Bacterial Urinary Tract Infections

Risk factors for development of UTI in women include the following:

• Sexual intercourse

• Diaphragm and spermicide use

• Antibiotic use

• New sex partner within the past year

• History of UTIs in first-degree female relatives

• History of recurrent UTIs

• First UTI at early age

Risk factors for UTI in males include the following:

• Benign prostatic hyperplasia with obstruction, common in men over 50 years

• Any other cause of obstruction of the urinary tract  (eg, prostate cancer, urethral stricture)

• Recent instrumentation or indwelling catheters

• Structural abnormalities, such as bladder diverticula

• Neurologic conditions that interfere with normal voiding (eg, spinal cord injury)

• Cognitive impairment, fecal incontinence or urinary incontinence

Even use of spermicide-coated condoms increases risk of UTI in women. The increased risk of UTI in women using antibiotics or spermicides probably occurs because of alterations in vaginal flora that allow overgrowth of Escherichia coli. In older women, soiling of the perineum due to fecal incontinence increases risk.

Anatomic, structural, and functional abnormalities are risk factors for UTI. A common consequence of anatomic abnormality is vesicoureteral reflux (VUR), which is present in 30 to 45% of young children with symptomatic UTI. VUR is usually caused by a congenital defect that results in incompetence of the ureterovesical valve. VUR can also be acquired in patients with a flaccid bladder due to spinal cord injury or after urinary tract surgery. Other anatomic abnormalities predisposing to UTI include urethral valves (a congenital obstructive abnormality), delayed bladder neck maturation, bladder diverticulum, and urethral duplications (see Overview of Congenital Genitourinary Anomalies).

Structural and functional urinary tract abnormalities that predispose to UTI usually involve obstruction of urine flow and poor bladder emptying. Urine flow can be compromised by calculi and tumors. Bladder emptying can be impaired by neurogenic dysfunction, pregnancy, uterine prolapse, cystocele, and prostatic enlargement. UTI caused by congenital factors manifests most commonly during childhood. Most other risk factors are more common in older patients.

Other risk factors for UTI include instrumentation (eg, bladder catheterization, stent placement, cystoscopy) and recent surgery.

1. 1. Weinstein MP, Towns ML, Quartey SM, et al: The clinical significance of positive blood cultures in the 1990s: A prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis 24(4):584-602, 1997. doi: 10.1093/clind/24.4.584

Infection of the urethra with bacteria (or with protozoa, viruses, or fungi) occurs when organisms that gain access to it acutely or chronically colonize the numerous periurethral glands in the bulbous and pendulous portions of the male urethra and in the entire female urethra. The sexually transmitted pathogens Chlamydia trachomatis (see Chlamydial, Mycoplasmal, and Ureaplasmal Infections), Neisseria gonorrhoeae (see Gonorrhea), Trichomonas vaginalis (see Trichomoniasis), and herpes simplex virus are common causes in both sexes.

Cystitis is infection of the bladder. It is common in women, in whom cases of uncomplicated cystitis are usually preceded by sexual intercourse (honeymoon cystitis). In men, bacterial infection of the bladder is usually complicated and usually results from ascending infection from the urethra or prostate or is secondary to urethral instrumentation. The most common cause of recurrent cystitis in men is chronic bacterial prostatitis.

Acute urethral syndrome, which occurs in women, is a syndrome involving dysuria, frequency, and pyuria (dysuria-pyuria syndrome), which thus resembles cystitis. However, in acute urethral syndrome (unlike in cystitis), routine urine cultures are either negative or show colony counts that are lower than the traditional criteria for diagnosis of bacterial cystitis. Urethritis due to organisms including Chlamydia trachomatis and Ureaplasma urealyticum, which are not detected on routine urine culture, are a possible cause of acute urethral syndrome.

Noninfectious causes have been proposed, but supporting evidence is not conclusive, and most noninfectious causes usually cause little or no pyuria. Possible noninfectious causes include anatomic abnormalities (eg, urethral stenosis), physiologic abnormalities (eg, pelvic floor muscle dysfunction), hormonal imbalances (eg, atrophic urethritis), localized trauma, gastrointestinal system symptoms, and inflammation.

Asymptomatic bacteriuria is absence of UTI signs or symptoms in a patient whose urine culture satisfies criteria for UTI. Pyuria may or may not be present. Because it is asymptomatic, such bacteriuria is found mainly when high-risk patients are screened or when urine culture is done for other reasons.

