Urinary Tract Infections Prof. Dr. Çağrı BÜKE Yeditepe University Medical Faculty Infectious Diseases and Clinical Microbiology

Urinary tract infections (UTIs) Ç. BÜKE UTI Urinary tract infections (UTIs) A urinary tract infection (UTI) is defined as microbial infiltration of the otherwise sterile urinary tract and is one of the most common bacterial infections world- wide UTIs encompass infections of the urethra (urethritis), bladder (cystitis), ureters (ureteritis), and kidney (pyelonephritis)

Ç. BÜKE UTI Epidemiology UTIs are the most frequent bacterial infection seen in the outpatient setting: 1 in 3 women will develop a UTI requiring antibiotic treatment by age 24, and UTIs are the second most common cause for prescription of antibiotics 50% experience at least 1 UTI during their lifetime

Epidemiology Ç. BÜKE UTI The incidence of cystitis is significantly higher in women than men, likely the result of anatomic differences Colonization of the vaginal introitus by gastrointestinal pathogens can also increase the likelihood of urinary tract infiltration Incidence in men rises dramatically after age 50

Epidemiology Ç. BÜKE UTI Other factors including; urinary tract obstruction, incomplete voiding, and aberrant structural anatomy also predispose individuals to UTIs Additional risk factors include; prior history of UTIs, vaginal intercourse within the past 2 weeks, use of contraception with spermicide, low vaginal estrogen levels, and individual genetic background

Epidemiology Ç. BÜKE UTI Worldwide, 150 million cases / year 90 % cystitis 10 % pyelonephritis 75 % sporadic 25 % recurrent 2 % complicated The risk of UTI in women increases after menapause After a UTI 20 – 40% will have a recurrence UTI is rare in young and middle-aged men İt often occurs due to catheterisation or urological procedures

Definition Ç. BÜKE UTI Bacteriuria; Presence of bacteria in the urine Significant bacteriuria; Presence of bacteria in the urine ≥ 105 cfu/ml for F and 104 cfu/ml for M Symptomatic bacteriuria Asymptomatic bacteriuria Contamination; Presence of bacteriuria in the urine ≤ 105 cfu/ml or 104 cfu/ml

Pathogenesis Ç. BÜKE UTI - Contamination - Colonization - Invazion of bladder (pili, adhesins) - Inflammatory response - Neutrophil infiltration - Bacterial multiplication - Biofilm formation Epitelial damage (by bacterial toxins and proteases Ascension to the kidney

Pathogenesis Ç. BÜKE UTI Inoculum size Virulence Adherence Ascending route most common 90% Colonization of urethra and peri-urethral tissue is the initial event More in woman than man due to short female urethra, so urethral organisms enter bladder in close proximity to perianal areas Once in the bladder, multiply, then pass up the ureters to the renal pelvis and parenchyma Hematogenous seeding less frequent 10%

Host protective factors in UTIs Ç. BÜKE UTI Host protective factors in UTIs Mechanical Dilution and flow of urine Length of urethra Interference Normal bacteria flora (meatus) Chemical Osmolality and pH of urine Prostatic fluid Anti-adherence mechanisms in bladder Urinary immunoglobulins Mucosal antibacterial activity

Host factors complicating bacteriuria Ç. BÜKE UTI Host factors complicating bacteriuria Residual bladder urine after voiding Turbulent urethral flow (stricture) Foreign bodies Stones Atrophic vaginal mucosa Vesico-ureteral reflux Sexual intercourse (insertive rectal sex) Antibiotics Spermicides

Host factors complicating bacteriuria Ç. BÜKE UTI Host factors complicating bacteriuria Urinary stasis Neurologic bladder Reflux into the ureters (pregnancy) Obstruction Congenital anatomical abnormalities Prostate hypertrophy (age) Stones, tumor Diabetes mellitus Foreign materials Stones Stents Catheters

Bacterial virulence factors in UTI Ç. BÜKE UTI Bacterial virulence factors in UTI E.coli strains expressing O-antigens cause high proportion of infections Capsular antigens of E.coli associated with clinical severity (antiphagocytic) P-fimbriae enhance attachment of E.coli to uroepithelial cells Motile bacteria ascend the ureter against urine flow

