Exam Review 2 Flashcards
What UTIs can occur in the upper urinary tract?
Pyelonephritis, intra-renal abscess; Perinephric abscess (usually late complications of pyelonephritis)
What UTIs can occur in the lower urinary tract?
Cystitis; Urethritis; Prostatitis
What is an uncomplicated UTI?
Infection in a structurally and neurologically normal urinary tract in otherwise healthy patients
What is a complicated UTI?
Infection in a urinary tract with functional or structural abnormalities (e.g. indwelling catheters and renal calculi); Infection in patients with an underlying condition that increases risk of treatment failure (diabetes, immunosuppression, indwelling bladder catheter)
What are symptoms of cystitis?
Dysuria, urinary urgency and frequency, bladder fullness/discomfort; NOTE: Hemorrhagic cystitis (bloody urine) reported in as many as 10% of cases of UTI in otherwise healthy women
What are symptoms of pyelonephritis?
Fever, sweating, nausea, vomiting, flank pain & pain in the costovertebral areas, dysuria, urinary frequency and urgency; if there is systemic involvement, there can be signs and symptoms of dehydration, hypotension
Who is at risk of renal abscess with UTI?
patients with urinary tract abnormalities, diabetic patients
What are symptoms of UTI in children
enuresis, fever, poor weight gain
How should a UTI be diagnosed?
Urinalysis: microscopic examination of urine (Presence of WBC (pyuria), RBC, bacteria); Urine dipstick test: rapid screening test (leukocyte esterase test to test for pyuria, Nitrate ® nitrite test (+ve in only 25%))
What is the gold standard for diagnosing UTI?
Microbiological analysis: Bacterial count >10^5 cfu/ml regarded as significant
When should a urine sample be cultured?
Pyelonephritis and complicated UTIs, Children, pregnant women, Patients with structural abnormalities of the urinary tract, men
Who should be screened for asymptomatic UTI?
Pregnant women, Patients undergoing urologic surgery, transurethral resection of prostate
What is the usual cause of UTI?
E. Coli!!! Sometimes S. saprophyticus
What are risk factors for UTI in women?
Short urethra, Sexual intercourse & lack of post coital voiding, Diaphragm, spermicide use, Pregnancy, Disruption of normal bacterial flora
What are UTI virulence factors?
Enhanced adherence to receptors on uroepithelial cells (Type 1 fimbriae and P fimbriae - pili!), flagella (enhanced motility), Production of hemolysin, Production of aerobactin (a siderophore, which allows for iron acquisition)
What are symptoms of acute bacterial prostatitis?
Symptoms similar to lower tract infection, Fever, perineal and back pain, Urinary retention (edema of prostate)
What findings are common in bacterial prostatitis?
Warm, swollen, tender prostate on rectal exam; Abnormal urinalysis with pyuria (WBC), positive urine culture, blood culture may be positive
What is treatment for bacterial prostatitis?
Treatment consists of LONGER course of antibiotics and pain control (NSAIDS)
What are the common treatments for UTIs?
Short course (3-day) therapy for uncomplicated infections; Longer duration (10-14 days) for complicated infection (e.g. pyelonephritis); Oral vs. intravenous agents (TMP/SMX, nitrofurantoin, Fluoroquinolones) - depends on tolerance/nausea
What are the risk factors for recurrent UTI?
Postmenopausal status; diabetes; Recent antimicrobial use; Behavioral risk factors (Frequency of sexual intercourse, Spermicide use, New partner, First UTI
When should UTI prophylaxis be given?
> 2 symptomatic UTIs within six months or >3 over 12 months
What are plasmids?
Extrachromosomal, Circular or linear, 2 kb to hundreds of kb in size, Non-essential, May carry ‘supplemental’ genetic information or may be cryptic, Employ host functions for most of DNA metabolism
What are insertion elements?
Simplest type of transposable element found in bacterial chromosomes and plasmids, Encode only genes for mobilization and insertion, Range in size from 768 bp to 5 kb, IS1 first identified in E. coli’s glactose operon is 768 bp long and is present with 4-19 copies in the E. coli chromosome, Ends of all known IS elements show inverted terminal repeats (ITRs).
What is transformation?
- Lysis of donor cell releases DNA into medium; 2. Donor DNA is taken up by recipient
What is conjugation?
Donor DNA is transferred directly into recipient through a connecting tube. Contact and transfer and promoted by a specialized plasmid in the donor cell.
What is transduction?
- Bacteriophage infects a cell; 2. Lysis of donor cell. Donor DNA is packaged and released into the bacteriophage; 3. Donor DNA is transferred when phage particle infects recipient cell.
What is R-plasmid conjugation?