Screening patients for asymptomatic bacteriuria is indicated for those at risk of complications if the bacteriuria is untreated (see the U.S. Preventive Services Task Force Reaffirmation Recommendation Statement, 2019). Such patients include

• Pregnant women at 12 to 16 weeks' gestation or at the first prenatal visit, if later (because of the risk of symptomatic UTI, including pyelonephritis, during pregnancy; and adverse pregnancy outcomes, including low-birth-weight neonate and preterm delivery)

• Patients who have had a kidney transplant within the previous 6 months

• Young children with gross vesicoureteral reflux (VUR)

• Before certain invasive genitourinary procedures that can cause mucosal bleeding (eg, transurethral resection of the prostate)

Certain patients (eg, postmenopausal women; patients with controlled diabetes; patients with ongoing use of urinary tract foreign objects such as stents, nephrostomy tubes, and indwelling catheters) often have persistent asymptomatic bacteriuria and sometimes pyuria. If they are asymptomatic, these patients should not be screened routinely, because they are at low risk. In patients with indwelling catheters, treatment of asymptomatic bacteriuria often fails to clear the bacteriuria and only leads to development of antibiotic-resistant organisms.

Pyelonephritis is bacterial infection of the kidney parenchyma. The term should not be used to describe tubulointerstitial nephropathy unless infection is documented. In women, pyelonephritis is a common cause of community-acquired bacteremias (1). Pyelonephritis is uncommon in men with a normal urinary tract.

In 95% of cases of pyelonephritis, the cause is ascension of bacteria through the urinary tract. Although obstruction (eg, strictures, calculi, tumors, neurogenic bladder, VUR) predisposes to pyelonephritis, most women with pyelonephritis have no demonstrable functional or anatomic defects. In men, pyelonephritis is always due to some functional or anatomic defect. Cystitis alone or anatomic defects may cause reflux. The risk of bacterial ascension is greatly enhanced when ureteral peristalsis is inhibited (eg, during pregnancy, by obstruction, by endotoxins of gram-negative bacteria). Pyelonephritis is common in young girls and in pregnant women after bladder catheterization.

Pyelonephritis not caused by bacterial ascension is caused by hematogenous spread, which is particularly characteristic of virulent organisms such as S. aureus, P. aeruginosa, Salmonella species, and Candida species.

The affected kidney is usually enlarged because of inflammatory polymorphonuclear neutrophils and edema. Infection is focal and patchy, beginning in the pelvis and medulla and extending into the cortex as an enlarging wedge. Cells mediating chronic inflammation appear within a few days, and medullary and subcortical abscesses may develop. Normal parenchymal tissue between foci of infection is common.

Papillary necrosis may occur in acute pyelonephritis associated with diabetes, obstruction, sickle cell disease, pyelonephritis in renal transplants, pyelonephritis due to candidiasis, or analgesic nephropathy.

Although acute pyelonephritis is frequently associated with renal scarring in children, similar scarring in adults is not detectable in the absence of reflux or obstruction.

1. 1. Tsay RW, Siu LK, Fung CP, et al: Characteristics of bacteremia between community-acquired and nosocomial Klebsiella pneumoniae infection: Risk factor for mortality and the impact of capsular serotypes as a herald for community-acquired infection. Arch Intern Med162(9):1021-1027, 2002. doi: 10.1001/archinte.162.9.1021

If a sexually transmitted infection (STI) is suspected, a urethral swab for STI testing is obtained prior to voiding. Urine collection is then by clean-catch or catheterization.

To obtain a clean-catch, midstream specimen, the urethral opening is washed with a mild, nonfoaming disinfectant and air dried. Contact of the urinary stream with the mucosa should be minimized by spreading the labia in women and by pulling back the foreskin in uncircumcised men. The first 5 mL of urine is not captured; the next 5 to 10 mL is collected in a sterile container.

A specimen obtained by catheterization is preferable in older women (who typically have difficulty obtaining a clean-catch specimen) and in women with vaginal bleeding or discharge. Many clinicians also use catheterization to obtain a specimen if evaluation includes a pelvic examination. Diagnosis in patients with indwelling catheters is discussed elsewhere.

Testing, particularly culturing, should be done within 2 hours of specimen collection; if not, the sample should be refrigerated.

