Mary K. Powers, MD
Raju Thomas, MD, MHA, FACS
BASICS
DESCRIPTION
• Urinary tract infection (UTI) is an inflammatory response of urothelium to bacterial invasion that is usually associated with bacteria and pyuria.
• Bacteriuria: Presence of bacteria in the urine, which is normally bacteria free
• Bacteriuria = valid indicator of bacterial infection or colonization
– Can be either symptomatic or asymptomatic
– Significant bacteriuria: Quantitative count >1 × 105 colony forming units (CFL/mL) in 2 consecutive specimens
– Majority of individuals with significant bacteria have significant pyuria
– Usually 1 organism
– >1 organism: Either contamination or polymicrobial infection
• Pyuria: Presence of WBC in the urine:
– Generally implies an inflammatory response or infection
– Significant pyuria: >10 WBCs/HPF centrifuged
– Close association between pyuria and bacteriuria; 96% of patients who are symptomatic and bacteriuric have >10 WBCs/HPF
• Sterile pyuria: Presence of WBCs in the urine in the absence of bacteriuria:
– Contamination: Vaginal or prepuce secretions
– Infections: Treated UTI, mycobacterial, TB, chlamydial, gonococcal, fungal (GU or systemic), viral, haemophilus, bilharzia
– Other infections: Appendicitis, diverticulitis, prostatitis
– Noninfectious: Nephritis, stones, foreign bodies, transplant rejection, trauma, malignancy, chemotherapy, nephrotoxic substances, drug-induced interstitial nephritis
• Cystitis: Clinical syndrome of dysuria, frequency, urgency occasionally with suprapubic pain
– Usually indicative of bacterial cystitis but can be associated with infections of the urethra or vagina or noninfections process such as interstitial cystitis, bladder carcinoma, or calculi
EPIDEMIOLOGY
Incidence (1)
• 0.3–0.5 episodes of bacteriuria per person per year among asymptomatic females aged 18–40
• Newborns:
– Males: 1.5–3.6%; females: 0.4–1.0%
• 1–5 yr:
– Males: 0.0–0.4%; females: 0.7–2.7%
• School-age:
– Males: 0.04–0.2%; females 0.7–2.3%
• Adult (middle-age):
– Males <1%; females 4–6%
• Older adults:
– Males 11–13%; females 6–33%
• Almost 100% prevalence of bacteriuria in individuals with long-term, indwelling catheters
Prevalence
• Pregnancy: 2–7% of all pregnant females (2)
• Elderly: 20% of females, 10% of males
– 24% of nursing home residents vs. 12% of healthy domiciliary elderly (3)
RISK FACTORS
Age, diabetes mellitus, sexual intercourse, use of diaphragm or spermatocide, delayed postcoital micturition, history of recent infection, immunosuppression, long-term indwelling catheters, pregnancy, neurologic disorders, foreign bodies, stones, obstructive uropathy, vesicoureteral reflux.
Genetics
Certain populations may be more susceptible to bacteriuria and recurrent UTIs due to distinct molecular defects causing impaired host responses. Certain receptor sites on epithelial cells may predispose some women to UTIs.
PATHOPHYSIOLOGY
• Urinary tract is normally sterile.
• Bacteriuria usually ascends up the urinary tract from colonizing flora of the gut, vagina, or distal urethra.
• Bacteriuria can also invade the urinary tract hematogenously or through direct transfer after instrumentation.
• Bacteria colonize the urinary tract and then multiply, causing inflammation with pyuria.
• Bacterial factors:
– Certain bacteria are more efficient at adhering to mucosal cells than others due to fimbria.
– Virulence factors: Hemolysis, adhesions, colicin, metabolic properties, etc.
• Host factors:
– Cystitis prone: Certain patients are more prone to bacteriuria (transitional cell bacterial receptor sites).
– Menstrual cycle: Bacteriuria may be influenced by hormones.
– Postmenopausal: Increasing incidence of bacteriuria
– Vaginal pH: Normally acidic pH; colonization with uropathogens may occur as vaginal pH rises
– Competitive organisms: Normal vaginal flora discourages uropathogenic colonization
– Buccal and vaginal cells: More receptive to uropathogens’ adherence in cystitis-prone patients
– Local production of IgA, IgG may play defense role.
– Production of mucous protective layer as a local bladder defense
– Blood group antigen (secretors) saturate or block bacterial adherence.
