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Bacterial Urinary Tract Infections

By

Talha H. Imam

, MD, University of Riverside School of Medicine

Reviewed/Revised Jan 2024
View PATIENT EDUCATION

Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain, and flank pain. Systemic symptoms and even sepsis may occur with kidney infection. Diagnosis is based on analysis and culture of urine. Treatment is with antibiotics and removal of any urinary tract catheters and obstructions.

References

  • 1. Foxman B: Epidemiology of urinary tract infections: Incidence, morbidity, and economic costs. Am J Med 13 Suppl 1A:5S-13S, 2002. doi: 10.1016/s0002-9343(02)01054-9

  • 2. Office of Women's Health (OASH): Urinary tract infections. Accessed January 5, 2024.

Pathophysiology of Bacterial UTIs

The urinary tract, from the kidneys to the urethral meatus, is normally sterile and resistant to bacterial colonization despite frequent contamination of the distal urethra with colonic bacteria. The major defense against urinary tract infection (UTI) is complete emptying of the bladder during urination. Other mechanisms that maintain the tract’s sterility include urine acidity, the vesicoureteral valve, and various immunologic and mucosal barriers.

About 95% of UTIs occur when bacteria ascend the urethra to the bladder and, in the case of pyelonephritis, ascend the ureter to the kidney. The remainder of UTIs are hematogenous. Systemic infection can result from UTI, particularly in older patients. Urinary tract infections are a common cause of hospital-acquired bacteremia Bacteremia Bacteremia is the presence of bacteria in the bloodstream. It can occur spontaneously, during certain tissue infections, with use of indwelling genitourinary or IV catheters, or after dental... read more (1 Pathophysiology reference Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more ).

Uncomplicated UTI is usually considered to be cystitis Cystitis Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more or pyelonephritis Acute pyelonephritis Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more that occurs in premenopausal adult women with no structural or functional abnormality of the urinary tract and who are not pregnant and have no significant comorbidity that could lead to more serious outcomes. Also, some experts consider UTIs to be uncomplicated even if they affect postmenopausal women or patients with well-controlled diabetes. In men, most UTIs occur in children or older patients, are due to anatomic abnormalities or instrumentation, and are considered complicated.

The rare UTIs that occur in men aged 15 to 50 years are usually in men who have unprotected anal intercourse or in those who have an uncircumcised penis, and they are generally considered uncomplicated. UTIs in men this age who do not have unprotected anal intercourse or an uncircumcised penis are very rare and, although also considered uncomplicated, warrant evaluation for urologic abnormalities.

Complicated UTI can involve either sex at any age. It is usually considered to be pyelonephritis or cystitis that does not fulfill criteria to be considered uncomplicated. A UTI is considered complicated if the patient is a child, is pregnant, or has any of the following:

Risk factors

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:

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 Fecal Incontinence Fecal incontinence is involuntary defecation. Diagnosis is clinical. Treatment is a bowel management program and perineal exercises, but sometimes colostomy is needed. (See also Evaluation of... read more increases risk.

Anatomic, structural, and functional abnormalities are risk factors for UTI. A common consequence of anatomic abnormality is vesicoureteral reflux Vesicoureteral Reflux (VUR) Vesicoureteral reflux is retrograde passage of urine from the bladder back into the ureter and sometimes also into the renal collecting system, depending on severity. Reflux predisposes to urinary... read more (VUR), which is present in 30 to 45% of young children with symptomatic UTI Urinary Tract Infection (UTI) in Children Urinary tract infection (UTI) in children is defined by ≥ 5 × 104 colonies/mL in a catheterized urine specimen or, in older children, by repeated voided specimens with ≥ 105... read more . 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 Overview of Congenital Genitourinary Anomalies Congenital anatomic anomalies of the genitourinary tract are more common than those of any other organ system. Urinary tract anomalies predispose patients to many complications, including urinary... read more ).