Bacterial virulence factors in UTI Ç. BÜKE UTI Bacterial virulence factors in UTI Bacterial urease (Proteus) alkalinizes urine, stone formation and survival of bacteria within stones Gram (-) endotoxin decreases ureteral peristalsis Hemolysin damages renal tubular epithelium and promotes invasive infection Aerobactin of E.coli promote iron accumulation for bacterial replication

Types of urinary tract problems Ç. BÜKE UTI Types of urinary tract problems Asymptomatic bacteriuria Dysuria Cystitis Acute uncomplicated cystitis Recurrent cystitis Complicated UTI Pyelonephritis UTIs in men, pregnant women, children Prostatitis Other Catheter associated UTI Candida in urine Sterile pyuria

Clinical symptoms of UTI Ç. BÜKE UTI Clinical symptoms of UTI Cystitis Frequency Dysuria Urgency Hematuria Pyuria (> 10/mm3) Bacteriuria (≥ 105 cfu/ml F) (≥ 104 cfu/ml M)

Cystitis in male Ç. BÜKE UTI Young men (rare in men under 50) Anatomic abnormalities Anal insertive sex, toys Older men Calculi Enlarged prostate (obstruction) Chronic prostatitis Organisms differ E. coli accounts for 40-50% Proteus and Providencia species accounting for next most frequent cause Most common cause of relapsing UTI is chronic bacterial prostatitis

Clinical symptoms of UTI Ç. BÜKE UTI Clinical symptoms of UTI Pyelonephritis; Cystitis symptoms + Fever Chills Nausea/vomiting Costo-vertebral angle tenderness Leucocytosis , CRP Pyuria (> 10/mm3) Bacteriuria (≥ 105 cfu/ml F) (≥ 104 cfu/ml M)

Recurrent UTIs Ç. BÜKE UTI Relapse: same organism in <2 weeks Suggests uneradicated focus Ab resistance Non compliance Reinfection: may be same or different organism: Interval >2 weeks Hygiene/wiping Post-coital Vaginal atrophy Post-void residual (prolapse)

Complicated urinary tract infection Ç. BÜKE UTI Complicated urinary tract infection May involve the bladder or kidneys Symptomatic urinary infection in individuals with functional or structural abnormalities of the urinary tract Child, male, pregnant female Kidney involvement, 2nd bacteraemia Abnormality Urologic procedure Catheterization Unusual or resistant organisms

Ç. BÜKE UTI Etiology The most common bacterial cause of uncomplicated community-acquired UTI is uropathogenic Escherichia coli (UPEC), representing >80% of infections Other pathogens commonly associated with uncomplicated UTI include; Staphylococcus saprophyticus, Klebsiella species, Proteus mirabilis, and Enterococcus faecalis

Diagnosis of UTIs Ç. BÜKE UTI History Dysuria – Frequency - Urgency Vaginitis -no pyuria and <102 cfu/ml) Candida Trichomonas atrophy of vaginal tissues Urethritis –pyuria and Chlamydia Neisseria gonorrhoeae Cystitis – pyuria and >104-5 cfu/ml, onset abrupt Pyelonephritis - pyuria and >104-5 cfu/ml,

Diagnosis of UTIs Ç. BÜKE UTI Physical examination Laboratory parameters Urin sample In adults, mid stream urine sample usually reliably represents the urine in the bladder The most reliable sample is obtained via suprapubic puncture Urine in bladder > 4 hours Samples from urinary bags or bedpans should not be used as they invariably will be contaminated

Diagnosis of UTIs Ç. BÜKE UTI Urinalysis Microscopy Dipstick Leukocyte esterase: rapid screening test for detecting pyuria Patients with symptoms and negative LE should have a urine microscopic examination for pyuria Urinary nitrite Nitrite is formed when bacteria reduce the nitrate that is normally found in the urine False negatives common, but false positives are rare

Diagnosis of UTIs Ç. BÜKE UTI Quantitative culture Specialized cultures (TB, fungi)

Interpratation of urine culture results Ç. BÜKE UTI Interpratation of urine culture results

