Yersinia enterocolitica: Invasion of Peyers patches (adhesin, invasin) Gets into the epithelium and disrupts normal phagocytic process Type Three Secretion effector proteins Disrupts cytoskeleton Block transcription of inflammatory cytokines Heat Stable enterotoxin Related to E. Coli heat stable toxin
Yersinia Enteric Infections, Enteric Diseases
Enterocolitis- 1 to 3 weeks duration - Fever, diarrhea, abdominal pain Mesenteric lymphadenitis - Fever, lower right quadrant pain (mistaken with appendicitis) Reactive polyarthritis occurs in about 15% of cases - Persists up to 1 year
Yersinia Enteric Infections, Diagnosis
Culture on enteric media, CIN agar (selective for Yersinia) Therapy- disease is self limited, efficacy of antibiotics not clearly demonstrated Epidemiology: Incidence in US about 1 per 100,000 More common in Northern Europe acquired from animal sources- Pork most common source
Disease: Neonatal meningitis and sepsis Pathogenesis: - Vaginal colonizaiton during pregnancy - Intestinal colonization of neonate - Invasion of epithelial cells in intestine, entry into circulation - Invasion of brain micro-vascular endothelial cells * S. fimbriae, unique surface proteins involved *No type three secretion
E. Coli expressing K1 capsular polysaccharide, Pathogenesis
Pathogenesis: Antiphagocytic K1 polysaccharide capsule - Identical to polysialic acid found on human embryonic nerve cell adgesion molecules -poorly immunogenic - Linear homopolymer of (2,8)linked N-acetylneuraminic acid - K1 capsule allows E. Coli to survive intracellularly in human brain micro-vascular endothelial cells
E. Coli expressing K1 capsular polysaccharide, Diagnosis
Culture from CSF, blood where there should not be any bacteria Antibiotic Therapy is critical: - Initially empiric to cover Group B sterptococci, E. Coli and Listeria monocytogenes (Ceftriaxon + amplicillin) Epidemiology: - E. Coli K1 is now the most common etiology of neonatal meningitis **Group B Sterptococcus now second due to pre-natal screening and treatment
Urinary Tract Infections, Uro-pathogenic E.Coli
Cystitis: Infection and inflammation of the baldder and sometimes the urethra - Dysuria (painful urination), frequency, urgency Pyelonephritis: ascension of the infection from the bladder to the kidneys. - Associated with systemic manifestations such as fever, nausea, vomiting, malaise. Also flank pain. It doesn't have to follow cystitis. Complications: - Bacteremia and sepsis - Recurring infections - UTI in pregnancy: * premature delivery, low birth weight * premature labor, spontaneous abortion
Pathogenesis: - Selection of uropathogenic strains from normal flora (most strains aren't uropathogenic) -E. Coli - Specific fimbrial adhesions: binding to epithelial receptors in bladder and kidney -Hemolysis: membrane damaging toxin (damaging neurtorphils) - Aerobactin (iron siderphore)- Iron in urine is hard to come by. Aerobactin is a molecule that can take iron away in the urine. Most fecal E. Coli don't have this. - Intracellular persistnce
Urinary Tract Infections, Diagnosis
Diagnosis: Uncomplicated cystitis: - Clinical observation - Microscopic analysis of pyuria - Leukocyte esterase assay (dipstick esterase) * Rapid determination of neutrophils in urine Acute pyelonephritis - Culture and susceptibility testing important Pregnancy - Qualittative culture regardless of presence of symptoms - Important during early prenatal care
Urinary Tract Infections, Therapy
Therapy: Antibiotics- Emerging resistance is a problem - Nitrofurantoin- 5 days (damages bacterial DNA) - Trimethoprim- sulfamethoxazole: 3 days (in areas that aren't many resistant strains) - Fosfomycin: Single dose (affects the early stage of cell wall synthesis. The resistant bacteria are crippled and won't be able to infect) -Ciprofloxacin: avoid due to selection for MRSA
Urinary Tract Infections, Therapy
Cystisis - Empiric Therapy usually adequate Acute pyelonephritis - If hospitalization required: initial IV antibiotics followed by oral course - Outpatient: Oral antibiotics 5-14 days Recurring infections (>3 infections per year)- Difficult - 6 month, low dose trimethoprim-sulfamethoxazole) *Foliate deficiency in women who are on low dose trimethoprim since it affects both our and bacterial enzyme) Asymptomatic bacteriuria in pregnancy should be treated
Young Children: - Symptoms may be non-specific - Uncircumcised boys under 3 months of age have > 10X incidence of febrile UTI (~20%)/ Girls more 2-3X more likely to have UTI with fever 3-12 months of age (6-8%) Vesicoureteral reflux associated with recurring infections Progressive renal scaring in children <5 years of age Permanent damage and measurable loss of renal function may result. Diagnosis involves imaging (ultrasound, voiding cystourethrogram) Usually resolves spontaneously.
