Acute uncomplicated UTI manifesting as cystitis is a common syndrome that affects otherwise healthy women. ^, About 10% of young, sexually active, premenopausal women experience a UTI each year, and 60% of all women have one or more such infections in their lifetimes. From 2% to 5% of women experience frequent recurrent infection for at least some period. After a first episode of cystitis, 21% of female college students in one study reported a second infection within 6 months. Among postmenopausal women aged 55 to 75 years who were enrolled in a Seattle health group, the incidence was seven infections per 100 patient-years; in 24 months, 7% of women had one infection, 1.6% had two infections, and 1% had three or more infections. Acute cystitis is associated with considerable short-term morbidity. Female college students reported that symptoms persisted for an average of 6.1 days, and, for ambulatory women, a mean duration of symptoms was 4.9 days, with 63% of patients reporting their usual activities were compromised by the infection. However, although a large number of women are affected and many have frequent recurrence of infection, there is no observed long-term morbidity. Acute, uncomplicated UTI is uncommon in healthy young men, with an estimated incidence of <0.1% per year.

Acute UTI is primarily a disease of extraintestinal (or “uropathogenic”) E. coli. These organisms are isolated in 80% to 85% of episodes of acute cystitis. ^{, ,} Infection occurs via the ascending route after bacterial strains originating in the gut colonize the vagina or periurethral area. Although urethral colonization with a potential uropathogen appears to be a prerequisite for infection, cystitis does not subsequently develop in most women with periurethral colonization. Strains of E. coli that colonize the periurethral area and subsequently cause UTI belong to a restricted number of phylogenetic E. coli groups and more frequently express diverse virulence factors. ^, A necessary characteristic for bladder infection is production of FimH, an adhesin attaching to receptors on uroepithelial cells. This surface protein, however, is common on E. coli strains, regardless of whether they cause infection. Other potential urovirulence characteristics include other adhesins, iron-sequestration systems, toxin secretion, and motility. The putative virulence factors produced by strains isolated from symptomatic infection overlap with those isolated from asymptomatic bacteriuria, and no single characteristic is uniquely correlated with symptomatic infection. Uropathogenic E. coli strains may be acquired during travel, from ingestion of food or water, from other household members including pets, and from sexual partners. ^, Clonal outbreaks may occur with transmission of a single strain within a community or larger geographic area. ^,

Other Enterobacteriaceae, most commonly Klebsiella pneumoniae and Proteus spp. , are isolated in less than 5% of premenopausal women but in 10% to 15% of postmenopausal women. ^,

Historically, Staphylococcus saprophyticus was hailed in some published series as an important uropathogen causing 5% to 10% of episodes, particularly in younger, sexually active women. Yet many geographic regions report little if any S. saprophyticus in women with active infection. ^, One report describes urogenital and rectal colonization in 7% and 40% of healthy women, respectively, leading to the question of whether this organism may primarily be a urinary contaminant with robust growth in traditional culture. Nonetheless, given its possession of virulence factors including adhesins, transport systems to support growth in urine, and urease production, a potential for uropathogenicity cannot be ruled out.

Other gram-positive organisms such as Enterococcus species and group B streptococci are uncommon pathogens in patients without foreign body material, though they are often present in midstream-voided specimens. Salmonella species and bacteria associated with sexually transmitted infections, such as Ureaplasma urealyticum, Gardnerella vaginalis, and Mycoplasma hominis, are occasionally isolated.

Acute, uncomplicated UTI is a consequence of the interaction of a virulent organism with host genetic susceptibility and behavioral variables. ^, The notion of genetic propensity is supported by two consistent observations: (1) an increased frequency of UTI in first-degree female relatives of women with recurrent infection ^{, ,} and (2) the fact that infection at a younger age is a major risk factor for recurrent cystitis in women of any age. ^{, ,} One well-characterized genetic association is being a nonsecretor of the ABO blood-group antigens. ^, Women with recurrent UTI are at least three times more likely to be nonsecretors than are those without recurrent infection. Nonsecretors express cell–surface glycosphingolipids on the vaginal epithelium, and presumably urethral mucosa, that differ from those expressed by secretors and bind uropathogenic E. coli more avidly. Other potential genetic determinants include polymorphisms of the IL-8 receptor CXCR1, TLRs, and the tumor necrosis factor promoter.

The most important behavioral association of UTI in premenopausal women is sexual intercourse. ^, In young, sexually active women, 75% to 90% of episodes are attributable to intercourse, and there is a correlation between frequency of intercourse and frequency of infection. Intercourse appears to promote infection by facilitating ascension of organisms from the periurethral area into the bladder, but disruption of the female uromicrobiota after interaction with that of her partner may also play a role. Spermicide use is another independent behavioral risk factor for acute cystitis in premenopausal women. Spermicides are bactericidal for the hydrogen peroxide–producing lactobacilli of the normal vaginal microbiota, which maintain the acidic pH. When these bacteria are not present, vaginal pH increases, facilitating colonization with potential uropathogens. Case-control studies have consistently demonstrated that behavioral variables popularly identified as risks for cystitis—such as type of underwear, bathing rather than showering, postcoital voiding, frequency of voiding, perineal hygiene practices, vaginal douching, and tampon use—are not associated with an increased risk of infection. ^,

A history of prior UTI at a younger age is the strongest association of recurrent acute cystitis in postmenopausal women. Sexual intercourse is not an important contributor in this population. ^, Estrogen deficiency has been proposed to promote recurrent UTI in these women through alterations in vaginal flora, including replacement of lactobacilli by potential uropathogens. However, prospective cohort studies and case-control studies uniformly demonstrate no association of oral or topical estrogen use with recurrent UTI, regardless of restoration of vaginal lactobacilli and acid pH. Acute uncomplicated UTI in men is uncommon, but reported risk factors have included intercourse with a female partner with recurrent UTI, not being circumcised, and anal intercourse.

