Duane R. Hickling, MD
Victor W. Nitti, MD, FACS
BASICS
DESCRIPTION
• Urinary tract infection (UTI) in a female is defined as a symptomatic urothelial inflammation secondary to bacterial adhesion and internalization within the urinary tract.
• Most common human bacterial infection.
• Tremendous economic impact
– ∼ $3.5 billion annually in the United States.
• Possibility of progression to urosepsis
• Anatomical: Lower (confined to bladder and/or urethra) vs. upper (involving the ureters and/or kidneys)
• Complicated: Structural or functional abnormality, or if immunosuppressed (See Section I in “Urinary tract infection (UTI), complicated, adult”)
• Recurrence (rUTI): 3 or more culture positive infections within 12 mo
– Reinfection: Different infecting uropathogen, negative culture between infections or infection occurs >2 wk after successful treatment
– Persistence: Recurrence within 2 wk of treatment and identical uropathogen
• Asymptomatic bacteriuria: 2 consecutive midstream urine specimens with isolation of the same bacterial strain in quantitative counts ≥105 in the absence of symptoms
EPIDEMIOLOGY
Incidence
• 13,320 cases per 100, 000 adult women/yr (1)
• 44% have at least 1 rUTI in 12 mo
• 5% more than 3 rUTIs in 12 mo
• Bacteriology of female UTI (2):
– Ambulatory: Escherichia coli (74.2%), Klebsiella pneumonia (6.2%), Enterococcus species (5.3%), Streptococcus agalactiae (2.8%), Proteus mirablis (2.0%), and Staphylococcus saprophyticus (1.4%)
– Nosocomial: E. coli (65.5%), Enterococcus species (8.0%), K. pneumonia (8.0%), Klebsiella oxytoca (8.9%), P. mirablis (2.2%), Pseudomonas aeruginosa (1.8%)
– Nursing home: E. coli (46.6%), Enterococcus species (11.4%), Proteus mirabilis (10.1%), K. pneumonia (9.7%), Pseudomonas aeruginosa (3.2%)
Prevalence
53,067 cases per 100,000 adult women (1)
RISK FACTORS
• Behavioral factors
– Sexual intercourse, spermicide use, barrier contraceptives, recent antibiotic use, dysfunctional voiding
• Anatomic Variations
– Perineal and urethral anatomy is thought to be important only in absence of other risk factors
– Urinary tract obstruction: Medullary sponge kidney, calyceal diverticula, ureteral obstruction, ureteropelvic junction obstruction, vesicoureteric reflux, primary bladder neck, urethral stricture, or benign prostatic hyperplasia
• Physiologic Factors
– Diabetes mellitus
1.2–2.2-fold increased risk
Theories: Hyperglycosuria, increased glycosylation of uroplakin Ia, less effective urinary glycoproteins, and impaired bladder contractility and emptying (diabetic cystopathy)
– Pregnancy
Prevalence of bacteriuria is similar to non-gravid females
However, 22–35% progression to pyelonephritis. Secondary to hydronephrosis of pregnancy
– Neurologic diseases
Detrusor-external sphincter dyssynergia
– Other: Alternations in toll-like receptors, anti-microbial peptides (defensins and cathelicidin), anti-bacterial adherence factors (eg, Tamm–Horsfall protein) and growth factors (eg., TGF-β1 and VEGF
– Postmenopausal female
Atrophic vaginitis, decreased levels of lactobacilli, incontinence, cystocele, elevated post-void residual
Genetics
• Positive female family history strongly predictive of UTI
• Greater binding of uropathogenic coliforms
– ABH blood group non-secretor status
– P1 status