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 Urinary Calculi Urinary calculi are solid particles in the urinary system. They may cause pain, nausea, vomiting, hematuria, and, possibly, chills and fever due to secondary infection. Diagnosis is based on... read more and tumors. Bladder emptying can be impaired by neurogenic dysfunction Neurogenic Bladder Neurogenic bladder is bladder dysfunction (flaccid or spastic) caused by neurologic damage. Symptoms can include overflow incontinence, frequency, urgency, urge incontinence, and retention.... read more , pregnancy, uterine prolapse Uterine and Apical Prolapse Uterine prolapse is descent of the uterus toward or past the introitus. Apical prolapse is descent of the vaginal vault or vaginal cuff after hysterectomy. Symptoms include vaginal pressure... read more Uterine and Apical Prolapse , cystocele Anterior and Posterior Vaginal Wall Prolapse Anterior and posterior vaginal wall prolapse involve protrusion of an organ into the vaginal canal. Anterior vaginal wall prolapse is commonly referred to as cystocele or urethrocele (when the... read more , and prostatic enlargement Benign Prostatic Hyperplasia (BPH) Benign prostatic hyperplasia (BPH) is nonmalignant adenomatous overgrowth of the periurethral prostate gland. Symptoms are those of bladder outlet obstruction—weak stream, hesitancy, urinary... read more . UTI caused by congenital factors manifests most commonly during childhood. Most other risk factors are more common in older patients.

Pathophysiology reference

  • 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

Etiology of Bacterial UTIs

  • Enteric, usually gram-negative aerobic bacteria (most often)

  • Gram-positive bacteria (less often)

In normal genitourinary tracts, strains of Escherichia coli with specific attachment factors for transitional epithelium of the bladder and ureters account for 75 to 95% of cases. The remaining gram-negative urinary pathogens are usually other enterobacteria, typically Klebsiella or Proteus mirabilis, and occasionally Pseudomonas aeruginosa. Among gram-positive bacteria, Staphylococcus saprophyticus is isolated in 5 to 10% of bacterial UTIs. Less common gram-positive bacterial isolates are Enterococcus faecalis (group D streptococci) and Streptococcus agalactiae (group B streptococci), which may be contaminants, particularly if they were isolated from patients with uncomplicated cystitis.

In hospitalized patients, E. coli accounts for about 50% of cases. The gram-negative species Klebsiella, Proteus, Enterobacter, Pseudomonas, and Serratia account for about 40%, and the gram-positive bacterial cocci E. faecalis, S. saprophyticus, and Staphylococcus aureus account for the remainder.

Classification of Bacterial UTIs

Urethritis

Cystitis

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 Prostatitis Prostatitis refers to a disparate group of prostate disorders that manifests with a combination of predominantly irritative or obstructive urinary symptoms and perineal pain. Some cases result... read more .

Acute urethral syndrome

Acute urethral syndrome, which occurs in women, is a syndrome involving dysuria Dysuria Dysuria is painful or uncomfortable urination, typically a sharp, burning sensation. Some disorders cause a painful ache over the bladder or perineum. Dysuria is an extremely common symptom... read more , frequency Urinary Frequency Urinary frequency is the need to urinate many times during the day, at night (nocturia), or both but in normal or less-than-normal volumes. Frequency may be accompanied by a sensation of an... read more , 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 Urethritis Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more 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

Asymptomatic bacteriuria Urine testing 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

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 Catheter-Associated Urinary Tract Infections A catheter-associated urinary tract infection (CAUTI) is a urinary tract infection (UTI) in which the positive culture was taken when an indwelling urinary catheter had been in place for >... read more ) 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.

Acute pyelonephritis

In 95% of cases of pyelonephritis, the cause is ascension of bacteria through the urinary tract. Although obstruction (eg, strictures Urethral Stricture Urethral stricture is scarring that obstructs the anterior urethral lumen. Urethral stricture can be Congenital Acquired Anything that damages the urethral epithelium or corpus spongiosum can... read more , calculi Urinary Calculi Urinary calculi are solid particles in the urinary system. They may cause pain, nausea, vomiting, hematuria, and, possibly, chills and fever due to secondary infection. Diagnosis is based on... read more , tumors, neurogenic bladder Neurogenic Bladder Neurogenic bladder is bladder dysfunction (flaccid or spastic) caused by neurologic damage. Symptoms can include overflow incontinence, frequency, urgency, urge incontinence, and retention.... read more , VUR Vesicoureteral Reflux (VUR) Vesicoureteral reflux is retrograde passage of urine from the bladder back into the ureter and sometimes also into the renal collecting system, depending on severity. Reflux predisposes to urinary... read more ) 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 Cystitis Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more 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 Bladder Catheterization Bladder catheterization is used to do the following: Obtain urine for examination Measure residual urine volume Relieve urinary retention or incontinence Deliver radiopaque contrast agents or... read more .

