Snapshot A 25-year-old, G1P0, woman who is 14 weeks pregnant presents to her obstetrician for routine prenatal screening. She reports feeling well except for mild nausea. She denies any dysuria, urinary frequency, or abnormal bleeding from the vagina or seen in the urine. A clean catch mid-stream urine sample is collected for urine culture. Urine culture reveals bacteriuria of ≥ 105 cfu/mL. She is started on oral nitrofurantoin for 5 days. (Asymptomatic bacteriuria in pregnancy) Introduction Clinical definition urinary tract infections (UTI) can either be asymptomatic or symptomatic and encompasses asymptomatic bacturia (ASB) there is bacteria in the urinary tract; however, the patient has no symptoms typically patients do not require treatment pregnant women require screening and treatment this is because ASB in pregnancy is associated with pre-term birth perinatal death pyelonephritis in the mother cystitis prostatitis pyelonephritis Epidemiology Incidence 50-80% of women acquire at least 1 UTI 20-30% of women with 1 UTI have recurrent infections Demographics more common in women, elderly, and infants Location bladder prostate kidneys Risk factors female due to the shorter female urethra benign prostatic hyperplasia frequent sexual intercourse obstruction (e.g., constipation) history of UTI incontinence diabetes mellitus vasicoureteral reflux spermicide use indwelling catheter intermittent catheterization can prevent a UTI labial adhesions peak incidence is 2 years of age pathogenesis decreased estrogen chronic irritation presents with dysuria difficulty urinating "dribbling" after urination vaginal pain and/or a "pulling sensation" physical exam labia minora fusion urethral meatus may be obstructed vaginal opening may not be visible treatment topical estrogen ETIOLOGY Pathogenesis in most cases bacteria ascends from the urethra to the bladder (cystitis) bacterial organisms can further ascend through the ureter and infect the kidney causing a renal parenchymal infection (pyelonephritis) note that infection and symptom development depends on the host e.g., genetic background, behavioral factors, and underlying disease pathogen environmental factors e.g., vaginal microflora, medical devices (e.g., indwelling catheters), and urinary retention for example, voiding and the host's innate immune response eliminates bacterial colonization in the bladder after sexual intercourse however, an indwelling catheter, stone, or any other foreign body provides a surface where bacteria can colonize hematogenous spread to the urinary tract can also result in a UTI; however, this is rare e.g., Salmonella, S. aureus, and Candida Classification It is important to distinguish between uncomplicated and complicated UTI uncomplicated UTI this describes acute cystitis or pyelonephritis in outpatient women who are not pregnant and do not have anatomic abnormalities or instrumentation within the urinary tract complicated UTI this describes UTI that is not uncomplicated Microbiology of Urinary Tract Infections Microbe Findings Comments E. coli Green metallic sheen on EMB agar Most common cause of UTI S. saprophyticus Second most common cause in sexually active women K. pneumoniae Large mucoid capsule and viscous colonies Third most common cause S. marcescens Red pigment production by select strains Third most common cause Enterococcus Typically a nosocomial infection that is drug-resistant P. mirabilis - "Swarming" appearance on agar - Urease positive - Can result in struvite stone formation P. aeruginosa Blue-green pigment Typically a nosocomial infection that is drug-resistant Presentation Symptoms/physical exam/findings ASB asymptomatic patient with an incidental finding of bacteruria on urine culture cystitis dysuria urinary frequency urgency nocturia suprapubic discomfort gross hematuria prostatitis dysuria frequency pain in the prostatic pelvic or perineal area bladder outlet obstruction fever and chills pyelonephritis fever this is the main feature that distinguishes pyelonephritis from cystitis costovertebral angle pain may be absent in mild pyelonephritis obstructive uropathy in patients with diabetes this is secondary to acute papillary necrosis that results in the papillae to slough and subsequently obstruct the ureter emphysematous pyelonephritis in patients with diabetes gas is produced in the renal and perinephric areas Imaging Ultrasound renal and bladder indications in children < 2-years-old with a first febrile UTI in children who are not appropriately responding to antimicrobial treatment of UTI in children with recurrent UTIs family history of renal or urologic disease unless severe illness or failure to respond to therapy, imaging should occur after resolution of the acute illness Voiding cystourethrogram indication test of choice to determine the presence of a vesicourethral reflux 2 or more febrile UTIs in children anomalies seen on renal ultrasound high fever with pathogen other than E. coli Studies Labs urine dipstick nitrite positivity suggests an E. coli infection or other infection of the Enterobacteriaceae family leukocyte esterase positive urease positivity S. saprophyticus Proteus coffin lid stones Klebsiella urinalysis > 10 white blood cells (WBCs)/mL > 1000 CFU/mL white blood cell casts a diagnostic finding of an upper urinary tract infection (e.g., pyelonephritis) urine culture gold standard for diagnosing UTI must be sent in pregnant patients to determine sensitivity assess for pregnancy Histology chronic pyelonephritis "thyroidization" of tubules due to eosinophilic casts contained in the tubules Differential Acute hemorrhagic cystitis can be caused by adenovirus Urethritis Nephrolithiasis Genitourinary malignancy Treatment Medical TMP-SMX, nitrofurantoin, fosfomycin indications first-line for uncomplicated UTI second-line agents include a fluoroquinolone or β-lactam nitrofurantoin, ampicillin, and cephalosporins can be used in the treatment of UTI in pregnant women parenteral β-lactam with or without aminoglycosides is used in pregnant women with pyelonephritis sulfonamides should not be used due to its possible teratogenic effects (in first trimester) and kernicterus development (near term) fluoroquinolones should also be avoided in pregnancy due to its negative effect on the development of fetal cartilage TMP-SMX or a fluoroquinolone is used in the treatment of prostatitis TMP-SMX can be used for uncomplicated or resolving pyelonephritis in a stable patient fluoroquinolones (e.g., ciprofloxacin) indication first-line for acute uncomplicated pyelonephritis fluconazole indication first-line treatment for Candida-related UTI amoxicillin-clavulanate no treatment indicated in asymptomatic bacteriuria in non-pregnant patients Operative nephrectomy indications treatment for xanthogranulomatous pyelonephritis percutaneous drainage indications treatment for emphysematous pyelonephritis and it may be followed by elective nephrectomy in urosepsis with an obstructing kidney stone Complications Uncomplicated UTI complications are uncommon Complicated UTI bacteremia urosepsis systemic inflammatory response syndrome (SIRS) renal and perinephric abscess emphysematous pyelonephritis xanthogranulomatous pyelonephritis associated with long-term urinary tract obstruction and infection this results in chronic destruction of the renal parenchyma via a granulomatous process malakoplakia renal papillary necrosis UTI in pregnancy pyelonephritis sepsis chorioamnionitis preterm labor low birth weight hypertension and pre-eclampsia UTI in men acute or chronic prostatitis urethritis acute epididymitis orchitis Prognosis ASB in elderly or catheterized patients does not increase the risk of death Recurrent UTI in children and adults does not result in chronic pyelonephritis or renal failure this is true when there are not anatomic abnormalities