GI Bacteria Flashcards
0
Q
What is diarrhea?
A
An increase in stool mass, frequency or fluidity.
1
Q
What are the three general pathogenic mechanisms for development of bacterial gastroenteritis?
A
- Ingestion of a preformed toxin with rapid onset of illness.
- Ingestion of organisms that produce toxins in vivo with rapid or delayed onset of illness.
- Ingestion of/infection by an enteroinvasive organism with delayed onset of illness.
2
Q
Physiology/structure of VIBRIO CHOLERAE
A
Gram-negative curved rods, motile, facultative anaerobes. Growth stimulated by Na+.
3
Q
What serogroups of Vibrio cholerae are associated with epidemics?
A
Serological differentiation based on O antigen (LPS). O1 and O139 serogroups only ones that produce cholera toxin (CT) and posses pathogenicity island encoding for intestinal colonization factors.
O1 subdivided into El Tor and classical. El Tor predominant biotype, classical more rare but more severe.
4
Q
What is the pathogenesis of Vibrio cholerae?
A
Colonizes proximal small bowel where it secretes CT, responsible for massive diarrhea, not an invasive disease. Purified CT is sufficient to produce symptoms of cholera. Bacterium serves as a delivery system for CT.
5
Q
Overall treatment of bacterial diarrheal diseases?
A
Usually treated with supportive care to replace fluid and electrolytes only.
6
Q
What is the epidemiology of traveler’s diarrhea?
A
Between 20% to 50% of travelers to developing nations will develop at least 1 episode of diarrhea. Most common medical ailment afflicting travelers. Avoidance of contaminated food/drink through prophylactic measures. Peel it, cook it, or leave it.
7
Q
Describe the mechanism of action of Cholera enterotoxin (CT)?
A
A-B subunit toxin, with 5 B and 1 A subunits. The B subunit is responsible for binding holotoxin to ganglioside receptors on enterocytes. A subunit enters the cell where it separates into A1 and A2 peptides. A1 affects a GTP binding Gprotein Gs-alpha, which activates Adenylate Cyclase permanently, resulting in an increase of cAMP production. Rising cAMP levels causes Cl-efflux through a phosphorylated CFTR, which prevents Na+ from being absorbed. Leads to large osmotic driving force of water secretion into bowel–>DIARRHEA.
8
Q
What is the epidemiology of cholera?
A
Cholera is the only diarrheal disease capable of pandemic spread. Currently in 7th pandemic, predominantly El Tor biotype. Transmission is FECAL-ORAL route via contaminated water or food.
9
Q
What is the environmental reservoir for Vibrio cholerae?
A
Aquatic sources like brackish water/ estuaries. Association with copepods, zooplankton, shellfish, aquatic plants. Short-term excretion following mild or asymptomatic infection (convalescent carrier) responsible for most cases. Extraintestinal reservoir in estuarine environment.
10
Q
What is the host susceptibility to Vibrio cholerae?
A
Large inoculum required for infection. Stomach acidity an important barrier, so hypochlorhydria (due to surgery, antacids, infection with Helicobacter pylori, which raise stomach pH) predisposes host to infection. Immune status important. High incidence in young children in endemic areas, all affected in non-endemic areas.
11
Q
What is the clinical presentation of Vibrio cholerae infection?
A
Wide spectrum of diarrheal illness: asymptomatic/mild to moderate or severe (cholera gravis). Characterized by voluminous watery diarrhea without abdominal cramps/fever. “Rice water stool” = Stool loses color/odor and flecks of floating mucus seen.
Fluid loss may exceed 1 L/hour. Dehydration and electrolyte loss lead to shock.
12
Q
What are the onset/symptoms of cholera gravis?
A
Cholera gravis one of the most rapidly fatal illnesses known. Rapid onset, healthy person can become hypotensive within one hour of onset of symptoms, and victim MAY die within 2-3 hours without treatment. Typically, time from first liquid stool to shock is 4-12 hours, with death at 18 hours-2 days.
13
Q
What is the treatment for Vibrio cholerae infection?
