Urinary Tract Infections Meral Sönmezoğlu Division of Infectious Diseases Yeditepe University Hospital

Learning objectives UTI’s Epidemiology Pathogenesis Risk Factors Types of cystitis Evaluation Therapy

Epidemiology UTI’s UTIs are the second most common cause for prescription of antibiotics Most infections are limited to the lower urinary tract 30 times more likely in young women than young men Incidence in men rises dramatically after age 50

Relative frequency of nosocomial (hospital-acquired) infections Site% of total Urinary tract34 Surgical site17 Bloodstream14 Pneumonia13 Other21

Pathogenesis UTI’s Bacteria travel: Ascending route via the urethra 95% Hematogenous (kidney-> bladder) Endocarditis Tuberculosis Direct (connection bowel- bladder)

Bacterial factors Inoculum size Virulence Adherence E. coli adhere to urothelial cells Proteus, Providencia adhere to lumen of catheter material

VirulenceHost factors InfectionNo infection

Host defense mechanisms 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

Risk factors UTI’s (I) Alteration/introduction of bacteria Antibiotics Spermicides Vaginal atrophy (age) Sex Insertive rectal sex Inserting toys Patient education: Void after intercourse, Proper wiping, front to back once

Risk factors UTI’s (II) Urinary stasis Neurologic bladder Reflux into the ureters (pregnancy) Obstruction Congenital anatomical abnormalities Prostate hypertrophy (age) Stones, tumor Diabetes mellitus Glycosuria Foreign materials Stones Stents Catheters

Pathogenesis of cystitis

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

Definitions (I) Asymptomatic bacteriuria: isolation of a specified quantitative count of bacteria in an appropriately collected urine specimen obtained from a person without symptoms or signs referable to urinary infection Acute uncomplicated UTI (cystitis): symptomatic bladder infection characterized by frequency, urgency, dysuria or suprapubic pain in a woman with a normal genitourinary tract

Definitions (II) Acute nonobstructive pyelonephritis: renal infection characterized by costovertebral angle pain often with fever sometimes with bacteraemia Complicated urinary tract infection: may involve the bladder or kidneys symptomatic urinary infection in individuals with functional or structural abnormalities of the urinary tract

What can the laboratory do with a sample of urine? Urinalysis Microscopy Dipstick Quantitative culture Specialized cultures (TB, fungi)

Urine 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

Urinary tract organism quantification Bladder urine is sterile Distal urethra is not sterile How can we differentiate: bladder bacteria (pathogens) from urethral bacteria (contaminants)?

What is a positive culture? Classic definition: > 10 5 cfu/ml With symptoms: > 10 3 cfu/ml 90% chance of actual infection

Microscopy A true UTI is accompanied by Pyuria >10 leukocytes/mm³ of uncentrifuged urine unless catheter in place Lack of epithelial cells >5/ mm³ indicates contamination Only one bacterial species (monoculture) >10 5 cfu Do not culture urine unless Indicated AND Abnormal UA

Dysuria Dysuria can be caused by Vaginitis -no pyuria and <10 2 cfu/ml) Candida Trichomonas atrophy of vaginal tissues Urethritis –pyuria and <10 2 cfu/ml, gradual Chlamydia Neisseria gonorrhoeae Cystitis – pyuria and >10 3 cfu/ml, onset abrupt

Asymptomatic bacteriuria - why screen? Screening of asymptomatic people for bacteriuria is only appropriate to prevent adverse events In pregnancy (Gp B strep) Prior to urologic surgery Undesirable outcomes associated with therapy: Antimicrobial resistance Adverse drug effects Costs C. difficile associated disease

Asymptomatic bacteriuria- Healthy, premenopausal women Bacteriuria increases risk for symptomatic UTI Not associated adverse outcomes Treatment of asymptomatic bacteriuria neither decreases frequency of symptomatic infection nor prevents further episodes of asymptomatic bacteriuria Screening for and treatment of asymptomatic bacteriuria is not indicated

Asymptomatic bacteriuria - Pregnant women fold increased risk of pyelonephritis during pregnancy More likely to experience premature delivery and to have low birthweight infants Treatment of bacteriuria decreases above risks Screen for bacteriuria by urine culture at least once in early pregnancy and treat for 3-7 days if positive

Asymptomatic bacteriuria - Elderly institutionalized subjects No decrease in rate of symptomatic infection improvement in survival chronic GU symptoms with Abx therapy Screening and treatment of asymptomatic bacteriuria in elderly institutionalized residents of long-term care facilities not recommended

Asymptomatic bacteriuria – Patients with indwelling catheters 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

Acute uncomplicated UTI (cystitis) Symptoms Dysuria, frequency, urgency Initial and terminal hematuria Suprapubic discomfort Low-grade fever may occur Exclude other causes STD Vaginitis Diagnosis Dipstick or microscopy Nitrite positive Positive LE/WBC (>10 WBC’s) Culture Not routinely necessary Carefully obtained clean catch cfu/ml 1 bacterial species only