Microscopic examination of urine is useful but not definitive. Pyuria is defined as ≥ 8 white blood cells (WBCs)/mcL of uncentrifuged urine, which corresponds to 2 to 5 WBCs/high-power field in spun sediment. Most truly infected patients have > 10 WBCs/mcL. The presence of bacteria in the absence of pyuria, especially when several strains are found, is usually due to contamination during sampling. Microscopic hematuria occurs in up to 50% of patients, but gross hematuria is uncommon. WBC casts, which may require special stains to differentiate from renal tubular casts, indicate only an inflammatory reaction; they can be present in pyelonephritis, glomerulonephritis, and noninfective tubulointerstitial nephritis.

Pyuria in the absence of bacteriuria and of urinary tract infection (UTI) is possible, for example, if patients have nephrolithiasis, a uroepithelial tumor, appendicitis, or inflammatory bowel disease or if the sample is contaminated by vaginal WBCs. Women who have dysuria and pyuria without significant bacteriuria may have interstitial cystitis/bladder pain syndrome.

Dipstick tests also are commonly used. A positive nitrite test on a freshly voided specimen (bacterial replication in the container renders results unreliable if the specimen is not tested rapidly) is highly specific for UTI, but the test is not very sensitive. The leukocyte esterase test is very specific for the presence of > 10 WBCs/mcL and is fairly sensitive. In adult women with uncomplicated UTI with typical symptoms, most clinicians consider positive microscopic and dipstick tests sufficient; in these cases, given the likely pathogens, cultures are unlikely to change treatment but add significant expense.

Cultures are recommended in patients whose characteristics and symptoms suggest complicated UTI or an indication for treatment of bacteriuria. Common examples include the following:

• Pregnant women

• Postmenopausal women

• Men

• Prepubertal children

• Patients with urinary tract abnormalities or recent instrumentation

• Patients with immunosuppression or significant comorbidities

• Patients whose symptoms suggest pyelonephritis or sepsis

• Patients with recurrent UTIs (≥ 3/year)

Samples containing large numbers of epithelial cells are contaminated and unlikely to be helpful. An uncontaminated specimen must be obtained for culture. Culture of a morning specimen is most likely to detect UTI. Samples left at room temperature for > 2 hours can give falsely high colony counts due to continuing bacterial proliferation. Criteria for culture positivity include isolation of a single bacterial species from a midstream, clean-catch, or catheterized urine specimen.

For asymptomatic bacteriuria, criteria for culture positivity based on the guidelines of the Infectious Diseases Society of America (see Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults, 2019) are

• Two consecutive clean-catch, voided specimens (for men, one specimen) from which the same bacterial strain is isolated in colony counts of >10⁵/mL

• Among women or men, in a catheter-obtained specimen, a single bacterial species is isolated in colony counts of > 10²/mL

For symptomatic patients, culture criteria are

• Uncomplicated cystitis in women: > 10³/mL

• Uncomplicated cystitis in women: > 10²/mL (This quantification may be considered to improve sensitivity to E. coli.)

• Acute, uncomplicated pyelonephritis in women: > 10⁴/mL

• Complicated UTI: > 10⁵/mL in women; or > 10⁴/mL in men or from a catheter-derived specimen in women

• Acute urethral syndrome: > 10²/mL of a single bacterial species

Any positive culture result, regardless of colony count, in a sample obtained via suprapubic bladder puncture should be considered a true positive.

In midstream urine, E. coli in mixed flora may be a true pathogen (1).

Occasionally, UTI is present despite lower colony counts, possibly because of prior antibiotic therapy, very dilute urine (specific gravity < 1.003), or obstruction to the flow of grossly infected urine. Repeating the culture improves the diagnostic accuracy of a positive result, ie, may differentiate between a contaminant and a true positive result. Newer molecular urine testing may sometimes reveal unusual pathogens in patients with refractory or recurrent UTI.

Clinical differentiation between upper and lower UTI is impossible in many patients, and testing is not usually advisable. When the patient has high fever, costovertebral angle tenderness, and gross pyuria with casts, pyelonephritis is highly likely. The best noninvasive technique for differentiating bladder from kidney infection appears to be the response to a short course of antibiotic therapy. If the urine has not cleared after 3 days of treatment, pyelonephritis should be sought.

Symptoms similar to those of cystitis and urethritis can occur in patients with vaginitis, which may cause dysuria due to the passage of urine across inflamed labia. Vaginitis can often be distinguished by the presence of vaginal discharge, vaginal odor, and dyspareunia.