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.

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.

Classification reference

  • 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

Symptoms and Signs of Bacterial UTIs

When symptoms are present, they may not correlate with the location of the infection within the urinary tract because there is considerable overlap; however, some generalizations are useful.

In urethritis, the main symptoms are dysuria Dysuria Dysuria is painful or uncomfortable urination, typically a sharp, burning sensation. Some disorders cause a painful ache over the bladder or perineum. Dysuria is an extremely common symptom... read more and, primarily in men, urethral discharge. Discharge can be purulent, whitish, or mucoid. Characteristics of the discharge, such as the amount of purulence, do not reliably differentiate gonococcal from nongonococcal urethritis.

Cystitis onset is usually sudden, typically with frequency, urgency, and burning or painful voiding of small volumes of urine. Nocturia, with suprapubic pain and often low back pain, is common. The urine is often turbid, and microscopic (or rarely gross) hematuria can occur. A low-grade fever may develop. Pneumaturia (passage of air in the urine) can occur when infection results from a vesicoenteric or vesicovaginal fistula or from emphysematous cystitis.

Diagnosis of Bacterial UTIs

  • Urinalysis

  • Sometimes urine culture

Diagnosis by culture is not always necessary. If done, diagnosis by culture requires demonstration of significant bacteriuria in properly collected urine.

Urine collection

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 (see Bacterial Urinary Tract Infections in Patients with Indwelling Bladder C... Diagnosis A catheter-associated urinary tract infection (CAUTI) is a urinary tract infection (UTI) in which the positive culture was taken when an indwelling urinary catheter had been in place for >... read more ).

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

Urine testing

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 Acute pyelonephritis Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more , glomerulonephritis Overview of Nephritic Syndrome Nephritic syndrome is defined by hematuria, variable degrees of proteinuria, usually dysmorphic red blood cells (RBCs), and often RBC casts on microscopic examination of urinary sediment. Often... read more , and noninfective tubulointerstitial nephritis Tubulointerstitial Nephritis Tubulointerstitial nephritis is primary injury to renal tubules and interstitium resulting in decreased renal function. The acute form is most often due to allergic drug reactions or to infections... read more Tubulointerstitial Nephritis .

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:

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.

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.

Infection localization

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.

Other testing

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 Diagnosis Sexually transmitted urethritis, cervicitis, proctitis, and pharyngitis (that are not due to gonorrhea) are caused predominantly by chlamydiae and less frequently by mycoplasmas. Chlamydiae... read more 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 Urinary tract imaging Urinary tract infection (UTI) in children is defined by ≥ 5 × 104 colonies/mL in a catheterized urine specimen or, in older children, by repeated voided specimens with ≥ 105... read more 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.

Diagnosis reference

  • 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

Treatment of Bacterial UTIs

  • Antibiotics

  • Occasionally surgery (eg, to drain abscesses, correct underlying structural abnormalities, or relieve obstruction)

All forms of symptomatic bacterial urinary tract infection (UTI) require antibiotics. For patients with troublesome dysuria Dysuria Dysuria is painful or uncomfortable urination, typically a sharp, burning sensation. Some disorders cause a painful ache over the bladder or perineum. Dysuria is an extremely common symptom... read more , phenazopyridine may help control symptoms until the antibiotics do (usually within 48 hours).

Choice of antibiotic should be based on the patient’s allergy and adherence history, local resistance patterns (if known), antibiotic availability and cost, and patient and provider tolerance for risk of treatment failure. Propensity for inducing antibiotic resistance should also be considered. When urine culture is done, choice of antibiotic should be modified when culture and sensitivity results are available to the most narrow-spectrum drug effective against the identified pathogen.