- The bacterium with an R-plasmid is multiple antibiotic resistant and can produce a sex pilus (serve as a genetic donor). 2. The sex pilus adheres to an F- female (recipient). One strand of the R-plasmid breaks. 3. The sex pilus retracts and a bridge is created between the two bacteria. One strand of the R-plasmid enters the recipient bacterium. 4. Both bacteria make a complementary strand of the R-plasmid and both are now multiple antibiotic resistant and capable of producing a sex pilus.
How can you inhibit transformation?
DNAase
How can you inhibit conjugation?
Physical barrier
For which bacteria is transduction important for resistance?
Vibrio cholera, Corynebacterium diphtheriae, Neisseria meningitidis
For which bacteria is conjugation important for resistance?
Bacillus spp.
What is pseudomonas aeruginosa and where is it found?
It’s an opportunistic pathogen found in soil, salad bars, shower heads; it causes disease in impaired hosts (VAP, CF); gram neg rods
What are common virulence factors?
Pili (fimbriae) - attachment; Siderophores - iron scavenging; Flagella - motility; LPS - immune system stimulation; Type III secretion system - toxins; biofilm
What does TLR5 recognize?
Flagella; only responds to invasive organisms; proinflammatory and participates in NFkB pathway; polymorphisms in TLR5 affect disease susceptibility; Activates the NLRC3 inflammasome – causes pathology
What pathway is TLR4 involved in?
JAK/STAT; recognizes LPS; Type I IFN
Where does LPS come from?
Gram negatives; actively shed from growing organisms, released from lysed – dying bacteria
What virulence factors does P. aeruginosa express?
Expression of flagella, pili, type III toxins
How do bacteria “communicate”?
Homoserine lactones (small highly diffusable molecules), Cyclic di GMP; Secretion of small molecules – taken up by surrounding organisms – along with a transcriptional activator – initiate gene expression in the “community”
How does P. aeruginosa avoid the immune system?
Biofilm mode of growth; loss of flagella (loss of motility);
LPS mutations – loss of the O-side chains; Lack of type III toxin expression
What are obligate anaerobes?
Unable to grow if > than 0.5% oxygen
What are moderate anaerobes?
Capable of growing between 2-8% oxygen
What are Microaerophillic bacteria?
Grows in presence of oxygen, but better in anaerobic conditions
What are Facultative bacteria (facultative anaerobes)?
Grows both in presence and absence of oxygen
Why can’t anaerobic bacteria function in oxygen?
They metabolize the oxygen, produce toxic byproducts, can’t detox, bacteria die
What does bacteroides fragilis do normally in host?
synthesizes vitamin K and deconjugates bile acids
What do anaerobic bacteria normally contribute to host?
Fermentation of undigested carbohydrates, Training immune system, Roles evaluated in disease states (obesity, inflammatory bowel disease, cancer etc)
What are common anaerobes?
Gram + bacilli: Clostridium perfringens, tetani, botulinum, difficile, Actinomyces, p. acnes; Gram - bacilli: Bacteroides fragilis, thetaiotaomicron
What do anaerobic cocci do to the body?
Brain abscesses, periodontal disease, pneumonias, skin and soft tissue infections, intra-abdominal infections; P. magnus: chronic bone and joint infections, especially prosthetic joints; P. prevotti and P. anaerobius: female genital tract and intra-abdominal infections
Which gram + anaerobes create spores?
Clostridium (C. perfringens, C. difficile, C. tetani, C. botulinum)
What is proprionibacterium?
Produces propionic acid as major byproduct of fermentation; Colonize skin, conjunctiva, external ear, oropharynx, female GU tract; P. acnes; Prosthetic devices (heart valves, ventricular shunts); virulence is low - “infection” occurs much later; non-spore forming gram + bacilli
What is clostridium?
Ubiquitous - Present in soil, water, sewage, normal flora in GI tracts of animals and humans; forms spores, resistant to heat, dessication, and disinfectants, can survive for years in adverse environments; Toxin elaboration (histolytic toxins, enterotoxins, neurotoxins)
What is Clostridium perfringens?
GI tract of humans and animals; Type A responsible for most human infections, is widely distributed in soil and water contaminated with feces; Self-limited gastroenteritis, soft tissue infections: cellulitis, fascitis or myonecrosis (gas gangrene)
What is Clostridial myonecrosis?
Caused by perfringens; Symptoms begin 1-4 days after inoculation and progresses rapidly to extensive muscle necrosis and shock; Local area with marked pain, swelling, serosanguinous discharge, bullae, slight crepitance; Treated with Surgical debridement, Antibiotics, Hyperbaric oxygen
What causes C diff?