Asemptomatic bacteriuria Ç. BÜKE UTI Asemptomatic bacteriuria Positive urine culture repeatedly (105 cfu/ml) in the absence of signs of UTIs Pyuria does not affect interpretation Tretment of asemptomatic bacteriuria only in Pregnant women Prior to urological invasive procedures Prevalance varies 1-5% to 100% Screening for and treatment of asymptomatic bacteriuria is not indicated Treatment does not prevent further episodes of asemptomatic bacteriuria

Asemptomatic bacteriuria Ç. BÜKE UTI Asemptomatic bacteriuria The risk of pyelonephritis is increased 20-30 fold during pregnancy Increased risk for premature delivery and to have low birthweight infants Treatment of bacteriuria decreases the risks Screen for bacteriuria by urine culture at least once in early pregnancy and treat for 3-7 days if positive

Asemptomatic bacteriuria Ç. BÜKE UTI Asemptomatic bacteriuria In patients with urinary catheter, antimicrobial therapy not associated with decrease in rate of symptomatic infection High incidence of recurrence, usually with more resistant organisms Asymptomatic bacteriuria or funguria should not be screened for or treated in patients with indwelling urethral catheter

Treatment of UTIs Ç. BÜKE UTI Acute uncomplicated UTIs (Cystitis) TMP-SMX (160/800 mg tablet twice daily for 3 days) > 20% resistance to TMP-SMX Nitrofurantoin monohydrate/macrocrystals (100 mg twice daily for 5 days); 1-20% resistance to nitrofurantoin Fosfomycin trometamol (3 g powder single dose Amoxicillin (500 mg three times a day) 30% resistance to amoxicillin Fluoroquinolones (ciprofloxacin 500 mg twice daily) are highly effective in 3-day regimens

Treatment of UTIs Ç. BÜKE UTI Acute pyelonephritis Mild to moderately ill patients Amox/clav 1 g twice daily Cefuroxime 500 mg three times a day Fluoroquinolone: ciprofloxacin, levofloxacin 500 mg once a day TMP-SMX Patients usually improve in 48-72 hours Treat for 1-2 weeks

Treatment of UTIs Ç. BÜKE UTI Acute pyelonephritis Severely ill patients Ceftriaxon 1 g twice daily Floroquinolon Ampicillin + aminoglycoside IV therapy until patient afebrile for 48-72 hours Treat for 2 weeks If fever persists and all children and men: Renal US, CT or MR ± IVP Look for perinephric abscess Exclude urinary obstruction

Treatment of UTIs in pregnancy Ç. BÜKE UTI Treatment of UTIs in pregnancy Ampicillin 500 mg three times a day for 7-10 days Amok/klav 1g twice daily for 7- 10 days Sefaleksin 250 mg BID-QID for 7- 10 days Nitrofurantoin 50-100mg QID for 7- 10 days

Urethritis Ç. BÜKE UTI Neisseria gonorrhoeae Chlamydia Ureoplasma Antibiotic therapy should cover both gonococcal urethritis and nongonococcal urethritis (NGU) If concomitant treatment for NGU is not provided, the risk of postgonococcal urethritis is approximately 50%.

Urethritis Ç. BÜKE UTI For uncomplicated gonococcal urethritis; Ceftriaxone, 250 mg IM single dose For treatment of NGU; Azithromycin, 1 g orally in a single dose, or Doxycycline, 100 mg orally twice a day for 7 days Alternatives; Erythromycin base 500 mg orally four times a day for 7 days Levofloxacin 500 mg orally once daily for 7 days

Prostatitis Ç. BÜKE UTI Fever, chills Dysuria, pain Marked local tenderness Excellent penetration by most antibiotic classes-easily cured Ciprofloxacin 500 mg twice daily for 6-8 weeks Levofloxacin 500 mg once a day for 6-8 weeks TMP-SMX 160/800 mg twice a day for 6-8 weeks

Urinary tuberculosis Ç. BÜKE UTI Hematogenous seeding can occur in cortex and forms granuloma Seeding in the medulla In both sites Granulomas form Erosion into collecting system Further spread to ureters, bladder, prostate… Requires high index of suspicion Clinical disease insidious Dysuria, renal functional defects Key finding is sterile pyuria PPD skin testing