A
Replace lost water and salts with oral rehydration solution (ORS) with IV therapy for severe cases. Antibiotics can shorten duration of diarrhea but are not essential: tetracycline, doxycycline, or Bactrim (trimethoprim-sulfamethoxazole) for children.
14
Q
What is the best mode of prevention/control of Vibrio cholerae?
A
Adequate sanitation (clean water/chlorination), adequately cooked seafood. Oral vaccines now available in other countries.
15
Q
What is the epidemiology of Vibrio parahaemolyticus?
A
Leading cause of seafood-borne bacterial gastroenteritis. “Recent history of seafood consumption!” Multiple outbreaks in coastal states associated with crabs, oysters, shrimp. Infections peak in summer.
16
Q
What is the clinical manifestation of Vibrio parahaemolyticus?
A
Gastroenteritis: mostly watery diarrhea, cramps, nausea, vomiting, sometimes fever and chills, rarely bloody diarrhea. Diarrhea is self-limited around 3 days. Also causes wound infections after exposure to warm seawater (eg. crab bites).
17
Q
What is the treatment for Vibrio parahaemolyticus?
A
Diarrhea self-limited. Rarely needs treatment. If treated use ORS and tetracycline.
18
Q
What is the epidemiology of Vibrio vulnificus?
A
Most common and important cause of serious illness associated with Vibrio in the US. Responsible for 95% of seafood-related deaths. Organism a common inhabitant of coastal waters and shellfish.
19
Q
What is the clinical presentation of Vibrio vulnificus?
A
Wound infection: cellulitis, vesicles/bullae followed by necrosis, sometimes progresses to sepsis or death. Occurs after exposure of wound to seawater during warm months. Classic presentation is that of a patient who lacerated his hand while cleaning seafood. Can occur in otherwise healthy people. More severe in patients with chronic diseases.
20
Q
What is the clinical presentation of Vibrio vulnificus in compromised hosts with pre-existing hepatic or chronic diseases?
A
Primary sepsis from eating contaminated seafood. Characterized by chills, fever, prostration, and hypotension. Usually secondary skin lesions on the extremities with erythematous or ecchymotic areas, necrotic ulcers. Patients at risk (cirrhosis and hemochromatosis) should avoid raw shellfish and those at patients with wounds should avoid seawater.
21
Q
What is the physiology of diarrheagenic Escherichia coli?
A
Gram negative rods. Facultative anaerobe. Oxidase test negative. Appear as lactose-fermenters on MacConkey agar (pink colonies). E. coli O157:H7 can be detected on MacConkey-Sorbitol agar. Other types cannot be differentiated based on phenotype in laboratory.
22
Q
What is the pathogenesis of Enterotoxigenic E. Coli (ETEC)?
A
Most common cause of traveler’s diarrhea. Produces cholera-like enterotoxin (same mechanism of action). ETEC adhere to small bowel enterocytes and induce watery diarrhea by secretion of heat-labile (LT) and/or heat-stable (ST) enterotoxins.
23
Q
What is the epidemiology of ETEC?
A
Found in contaminated food and water. Major cause of childhood diarrhea in developing countries. Leading cause of traveler’s diarrhea.
24
What is the clinical manifestation of ETEC and how would you treat?
Acute watery diarrhea. No fever. Treat with rehydration ORS.
25
What is the pathogenesis of Enteropathogenic E. coli (EPEC)?
EPEC adhere to small bowel enterocytes, destroy normal microvillar architecture, induce attaching and effacing lesion.
1. Initial adhesion. 2. Protein translocation of effector molecules by Type III secretion (TTSS). 3. Pedestal formation. Cytoskeletal derangements accompanied by inflammatory response and diarrhea.
26
What is the epidemiology of EPEC?
Person to person transmission. Fecal-oral transmission. Leading cause of infantile diarrhea in developing countries.
27
What is the clinical manifestation of EPEC and how would you treat?
Severe acute diarrhea or dysentery (severe diarrhea with blood and pus) and vomiting. Treat with ORS. May be persistent/chronic diarrhea. Usually short duration but can be protracted and deadly.
