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Microbiology: Clinical Aspects of Urinary Tract Infections (Brown) DEFINITIONS: Significant Bacteriuria: >105 cfu/mL of urine (only needs to be 102 cfu/mL in symptomatic patients) Asymptomatic Bacteriuria: significant bacteriuria in the absence of any symptoms suggestive of UTI Cystitis (Lower UTI): infection confined to superficial bladder mucosa Pyelonephritis: infection that involves the renal parnenchyma Uncomplicated UTI: cystits or pyelonephritis that occurs in an otherwise healthy, non-pregnant woman with no underlying structure or functional abnormality of the urinary tract Complicated UTI: associated with any of the following o Obstruction: of any site of the urinary tract (enlarged prostate, uterine/bladder prolapsed, stones, tumor) o Foreign body: catheter or stent o Incomplete voiding: detrusor muscle dysfunction (neurologic disease, medications) o Vesicoureteral reflex: urine travels up the ureters instead of out the urethra (usually only in kids) o Recent history of instrumentation/invasive urologic procedure o Renal transplant recipient: always classified as complicated o Male: always classify as potentially complicated o Pregancy: always classified as complicated o Diabetes o Immunocompromise o Health-care associated infection o Multi-drug resistant infection Recurrence: relapse or reinfection (most often) o Relapse: recurrence due to the same microorganism (not completely eradicated; within 2 weeks) o Reinfection: recurrence due to a different microorganism (usually after 2 weeks) EPIDEMIOLOGY: Extremely common: o Second most common CA infection o Most common health care associated infection (CMS no longer reimburses hospitals for costs due to UTIs because they are seen as preventable) Can cause bacteremia: most common source of Gram negative bacteremia Can cause chronic renal failure: early childhood UTIs Prevalence by Age Group: o Infant: more common in males than females, although rare in general o 1-15 years: more common in females (4-5%) o 16-35 years: more common in females (increases to 20%- sexual activity) o 36-65 years: more common in females, but males also increase (due to benign prostatic hypertrophy) o 65+ years: still more common in females, but very high rates in both genders (again, mainly due to BPH) Natural History of UTI: o Bacteriuria in school children = population at greater risk for bacteriuria in adulthood o Asymptomatic bacteriuria occurs in some pregnancies and many of those will develop pyelonephritis during pregnancy if untreated o Symptomatic and asymptomatic UTIs will resolve without treatment, but antimicrobial therapy increases probability of cure and speeds symptom resolution PATHOGENESIS: Bacteria originating in intestine normally colonize vaginal introitus, periurethra and distal urethral meatus Infection occurs by ascending route: o This is why it is more common in women (shorter urethra); in addition, prostatic antibacterial secretions may also contribute to decreased incidence in men o Sexual intercourse facilitates entry of organisms into the bladder (dose-response relationship between frequency of intercourse and risk of UTI) Host Defenses: o Urine characteristics (high osmolality, low pH, presence of organic acids) o Flushing out of bladder urine during voiding o Inhibitors of bacterial adherence to uroepithelial cells (Tamm-Horsfall protein, bladder MPS, sIgA) o Role of humoral immunity poorly understood Once established in bladder, can ascend to kidney: kidney can also be infected via hematogenous route (rare) CLINICAL PRESENTATION: Cystitis: Mild infection: o Dysuria, urgency, frequency, possible hematuria o Suprapubic or low back pain o NO signs of systemic infection (fever, chills etc.) Physical Exam: suprapubic tenderness Differential: perhaps vaginitis or urethrisis, but the urgency and frequency are pretty characteristic of cystitis Pyelonephritis: Symptoms: o Symptoms of cystitis may or may not be present o May have flank pain/tenderness o Signs of systemic toxicity present: fevers, chills, N/V/D, hypotension Physical Exam: fever and costovertebral angle tenderness Presentation in the elderly is a diagnosis of exclusion: presence of bacteriuria high in elderly to begin with; need to thoroughly asses and may present as one of the following o Unexplained fever o New onset incontinence o Change in mental status UTIs in Pediatric Population: Infants: non-specific presentation o Poor feeding o Failure to gain weight o GI symptoms o Unexplained fever (including febrile seizures) Toddlers/Preschoolers: o Lower tract symptoms o Recurrence of daytime/nocturnal enuresis o Fever School-Aged: same as adults EVALUATION: Urine specimen required: Midstream “clean catch” Stick on bags for infants and toddlers Catheterization may be used to obtain specimen Once obtained: Dipstick: to detect presence of RBCs, WBCs and bacteria o WBCs in urine (pyuria) is supportive of UTI Patients with Pyuria: o Spin Specimen: 5-10 leukocytes per high-power field considered significant Before Knowing Presence of Pyruria: o Gram Stain of Unspun Specimen: 1 or more bacteria per high-power field considered significant Represents growth of greater than 105 cfu/mL in urine culture Easy way to detect pyuria, bacteriuria and morphology of infecting agent all at once Managing Uncomplicated Cystitis: o Treat empirically: healthy, non-pregnant woman who presents with classic signs of cystitis o Culture of urine is not recommended: results would not be available in clinically meaningful time frame Microbiology is predictable May use urine dipstick to confirm diagnostic impression Treatment of Complicated Cystitis and Pyelonephritis: requires urine culture Differentiating Lower UTIs (Cystitis) from Upper UTIs (Pyelonephritis): o Usually based on clinical grounds: Issue is that ~30% of women with symptoms of cystitis may have subclinical pyelonephritis Laboratory tests attempt to localize infection more accurately WBC Casts: specific for pyelonephritis (ie. if present, its pyelonephritis) but not sensitive because they are not present in all cases of pyelonephritis Smell and appearance of urine is not evidence of a UTI: rather, evidence of hydration and recent dietary intake MICROBIOLOGY: Cystitis: E.coli: 80% S.saprophyticus: 10-20% Rarely: Proteus, Klebsiella, Enterococcus Pyelonephritis: E.coli: mainly Klebsiella, Proteus Rarely: coagulase-negative staph (epidermidis, albus) Complicated Infections and Healthy Care-Associated UTIs: E.coli: still an important cause Others: Proteus, Klebsiella, Enterobacter, Serratia, Citrobacter, Pseudomonas, Enterococcus Pediatric Population: E.coli: mainly Klebsiella, Proteus Rarely: coagulase-negative staph (epidermidis, albus) MANAGEMENT: No questions from this lecture on this* Important Points: o Asymptomatic Bacteriuria: only treated in certain circumstances Pregnancy Prior to invasive instrumentation of urinary tract or urologic surgery Renal transplant patient (during first 6 months post-transplant) o Imaging: Reserved for only some patients: Complicated infections Recurrent pyelonephritis Pyelonephritis that does not respond to appropriate antibiotic therapy (in 72-96 hours) CAT scans, ultrasounds, and specialized procedures in children looking for vesicoureteral reflux