The classic clinical manifestation of symptomatic lower UTI is the acute onset of one or more irritative bladder symptoms, such as urgency, frequency, dysuria, stranguria, and hesitancy. ^, Gross hematuria may also occur, likely reflecting more severe mucosal inflammation. The most important differential diagnoses to exclude are sexually transmitted infections ; vulvovaginal candidiasis and noninfectious syndromes such as interstitial cystitis should also be considered. The combination of new-onset frequency, dysuria, and urgency, together with the absence of vaginal discharge and pain, has a positive predictive value for acute cystitis of 90%. Women with recurrent UTI also have >90% accuracy in self-diagnosis on the basis of symptoms.

A urine culture is not recommended routinely for women with a clinical presentation consistent with acute uncomplicated cystitis given a high pretest probability of infection, predictable microbiology, and prompt clinical response with empirical antimicrobial therapy. ^{, ,} Urine culture results are negative in up to 20% of women with a characteristic clinical presentation, and these women have a clinical response to antimicrobial therapy similar to that of women with positive cultures. These women with low organism counts isolated in urine culture may have urethritis, rather than cystitis. However, both urinary frequency and increased fluid intake are characteristic of patients with acute cystitis; limited dwell time and/or dilution of urine in the bladder seem the likely explanation for lower bacterial counts. Finally, fastidious organisms may not be identified by routine laboratory procedures used in processing urine specimens.

A urine specimen for culture should be obtained, however, in certain instances. When the clinical presentation is not characteristic, a urine culture may help confirm or exclude the diagnosis of UTI. Any quantitative count of an Enterobacteriaceae is considered positive. Enterococcus spp. or group B streptococcus in any quantitative count should be interpreted as contamination. Failure to respond to appropriate empirical therapy or early (<1 month) recurrence after therapy is suggestive of infection with a resistant organism. In these situations, a urine culture should be obtained to confirm resistance and facilitate selection of an effective regimen.

The presence of pyuria, identified by routine urinalysis or leukocyte esterase dipstick testing, is a consistent accompaniment of acute cystitis. ^, The absence of pyuria is suggestive of an alternative diagnosis but does not rule out UTI in women with a consistent clinical presentation, particularly given increasing rates of self-hydration among women before seeking medical attention for lower UTI. ^, Thus routine screening for pyuria is not strictly necessary for diagnosis or management of acute cystitis. ^, A urine nitrite dipstick test screens for the presence of bacteria, rather than leukocytes, and results are usually positive in women with infection. False-negative nitrite test results may occur when there is infection with bacteria that do not reduce nitrate, such as Enterococcus species, or when urine has not been retained in the bladder a sufficient time to allow bacteria to convert nitrate to nitrite. Nitrite tests uncommonly have false-positive results, but these may occur when blood, urobilinogen, or some dyes are present in the urine.

For many women, acute uncomplicated cystitis may spontaneously resolve both clinically and microbiologically within a few days or weeks. In a clinical trial in which participants were randomly assigned to antibiotic therapy or placebo, 28% of 277 women who received placebo were asymptomatic by 1 week, and 45% had negative culture results by 6 weeks. In another study, 54% of women who received placebo were asymptomatic by 3 days and 52% at 7 days. Antimicrobial treatment, however, is associated with significantly shorter symptom durations. The rates of clinical cure were 77% with nitrofurantoin versus 54% with placebo at 3 days and 88% and 52%, respectively, at 7 days. After initiation of antimicrobial therapy, 54% of women reported symptom improvement by 6 hours, 87% by 24 hours, and 91% by 48 hours. In another case series, 72% of women reported complete symptom resolution by the fourth day of effective treatment. In a trial of antiinflammatory therapy with ibuprofen alone compared with empiric fosfomycin therapy for women with mild-to-moderate symptoms, women receiving fosfomycin had more rapid symptom resolution and fewer cases of pyelonephritis, though these were few in both arms.

Many antimicrobial agents are effective for treatment of acute cystitis ( Table 38.4 ). The anticipated cure rate for recommended first-line empirical regimens is 70% to 95%. ^{, ,} While TMP/sulfamethoxazole (TMP/SMX) was a mainstay of empirical treatment of acute cystitis for decades and remains highly effective against susceptible organisms, ^, increasing rates of TMP/SMX resistance in community E. coli isolates compromised its use as first-line empirical therapy. As a result, older antibacterial agents have been repositioned as first-line therapy: nitrofurantoin, pivmecillinam, and oral fosfomycin have indications restricted to acute cystitis. These medicines do not induce cross-resistance with other classes of antimicrobial agents and, to date, limited resistance has been observed in community uropathogens. ^, In particular, despite high nitrofurantoin consumption worldwide in the past decade, E. coli strains remain overwhelmingly susceptible, likely due to nitrofurantoin’s multiple mechanisms of action.

