxomicin.
For treatment of a second recurrence of CDI, we suggest intermittent and tapering vancomycin therapy or fidaxomicin. For treatment of subsequent recurrences of CDI, we suggest administering either fidaxomicin or vancomycin followed by rifaximin (Grade 2C).
We recommend urgent surgical evaluation for patients with a white blood cell count ≥20,000 cells/microL and/or a plasma lactate between 2.2 and 4.9 mEq/L (Grade 1B). In addition, surgical intervention should be strongly considered in the setting of peritoneal signs, severe ileus, or toxic megacolon.]
What is the treatment for secondary spontaneous bacterial peritonitis?
Laparotomy to find source
[UpToDate: Patients with suspected secondary bacterial peritonitis should receive broader coverage with cefotaxime and metronidazole. A similar regimen should be used with polymicrobial bacterascites.
A diagnosis of SBP is made if the polymorphonuclear cell (PMN, also referred to as neutrophils) count in the ascitic fluid is ≥250 cells/mm3, culture results are positive, and secondary causes of peritonitis are excluded. However, in selected cases, fluid chemistries may be needed to support the diagnosis or to differentiate SBP from secondary bacterial peritonitis.
The distinction of secondary bacterial peritonitis from SBP is crucial because the former usually requires antibiotics and surgical treatment, whereas the latter only requires antibiotics.]
What is the most common cause for laparotomy in HIV patients?
Opportunistic infections
[CMV infection is most common. Neoplastic diseaseis the 2nd most common cause for laparotomy in HIV patients.]
What is the most common class of bacteria in ICU pneumonia?
Gram negative rods
[UpToDate: Hospital-acquired (or nosocomial) pneumonia (HAP) and ventilator-associated pneumonia (VAP) may be caused by a wide variety of pathogens and can be polymicrobial. Common pathogens include aerobic gram-negative bacilli (eg, Escherichia coli, Klebsiella pneumoniae, Enterobacter spp, Pseudomonas aeruginosa, Acinetobacter spp) and gram-positive cocci (eg, Staphylococcus aureus, including methicillin-resistant S. aureus [MRSA], Streptococcus spp). Nosocomial pneumonia due to viruses or fungi is significantly less common, except in the immunocompromised patient.
There is a paucity of data regarding whether the pathogens that cause VAP differ from those that cause HAP in patients who are not mechanically ventilated. One prospective observational study evaluated 158,519 patients admitted to a single center over a four-year period. A total of 327 episodes of VAP and 261 episodes of HAP in nonventilated patients were identified:
- The infecting flora in patients with VAP included methicillin-susceptible S. aureus (MSSA; 9%), MRSA (18 percent), P. aeruginosa (18%), Stenotrophomonas maltophilia (7%), Acinetobacter spp (8%), and other spp (9%).
- The infecting flora in nonventilated patients with HAP was similar, except non-Enterobacteriaceae gram-negative bacilli (P. aeruginosa, Acinetobacter, and S. maltophilia) were less likely. Specifically, it included MSSA (13%), MRSA (20%), P. aeruginosa (9%), S. maltophilia (1%), Acinetobacter spp (3%), and other spp (18%).
These findings are supported by a prospective, multicenter, observational study of 398 intensive care unit (ICU) patients with suspected VAP. In this study, there was a similar distribution of pathogens: MRSA (14.8%), P. aeruginosa (14.3%), and other Staphylococcus species (8.8%).
Of 8474 cases of VAP reported to the United States Centers for Disease Control and Prevention from 2009 to 2010, the distribution of pathogens associated was S. aureus (24.1%), P. aeruginosa (16.6%), Klebsiella species (10.1%), Enterobacter species (8.6%), Acinetobacter baumannii (6.6%), and E. coli (5.9%). Similar findings were observed in another surveillance study.]
The microflora of which part of the gastrointestinal tract contains 10^7 bacteria consisting of gram positive cocci, gram positive rods and gram negative rods?
Distal small bowel
What is the treatment for necrotizing fasciitis?
Early debridement, high-dose penicillin
[May want broad spectrum antibiotics if though to be poly-organismal]
[UpToDate: Treatment of necrotizing infection consists of early and aggressive surgical exploration and debridement of necrotic tissue, together with broad-spectrum empiric antibiotic therapy and hemodynamic support. Surgery is indicated in the setting of severe pain, toxicity, fever, and elevated serum creatine kinase (CK) level, with or without radiographic evidence of fasciitis. Use of antibiotic therapy without debridement is associated with a mortality rate approaching 100%. Hemodynamic instability may require aggressive supportive care with fluids and vasopressors.