• Alterations in HSPA1B, CXCR1&2, TLR2&4, and TGF-β1 genes
PATHOPHYSIOLOGY
• Routes of infection:
– Ascending (majority)
From extra urinary sources such as the distal gut or vaginal epithelium (majority)
– Hematogenous (rare)
Increased with ureteral obstruction
Staphylococcus bacteremia or Candidal fungemia
– Quiescent intracellular reservoirs
Dormant uropathogenic bacteria residing within urothelial cells
Evade host immune responses and can emerge at any given time to reinfect host
• Adherence and internalization
– Mediated via bacterial FimH and terminal mannose units of host uroplakin Ia
ASSOCIATED CONDITIONS
• Postmenopausal
• Diabetes mellitus
• Urolithiasis
• Anatomic or function abnormalities of the urinary tract
GENERAL PREVENTION
• Avoidance of spermicidal products and barrier contraceptives
• Although hygiene, pericoital voiding, hydration has not been shown to be uniformly effective in UTI prevention women are encouraged to clean perineum wiping front to back and should empty bladder before, and after intercourse
DIAGNOSIS
HISTORY
• UTI signs/symptoms: General malaise, frequency, urgency, urge incontinence, dysuria, suprapubic pain pressure, cloudy urine, foul smelling urine, hematuria
• Pyelonephritis: Fever, chills, flank pain
• Negatively predictive: Vaginal discharge, foul vaginal odor, pruritus, urethral discharge
– Suggestive of vaginitis or urethritis
• Review previous UTI episodes: Number, frequency, temporal associations (eg, sexual activity), results of documented urine cultures, treatment, and treatment efficacy
• Medical/surgical history: Childhood UTIs, structural/functional abnormalities, immunocompromise, recent hospitalization, genitourinary manipulation/surgery
• Gynecologic history: Menstrual cycle, birth control, menopausal status, STI/STD’s, pelvic organ prolapse
PHYSICAL EXAM
• Vital signs: Hemodynamic instability can be associated with pyelonephritis/urosepsis
• Abdominal exam: Suprapubic tenderness, bladder distension suggestive of urinary retention
• Costovertebral angle tenderness with pyelonephritis
• Pelvic exam:
– Assessment of vaginal epithelium
– Vaginal discharge
– Pelvic organ prolapse
– Urethral abnormalities:
Diverticulum: Suburethral tenderness, cystic mass, and/or expression of urethral discharge
Skene’s gland infection: Expression of discharge from Skene’s gland duct
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis
– Leukocyte esterase
Sensitivity 68–98%
Specificity 59–96%
Positive predictive value 19–86%
Negative predictive value 91–97%
– Nitrite
Sensitivity 19–45%
Specificity 95–98%
Positive predictive value 50–78%
Negative predictive value 82–89%
– Leukocyte esterase and nitrite
Sensitivity 35–84%
Specificity 98–100%
Positive predictive value 84%
Negative predictive value 98%
• Microscopy
– Bacterial counts >30,000 cfu/mL for detection
– ≥1 bacteria per hpf (uncentrifuged urine) correlates to ≥105 cfu/ml via culture
– Pyuria: ≥10 WBCs/hpf
• One study has suggested that midstream urine generally is not indicated in the treatment of healthy premenopausal women with presumptive cystitis.
– Cultures can be complicated by the potential for contamination of the voided urine specimen by periurethral organisms (enterococci and group B streptococci), which cannot be distinguished from bladder organisms.
