Bacterial infections of the urinary tract

Brief description of urinary tract infections

1. Bacterial Infections of the Urinary Tract MEHER RIZVI Associate Professor Department of Microbiology & Immunology

2. Clinical syndromes Cystitis Pyelonephritis Urosepsis Urethritis Dysuria, frequency, urgency, suprapubic pain, hematuria Fever, flank pain, chills, nausea/vomiting Above symptoms, shock Discharge, itching, dysuria , frequency: Suspect STDs

3. Epidemiology of UTI Community acquired UTI Hospital acquired UTI: Most common health care associated infection (CAUTI) Worldwide: 150 million cases/ year Simple Complicated

4. Pyelonephritis 10% Cystitis 90% Complicated UTI Calculi/stones 2%

5. Pathogenesis CYSTITIS

6. Host protective factors Normal flora in urethra Flushing mechanism of urine Acid pH of urine (4.6-6) ↑ Urea concentration ↑ Osmolality Acid vaginal pH (3.5-4.5) Systemic/local antibodies Inflammatory response mounted in bladder Flushing mechanism of urine

7. Host Risk factors Complicated UTI: If anatomic/ functional/ metabolic abnormalities of urinary tract present Pregnancy ( Incomplete emptying) Residual urine in bladder: Stone, Benign hypertrophy of prostate (BPH Men > 50 years ) Diabetes (Glucose in urine facilitates bacterial growth) Post-menopausal women ( Estrogen deficiency leads to ↑ vaginal pH Neurogenic bladder (Incomplete emptying) Renal failure/ renal transplantation In dwelling catheter (Biofilm production)- Most common cause of HAI termed as CAUTI Simple uncomplicated UTI Female gender (short and broad urethra) Infant boys (vesicular-ureteric reflux) Genetic susceptibility

8. Both Gram-negative and Gram-positive bacteria cause UTI Uropathogenic Escherichia coli (UPEC) cause majority of both uncomplicated and complicated UTIs Escherichia coli Klebsiella pneumoniae Staphylococcus saprophyticus Enterococcus faecalis Group B Streptococcus Proteus mirabilis Pseudomonas aeruginosa Staphylococcus aureus Candida spp. Escherichia coli Enterococcus faecalis Klebsiella pneumoniae Candida spp Staphylococcus aureus Pseudomonas aeruginosa Proteus mirabilis Group B Streptococcus Uncomplicated UTI Complicated UTI Etiology

9. Prevalence of bacteria in UTI

10. Bacterial virulence factors Uropathogenic Escherichia coli Somatic O antigens: (O2,O4,O6) Capsule: pyelonephritis (inhibits phagocytosis) P fimbriae: initiates attachment to uro -epithelial cells Flagella: Motility allows the bacteria to ascend up to the bladder/ureter against urine flow Haemolysins : In pyelonephritis damage renal epithelium Cytotoxic necrotizing factor: Cytotoxic to bladder and renal epithelium Other Uropathogenic bacteria Pili: for adherence Capsule: Klebsiella pneumoniae Haemolysin : Proteus mirabilis Biofilm: Pseudomonas aeruginosa Urease: Proteus mirabilis, S. saprophyticus , Klebsiella pneumonia Protease: Pseudomonas aeruginosa Proteus mirabilis: Urease enzyme splits urea to ammonia: → Urine is alkalinized : Damages renal epithelium → Complicated UTI Alkaline pH increases precipitation of calcium and phosphates → Stone/Calculi formation → Obstruction →Recurrent /Complicated UTI

11. Ascending and Descending UTI

12. Etiology Descending UTI S. aureus M. Tuberculosis Salmonella typhi Candida albicans Etiology Ascending UTI Escherichia coli Klebsiella pneumoniae Proteus mirabilis Ascending UTI Descending/ hematogenous UTI Source of uropathogens : Enteric bacteria from GI tract Source of pathogens: Blood stream

13. Complicated UTI- catheterized patient (CAUTI)

14. Most common route More common in women due to: Short and wide urethra Proximity to perineum. If left untreated, can ascend to the ureters (esp. if vesiculo -reflex present) and to renal pelvis and renal parenchyma Ascending UTI Urethral commensals can ascend easily

15. Haematogenous seeding less frequent than ascending infection Common etiology: Bacteremia due to Staphylococcus aureus Salmonella typhi Mycobacterium tuberculosis Descending UTI Hospital acquired UTI Associated with lower urinary tract instrumentation Catheterization Cystoscopy

16. KEY POINTS

17. Laboratory Diagnosis Early morning urine sample is best as has highest concentration of bacteria. Or Collect urine after 4 hrs of prior voiding ( To prevent false negative findings) Protocol: Collection of urine Transport to laboratory Screening tests Culture Antimicrobial sensitivity Sterile, wide mouthed screw capped container All samples for Culture & sensitivity (C/s) should be collected before instituting antimicrobial therapy

18. In pregnant women. Men. If diagnosis unclear from history and physical exam If unusual or antimicrobial-resistant organism suspected If suspected relapse or treatment failure Urine culture usually not required in suspected cases of acute, uncomplicated cystitis as: Symptoms are clear cut Spectrum of causative organisms is predictable Urine culture results are often not available until after completion of short-course empirical treatments. The role of urine culture is 2-fold: To provide retrospective confirmation of the presence of bacteriuria To provide specific information about the organism and its antimicrobial susceptibility. However all samples should not be tested for C/s before instituting antimicrobial therapy When is urine culture essential?