Thus they are ecologically attractive for treatment of acute cystitis. ^{, ,} Pivmecillinam, however, is not available in many countries, and in countries where fosfomycin is also used parenterally, resistance rates to this antibiotic are increasing. The fluoroquinolones with urinary excretion—norfloxacin, ciprofloxacin, and levofloxacin—are no longer recommended as first-line therapy because widespread use promotes the emergence of resistance, particularly among Enterobacteriaceae. Oral β-lactam antimicrobial agents including amoxicillin, amoxicillin/clavulanic acid, and cephalosporins are reported to be 10% to 15% less effective than first-line agents. ^, The β-lactam agents are useful, however, for treatment in pregnant women given their favorable safety profile.

To limit adverse effects, cost, and emergence of bacterial resistance, the shortest effective duration of antimicrobial therapy should be prescribed. For TMP/SMX and the fluoroquinolones, 3 days is optimum. ^, The minimum duration of nitrofurantoin therapy is 5 days. ^, For β-lactam antimicrobial agents, 7 days is recommended; shorter courses are less effective. Fosfomycin is approved only as single-dose therapy, though a single dose is clinically and microbiologically inferior to 5 days of nitrofurantoin. For other agents, a single dose is generally 5% to 10% less effective than recommended longer regimens. ^,

Antimicrobial susceptibility of uropathogenic E. coli strains acquired in the community evolves continually in response to antimicrobial pressure. ^, Resistance in community isolates has compromised the efficacy of ampicillin, cephalosporins, TMP/SMX, and fluoroquinolones. ^, Recent prior antimicrobial therapy is a strong risk factor for isolation of a resistant organism. If the local prevalence of resistance to an antimicrobial agent in community E. coli strains exceeds 20%, that agent should not be used for first-line empirical therapy. The current increase in extended-spectrum β-lactamase (ESBL)–producing E. coli in community-acquired infections, attributed to global expansion of the E. coli clone ST131, is of particular concern because these strains are usually also resistant to TMP/SMX and fluoroquinolones. ^, Optimal treatment of infection with ESBL-producing E. coli is not yet well defined. Nitrofurantoin, pivmecillinam, and fosfomycin currently remain effective for most of these strains. ^,

Young women with a characteristic clinical presentation and prompt response following appropriate empirical therapy do not require further diagnostic imaging or urologic investigation. Less than 5% of these women have urologic abnormalities, and the few women in whom abnormalities are identified usually do not require further intervention. However, investigation may be appropriate to rule out alternative pathologic processes when the diagnosis is uncertain or clinical presentation is atypical.

Management strategies for recurrent lower UTI range from nonpharmacologic approaches to daily antibiotic prophylaxis; given perpetually increasing antimicrobial resistance rates, daily antibiotic prophylaxis should be considered last resort and initiated only when underlying risk factors cannot be corrected or mitigated.

Increased daily hydration can significantly reduce incidence of recurrent UTI. A randomized clinical trial comparing increased water intake (1.5 L added to baseline daily water intake) compared with usual behavior in otherwise healthy women with recurrent UTI who at baseline took in ≤1.5 L of water resulted in nearly half as many UTI episodes over the 12-month study period.

Other proposed nonantimicrobial approaches for prevention include daily intake of cranberry products, oral or vaginal probiotics to reestablish normal vaginal flora, estrogen replacement for postmenopausal women, and oral or bladder-instilled hyaluronic acid with chondroitin sulfate to reinstate the glucosaminoglycan layer. ^, Initial studies reported that daily intake of cranberry juice or tablets decreased episodes of recurrent cystitis by 30% in comparison with placebo. The proposed mechanism for this effect is inhibition of the P fimbria–mediated adherence of E. coli to uroepithelial cells by the proanthocyanidins present in cranberry products and excreted in the urine. However, more recent clinical trials report no benefit of daily cranberry juice in comparison with placebo for prevention of active infection or bacteriuria, and cranberry capsules were less effective than TMP/SMX prophylaxis. Though there seems to be a protective effect of host Lactobacillus spp. in some epidemiologic studies, trials of oral or vaginal Lactobacillus probiotics do not support efficacy of these products in preventing UTI. The role of estrogen replacement to prevent urinary tract infection in postmenopausal women is controversial. ^, In prospective clinical trials, researchers have uniformly reported no benefit of systemic estrogen over placebo, despite restoration of an acidic vaginal pH and increased vaginal colonization with lactobacilli in women who received estrogen. Two small clinical trials comparing vaginal estrogen with placebo in postmenopausal women with frequent, recurrent infection demonstrated a decreased frequency of symptomatic episodes in women treated with topical estrogen therapy, but in a comparative trial, an estrogen-containing pessary was substantially less effective than nitrofurantoin prophylaxis. ^, Currently, topical vaginal estrogen should likely only be considered for use to prevent infection in selected women with a high frequency of recurrent infection. Finally, trials have not demonstrated efficacy of either oral or bladder-instilled hyaluronic acid and chondroitin sulfate. ^,

Several other nonantimicrobial approaches for prevention of recurrent UTI remain under investigation. ^{, ,} These include strategies to block bacterial FimH adhesion with d -mannose, using vitamin D to enhance antimicrobial peptide production, vaccination using FimH or iron receptors, and immune stimulation with heat-killed whole bacteria. Trials with one of the whole bacterial immunostimulants (OM-89S), however, have shown no benefit. The clinical efficacy of any of these proposed interventions remains uncertain.

In women whose recurrent UTI is linked to sexual activity, postcoital antibiotic prophylaxis can significantly reduce UTI episodes. ^, To reduce emergence of antimicrobial resistance, however, only nitrofurantoin (50 mg or 100 mg as a single dose) should be prescribed given its minimal collateral effects on the intestinal microbiota.