Surgical correction is usually required for obstructive uropathy Obstructive Uropathy Obstructive uropathy is structural or functional hindrance of normal urine flow, sometimes leading to renal dysfunction (obstructive nephropathy). Symptoms, less likely in chronic obstruction... read more , anatomic abnormalities, and neuropathic urinary tract lesions such as compression of the spinal cord Spinal Cord Compression Various lesions can compress the spinal cord, causing segmental sensory, motor, reflex, and sphincter deficits. Diagnosis is by MRI. Treatment is directed at relieving compression. (See also... read more Spinal Cord Compression . Catheter drainage of an obstructed urinary tract aids in prompt control of UTI. Occasionally, a renal cortical abscess or perinephric abscess requires surgical drainage. Instrumentation of the lower urinary tract in the presence of infected urine should be deferred if possible. Sterilization of the urine before instrumentation and antibiotic therapy for 3 to 7 days after instrumentation can prevent life-threatening urosepsis.

Urethritis

Sexually active patients with symptoms are usually treated presumptively for sexually transmitted infections (STIs) pending test results. A typical regimen is ceftriaxone 500 mg IM plus either azithromycin 2 g orally once or doxycycline 100 mg orally twice a day for 7 days. All sex partners within 60 days should be evaluated. Men diagnosed with urethritis should be tested for HIV Treatment Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more Treatment and syphilis Treatment Syphilis is caused by the spirochete Treponema pallidum and is characterized by 3 sequential symptomatic stages separated by periods of asymptomatic latent infection. Common manifestations... read more Treatment in accordance with the Centers for Disease Control and Prevention's 2021 STI Treatment Guidelines.

Cystitis

First-line treatment of uncomplicated cystitis in patients who do not have risk factors for a multidrug-resistant gram-negative organism is nitrofurantoin 100 mg orally twice a day for 5 days (it is contraindicated if creatinine clearance is < 60 mL/min), trimethoprim/sulfamethoxazole (TMP/SMX) 160/800 mg orally twice a day for 3 days, or fosfomycin 3 g orally once. Less desirable choices include a fluoroquinolone or a beta-lactam antibiotic. If cystitis recurs within a week or two, a broader spectrum antibiotic (eg, a fluoroquinolone) can be used and the urine should be cultured.

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.

Acute urethral syndrome

Treatment depends on clinical findings and urine culture results:

Asymptomatic bacteriuria

Typically, asymptomatic bacteriuria in patients with diabetes, older patients, or patients with chronically indwelling bladder catheters Catheter-Associated Urinary Tract Infections A catheter-associated urinary tract infection (CAUTI) is a urinary tract infection (UTI) in which the positive culture was taken when an indwelling urinary catheter had been in place for >... read more should not be treated. However, patients at risk of complications from asymptomatic bacteriuria (see Urinary Tract Infections (UTI): Screening Asymptomatic bacteriuria ) should have any treatable causes addressed and be given antibiotics as for cystitis Treatment Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more . In pregnant women, only a few antibiotics can be safely used. Oral beta-lactams, sulfonamides, and nitrofurantoin are considered safe in early pregnancy, but trimethoprim should be avoided during the first trimester, and sulfamethoxazole should be avoided during the third trimester, particularly near parturition. Patients with untreatable obstructive problems (eg, calculi Urinary Calculi Urinary calculi are solid particles in the urinary system. They may cause pain, nausea, vomiting, hematuria, and, possibly, chills and fever due to secondary infection. Diagnosis is based on... read more , reflux Vesicoureteral Reflux (VUR) Vesicoureteral reflux is retrograde passage of urine from the bladder back into the ureter and sometimes also into the renal collecting system, depending on severity. Reflux predisposes to urinary... read more ) may require long-term suppressive therapy.

Acute pyelonephritis

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

Ciprofloxacin 500 mg orally twice a day for 7 days or levofloxacin 750 mg orally once a day for 5 to 7 days are first-line antibiotics if < 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 Treatment references Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more ). However, local sensitivity patterns should be considered because in some parts of the United States, > 20% of E. coli are resistant to sulfa.