ASSOCIATED CONDITIONS
Diabetes mellitus, pregnancy, immunosuppression, structural urinary tract abnormalities, indwelling catheters
GENERAL PREVENTION
• Screening and treatment of asymptomatic bacteriuria in at-risk populations such as pregnant patients or prior to urologic intervention can prevent subsequent morbidity of UTIs.
• Screening of asymptomatic spinal cord injury patients or those with indwelling Foley catheter is not recommended.
• Bacteriuria and pyuria from an incompletely treated UTI may be avoided with the appropriate use of antibiotic class with sufficient duration; patient compliance should be encouraged.
DIAGNOSIS
HISTORY
• Dysuria, frequency, urgency, malaise, rarely low-grade fever, malodorous urine
• Occasionally hematuria (gross): Especially in the female patient; uncommon in children and men
• Fever and flank pain with upper tract origin: Pyelonephritis
• Asymptomatic or atypical symptoms: Young and old patients
• Young patients: Abdominal discomfort, failure to thrive, fever, vomiting, jaundice
• Older patients: May be asymptomatic or have incontinence, fevers, frequency, and urgency
• Varied symptoms with sterile pyuria associated with differeing conditions
• History of childhood fevers: May imply UTIs and associated congenital abnormalities
• Problems with toilet training, urgency, incontinence
• UTI family history: Mothers, daughters, sisters
• History of a risk factor for bacteriuria
PHYSICAL EXAM
• Suprapubic tenderness: Cystitis
• Flank tenderness: Pyelonephritis
• Fever: Usually with upper tract infection
• Children may have abdominal discomfort, tenderness, or distention.
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Indications for screening:
– Symptomatic patients
– Pregnant women
– Prior to genitourinary procedures
• Urine dipstick: Best for screening:
– Leukocyte esterase test:
Detects enzyme release by WBCs
Sensitivity 90%, specificity 95% for UTI
– Conversion of nitrate to nitrite (Griess test): 70–80% sensitivity for UTI
– Catalase test: Cannot differentiate infection from inflammation
• Microscopy:
– Rapid in-office test: 80% accurate; usually fresh unspun
– Centrifugation: Increases finding 10-fold
– Difficult to see bacteria if <1 × 105 CFU/mL
– Vaginal organisms may be misread as uropathogens: Lactobacilli and Corynebacterium
• Gram stain: Increases identification of bacteria with sensitivity and specificity of 96.2% and 93.0%, respectively
• Urine culture:
– Clean-catch midstream urine: Commonly used
– Catheterized urine: May be necessary to assure diagnosis or in special situations (ie, children, patients unable to void, the debilitated, the obese)
– Segmented urine specimen, initial 10 mL, midstream, post exam: For localization of bacteria or WBCs
– Quantitative counts in UTI are usually >1 × 105 CFU/mL with a uropathogen
Range 1 × 102 to 1 × 106
<105 per milliliter in 47% of patients
<104 per milliliter in 30% of patients
>102 per milliliter: Uropathogen; suspect UTI
• Conditions causing variation: Hydration, bacterial growth rate, urinary pH, pyelonephritis, catheterized specimen:
– Multiple organisms usually indicate contamination or polymicrobial infection
• Uncomplicated infections: Escherichia coli, other Enterobacteriaceae, Staphylococcus saprophyticus, enterococci
• Complicated infections: E. coli, other Enterobacteriaceae, Pseudomonas, S. aureus, coagulase negative staph, enterococci
• Contaminants: Lactobacilli, streptococci, diphtheroids, Gardnerella, Mycoplasma, coagulation-negative staph
Imaging
• Bacteriuria:
– Childhood: US, VCUG, radionuclide cystogram, IV pyelogram
– Adult: Only indicated if suspicious of pathology or childhood history, obstruction, stone disease, hematuria, febrile infections, failure to respond to therapy, recurrent UTIs
– Imaging in routine UTIs involving normal adult females: Very low yield of pathology
• Pyuria:
– Associated with infection and bacteriuria: Same indications
– Sterile pyuria evaluation for other causes
– Isotopic function studies and cystogram
– CT: Localization of nidus or abnormality responsible for bacteriuria/pyuria (ie, abscess)
Diagnostic Procedures/Surgery
Localization of bacteria: Segmented urine, ureteral catheterization, immunologic antibody studies
DIFFERENTIAL DIAGNOSIS
• Cystitis: Pyuria, positive culture, abrupt onset
• Urethritis: Pyuria, negative urine culture, gradual onset
• Vaginitis: No pyuria, vaginal discharge, pruritus
• Pyelonephritis
• Noninfectious causes
– Interstitial cystitis
– Nonuropathogenic cause, as in sterile pyuria
• Contamination with vaginal/skin flora
TREATMENT
GENERAL MEASURES
• Obtain urine culture:
– Indwelling catheters should be used as infrequently as possible
– In patients with indwelling catheter, urine specimen for culture should be obtained at the time catheter is changed under sterile conditions from newly placed catheter
MEDICATION
• Asymptomatic bacteriuria is treated as a UTI in childhood, prior to urologic surgery, and in pregnancy.