28
What is the pathogenesis of Enterohemorrhagic E. Coli (EHEC)?
EHEC also induces attaching and effacing lesion, but in the COLON. Produces Shiga toxin (Stx), which inhibits protein synthesis. Systemic absorption of Stx leads to life-threatening complications from enterohemorrhagic colitis (bloody diarrhea). Hemolytic Uremic Syndrome.
29
What are the clinical manifestations of EHEC?
Watery and bloody diarrhea, may be complicated by HUS.
Hemolytic-Uremic Syndrome (HUS)- hemolytic anemia (destruction of RBCs), acute kidney failure (uremia), and low platelet count (thrombocytopenia). E. coli O157 is one of most common serotypes that cause HUS.
30
What is the epidemiology of EHEC?
Food, water, and person-to-person transmission. Major cause of bloody diarrhea in developed nations. Reservoir in cattle. Contaminated food: Beef, juice, produce. Water: drinking, swimming (water amusement park). Petting zoos.
31
What is the pathogenesis of Enteroaggregative E. coli (EAEC)?
Adheres to small and large bowel epithelia in a thick biofilm and elaborates secretory enterotoxins and cytotoxins.
32
What is the epidemiology of EAEC?
Mode of transmission unknown. Important cause of chronic diarrhea in developing countries.
33
What is the clinical manifestation of EAEC?
Mucoid diarrhea, often chronic/persistent. Intermittent diarrhea. Associated with growth retardation in children in developing countries. Emerging cause of diarrhea in travelers, HIV positive.
34
What is the pathogenesis of Enteroinvasive E. Coli (EIEC)?
EIEC invades the colonic epithelial cell, lyses phagosome and moves through the cell by nucleating actin microfilaments. May move laterally through epithelium by direct cell-to-cell spread. Might exit and re-enter baso-lateral plasma membrane.
35
What is the epidemiology of EIEC?
Contaminated food in developed countries. Outbreaks in developed countries.
36
What is the clinical manifestation of EIEC?
Watery diarrhea or dystentery
37
Laboratory diagnosis of E. coli?
EHEC strains can be routinely detected using culture and immunologic assays in lab. Stool samples can be cultured on selective and differential media (MacConkey sorbitol) for detcting O157:H7 serotypes. Other types of E. coli difficult to diagnose in clinical micro lab b/c no commercial diagnostic tests for use.
38
What is the physiology of Shigella species?
Gram negative rod-shaped, facultative anaerobe. (Enterobacteraceae member). Oxidase negative, non-motile, non-lactose fermenting on MacConkey agar. Highly infectious! (~10 organisms).
39
How do you differentiate between Shigella and Salmonella? Both are non-lactose fermenting and show up as yellow on MacConkey agar.
Hektoen Enteric Agar (HEK) used to differentiate. Salmonella shows up as Black colonies on Hektoen Enteric agar because it produces hydrogen sulfide. HEK contains indicators of lactose fermentation and hydrogen sulfide production; as well as inhibitors to prevent the growth of gram positive bacteria.
40
What are the 4 recognized species of Shigella that cause GI infection?
S. dysenteriae (serosubgroup A), S. flexneri (B), S. boydii (C), S. sonnei (D). From a genetics point of view, Shigella and E. coli are the same organism but are differentiated for epidemiologic purposes and treatment differences.
41
What is the pathogenesis of Shigella species?
1. Shigella cross the M (microfold) cells of the follicle-associated epithelium that covers lymphoid nodules of colonic mucosal tissue. 2. Shigella cause extensive apoptosis of macrophages in subepithelial location. 3. Bacteria escape into the tissues and enter basolaterally into epithelial cells. 4. Cell-to-cell spreading generates efficient intracellular colonization. 5. Caspase-1 mediates apoptosis and initiates inflammation through release of mature interleukin-1beta. 6. Inflammation amplified by intracellular bacteria that activate NOD1 pathway (PGN release, NF-kappaB activation, chemokine expression).