Acute uncomplicated UTI (cystitis) Bacteria E. coli in 80-90% Staph. saprophyticus in 5-15% Proteus and Klebsiella species Adult female No anatomic/functional/immunologic abnormalities Non-pregnant

Acute uncomplicated UTI - Therapy Resistance varies 30% resistant to amoxicillin 1-20% to nitrofurantoin 5-15% to TMP-SMX Recommend: course of TMP-SMX as first choice (3 days) Fluoroquinolone as second (3 days) Nitrofurantoin (7 days) Does not penetrate in kidney

IDSA guideline TMP-SMX (160/800 mg tablet twice daily for 3 days) Nitrofurantoin monohydrate/macrocrystals (100 mg twice daily for 5 days); Fosfomycin trometamol (3 g powder single dose Pivmecillinam (400 mg bid for 3–7 days Fluoroquinolones are highly effective in 3-day regimens

Other treatment – non antimicrobial Acidification Acid urine is antibacterial Cranberry juice has precursors to hippuric acid and so acidifies urine BUT Have to avoid diet that alkalizes urine – milk, fruit juice Acid can precipitate stones in the urine (oxalic acid stones from ascorbic acid intake)

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

Complicated UTI Child, male, pregnant female Kidney involvement, 2 nd bacteraemia Abnormality Anatomy, function, immunology Urologic procedure Catheterization Unusual or resistant organisms

Acute pyelonephritis Usually E. coli Obtain urine culture If hospitalized obtain blood cultures Mostly an ascending infection Disease severity Mild Life threatening urosepsis

Acute pyelonephritis - Therapy Mild to moderately ill patients TMP-SMX (bactrim) amox/clav, cefuroxime or fluoroquinolone Patients usually improve in hours Treat for 1-2 weeks Severely ill patients Ampicillin + aminoglycoside IV therapy until patient afebrile for 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

Management: UTI in Pregnancy Nitrofurantoin mg QID X days Amok/klav 250mg QID X days Sefaleksin 250 mg BID-QID X days

Complicated UTI: > 2 UTI’s / year Antibiotic resistance Any UTI in a male.

Cystitis in males 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

UTI’s in males (other than pyelonephritis) Urethritis (STI’s) Gonorrhea Chlamydia Ureoplasma Prostatitis Same organisms as above For older males (in addition to above): Gram negative rods Enterococci

Acute prostatitis Fever, chills Dysuria, pain Marked local tenderness Excellent penetration by most antibiotic classes-easily cured Complications Prostatic abscess Chronic prostatitis

Chronic pain Dysuria Recurrent “UTI’s” – same organism Poor antibiotic penetration-difficult to treat Biofilm Calculi Preferred agents Fluoroquinolones TMP-SMX

Role of the catheter in UTI Conduit Internal lumen Migration of bacteria along external surface Foreign body Biofilm formation Protects from host defense Protects from antibiotics Incomplete emptying

Situations When a Urinary Catheter is Used  A urinary catheter is used in many different situations: A urinary catheter may be inserted to drain the bladder before or during a surgical procedure, during recovery from a serious illness or injury, or to collect urine for testing A urinary catheter may be used for a person who is incontinent of urine, if the person has wounds or pressure ulcers that would be made worse by contact with urine A urinary catheter is necessary when a person is unable to urinate because of an obstruction in the urethra

Types of catheters  A condom catheter, consists of a soft plastic or rubber sheath, tubing, and a collection bag for the urine. The sheath is placed over the penis and the collection bag is attached to the leg. Collects urine when there is no need for catheter insertion.  A straight catheter, is used when the catheter is to be inserted and removed immediately.  An indwelling catheter, also known as Foley catheter, is left inside the bladder to provide continuous urine drainage.  A suprapubic catheter is a type of indwelling catheter. The suprapubic catheter is inserted into the bladder through a surgical incision made in the abdominal wall, right above the pubic bone.  A 3-way catheter for continuous bladder irrigation (CBI) is a type of indwelling catheter. It is inserted to irrigate the bladder to prevent obstruction (i.e bleeding)

Catheters Straight Suprapubic Indwelling Condom

From: Johnson and Feehally, Comprehensive Clinical Nephrology, 2000, Elsevier Genitourinary tuberculosis

Hematogenous seeding can occur in cortex and forms granuloma Seeding in the medulla In both sites Granulomas form Caseation Erosion into collecting system Further spread to ureters, bladder, prostate…

Genitourinary tuberculosis Requires high index of suspicion Clinical disease insidious Dysuria, renal functional defects Key finding is sterile pyuria PPD skin testing Culture M. tuberculosis from urine Early AM sample (urine concentrated) Multiple urine samples Imaging

Community-Acquired UTI E.coli K.pneumoniae Proteus S.saprophyticus S.epi & gm - enterics Enterococcus

National data

Turkish study

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TUS 2013 Böbrek tubullerinde latent kalan DNA virusu a) BK virüsü b) Poxvirüs c) Herpes virüs d) Poliovirüs

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TUS 2015