– Persistent or recurrent bacteriuria may need treatment for more prolonged periods followed by chronic low-dose medication.
TMP-SMX (Trimethoprim-sulfamethoxazole) 40/200 mg daily
Nitrofurantoin 50–100 mg daily
Cephalexin 250 mg daily
– Postmenopausal: Treated only if symptomatic or associated with complicating factors:
– Diabetes, obstruction, immunosuppression (14–21 days of therapy)
Norfloxacin 400 mg PO BID
Ciprofloxacin 500 mg PO BID
Gentamicin 1–1.7 mg/kg IV Q8h
Ceftriaxone 1–2 mg IV/Q 24 h
– Catheter-associated bacteriuria, if asymptomatic, should not be treated (may be due to colonization).
• Bacteriuria in pregnancy should be treated, as untreated bacteriuria is linked with prematurity, IUGR, low birth weight, and neonatal death.
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
N/A
Complementary & Alternative Therapies
Cranberry juice may decrease frequency of bacteriuria and pyuria in selected populations.
ONGOING CARE
PROGNOSIS
Variable severity ranging from asymptomatic bacteriuria to severe UTI with urosepsis and secondary organ failure
COMPLICATIONS
20–40% of untreated bacteriuria in pregnancy leads to pyelonephritis
FOLLOW-UP
Patient Monitoring
• Repeat exam: 2 wk posttreatment, not necessary in young women who are asymptomatic after therapy
– Microscopic urinalysis and culture
• Periodic office visits to verify sterile urine
• 2008 USPSTF guidelines:
– In pregnant women, high certainty exists that net benefit of screening for asymptomatic bacteriuria is substantial (1)[A].
– In men and nonpregnant women, there is moderate certainty that the harms of screening for asymptomatic bacteriuria outweigh the benefits. (1)[D]
– Adults with diabetes were included in this recommendation, for the general adult population, the USPSTF did not consider evidence for screening specific patient groups at high risk for severe UTIs, including transplant recipients, patients with sickle cell disease, and those with recurrent UTIs.
Patient Resources
http://patienteducationcenter.org/articles/asymptomatic-bacteriuria/
REFERENCES
1. Screening for asymptomatic bacteriuria in adults: US Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med. 2008;149:43–47.
2. Genao L, Buhr GT. Urinary tract infections in older adults residing in long-term care facilities. Ann Longterm Care. 2012;20(4):33–38.
3. Imade PE, et al. Asymptomatic bacteriuria among pregnant women. N Am J Med Sci. 2010;2(6):263–266.
ADDITIONAL READING
• D’Hondt F, Everaert K. Urinary tract infections in patients with spinal cord injuries. Curr Infect Dis Rep. 2011;13(6):544.
• Siddiq DM, Darouiche RO. New strategies to prevent catheter-associated urinary tract infections. Nat Rev Urol. 2012;9(6):305.
See Also (Topic, Algorithm, Media)
• Bacteruria and Pyuria Image 
• Cystitis, General Considerations
• Pyuria Algorithm 
• Urinary Tract Infection (UTI), Adult Female
• Urinary Tract Infection (UTI), Adult Male
• Urinary Tract Infection (UTI), Catheter-related
• Urinary Tract Infection (UTI), Pediatric
CODES
ICD9
• 590.80 Pyelonephritis, unspecified
• 595.9 Cystitis, unspecified
• 599.0 Urinary tract infection, site not specified
ICD10
• N12 Tubulo-interstitial nephritis, not spcf as acute or chronic
• N30.90 Cystitis, unspecified without hematuria
• N39.0 Urinary tract infection, site not specified
CLINICAL/SURGICAL PEARLS
Screening of asymptomatic spinal cord injury patients or those with indwelling Foley catheter is not recommended.