Although locally invasive, Shigella does not cause bacteremia or disseminate.
42
What is the clinical presentation of Shigella infection (Shigellosis)?
Severe presentation. Patients present with high fever, abdominal cramps/pain, "inflammatory" bloody, mucoid diarrhea (dysentery) and vomiting. Shigella primarily affects distal colon with acute mucosal inflammation, erosion, and purulent exudate. Segment of colon shows pale, granular, inflamed mucosa, with patches of coagulated exudate from a massive recruitment of PMNs inducing rupture of epithelial barrier. Incubation period usually 1-3 days.
43
What is the epidemiology of Shigella species?
Strictly a human pathogen (no animal reservoir). Transmission is fecal-oral. Third most common bacterial enteropathogen reported in the US. In US most cases are Shigella sonnei. Shigella dysenteriae was most common in Europe and US at the beginning of century, now rare. S. dysenteriae infection limited to imported cases from Mexico/C. America. Shigella in US most common in day care centers, areas with crowded living conditions, urban centers, residential institutions.
44
How does the laboratory diagnose Shigella?
Fecal culture is method of diagnosis. Differential and selective media used to isolate Shigella species from stool samples. Cary-Blair transport media used to collect stool and send to micro lab.
45
What is the treatment/prevention of Shigella species?
Fluoroquinolone. No vaccine. Most episodes self-limited. Severe dysentery or disease in compromised patients benefits from antibiotic treatment. Ampicillin and Bactrim (trimethoprim-sulfamethoxaole) resistance now common. Fluoroquinolone resistance remains rare in US.
46
What is the physiology of Salmonella species?
Gram negative, rod-shaped, facultative anaerobe. Member of Enterobacteraceae. Oxidase-negative, motile, non-lactose fermenter (on MacConkey agar).
47
What are the species of Salmonella?
Salmonella enterica and Salmonella bongori. 6 subspecies within S. enterica (I through VI). Salmonella enterica subsp. enterica (Subspecies I) contains most important of human strains.
>2500 serotypes based on O (LPS) and H (flagellar) antigens.
48
What is the pathogenesis of Salmonella species?
Salmonella crosses intestinal barrier, survives in intestinal tissues, and spreads systemically. Salmonella cross M cells of follicle-associated epithelium mainly in Peyer's patches of ileal portion of small intestine (also colon possibly). Salmonella causes macrophage apoptosis in subepithelial location through effectors injected using type III secretory system (TTSS) encoded by Spi1 (Salmonella pathogenicity island 1). Apoptosis triggers inflammation. Salmonella also switches to expression of Spi2, which encodes a TTSS that injects effector proteins from endocytic vacuole into cell cytoplasm, enabling bacteria to modify vacuole to a Salmonella-containing vacuole that supports bacterial survival and multiplication. Provides bacteria with capacity to invade epithelial cells basolaterally (Spi1 effectors) and disseminate systemically.
49
What is the general clinical presentation of Salmonella spps?
Gastroenteritis, enteric fever (systemic illness with fever and abdominal symptoms), bacteremia, endovascular infection, focal metastatic infections (osteomyelitis or abscesses), and an asymptomatic chronic carrier state involving gall bladder. Typhoidal vs. nontyphoidal Salmonella infection.
50
What is the clinical presentation of Typhoid fever?
Presents nonspecifically with abdominal pain, fever, chills, and constitutional symptoms. During acute phase: fever and bacteremia. Followed by: abdominal pain and rash (rose spots- faint salmon-colored macules on trunk/abdomen). Sequelae: hepatosplenomegaly, intestinal bleeding/perforation (ileocecal lymphatic hyperplasia of Peyer's patches), and secondary bacteremia/peritonitis.
51
What is the clinical presentation of nontyphoidal Salmonella?
Enteric infection may be clinically mild, even asymptomatic, indistinguishable from gastroenteritis caused by many other pathogens. Gastroenteritis characterized by nausea, vomiting, fever, diarrhea (may be bloody), cramping. Usually occurs within 1-3 days of ingesting contaminated food or water. Higher ingested dose of bacteria correlated with increase in severity of diarrhea, duration of illness, and weight loss.