Likewise, in patients fulfilling criteria for daily antibiotic prophylaxis, which are an inability to correct or mitigate underlying risk factors and the occurrence of two UTI episodes in the previous 6 months or three episodes in the previous year, nitrofurantoin (50 or 100 mg taken at bedtime) is the first-line agent, as regular intake of other antibiotics such as fluoroquinolones or TMP/SMX will result in rapid emergence of resistant Enterobacteriaceae. Daily prophylaxis should be prescribed initially for 3 or 6 months at most, with regular reevaluation of the need for prophylaxis. Patients and their primary care physicians should be advised that long-term daily nitrofurantoin administration has been associated with rare occurrences of pulmonary or hepatic hypersensitivity, since tissue fibrosis may ensue if nitrofurantoin is not discontinued. The incidence of hypersensitivity is exceedingly rare, however, and this event has almost never been observed in patients taking short courses (≤14 days) of nitrofurantoin since the medicine’s introduction to the market in 1953. ^,

Self-treatment (“pill in the pocket”) is an effective strategy for managing recurrent infections, especially given women’s accuracy in self-diagnosing UTI. While a 3-day course of TMP/SMX or ciprofloxacin has been shown to be effective for empirical self-treatment in clinical trials, self-treatment with these agents is no longer recommended due to resistance development. Instead, a 5-day course of nitrofurantoin 100 mg taken three times daily can be prescribed. In the event of nitrofurantoin intolerance or resistance, single-dose oral fosfomycin may be tried.

Pyelonephritis is much less common than cystitis. The ratio of pyelonephritis to cystitis episodes is reported to be between 1:18 and 1:29 in women with recurrent infection. The highest incidence is among women aged 20 to 30 years. Pyelonephritis is associated with substantial morbidity; hospitalization is required for up to 20% of affected nonpregnant women. Severe manifestations such as sepsis syndrome are, however, uncommon. Acute pyelonephritis complicates 1% to 2% of pregnancies. When this complication occurs at the end of the second trimester or early in the third trimester, preterm labor and delivery may occur and lead to poor fetal outcomes, as with any febrile illness in later pregnancy.

Acute nonobstructive pyelonephritis is rarely a direct cause of renal failure. Renal scarring is a complication of pyelonephritis in some women with more severe clinical presentations. In an Israeli study, 30% of a cohort of 203 women admitted for acute pyelonephritis were reassessed 10 to 20 years after admission; renal scars were detected in 46% of these women on technetium (Tc) 99m–labeled dimercaptosuccinic acid scanning. However, the renal scars were not associated with hypertension or renal impairment. The histologic finding of “chronic pyelonephritis” in patients with renal failure was formerly attributed to infection. However, this condition is now recognized as an end stage of many chronic inflammatory conditions of the kidney, and it is attributable to infection in only a few patients in whom there is a clear history of recurrent renal infection.

E. coli is isolated in 85% to 90% of women who present with acute pyelonephritis. ^, Infecting strains are characterized by production of the P fimbria adhesin Gal(α1–4) Galβ disaccharide galabiose. This surface protein appears to have a direct role in the pathogenesis of pyelonephritis through induction of mucosal inflammation. ^, A familial susceptibility to pyelonephritis has been reported and attributed to polymorphisms with decreased expression of the IL-8 receptor. Other genetic and behavioral risk factors for pyelonephritis in healthy women are similar to those described for acute cystitis. For premenopausal women, these associations are frequency of sexual intercourse, history of UTI, history of UTI in the patient’s mother, a new sexual partner, and recent spermicide use. The strongest association is with recent sexual intercourse. Women who experience pyelonephritis as children remain at increased risk of pyelonephritis as adults but experience a lower frequency of episodes. Diabetes is also an independent risk factor for pyelonephritis. Young diabetic women are 15 times more likely to be hospitalized for pyelonephritis than age-matched nondiabetic women. Behavioral risk factors associated with pyelonephritis in postmenopausal women have not yet been identified.

The classic clinical manifestation of renal infection is costovertebral angle pain or tenderness, often accompanied by fever, with or without a prodrome of lower urinary tract symptoms. There is a wide spectrum of severity, however, from mild irritative symptoms with minimal costovertebral angle tenderness to severe symptoms that may include high fever, nausea and vomiting, and severe pain. Acute cholecystitis, renal colic, and pelvic inflammatory disease (PID) are occasionally confused with pyelonephritis. When patients present with severe symptoms, underlying complicating factors such as obstruction and abscess must be excluded through urgent imaging. A urine specimen for culture should be obtained before initiation of antimicrobial therapy in every case of suspected pyelonephritis to confirm diagnosis and guide therapy.

Bacteremia is identified in 10% to 25% of women presenting with acute pyelonephritis if blood culture specimens are collected routinely. However, the clinical utility of routine blood cultures is limited because bacteremia does not alter therapy, nor is it predictive of outcome. ^, They should thus be obtained selectively, typically only if the diagnosis is uncertain or the presentation is severe.

Additional investigations recommended for most patients presenting with acute pyelonephritis are measurements of peripheral leukocyte count, C-reactive protein (CRP), and serum creatinine level. The CRP is typically elevated within the first days of symptoms and is useful as a parameter to monitor the response to therapy; its peak value correlates with severity of presentation. Elevated CRP at discharge has been associated with prolonged hospitalization and postdischarge recurrence.