Imaging
• Generally unnecessary; obtain if suspect complicated UTI
– Indications: persistent fever (72 h after initiation of treatment), suspected urolithiasis (urine pH ≥8.0, history of calculi, very severe flank pain), unexplained/persistent hematuria, bacterial persistence, analgesic abuse, urinary retention
– First line: renal ultrasound
– CT ± intravenous contrast: alternative for further evaluation or renal abscess, renal mass, or urolithiasis
Diagnostic Procedures/Surgery
• Cystoscopy not necessary unless hematuria, bacterial persistence, recurrent UTIs
• Urodynamic testing: urinary retention, voiding dysfunction, neurologic disease
Pathologic Findings
Cystoscopy: generalized erythema and edema of urothelium
DIFFERENTIAL DIAGNOSIS
• Urothelial malignancy: Persistent microscopic or gross hematuria, lower urinary tract symptoms recommendation is for cystoscopy and CT urogram
• Urolithiasis
• Vaginitis: Vaginal discharge, odor, pruritus, dyspareunia
• Urethritis: Urethral discharge, dysuria, pruritus, STI history
• Painful bladder syndrome: Characterized by bladder pain with filling that is alleviated with voiding, chronic frequency, and urgency
TREATMENT
GENERAL MEASURES
• Empiric antimicrobials ideally started after urine specimen collected
– Adjust to urine C+S if necessary
• NSAIDs for discomfort
MEDICATION
First Line
• Acute UTI
– Algorithm outlines an approach to choosing an optimal empiric antimicrobial for uncomplicated cystitis (3,4)
– If complicated UTI, urine specimen should be collected prior to treatment and treatment duration should be adjusted to 10–14 days
– If patient is systemically unwell/urosepsis consider broad spectrum IV antimicrobials such as 2nd- or 3rd-generation cephalosporins ± urinary tract imaging
Second Line
• Prevention:
– Intravaginal estrogen in post-menopausal women: Creams, suppositories, vaginal ring
– Methenamine salts: Hydrolyzed to ammonia and formaldehyde in urine (bacteriostatic)
Cochrane review: Only short-term efficacy
Improved efficacy with vitamin C
– D-mannose: Fim H inhibitor; no clinical studies
– Antimicrobials for recurrent UTI
Self-start therapy: Start 3-day course after onset of symptoms; contact provider if symptoms persist beyond 48 h
Postcoital prophylaxis (See Section II)
Continuous prophylaxis
SURGERY/OTHER PROCEDURES
• Rarely indicated unless the following present:
– Obstruction and urosepsis: Stent or percutaneous nephrostomy tube (PCNT)
– Renal abscess drainage: Percutaneous drainage
– Urethral diverticulum
– Emphysematous pyelonephritis: Drainage or nephrectomy
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
N/A
Complementary & Alternative Therapies
• Cranberry supplements
– Some data to suggest cranberry supplements are effective at preventing rUTI (relative risk 0.62; 95% CI 0.49–0.8) (4)
– Twice daily dosing more effective
ONGOING CARE
PROGNOSIS
• Typically will have prompt symptomatic response to antimicrobial therapy
• Recurrence can occur
COMPLICATIONS
Urosepsis, pyonephritis, renal abscess, emphysematous cystitis or pyelonephritis (diabetic or immunocompromised patients)
FOLLOW-UP
Patient Monitoring
• Routine follow-up urine cultures not recommended
• Annual chest x-ray when using nitrofurantoin prophylaxis long-term
Patient Resources
Urology Care Foundation: Urinary Tract Infections in adults. http://www.urologyhealth.org/urology/index.cfm?article=47
REFERENCES
1. Griebling TL. Urinary tract infections in women. Urologic Diseases in America. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NIH Publication No. 07-5512. Litwin MS, Saigal CS, eds. Washington, DC: US Government Publishing Office; 2007; chapter 18, pp. 587–619.
2. Foxman B. The epidemiology of urinary tract infection. Nat Rev Urol. Nature Publishing Group; 20101;7(12):653–660.
3. Gupta K, Hooton TM, Naber KG, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Diseases. 2011;52(5):e103–e120.
4. Wang C-H, Fang CC, Chen NC, et al. Cranberry-containing products for prevention of urinary tract infections in susceptible populations: A systematic review and meta-analysis of randomized controlled trials. Arch Intern Med.2012;172(13):988.
ADDITIONAL READING
Hooton TM, Roberts PL, Cox ME, et al. Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med. 2013; doi:10.1056/NEJMoa1302186.
See Also (Topic, Algorithm, Media)
• Bacteruria and Pyuria
• Cystitis, General Considerations
• Pregnancy, Bacteruria, Pyuria, and UTI
• Pyelonephritis
• Urinary Tract Infection (UTI), Adult Female Algorithm 
• Urinary Tract Infection (UTI), Complicated, Adult
CODES
ICD9
• 595.9 Cystitis, unspecified
• 597.80 Urethritis, unspecified
• 599.0 Urinary tract infection, site not specified
ICD10
• N30.90 Cystitis, unspecified without hematuria
• N34.2 Other urethritis
• N39.0 Urinary tract infection, site not specified
CLINICAL/SURGICAL PEARLS
Always consider urolithiasis with UTI when flank pain is severe.