52
What is the epidemiology of Salmonella?
Principal reservoirs for nontyphoidal Salmonella are birds, mammals, reptiles, amphibians (think pets!). Transmission is fecal-oral or contaminated food. Major food vehicles of transmission are of animal origin: poultry, eggs, milk. Usually results from improperly handled food contaminated by animal/human fecal material or acquired by fecal-oral route from other humans, or farm/pet animals.
In contrast, S. Typhi or S. Paratyphi (typhoidal Salmonella) colonize humans, transmitted via consumption of fecally contaminated food/water, and cause systemic illness with little to no diarrhea. Typhoid fever is highly endemic in resource poor countries.
53
What is the treatment for nontyphoidal Salmonella?
Gastroenteritis is usually self-limited. Fever generally resolves within 48-72 hours, diarrhea within 4-10 days, but shedding may last for weeks/months in children. Immunocompromised individuals/with underlying conditions, more likely to have bacteremic infections/complications (like osteomyelitis). Antimicrobial treatment usually not indicated except in severe disease (high fever, severe diarrhea, immunosuppressed individuals) as it may prolong shedding.
54
What is the treatment for typhoidal Salmonella infection/ typhoid (enteric) fever?
Typhoid fever always treated with antibiotics. Multi-drug resistance increasing in world. Two licensed typhoid vaccines (live oral attenuated and polysaccharide) that offer incomplete protection but should be considered for travelers to endemic regions.
55
What is the laboratory diagnosis of Salmonella?
Culture is the method of diagnosis. Differential and selective media used to isolate Salmonella from stool samples. Cary-Blair (special transport media) used to collect stool sample and send to clinical micro lab. Enteric/Typhoid fever difficult to diagnose b/c organism often absent from stool when diagnosis considered.
56
What is the physiology of Campylobacter jejuni?
Gram-negative, characteristic curved "sea gull" S-shaped rods. Motile (flagella- motility important for virulence). Oxidase positive, catalase positive. Microaerophillic. Ability to hydrolyze sodium hippurate. [Requires special growth conditions, microaerobic atmosphere and 42C.] Extensive genetic variation.
57
What is the pathogenesis of Campylobacter jejuni?
Tissue invasive pathogenesis, mechanism similar to Salmonella/Shigella. Acute inflammatory enteritis, extends down intestine to affect colon and rectum. Histology shows acute inflammation of mucosa with edema, infiltration by PMNs, and crypt abcess formation. Campylobacters must survive gastric acidity to colonize jejunum/ileum-- lowering gastric acidity facilitates infection.
58
What are the clinical manifestations of Campylobacter jejuni infections?
Incubation period of 1-3 days, followed by fever, possibly severe abdominal cramping, diarrhea (watery or bloody) lasting several days to 1 week. Intense, continuous abdominal pain radiating to right iliac fossa ('pseudo-appendicitis'). Pain caused by terminal ileitis and mesenteric adenitis. Campylobacter enteritis indistinguishable from Salmonella/Shigella infections. 10-20% have a relapse or prolonged disease mimicking inflammatory bowel disease. Rare complication is Guillain-Barré syndrome (GBS).
59
What are the manifestations of Guillain-Barre syndrome (GBS) and what infectious bacterium may lead to this?
GBS is an acute, self-limited, immune-mediated attack on the peripheral nervous system resulting in ascending motor paralysis. GBS following Campylobacter infection is thought to occur because C. jejuni produces ganglioside-like structure on outer core of lipooligosaccharide. Immune response to these ganglioside mimics cross-reacts with relevant ganglioside targets in peripheral nerve tissue. Immune reaction leads to demyelination or axonal degeneration in peripheral nerves.
60
What is the epidemiology of C. jejuni?
Either #1 or #2 of the most common reported enteropathogens (causes of bacterial diarrhea) in the US. Salmonella is the other one depending on the region. Reservoirs in water and GI tract of fowl/chicken. Commensal in avian GI tract. Improperly cooked poultry is main vehicle of transmission, also unpasteurized milk.