Routine diagnostic imaging is not indicated when the clinical presentation is characteristic, symptoms are mild or moderate, and response to antimicrobial therapy is prompt. ^, Patients whose clinical presentations are severe, in whom treatment fails, or who experience early posttreatment recurrence should undergo prompt imaging to rule out obstruction or abscesses and to determine whether intervention is necessary. Ultrasonography is often the initial imaging modality because it is safe and widely accessible. In women with pyelonephritis and no preexisting structural abnormalities, it usually yields normal results, but enlargement and edema in one or both kidneys are observed in 20% of patients. Ultrasonography is less sensitive or specific for pyelonephritis than is either computed tomography (CT) or magnetic resonance imaging (MRI).

The optimal diagnostic imaging is contrast-enhanced CT, though this may be associated with a risk of developing contrast-induced nephropathy. In addition to renal enlargement and edema, dilation of the collecting system in the absence of obstruction, wedge-shaped areas of decreased attenuation, and rounded low-attenuation masses with delayed enhancement may be observed. Obstruction of renal tubules by inflammatory debris or impaired function with tubular ischemia may result in a “striated nephrogram.” Abnormalities within the renal cortex and medulla, inflammatory changes in Gerota fascia or the renal sinuses, and thickening of the urothelium are sometimes observed. “Acute focal pyelonephritis” (also called “acute lobar nephronia”) is infection confined to a single lobe and may be more common in women who have diabetes or are immunocompromised. The response to treatment is similar, however, for patients with or without this finding.

Most women with pyelonephritis receive treatment as outpatients. ^, Indications for hospitalization include hemodynamic instability, the need to exclude complicating factors such as obstruction and abscess, and the necessity of monitoring or treatment of associated medical illnesses. Traditionally, uncertain gastrointestinal absorption and pregnancy were also indications for hospitalization, but increased availability of outpatient parenteral therapy with close outpatient clinical follow-up may obviate the need for it.

Appropriate supportive management for hypotension, nausea and vomiting, and pain should be initiated promptly. When oral tolerance is uncertain because of nausea and vomiting, a strategy frequently used in emergency department management is to provide a single parenteral dose of ceftriaxone, 1 g, or of gentamicin, 120 mg, followed by oral therapy once gastrointestinal symptoms are controlled.

Many parenteral antimicrobial regimens are effective for pyelonephritis ( Table 38.5 ). Options for empiric parenteral therapy include third-generation cephalosporins such as cefotaxime and ceftriaxone, aminoglycosides, and fluoroquinolones such as ciprofloxacin. ^, Aminoglycosides have unique efficacy for the treatment of renal infection as they are bound in high concentrations in the renal cortex. Ceftriaxone therapy is the preferred empirical regimen for pregnant women. Although it is suggested that gentamicin be avoided in pregnancy because of potential fetal ototoxicity, excess otologic impairment has not been reported in large cohorts of newborn infants stratified by gentamicin exposure in utero. Thus when cephalosporins cannot be used because of antimicrobial resistance or patient intolerance, gentamicin remains an alternate antimicrobial for treatment of pregnant women. For ESBL-producing E. coli resistant to all first-line therapies, a carbapenem (imipenem/cilastatin, meropenem) is recommended.

Oral therapy selected according to culture results can then be prescribed to complete the antimicrobial course. In most young, nonpregnant women, acute pyelonephritis is effectively managed with outpatient oral therapy ( Table 38.5 ). ^, The recommended empirical antimicrobial choice is ciprofloxacin. Oral TMP/SMX is effective, but because of the high prevalence of TMP/SMX-resistant E. coli in some areas, this agent is recommended only when the infecting organism is known to be susceptible. Other oral regimens are also effective and may be appropriate, depending on organism susceptibility and the patient’s tolerance. Several trials have shown that 5- to 7-day antibiotic durations are noninferior to 14-day durations, even in patients with concomitant bacteremia. ^, Ciprofloxacin 500 mg twice daily given for 5 or 7 days ^, or a course of a single dose of ceftriaxone 1 g and cefixime 400 mg daily for 6 days are effective shorter regimens.

A satisfactory clinical response is usually observed by 48 to 72 hours after initiation of antimicrobial therapy. Risk factors predictive of a poor outcome are hospitalization, isolation of a resistant organism, concurrent diabetes mellitus, and history of renal stones. Prophylactic antimicrobial strategies similar to those for recurrent cystitis are effective for prevention of recurrent uncomplicated pyelonephritis.

Patients with indwelling devices or persistent obstruction may experience frequent recurrent infections. In men with spinal cord injury in whom voiding is managed with an indwelling catheter, UTI incidence is 2.72 infections/1000 days; when voiding is managed with intermittent catheterization, the infection incidence is 0.41/1000 days. In residents of long-term care facilities with long-term indwelling urethral catheters, the incidence of symptomatic infection is 3.2/1000 catheter days.

These patients are also at risk for local suppurative complications, such as renal or perinephric abscess, or metastatic infection after bacteremia, such as septic arthritis, osteomyelitis, or endocarditis. Serious complications are more common in patients who are diabetic, are immunocompromised, or have long-term urologic devices or obstruction. Renal functional impairment in patients with complicated UTI is usually attributable to the underlying abnormality or to organ failure complicating septic shock, rather than being a direct consequence of infection. For instance, introduction of voiding strategies to maintain low bladder pressure and to prevent reflux have almost eliminated the complication of chronic renal failure in persons with spinal cord injury, despite a continued high incidence of UTI in these patients.