Antibiotic exposure associated with overgrowth of C. difficile; Enterotoxin (toxin A) produces chemotaxis, induces cytokine production and hypersecretion of fluid, development of hemorrhagic necrosis; Cytotoxin (toxin B) induces polymerization of actin with loss of cellular cytoskeleton
How do you treat C diff?
Discontinue antibiotics, Metronidazole (PO or IV) or vancomycin (PO) are treatments of choice, Fecal microbial transplant (FMT); NOTE: Relapse in 20-30% (spores are resistant; imbalanced colonic flora)
What is Clostridium tetani?
Disease in un-vaccinated or inadequately immunized (disease does not induce immunity); Spore (found in soil, GI tract of animals) inoculated into wound; Tetanospasmin (heat-labile neurotoxin) blocks release of inhibitory neurotransmitters (eg. GABA) into synapses, allowing excitatory synapses to be unregulated. This results in muscle spasms - binding is irreversible
What are symptoms of tetanus?
Trismus (lock jaw), risus sardonicus (contraction of facial muscles), Sweating, hyperthermia, cardiac arrythmias, labile blood pressure; can cause infection in umbilical stump or twisting of cord
How is tetanus treated?
Debridement of wound, Metronidazole, Tetanus immunoglobulin, Vaccination with tetanus toxoid
What is Clostridium botulinum?
Blocks neurotransmission at peripheral cholinergic synapses, Prevents release of acetylcholine, resulting in muscle relaxation; can get foodborne botulism or infant botulsim (from spores)
What is the difference between foodborne and infant botulism?
Foodborne: consumption of preformed toxin; Infant: Disease associated with neurotoxin produced in vivo
What are symptoms of botulism?
Symmetric cranial nerve palsies (III, IV, VI, VII) causing 4Ds: diplopia, dysphonia, dysarthria, and dysphagia; Symmetric flaccid paralysis
How is botulism treated?
Supportive care, Elimination of organism from GI tract (Gastric lavage, Metronidazole or penicillin); Botulinum Immunoglobulin (BIG): pooled plasma from adults immunized with pentavalent (ABCDE) botulinum toxoid
How is S. pneumonia treated - in peds? In adults?
Peds: Beta-lactam antibiotics (PCN - ampicillin) or cephalosporins (ceftriaxone); adults: macrolide (azithromycin), if co-morbidity: fluoroquinolone or beta-lactam plus macrolide
What is mycoplasma?
Does not have a cell wall - Cell membrane contains sterols not present in other bacteria; diagnosis usually by serology (IgG); TLR2 important for binding to respiratory epithelium; Remains extracellular; Acts as a super antigen stimulating PMNs and macrophages to release cytokines; Causes local destruction of cilia, interferes with normal airway clearance which leads to mechanical irritation and persistent cough
What is “walking pneumonia”?
Mycoplasma - lacks seasonal pattern, spread by droplet secretions
Who gets mycoplasma?
children and young adults
What are symptoms of mycoplasma?
Mild respiratory symptoms
How do you treat mycoplasma?
Macrolides (erythromycin, azithromycin, clarithromycin), Fluoroquinolones (levofloxacin)
What are Chlamydophila pneumonias?
Infect non-ciliated columnar cells, Multiply in alveolar macrophages, Perivascular and peribronchiolar infiltrates, Clinical symptoms due to host immune response
What is C. trachomatis pneumonia?
Neonatal infection presents at 1-3 months of age, Staccato-like cough, rapid respiratory rate; NOTE: NO FEVER
How is C. trachomatis pneumonia treated?
erythromycin
How is C. trachomatis diagnosed?
minimal chest findings, xray hyperinflation and diffuse infiltrates, peripheral eosinophilia
What is Legionella?
2-6% community acquired pneumonias; Gram negative bacilli- don’t stain with common reagents; Organisms contaminate water sources: air conditioning systems and water tanks
Who are at risk for Legionella?
immunocompromised, hospitalized, and outbreak situations
What is Legionella pathogenesis?
Aspiration or inhalation of organism; Flagellae and pili allow attachment to respiratory epithelium and macrophages
What are the virulence factors for Legionella?
Exotoxins: (hemolysin, cytotoxin, deoxyribonuclease, ribonuclease) cause destruction by killing the infected respiratory cells leading to formation of microabscesses; Immunity primarily cell mediated immunity (T cells)
What are the symptoms of Legionnaires disease?
influenza like illness or severe manifestation= pneumonia, Fever (105), rigors, cough, headache; Multilobular infiltrates and microabscesses; Extrapulmonary manifestations: CNS, diarrhea, abdominal pain, nausea; high mortality
What is the serology for Legionnaires?
Serology >1:128 positive however late development of antibodies; Culture on special media
How is Legionnaires treated?
macrolide or levofloxacin
What is Bordetella pertussis?