Late adolescence- Adults Women- majority of cases - Sexual activity -Spermicide use (disrupt normal flora and increase vaginal colonization) -bacterial vaginosis (increase vaginal colonization with E coli) -ABO non-secretor status (Some ABO precursors bind E Coli) -Pregnancy (Hormonal effects, mechanical issues which increase risk)
Elderly: Associated lack of estrogenic hormones in women, loss of bladder tone, incontinence, prostatic hypertrophy in men, catherterization. Hospitalized: Associated with instrumentation, Greater risk for bacterimia and sepsis, greater variety of bacteria, antibiotic resistance is a greater problem. Other predisposing conditions: Diabetes, spinal cord injuries, HIV infection, MS
Multiple antibiotic resistance Sepsis, pneumonia, UTI Some strains are pigmented red Using bug in bio warfare, used in SF (outbreak of sepsis was seen)
Opportunistic enteric pathogens/Proteus mirabilis
Normal commensal bacteria Urease production (raises the PH in urine and contributes to the formation of stones which can cause obstructions in the urinary tract), swarming motility UTI: frequently sever, frequent pyelonephritis-associated bacteremia, infections may involve stone formation as a result of urease production
Question: Antibiotics are indicated for which of the following?
1. Recurring UTI in a non-pregnant otherwise healthy 23 yo woman 2. Asymptomatic bacteriuria in a pregnant woman 3. Recurring pyelonephritis in a 1 yo girl 4. All of the above Antibiotic is indicated for any kind of Urinary Tract Infection
Gram negative, oxidase positive bacillus - Obligate respirer (can use nitrate in absence of oxygen) Green pigments (pyocyanin)- Frequently they have green pigments Persists in soil and moist environments Can live in harsh and nasty environments
- Differentiate between enteric gram negative rods vs. all other gram negative rods - The oxidase test is based on oxidation of phenylenediamine by cytochrome C oxidase. The test is useful for the differentiation of Enterobacteriaceae (oxidase negative), from other Gram-negative bacilli.
Pseudomonas aeruginosa, Diseases
Opportunistic infections Pneumonia in cystic fibrosis patients Nasocomial ventilator- associated pneumonia, UTI, sepsis Burn wound infections, sepsis Eye infections (infectious keratitis) osteochondritis of foot following piercing injury External otitis (swimmer's ear) - Malignant external otitis (diabetics at risk) Hot tub folliculitis Body piercing- associated infections
Pseudomonas Aeruginosa, Pathogenesis
Adherence to mucins, extracellular matrix components - Quorum sensing important for biofilm formation Secretion of proteases, phospholipases Pyocyanin (green pigment) induces IL-8, neutrophil recruitment, neutrophil apoptosis, oxidative damage to host cells Alginate antiphagocytic polysccharide ( Seen in cystic fibrosis patients) Exotoxin A Single chain with A and B domains Binds to cell surface receptor (α2-macroglobulin receptor (LRP)) ADP-ribosyl transferase modifies EF2 - Inhibits protein translation
Toxins (effector proteins) injected by type 3 secretion system Exotoxins S, T - Two domains (GTPase activating and ADP ribosylase domain) ExoU- Phospholipase- Cytotoxic effects, cell lysis due to membrane damage ExoY- Adenylate cyclase toxin (also seen B. Pertussis)
Pseudomonas aeruginosa and Cystic fibrosis
Colonization from environmental exposure Biofilm production under control of quorum sensing Selectiion for mucoid, alginate-producing strains - Resistance to antibiotics, reactive O2 species Acute to chronic transition: - Downregulation of mutation of flagella production and motility - Selection for mutations which inactivate virulence factors, biofilm formation - Selection for mutations which upregulate efflux pumps - Antibiotic resistance
Diagnosis: Culture Therapy: Antibiotics - Innate and acquired antibiotic resistance complicates therapy - Acquisition of antibiotic resistance frequently involves mitation in porins and efflux systems.
Question: Which of the following virulence factors of P. aeroginosa?
1. Type 3 secretion toxins 2. Adherence to ECM 3. Biofilms 4. All of the above
Acinetobacter baumanii= Iraqibacter
Ubiquitous on hospital surfaces, present on skin and nasopharynx of healthy individuals. Multiply resistant Respiratory tract infections, UTI, sepsis in compromised patients.
Question: The mechanism of action of Pseudomonas exotoxin A is most similar to:
A. Diphtheria toxin- affects protein synthesis just like exotoxin A B. Shiga toxin C. Cholera toxin D. Pertussis toxin
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