Host impairment rather than organism virulence is the major determinant of infection. E. coli remains the organism most frequently isolated in complicated urinary tract infection. ^, The E. coli strains are characterized by a low frequency of expression of virulence factors in comparison with strains isolated in uncomplicated infection. Many other bacteria and yeast species are also isolated. ^{, ,} Enterobacteriaceae such as Klebsiella species, Enterobacter species, Serratia species, Citrobacter species, Proteus mirabilis, Morganella morganii, and Providencia stuartii are common. Other gram-negative organisms that may be isolated include Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter species. Gram-positive organisms are also frequently isolated including group B streptococci, Enterococcus species, and coagulase-negative staphylococci. S. aureus is less commonly isolated. Candida species may be isolated, usually from patients who have diabetes or indwelling urologic devices or who are undergoing broad-spectrum antimicrobial therapy. Organisms isolated from patients with complicated UTI often have increased antimicrobial resistance. Risk factors for isolation of a resistant organism include a history of recent antimicrobial therapy or hospitalization, indwelling urethral catheter, invasive urologic procedures, and nursing home residence.

Biofilm formation is universal in patients with chronic indwelling urinary devices. Following insertion, a conditioning layer composed of proteins and other host components immediately coats the device. This conditioning layer provides a surface for subsequent attachment of bacteria or yeast that originate from the periurethral flora or drainage bags or are introduced after disruption of the closed drainage system. Organisms grow along the device, elaborating an extracellular polysaccharide substance, and colonies of microorganisms persist within this relatively protected environment. Organisms ascend in the biofilm along the interior and exterior surfaces of the device and reach the bladder within days. The initial infection is usually with a single organism, but a polymicrobial flora is invariably present on long-term indwelling devices. ^, Urease-producing organisms such as P. mirabilis, K. pneumoniae, M. morganii, and P. stuartii are isolated more frequently from individuals with long-term indwelling catheters and persist longer than other organisms, such as Enterococcus species. Complications attributed to biofilm formation with urease-producing organisms include development of renal or bladder stones and obstruction of the device.

Although the most common device is the urethral catheter, the process of biofilm formation is similar with other indwelling devices, such as ureteric stents and nephrostomy tubes. From 34% to 42% of ureteral stents are found at removal to be colonized with bacteria or yeast species, often with multiple organisms. More than 50% of organisms identified by stent biofilm analysis are not isolated from culture of urine specimens collected at the same time.

Uncommon bacteria are occasionally a cause of infection. Some of these organisms may not be identified with standard laboratory procedures for processing urine specimens. Corynebacterium urealyticum is a urease-producing gram-positive rod associated with the unique clinical manifestations of encrusted cystitis or pyelonephritis. This infection is characterized by ulcerative inflammation and struvite encrustations on the bladder or renal pelvis wall. Pyelitis, if untreated, may lead to destruction of the kidney. U. urealyticum is another urease-producing bacterium that may cause cystitis or pyelonephritis, often with urolithiasis. Case reports suggest a predisposition in immunocompromised individuals, particularly those with hypogammaglobulinemia; healthy persons may also become infected. Aerococcus sanguinicola is a rare cause of complicated urinary tract infection; the diagnosis is usually made by isolation of the organism in blood culture. Aerococcus urinae was isolated in 0.3% to 0.8% of urine specimens in one clinical microbiology laboratory, usually from older persons with underlying abnormalities and bacteremia. Anaerobic organisms are seldom identified in the absence of suppurative complications such as abscess.

Genitourinary abnormalities facilitate infection through increased entry of organisms into the bladder (e.g., by intermittent catheterization and urologic procedures) and subsequent persistence due to incomplete voiding (e.g., as a result of obstruction, urolithiasis, diverticula, and reflux), or in biofilm on urologic devices. ^, Asymptomatic bacteriuria is common in patients with persistent abnormalities and universal in patients with long-term indwelling catheters. The determinants that lead to symptomatic infection in chronically bacteriuric individuals are not well characterized. However, obstruction and mucosal trauma with bleeding are well-recognized risk factors for bacteremia and sepsis in patients with preexisting bacteriuria.

Obstructive and catheter-related complicated UTIs manifest across a wide clinical spectrum of signs and symptoms, from mild, irritative symptoms of lower-tract infection to pyelonephritis and bacteremia including septic shock. ^{, ,} Localizing signs and symptoms consistent with cystitis or pyelonephritis are usually present. Patients with indwelling urethral catheters or other indwelling devices usually present with fever alone, although costovertebral angle pain or tenderness, hematuria, or catheter obstruction, if present, identifies a genitourinary source. Patients with chronic neurologic impairment sometimes report symptoms that are not classic for UTI. For instance, spinal cord–injured patients experience increased bladder and leg spasms or autonomic dysreflexia, whereas patients with multiple sclerosis may present with fatigue or deterioration in neurologic function.

A urine specimen for culture should be obtained before initiation of antimicrobial therapy for every patient; given the wide variety of potential infecting organisms and increased likelihood of resistant strains, microbiologic characterization is necessary to optimize antimicrobial management.

The presence of biofilm on devices such as indwelling catheters and stents may complicate interpretation of culture results. ^, The catheter should be replaced, and the new catheter should be used to sample bladder urine and avoid contamination by organisms present in the biofilm of the old catheter. ^, Renal function should be assessed in every patient with complicated UTI. A second urine culture after antimicrobial therapy is not recommended if the patient remains asymptomatic.