61
What is the laboratory diagnosis of Campylobacter jejuni?
Stool culture with selective media. Gram-stain of stool sample. Gram negative curved rods! Catalase +, Oxidase +
62
What is the treatment of C. jejuni?
Antibiotics effective only if given early! Antibiotic resistance varies geographically. Otherwise, ORS.
63
What is the physiology/structure of Clostridium difficile?
Gram-positive, spore-forming, large rods. Anaerobe. Not readily detected by culture. Normally present in gut in low numbers.
64
What is the pathogenesis of C. difficile?
C. difficile usually follows after patients have been treated with broad spectrum antibiotics that disrupt the intestinal flora and allows organism to increase and express toxins/virulence factors leading to disease. Two major toxins: TcdA and TcdB, which target Ras superfamily of GTPases.
65
What is the mechanism of action of the C. difficile toxins TcdA and TcdB?
Both toxin A and B are glucosyltransferases that inactivate Rho, Rac, and Cdc42 in target cells. Both toxins enter cell through receptor-mediated endocytosis and require acidified endosome for translocation. Receptor for TcdA a disaccharide found on I, X, and Y blood antigens present in variety of cells. Receptor for TcdB unknown. Both toxins cause cytopathic effects, with TcdB having more potent effect. TcdA increases permeability of colonic epithelial layers and effects chemokine expression. Both toxins disrupt tight junctions of epithelial barriers and enhance neutrophil migration into the intestine. TcdA primary factor in CDAD (C. difficile-Associated Disease) but evidence that TcdB may act as potent enterotoxin in absence of TcdA.
66
What is the epidemiology of C. difficile?
One of most common causes of antibiotic-associated diarrhea in healthcare settings, becoming more recognized as a community acquired infection. Approx 5-30% of hospital patients who receive antimicrobial agents go on to develop CDAD. Recent circulation of highly virulent epidemic strain B1-NAP1 in US healthcare facilities. Patients infected with this B1-NAP1 strain may have more severe disease because produces binary toxin, which produces TcdA and TcdB at higher quantities. Risk factors include age, surgery, chemotherapy, laxatives, defects in humoral immunity.
67
What is the clinical manifestation of C. difficile?
Spectrum of illness from asymptomatic carriage to fulminant, relapsing, and fatal colitis. Endoscopic evidence of pseudomembranous colitis in colon indicates severe disease. Onset of symptoms may be few days to months following antimicrobial therapy. Diarrhea may be mild or severe. Fever, abdominal cramping, leukocytosis can be present. Toxic megacolon is a severe, life-threatening complication from CDAD. Relapse rate of CDAD among treated patients has increased in recent years and is associated with emergence of Nap1 strain.
68
What is the laboratory diagnosis for C. difficile?
TcdA and TcdB detected in stool using immunoassay (ELISA) or bioassay (toxin neutralization in cell culture system). Assays only detect 70-85% of cases and multiple stool samples may be required to increase detection. At HUP: two-step procedure, first step is a sensitive ELISA to detect glutamate dehydrogenase in stool (byproduct of C. diff growth along w other bacteria). If positive, PCR performed on stool to detect genes tcdB, tcdA.
69
What is the treatment for CDAD?
Treated by discontinuing offending antimicrobial agents and in seriously ill patients, oral therapy with Vancomycin or Metronidazole. Also, treatment with probiotics (Lactobacillus spp, Saccharomyces boulardii). Fecal implants, anion-exchange resins to absorb toxin, pulse-dosing with vancomycin.
70
What are the major site for anaerobes?
Oral cavity (gingival crevices), GI tract (in colon 1000 anaerobes per aerobe), female genital tract.
71
What is the general pathogenesis of anaerobic infection?
Generally results from disruption of mucosal surface followed by infiltration of resident flora into sterile site. Strict anaerobes thrive only at sites poorly perfused and not exposed to air. Many species of anaerobes. Most anaerobic infection is polymicrobial, synergize to cause infection.
72
What are the characteristics of anaerobes?