Patients not eligible for outpatient treatment should be hospitalized and given parenteral therapy selected on the basis of local sensitivity patterns. First-line antibiotics are usually renally excreted fluoroquinolones, such as ciprofloxacin and levofloxacin. Other choices, such as ampicillin plus gentamicin, the aminoglycoside plazomicin (2 Treatment references Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more ), broad-spectrum cephalosporins (eg, ceftriaxone, cefotaxime, cefepime), aztreonam, beta-lactam/beta-lactam inhibitor combinations (ampicillin/sulbactam, ticarcillin/clavulanate, piperacillin/tazobactam), and imipenem/cilastatin, are usually reserved for patients with more complicated pyelonephritis (eg, with obstruction, calculi, resistant bacteria, or a hospital-acquired infection) or recent urinary tract instrumentation.

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 < 24 weeks' gestation. Outpatient treatment is with cephalosporins. Otherwise, first-line IV antibiotics include cephalosporins, aztreonam, or ampicillin plus gentamicin. If pyelonephritis is severe, possibilities include piperacillin/tazobactam or meropenem. Fluoroquinolones and TMP/SMX should be avoided. Because recurrence is common, some authorities recommend prophylaxis after the acute infection resolves with nitrofurantoin 100 mg orally or cephalexin 250 mg orally every night during the remainder of the pregnancy and for 4 to 6 weeks after pregnancy.

Treatment references

  • 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. Wagenlehner FME, Cloutier DJ, Komirenko AS, et al: Once-daily plazomicin for complicated urinary tract infections. N Engl J Med 380(8):729-740, 2019. doi: 10.1056/NEJMoa1801467

Prevention of Bacterial UTIs

In women who experience 3 urinary tract infections (UTIs)/year, behavioral measures are recommended, including increasing fluid intake, avoiding spermicides and diaphragm use, not delaying urination, wiping front to back after defecation, avoiding douching, and urinating immediately after sexual intercourse. If these techniques are unsuccessful, antibiotic prophylaxis should be considered. Common options are continuous and postcoital prophylaxis.

The use of cranberry Cranberry Cranberries are fruit that can be consumed whole or made into food products such as jellies and juices. (See also Overview of Dietary Supplements and National Institutes of Health (NIH): Cranberry... read more products, in addition to other behavioral measures, may be considered another strategy to prevent recurrent cystitis. This approach is based on evidence suggesting that cranberry products may decrease the frequency of simple cystitis and in people who have undergone an intervention involving the bladder (1 Prevention references Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more ). However, further assessment is required in well-designed randomized controlled trials to further clarify who would benefit from cranberry products.

Continuous prophylaxis commonly begins with a 6-month trial. If UTI recurs after 6 months of prophylactic therapy, prophylaxis may be reinstituted for 2 or 3 years. Choice of antibiotic depends on susceptibility patterns of prior infections. Common options are trimethoprim/sulfamethoxazole 40/200 mg orally once a day or 3 times a week, nitrofurantoin 50 or 100 mg orally once a day, cephalexin 125 to 250 mg orally once a day, and fosfomycin 3 g orally every 10 days. Fluoroquinolones are effective but are not usually recommended because resistance is increasing. Also, fluoroquinolones are contraindicated in pregnant women and children. Nitrofurantoin is contraindicated if creatinine clearance is < 60 mL/min. Long-term use can rarely cause damage to the lungs, liver, and nervous system. Methenamine has been demonstrated to be efficacious in the prevention of UTI in older adults with CrCl > 30 ml/min (2 Prevention references Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more ).

Postcoital prophylaxis in women may be more effective if UTIs are temporally related to sexual intercourse. Usually, a single dose of one of the antibiotics used for continuous prophylaxis (other than fosfomycin) is effective.

Contraception is recommended for women using a fluoroquinolone because these medications can potentially injure a fetus. Although concern exists that antibiotics may decrease the effectiveness of oral contraceptives, pharmacokinetic studies have not shown a significant or consistent effect. Nonetheless, some experts still recommend that women who use oral contraceptives use barrier contraceptives while they are taking antibiotics.