The approach to diagnostic imaging is determined by the clinical presentation and the patient’s previous history. Urgent imaging or urologic investigation is indicated for patients who have severe systemic symptoms or whose symptoms do not respond to appropriate antimicrobial therapy. The goal of early imaging is to identify obstruction or abscesses, for which immediate drainage may be necessary for source control. When the underlying abnormality is already well characterized (e.g., indwelling catheter and neurogenic bladder), further investigations may still be appropriate if infections have changed in frequency, as risks for urolithiasis and suppurative complications are elevated.

While a plain radiograph of the abdomen may identify emphysematous infections and some stones, CT is the imaging modality of choice. It identifies calculi, gas, hemorrhage, calcification, obstruction, renal enlargement, and inflammatory masses. Contrast media–enhanced scans are recommended (though are associated with risk of contrast-induced nephropathy), with helical and multislice CT to study different phases of contrast excretion. Ultrasound examination is less sensitive and specific than other imaging modalities such as spiral CT and MRI but may be more accessible.

The antimicrobial regimen selected is individualized on the basis of site of infection, severity of manifestations, known or presumed infecting organism and susceptibility, and the patient’s tolerance. When presenting symptoms are mild, it is preferable to delay initiation of antimicrobial therapy until results of the urine culture are available. Patients presenting to the emergency department with UTI without signs of septic shock do not have worse outcomes if antibiotic therapy is not given immediately.

For severe symptoms, empirical antimicrobial therapy is initiated pending urine culture results. Previous urine culture results, if available, and recent antimicrobial therapy received by the patient should be considered in the selection of the empiric regimen. Parenteral therapy is indicated for patients with hemodynamic instability, patients who cannot tolerate or absorb oral medications, or who are known or suspected to have an infecting organism resistant to available oral options. Patients with sepsis including septic shock should receive initial empirical broad-spectrum antimicrobial therapy. Appropriate regimens for these patients may include an aminoglycoside, with or without ampicillin; a cephalosporin with an aminoglycoside; a carbapenem (imipenem, meropenem); an extended-spectrum cephalosporin, or a β-lactam/β-lactamase inhibitor. The β-lactam/β-lactamase inhibitors—ceftazidime/avibactam and ceftolozane/tazobactam—are effective for the treatment of complicated infection with resistant organisms. Intravenous fosfomycin has also been used for some highly resistant organisms; given potential for resistance development, it should be used in combination with another broad-spectrum antimicrobial.

Fluoroquinolones with good urinary excretion and broad gram-negative coverage—norfloxacin, ciprofloxacin, and levofloxacin—are indicated for empirical oral therapy ; norfloxacin is useful for catheter-related bladder infection but is not effective for renal or prostate infection. Many other oral agents are effective and may be appropriate, depending on patient tolerance and the specific infecting organism. These include TMP/SMX, amoxicillin, amoxicillin/clavulanic acid, oral cephalosporins, and doxycycline. Nitrofurantoin may be effective for treatment of catheter-related bladder infection, but it is not effective for renal or prostate infection and is contraindicated for treatment of patients with renal failure because peripheral neuropathy has been reported to occur with accumulation of toxic metabolites.

Substantial clinical improvement is expected by 48 to 72 hours after initiation of effective antimicrobial therapy. Empirical therapy is then reassessed according to culture results, with switch to a more narrow-spectrum agent. Treatment courses of 5 to 7 days are effective for both catheter-related UTI confined to the lower urinary tract and obstructive pyelonephritis, where the obstruction has been removed and the patient has responded to initial therapy.

When symptoms recur early after appropriate antimicrobial treatment for a susceptible organism, further evaluation is necessary to identify abnormalities such as abscesses. Indwelling devices should be removed whenever possible; duration of catheter use is the most important risk factor for UTI. Evidence-based infection control guidelines provide recommendations for prevention of catheter-acquired UTI, and multifaceted programs are effective in decreasing catheter use and infection rates. Specific practices include catheter use for restricted indications, limiting duration of use, safe practices for insertion and care, and appropriate catheter size. Interventions not shown to be effective and not recommended are use of different catheter materials, antimicrobial coating of catheters, antiseptic or antimicrobial meatal care, and instillation of antiseptics into the drainage bag. Patients with long-term indwelling catheters and other indwelling devices experience infection because of biofilm formation on these devices; the prevention of catheter-acquired infection will ultimately require development of biofilm-resistant biomaterials. ^,

Long-term prophylactic antimicrobial therapy is not recommended. ^{, ,} When patients with impaired voiding or indwelling devices are given prophylactic antimicrobial agents, there is little, if any, decrease in symptomatic infection, and rapid reinfection with resistant organisms is uniformly observed. For selected patients with a persistent abnormality and symptomatic relapsing infection with an organism that cannot be eradicated, suppressive therapy may be considered. Antimicrobial options are limited, however, given rapid emergence of resistance; nitrofurantoin should be favored where possible given low rates of emergence of multidrug resistance despite its long-term use, and the patient and general practitioner should be reminded that nitrofurantoin suffices to sterilize the urine but does not treat active soft tissue infection. If the patient remains clinically stable and the urine is sterile, this dose is usually decreased to about half (for nitrofurantoin, from 100 mg qd to 50 mg qd) after 4 to 6 weeks. Suppressive therapy is not recommended for patients with indwelling devices because biofilm formation facilitates rapid reinfection and emergence of resistant organisms. However, short-term use of such therapy (several weeks or months) for patients with complex urologic abnormalities and indwelling devices may occasionally be considered as part of a palliative care strategy.