Fastidious, gram negative coccobacilii; Spread by respiratory droplets; No bacteremia; Toxins cause local tissue damage (A-B toxin)
How is pertussis confirmed?
culture and/or PCR
How is pertussis treated?
Erythromycin or azithromycin (better tolerated, shorter course); VACCINATE!
What is distinctive about TB bacillus?
cell wall is made of lipids, VERY slow growing - long period of treatment
How is TB spread?
Entry portal is the lungs - spread by inhalation of droplet
What happens in the Primary TB infection?
TB reaches alveoli; Replicates intracellularly within alveolar macrophages; Prevents acidification of phagosome w/in macrophage; Lack of immediate host immune response
How does the body fight TB?
CD4 to alveolar macrophage; Proliferation of CD4; Release of IFNg; additional macrophage phagocytosis; TNFa released; granuloma formed - all of this is a problem if you are on TNF inhibitor!
What happens after immune response to TB?
Patient asymptomatic or mild viral like syndrome in 85% of cases; Enlargement of hilar and peribronchial lymph nodes; Ghon complex with fibrosis and calcification of hilar nodes; Development of positive PPD
Who is at risk for developing cavitary active TB?
Adolescents! Weird…
What is tuberculosis pleurisy?
HYPERSENSITIVITY REACTION TO SMALL # OF ORGANISMS REACHING PLEURA IN PRIMARY INFECTION; EXUDATIVE PLEURAL EFFUSION; CULTURE NEGATIVE
Where can TB hang out?
Lymph nodes (formation of scrofula); bones; renal TB - asymptomatic until calyx/pelvis ulcerated
What happens in active TB?
Caseating necrosis, liquefaction, drainage into the bronchial tree; Cavity formation
What kind of TB is most contagious?
Cavitary disease
What are active TB symptoms?
Systemic symptoms non-specific: fever, fatigue, night sweats, weight loss; Pulmonary symptoms: cough, productive or dry; Hemoptysis - coughing up blood - (can be emergency symptom)
How is TB diagnosed?
Sputum smear (but negative in 50% of non-cavitary); Sputum culture = gold standard (takes 2-6 wks); broth media
What are keys to TB treatment?
Directly Observed Therapy; always use at least 2 drugs (start w/ 4 pending sensitivities); 6-9 months of treatment
What is the first line drug for TB?
Isoniazid (INH) - bacteriocidal, good CNS coverage, can be used during pregnancy; passes through placenta and into breast milk
What does INH do?
Inhibits synthesis of mycolic acid, a major component of bacterial cell wall
What toxicity can INH cause?
Hepatitis, neuropathy
What does Rifampin do for TB?
Bacteriocidal, shortens treatment length (6-9 months w/, 18-24 w/out); can be used in pregnancy, good CNS coverage
How does Rifampin work?
Inhibits DNA-dependent RNA polymerase in susceptible strains of bacteria
What are side effects of Rifampin?
GI upset, Can cause cholestatic jaundice, Skin rash, Thrombocytopenia (rare); major drug-drug reaction
What’s the super weird thing about Rifampin?
Turns pee orange!
What is the drug-drug reaction of Rifampin?
Induces CYP450 - affects protease inhibitors (used in HIV)
What does Pyrazinamide (PZA) do for TB?
Main role in sensitive disease is to reduce length of treatment from 9 months to 6 months; NOTE: do not use in pregnancy
What are the side effects of PZA?
Hyperuricemia - may cause gout (in which case STOP), hepatic toxicity
What does Ethambutol (ETB) do in TB?
Prevention of resistance
What is the toxicity associated w/ ETB?
Retrobulbar neuritis - red-green color blindness, blurred vision; do regular vision checks
What is New Delhi Metallo-Beta Lactamase-1 (NDM-1)?
a transmissible genetic element (plasmid with integrons) encoding multiple antibiotic resistance genes including carbapenems, beta-lactams, macrolides, quinolones, rifampin - and spreading to lots of different bacteria!
What is the key example of cross-resistance?
Methicillin resistance confers resistance to all beta-lactams, penicillins and cephalosporins (PBP-2a)
What can be causes of cross-resistance?
Drug efflux pumps or overlapping targets
Why is transfer of efflux pump resistance not easy to do?
complex genetic machinery needed for the pump to be functional
Which antibiotics are routinely used in animal feed?
Macrolides, tetracyclines, glycopeptides
How can we control the spread of antimicrobial resistance?
- Eliminate the use of antimicrobials in animal feed; 2. Restrict use of antibiotics for inappropriate indications; 3. Antibiotic restriction in hospital settings; 4. Enforce infection control policies; 5. tax antibiotics?