Organisms that fail to grow in air (including microaerophilic). Foul odor, gas production. Vary in tolerance for exposure to air depending on levels of superoxide dismutase and catalase. Pathogenic anaerobes tend to be more aerotolerant.
73
What is the physiology of Bacteroides fragilis?
Gram negative rod, obligate anaerobe, encapsulated. Grows in presence of bile-esculin. Common inhabitant of human gut. Most common of anaerobes isolated from clinical infections.
74
What is the pathogenesis of Bacteroides fragilis?
Microbes escape if gut wall breached. Generalized inflammatory response (peritonitis) results. Infectious process often contained and forms discrete areas of infection with poor perfusion/oxygenation where anaerobes take over. Capsular polysaccharide induces abscess formation. Ex. Ruptured appendix results in abscess formation with acute inflammatory response, neutrophil influx, central necrosis, thick fibrin/collagen capsule. B. fragilis induces abscess formation due to capsular polysaccharide which resists phagocytosis. CD4+ reaction to capsular polysaccharide that may contribute to abscess.
75
What is the clinical presentation of B. fragilis?
Abscess formation. Infection typically an abscess in normally sterile spaces where there has been exposure to contents of gut lumen.
76
What is the laboratory diagnosis of B. fragilis?
Successful culture requires maintaining oxygen-free anaerobic environment, special transport medium/handling procedures.
77
What is the treatment of B. fragilis infections?
Surgical debridement, drainage of necrotic tissue. Metronidazole (Flagyl) is treatment of choice against B. fragilis, has excellent activity against anaerobes. B. fragilis typically expresses beta-lactamase. Therapy should consider polymicrobial etiology.
78
What is the physiology of Helicobacter pylori?
Gram negative curved or spiral rod. Highly motile (flagella). Urease positive. Resides in thick mucus lining of stomach (niche protection from acid, competitors, and host immune responses). Survival in acid-rich environment of stomach lining. High urease activity- produces bases (ammonia) from urea to neutralize acid in local environment.
79
What is the pathogenesis of Helicobacter pylori?
Strains expressing Cytotoxic associated antigen (CagA) 60-70% more likely to cause disease. CagA secreted into host via Type IV secretion system. Inhibits clearance of pathogen by altering host cell signaling through tyrosine phosphorylation activity. Induction of chemokines (IL-8) attract neutrophils and results in chronic inflammation, elevated gastrin secretion, and increased gastric acid levels. Gene vacA encodes for vacuolating cytotoxin VacA, a protein toxin responsible for gastric epithelial erosion. H. pylori strains expressing vacA more common among patients with peptic ulcer disease and distal gastric cancer than patients with superficial gastritis alone. Thought that host response to infection (inflammation at infection sites, hypersecretion of acid) that leads to symptoms.
80
What is the epidemiology of Helicobacter pylori?
Primary reservoir in humans. Person to person transmission, especially within families. Oral-fecal route. Disease requires years of infection. Infection rate increases with age in developed countries. Most infected individuals are asymptomatic. 1/3 of world's population infected. Approximately 20% of infected individuals develop ulceration and 1% neoplasia. Higher rates of infection in developing countries (SES correlated). Risk decreases with improved hygiene. Infection persists for life unless treated.
81
What is the clinical manifestation of H. pylori infection?
Strong association of H. pylori infection with complications seen in upper GI tract: gastritis, peptic ulcers, gastric adenocarcinoma. Gastritis- strong association with H. pylori.
Gastric ulcers- less common.
Duodenal ulcers- common, thought to result from hyper-secretion of acid in early gastritis.
Chronic superficial gastritis may lead to long-term complications of H. pylori: peptic ulcer disease, atrophic gastritis (loss of epithelial glands) and gastric adenocarcinoma.
82
What is the laboratory diagnosis of H. pylori?
Microscopy of biopsy from endoscopy with special stains of tissue. Urease biochemical test. Detection of host antibodies (excellent for screening, not good for determining outcome of treatment).
83
What is the treatment of H. pylori infection?