19. Collection of sample Adult patient: Instructions Infants: Instructions to care giver Wash external genitalia (Glans and labia) with soap and water. Do not use antiseptics! Collect mid stream urine sample in sterile wide mouthed, screw capped container Rationale: First voided urine washes off commensals from distal urethra. Midstream urine sample represents true bladder condition. Non-invasive collection methods Clean catch urine Urine collection bags Urine collection pads Invasive collection methods Suprapubic aspiration In-out catheterization

20. Collection of sample from catheterized patient Instructions to care giver

21. Laboratory processing of urine specimens: The patient’s urine sample should be transported and processed immediately (maximum within 2 hours of collection) If delay occurs: Samples should be stored in the refrigerator at 4 C for a maximum of 24 hours Use Boric acid- a bacteriostatic preservative Rationale: Bacteria can multiply in urine and lead to false positive results (urine is a good culture media)

22. Screening of samples Microscopy Leucocyte esterase: Rapid, sensitive dipstick method for detection of pus cells (pyuria). Dipstick analysis: Two in one method: Detects pyuria using leucocyte esterase and nitrite production for bacteriuria A wet mount of uncentrifuged urine specimen examined microscopically ( under high power) reveals the presence of pus cells, bacteria, erythrocytes, casts 6- 10 pus cells are considered significant (significant pyuria) and have to be correlated with the presence of significant bacteriuria

23. Culture Media: Cysteine lactose electrolyte deficient medium (CLED) Allows all bacteria to grow. Semi quantitative count: A measured quantity of urine is taken with a calibrated sterile loop and cultured on CLED Interpretation 1-2 types of colonies: UTI present ≥ 3 types of colonies: Contaminated sample. A repeat sample requested Significant bacteriuria: 10 4 colony forming units (cfu) /ml in symptomatic patient ( Kass Count) Suprapubic aspirate: Any bacterial count is significant!

24. CLED >3 types of conlonies : Contaminated sample Lactose fermenting colony cfu ≥ 10 4 Non-Lactose fermenting colony cfu ≥ 10 4 Non-Lactose fermenting: Proteus mirabilis: oxidase negative Pseudomonas aeruginosa: oxidase positive Lactose fermenting bacteria: Escherichia coli Klebsiella pneumoniae

25. Asymptomatic bacteriuria: Repeated positive urine culture (10 5 cfu/ml) Investigate & treat only pregnant women / early morning

26. Insignificant count 10 3 Significant count 10 4 -10 5 Interpretation after 24 hour incubation at 37 C Bacterial Identification Antimicrobial sensitivity done by automated system

27. Sterile pyuria Large number of Pus cells observed in urine -: Pyuria Culture repeatedly negative- Sterile pyuria Interpretation: Fastidious etiology. Organism does not grow on CLED Cause: Mycobacterium tuberculosis Chlamydia trachomatis Virus e.g. adenovirus Clinical features of tubercular infection Symptoms of bacterial cystitis Symptoms of pyelonephritis Unusual: Fever, weight loss, night sweats Routine investigations: Complete blood cell (CBC) count Erythrocyte sedimentation rate (ESR) C-reactive protein (CRP)

28. Laboratory Diagnosis: M. tuberculosis Serial early-morning urine cultures (at least 3) for acid-fast bacilli (AFB) are collected in a sterile flask. Reason: Mycobacteria are not excreted on all days and when excreted are present in small numbers. Diagnosis of kidney infection with Mycobacterium tuberculosis does not require counting of bacteria in the urine specimen. Any number is significant. Culture: Lowenstein Jensen Medium: Time taken- 4-8 wks Bactec 460- Time taken 2-3 days PCR: Most sensitive and specific- Species-specific IS6110 PCR test

29. Acute uncomplicated cystitis: Recommended agents Nitrofurantoin monohydrate / macrocrystals Trimethoprim-sulfamethoxazole Avoid in pregnancy Fosfomycin trometamol Acute uncomplicated cystitis: Alternative agents Fluoroquinolones Reserve for more serious conditions; avoid in pregnancy Beta- lactams Resistance varies by agent Treatment for UTI Antibiotics to avoid in G6PD deficiency: Nitrofurantoin Fluoroquinolones Sulfamethoxazole

30. Parenteral : In hospitalized patients with pyelonephritis ( community acquired ) Aminoglycoside Extended spectrum cephalosporin Fluoroquinolones 80 % of hospital acquired associated with catheterization. Multi resistant organisms such as MRSA and vancomycin resistant enterococci ( VRE ) cause UTI. MRSA: Vancomycin VRE: Linezolid Treatment: Acute uncomplicated pyelonephritis Treatment: Hospital acquired urinary Infections