Men with symptoms of cystitis that do not respond to usual antimicrobial therapy may have prostatitis.

Seriously ill patients require evaluation for sepsisacute abdomen.

Patients who have dysuria/pyuria but no bacteriuria should have testing for a sexually transmitted infection (STI), typically using nucleic acid-based testing of swabs from the urethra and cervix (see Chlamydial Infections: Diagnosis).

Most adults do not require assessment for structural abnormalities unless the following occur:

• The patient has ≥ 2 episodes of pyelonephritis.

• Infections are complicated.

• Nephrolithiasis is suspected.

• There is painless gross hematuria or new renal insufficiency.

• Fever persists for ≥ 72 hours.

Urinary tract imaging choices include ultrasonography, CT, and intravenous urography (IVU). Occasionally, voiding cystourethrography, retrograde urethrography, or cystoscopy is warranted. Urologic investigation is not routinely needed in women with symptomatic cystitis or asymptomatic recurrent cystitis, because findings do not influence therapy. Children with UTI often require imaging.

1. 1. Hooton TM, Roberts PL, Cox ME, et al: Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med 369(20):1883-1891, 2013. doi: 10.1056/NEJMoa1302186

HIV and syphilis in accordance with the Centers for Disease Control and Prevention's 2021 STI Treatment Guidelines.

First-line treatment of uncomplicated<

Complicated cystitis should be treated with empiric broad-spectrum antibiotics chosen based on local pathogens and resistance patterns and adjusted based on culture results. Urinary tract abnormalities must also be managed.

Treatment depends on clinical findings and urine culture results:

• Women with dysuria, pyuria, and colony growth of > 10²/mL of a single bacterial species on urine culture can be treated as for uncomplicated cystitis.

• Women who have dysuria and pyuria with no bacteriuria should be evaluated for an STI (including for N. gonorrhoeae and C. trachomatis).

• Women who have dysuria but neither pyuria nor bacteriuria do not have the true urethral syndrome. They should be evaluated for noninfectious causes of dysuria. Evaluation may include therapeutic trials, for example, of behavioral treatments (eg, biofeedback and pelvic musculature relaxation), surgery (for urethral stenosis), and medications (eg, hormone replacement for suspected atrophic urethritis, anesthetics, antispasmodics).

Typically, asymptomatic bacteriuria in patients with diabetes, older patients, or patients with chronically indwelling bladder catheters should not be treated. However, patients at risk of complications from asymptomatic bacteriuria (see Urinary Tract Infections (UTI): Screening) should have any treatable causes addressed and be given antibiotics as for cystitiscalculi, reflux) may require long-term suppressive therapy.

Antibiotics are required. Outpatient treatment with oral antibiotics is possible if all of the following criteria are satisfied:

• Patients are expected to be adherent

• Patients are immunocompetent

• Patients have no nausea or vomiting or evidence of volume depletion or septicemia

• Patients have no factors suggesting complicated UTI

< 10% of the uropathogens in the community are resistant. A second option is usually TMP/SMX 160/800 mg orally twice a day for 14 days (1). However, local sensitivity patterns should be considered because in some parts of the United States, > 20% of E. coli are resistant to sulfa.

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Parenteral therapy is continued until defervescence and other signs of clinical improvement occur. In > 80% of patients, improvement occurs within 72 hours. Oral therapy can then begin, and the patient can be discharged for the remainder of a 7- to 14-day treatment course. Complicated cases require longer courses of IV antibiotics with total duration of 2 to 3 weeks and urologic correction of anatomic defects.

Outpatient management can be considered in pregnant women with pyelonephritis, but only if symptoms are mild, close follow-up is available, and (preferably) pregnancy is <

1. 1. 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 Dis52(5):e103-120, 2011. doi: 10.1093/cid/ciq257

2. 2. Wagenlehner FME, Cloutier DJ, Komirenko AS, et alN Engl J Med  380(8):729-740, 2019. doi: 10.1056/NEJMoa1801467

1. 1. Jepson RG, Williams G, Craig JC: Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev 10(10);CD001321, 2012. doi: 10.1002/14651858.CD001321.pub5

2. 2. Chwa A, Kavanagh K, Linnebur ASA, et alTher Adv Drug Saf 2019. v.10. doi: 10.1177/2042098619876749