Effectiveness dependent on compliance. Debate on whether should treat if presence of H. pylori but no symptoms. Eradication of H. pylori heals ulcers and decreases relapse, also leads to regression of MALT lymphoma. Monotherapy ineffective. Combination therapy require to raise gastric pH to render antibiotics more effective. Clarithromycin (macrolide) and amoxicillin plus proton pump inhibitor (omeprazole). No vaccine.
84
What is the physiology of enterococcal species?
Gram positive cocci in singles, pairs, and chains. Facultative anaerobe. Major habitat is GI tract of humans and other animals b/c of ability to grow in bile salts.
85
What is the pathogenesis of enterococcus spps?
Gut colonization precedes disease in susceptible hosts. Host factors are primary determinants of pathogenesis. Ability to exist as a biofilm important to catheter-related infection and difficulty to eradicated with antibiotics.
86
What are the species of Enterococcus and what is their epidemiology?
E. faecalis and E. faecium. E. faecalis more common but E. faecium more multi-drug resistant. Second most common cause of nosocomial infection. Spread within hospital setting. Hospital personnel important reservoir for infecting strains (hands!)
87
What are the clinical manifestations of enterococci?
1. UTI (catheters)
2. Bacteremia/septicemia (esp. catheter associated)
3. Endocarditis
4. Intra-abdominal/pelvic infections
~30% mortality associated with enterococcal bacteremia. Adheres to hear valves and renal epithelium accounting for ability to cause endocarditis and UTI.
88
What is the laboratory diagnosis of E. faecalis and E. faecium?
Readily grown in culture as gram positive cocci, nonhemolytic colonies in blood agar.
89
What is the treatment for enterococci spps?
Multi-drug resistance of enterococcal infections. Vancomycin-resistant strains (VRE) usually resistant to other commonly use drugs. Cephalosporins used for VRE. Ampicillin used for non-beta-lactamase producing strains. Treatment dictated by resistance testing in clinical micro lab. No vaccine.
90
What is the mechanism by which VRE is resistant to vancomycin?
Resistance spreads b/c enterococci are common and adept at conjugative transfer of plasmids/transposons. Increasing dependence on vancomycin and cephalosporins in ICUs selected for increase in VRE in these settings. VRE acquired a mobile genetic element that allows organism to detect Vancomycin (glycopeptide antibiotic) and express an altered stem peptide that still allows for cross-linking but reduces affinity for vancomycin by 1000-fold.
91
Name the most likely pathogen and treatment:
| Diarrhea after eating raw poultry products.
Salmonella enterica and Campylobacter jejuni. ORS/supportive care.
92
Name the most likely pathogen and treatment: A child with watery diarrhea. Has a pet snake.
Salmonella.
93
Name the most likely pathogen and treatment:
| Watery diarrhea in a traveler to a developing country.
ETEC. (mild version). Traveler's diarrhea. Supportive care.
94
Name the most likely pathogen and treatment: Gram-positive catheter-related infection in an elderly ICU patient on vancomycin and 3rd generation cephalosporin.
VRE. Vancomycin Resistant Enterococcus faecium.
Treat with? Gentamycin/streptamycin.
95
Name the most likely pathogen and treatment:
| Bloody diarrhea in the same patient a week after completing antibiotic treatment.
Clostridium difficile. Treat with Vancomycin or Flagyl (metronidazole).
96
Name the most likely pathogen and treatment: A 30 year old recent immigrant from Turkey with epigastric pain and evidence of blood in his stool.
Helicobacter pylori. Evidence of blood in stool... not diarrhea.
Treat with combination therapy and proton pump inhibitor.
97
Name the most likely pathogen and treatment: Ascending paralysis 10 days following a bout of watery diarrhea.
Guillain-Barré syndrome. Campylobacter jejuni.
98
Name the most likely pathogen and treatment: 14 days of daily fevers in a second-year medical student recently back from spending summer in India. Constipated. Rose spots.
Typhoid fever. Salmonella Typhi. Treat with Ampicillin, Ceftriaxone, or Ciprofloxacin.