In pregnant women, effective prophylaxis of UTI is similar to that in nonpregnant women, including use of postcoital prophylaxis. Appropriate patients include those with acute pyelonephritis during a pregnancy, patients with > 1 episode (despite treatment) of UTI or bacteriuria during pregnancy, and patients who required prophylaxis for recurrent UTI before pregnancy.

In postmenopausal women, antibiotic prophylaxis is similar to that described previously. Additionally, topical estrogen therapy markedly reduces the incidence of recurrent UTI in women with atrophic vaginitis or atrophic urethritis.

Prevention references

  • 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. Chwa A, Kavanagh K, Linnebur ASA, et al: Evaluation of methenamine for urinary tract infection prevention in older adults: A review of the evidence. Ther Adv Drug Saf 2019. v.10. doi: 10.1177/2042098619876749

Key Points

  • The most common causes of bacterial UTI and UTI overall are E. coli and other gram-negative enteric bacteria.

  • Do not test for or treat asymptomatic bacteriuria except in pregnant women, immunocompromised patients, or before an invasive urologic procedure.

  • In general, culture urine in suspected complicated UTI but not in uncomplicated cystitis.

  • Test patients for structural abnormalities if infections recur or are complicated, nephrolithiasis is suspected, there is painless hematuria or new renal insufficiency, or fever persists for 72 hours.

  • If available, consider local resistance patterns when choosing antibiotic therapy for UTI.

  • For women with 3 UTIs/year despite behavioral prophylactic measures, consider continuous or postcoital antibiotic prophylaxis.

Drugs Mentioned In This Article

Drug Name Select Trade
Aluvea , BP-50% Urea , BP-K50, Carmol, CEM-Urea, Cerovel, DermacinRx Urea, Epimide-50, Gord Urea, Gordons Urea, Hydro 35 , Hydro 40, Kerafoam, Kerafoam 42, Keralac, Keralac Nailstik, Keratol, Keratol Plus, Kerol, Kerol AD, Kerol ZX, Latrix, Mectalyte, Nutraplus, RE Urea 40, RE Urea 50 , Rea Lo, Remeven, RE-U40, RYNODERM , U40, U-Kera, Ultra Mide 25, Ultralytic-2, Umecta, Umecta Nail Film, URALISS, Uramaxin , Uramaxin GT, Urea, Ureacin-10, Ureacin-20, Urealac , Ureaphil, Uredeb, URE-K , Uremez-40, Ure-Na, Uresol, Utopic, Vanamide, Xurea, X-VIATE
AZO Urinary Pain Relief Maximum Strength, Azo-100, Azo-Gesic, Azo-Septic, Azo-Standard, Phenazo, Prodium, Pyridium, Urinary Analgesic , Uristat, Uristat Relief, Uristat Ultra, URO-PAIN
Ceftri-IM , Ceftrisol Plus, Rocephin
Azasite, Zithromax, Zithromax Powder, Zithromax Single-Dose , Zithromax Tri-Pak, Zithromax Z-Pak, Zmax, Zmax Pediatric
Acticlate, Adoxa, Adoxa Pak, Avidoxy, Doryx, Doxal, Doxy 100, LYMEPAK, Mondoxyne NL, Monodox, Morgidox 1x, Morgidox 1x Kit, Morgidox 2x , Morgidox 2x Kit, Okebo, Oracea, Oraxyl, Periostat, TARGADOX, Vibramycin, Vibra-Tabs
Furadantin, Macrobid, Macrodantin, Urotoin
Primsol, Proloprim, TRIMPEX
Monurol
Cetraxal , Ciloxan, Cipro, Cipro XR, OTIPRIO, Proquin XR
Iquix, Levaquin, Levaquin Leva-Pak, Quixin
Principen
Garamycin, Genoptic, Genoptic SOP, Gentacidin, Gentafair, Gentak , Gentasol, Ocu-Mycin
ZEMDRI
Claforan
Maxipime
Azactam, Cayston
Unasyn
Zosyn, Zosyn Powder
Primaxin, Primaxin IM
Merrem
Biocef, Daxbia , Keflex, Keftab, Panixine
AZO Cranberry, Cranberry, Ellura, TheraCran , TheraCran HP, TheraCran HP for Kids, TheraCran One
Hiprex, Mandelamine, Urex
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