The optimal approach to empiric antibiotic therapy for necrotizing infection is uncertain; data are limited since most clinical trials exclude such patients. In general, empiric treatment of necrotizing infection should consist of broad-spectrum antimicrobial therapy, including activity against gram-positive, gram-negative, and anaerobic organisms; special consideration for group A Streptococcus (GAS) and Clostridium species should be taken. Acceptable regimens include administration of:
- A carbapenem or beta-lactam-beta-lactamase inhibitor, plus
- Clindamycin (dosed at 600 to 900 mg intravenously every eight hours in adults or 40 mg/kg per day divided every eight hours in neonates and children) for its antitoxin effects against toxin-elaborating strains of streptococci and staphylococci), plus
- An agent with activity against methicillin-resistant S. aureus (MRSA; such as vancomycin, daptomycin, or linezolid). In neonates and children, vancomycin (15 mg/kg/dose every 6 to 8 hours) is the usual empiric antibiotic for MRSA; the 6-hour dosing interval is employed for sicker children.]
How do circulating levels of insulin and glucose differ in early vs late gram-negative sepsis?
- Early gram-negative sepsis: Decreased insulin and increased glucose (impaired utilization)
- Late gram-negative sepsis: Increased insulin and increased glucose secondary to insulin resistance
[UpToDate: Hyperglycemia associated with critical illness (also called stress hyperglycemia or stress diabetes) is a consequence of many factors, including increased cortisol, catecholamines, glucagon, growth hormone, gluconeogenesis, and glycogenolysis. Insulin resistance may also be a contributing factor, since it has been demonstrated in more than 80% of critically ill patients.
Sepsis is a relatively common cause of hypoglycemia. Cytokine accelerated glucose utilization is usually matched by increased glucose production. Hypoglycemia develops when the latter fails to keep pace perhaps because of cytokine induced inhibition of gluconeogenesis in the setting of glycogen depletion.]
Primary spontaneous bacterial peritonitis is monobacterial and most commonly caused by which 3 bacteria?
- E. Coli (50%)
- Streptococcus (30%)
- Klebsiella (10%)
[Fluid cultures are negative in many cases of SBP]
[UpToDate: Pathogens commonly associated with SBP included Escherichia coli, streptococcal species, and Klebsiella pneumoniae.]
What is the most common source of fever more than 5 days after surgery?
Wound infection
[UpToDate: SSI is a common cause of fever more than one week after surgery; many patients have already been discharged from the hospital by this time.
Central venous catheters, if used, can be a source of infection and fever.
Fever from antibiotic-associated diarrhea, typically attributed to Clostridium difficile, also occurs more commonly during this period.
Febrile drug reactions are a frequent cause of subacute fever. Beta-lactam antibiotics and sulfa-containing products are commonly implicated, but other medications, such as H2-blockers, procainamide, phenytoin, and heparin, should be considered.
Thrombophlebitis should be considered as a cause of subacute fever in a patient with impaired mobility. Deep venous thrombosis and pulmonary embolism can cause fever and are more frequent in patients who are debilitated either by chronic medical problems or by the surgery.
Patients who require critical care after surgery are at higher risk for the development of subacute fever. These patients typically develop a variety of postoperative complications. Nosocomial infections are more common in these patients because of their treatment with invasive medical devices. Device-related infections due to bacteria and fungi include intravascular catheter-related infection with or without bacteremia, VAP, UTI, and sinusitis.]
What is the risk of an infant contracting HIV from HIV positive mother?
30%
[UpToDate: Without antiretroviral preventive interventions, the risk of perinatal HIV transmission has varied between 15% and 45%, depending on maternal risk factors and whether breastfeeding is practiced. The most important risk factors for transmission have consistently been maternal plasma and breast milk viral load followed by maternal immunologic status and clinical stage, as suggested by observational studies and clinical trials in non-breastfed and breastfed populations. Analyses of viral load levels in the original trial of zidovudine to prevent MTCT (PACTG 076), as well as studies from Thailand, West Africa, Uganda, and Kenya, all demonstrate a direct positive correlation between maternal plasma viral load and risk of transmission to the infant.
A majority of in utero transmission is thought to occur during the third trimester. This conclusion is based on low rates of viral detection using HIV NAT on fetal tissue from abortions in the first and second trimester as well as statistical modeling analyses. In a study of long versus short antenatal zidovudine prophylaxis for prevention of mother-to-child transmission, the rate of in utero transmission was 5.1% when starting zidovudine at 36 weeks gestation compared with 1.6% when starting zidovudine at 28 weeks gestation, suggesting that a significant proportion of transmission may occur between 28 to 36 weeks gestation, and a smaller residual amount of in utero infection may occur earlier in pregnancy. Mechanisms of transmission are thought to be related to breakdown of the integrity of the placenta, leading to microtransfusions of viremic maternal blood across the placenta to the fetus. A number of studies have shown that genital tract infections and placental inflammation, especially chorioamnionitis, can increase in utero HIV transmission.
Transmission during the time of labor and delivery is postulated to occur through contact of infant mucosal membranes with HIV virus in blood and secretions during the birth process. In the absence of antiretroviral treatment, duration of membrane rupture greater than four hours has been associated with increased risk of transmission. In addition, microtransfusions across the placenta during labor contractions also likely contribute to the heightened risk of transmission during the labor and delivery period.]