Novel nonantibiotic approaches are being attempted for UTI due to impaired bladder emptying and other underlying abnormalities. “Bacterial interference,” in which asymptomatic bacteriuria with a nonpathogenic E. coli strain is established to prevent infection by other more virulent strains, has been attempted yet without long-term success. There is currently avid interest in bacteriophage therapy, though most data stem from individual case reports with little long-term follow-up, where phages were often given in addition to antibiotics. In one randomized trial of men with UTI, a standard phage cocktail (not individualized to participants’ infecting strains) instilled into the bladder led to lower rates of microbiologic cure than placebo or antibiotic therapy.

Acute bacterial prostatitis is a severe infection and a urologic emergency. It is usually community acquired, although infection may occur after prostate biopsy. Affected men present with severe systemic manifestations including fever and marked urinary symptoms of dysuria and frequency. Urinary obstruction and intense suprapubic pain are often present. Bacteremia is reported in roughly a quarter of episodes.

E. coli is isolated in approximately 70% of episodes. These strains are characterized by the presence of multiple virulence factors. Proteus species, Klebsiella species, P. aeruginosa, S. aureus, and Enterococcus species are each isolated in less than 10% of cases.

Diagnosis is clinical and is supported by physical examination, laboratory studies, and occasionally imaging findings. Although there may be theoretical concern that digital rectal examination could cause bacteremia in acute prostatitis due to a high bacterial load in the prostate, there is no clinical evidence confirming the association. While extensive prostate massage should be avoided, a brief, gentle examination to identify acute tenderness or any gross abnormalities such as fluctuance may be key to distinguishing acute prostatitis from pyelonephritis in men.

There is no gold standard for the laboratory diagnosis of acute bacterial prostatitis, but urinalysis and urine culture are important for confirming clinical suspicion and guiding antibiotic therapy, respectively. Blood cultures are not universally required, and in one study, they contributed to microbiologic diagnosis in only 5% of patients. Yet blood culture collection is justified given the possible diagnostic uncertainty early in the course of the disease, as well as the clinical reality that urine may be collected only after the first dose of antibiotic has been given, reducing diagnostic sensitivity. Prostate-specific antigen has not shown sufficient sensitivity or specificity to be used as a diagnostic tool. Imaging is not required for initial diagnosis of acute prostatitis. Both transrectal ultrasound and MRI can be useful for identification of prostatic abscess; however, routine evaluation for abscesses is not recommended, as studies have shown low (0%–2.7%) rates.

Management includes bladder drainage by insertion of a urethral or suprapubic catheter and initiation of empirical parenteral antimicrobial therapy. Most antimicrobial agents are active in the acutely inflamed prostate. A combination of a β-lactam and an aminoglycoside is still considered first-line therapy, although other broad-spectrum parenteral antibiotics, such as piperacillin/tazobactam and carbapenems, are also effective. Once the infecting organism and susceptibility are confirmed and there has been an adequate clinical response to parenteral therapy, the antibiotic is modified to oral therapy to complete a 2- to 4-week course. These durations are based on expert opinion, but evidence from a recent randomized trial suggests that 2 weeks should be the minimum duration. The trial compared 1 versus 2 weeks of ofloxacin therapy in acute prostatitis due to susceptible uropathogens and failed to show noninferiority, with 56% and 78% experiencing treatment success, respectively, at 6 weeks.

A fluoroquinolone, either ciprofloxacin or levofloxacin, is recommended as oral therapy if the infecting organism is susceptible. When there is not a prompt clinical response following bladder drainage and initiation of effective antimicrobial therapy, CT or MRI is indicated to search for the uncommon complication of prostate abscess. When an abscess is identified, transrectal ultrasonography-guided aspiration is usually effective for drainage. A small proportion of patients, 10% to 15%, develop chronic bacterial prostatitis following acute prostatitis.

Chronic bacterial prostatitis occurs in men with persistent prostate infection. ^, Bacteria enter the prostate from the urethra and persist because of limited antimicrobial diffusion or activity in the gland, as well as the frequent presence of infected prostate stones in older men. A common clinical presentation is recurrent acute cystitis because bacteria in the prostate intermittently enter the bladder. The same organism is often repeatedly isolated, but the intervals between symptomatic episodes may last months or even years. Other symptoms are generally mild, such as irritative voiding symptoms and discomfort localized to the testicles, lower back, or perineum. Results of the prostate examination are usually normal, but tenderness may occasionally be elicited.

Chronic bacterial prostatitis is documented microbiologically in only 10% of men who present with the clinical syndrome of chronic prostatitis or chronic pelvic pain syndrome (CPPS). Gram-negative organisms including Enterobacteriaceae and P. aeruginosa are the bacteria most commonly isolated; gram-positive Enterococcus species, S. aureus, coagulase-negative staphylococci, and group B streptococci may also be isolated, though their presence can be confusing because it may also reflect culture contamination by fecal or skin flora. Sexually transmitted organisms such as Chlamydia trachomatis, U. urealyticum, Mycoplasma genitalium, and Trichomonas vaginalis are uncommon and, when present, are usually identified in younger men.

Confirmation of the diagnosis requires the two-glass test, in which a midstream urine sample is collected for urinalysis and culture, prostate massage is then performed for roughly a minute, and immediately thereafter first-stream urine is collected for urinalysis and culture. In a positive test, the postmassage sample will reveal more pyuria and at least one log more bacterial colony-forming units than the premassage specimen.

The test’s sensitivity and specificity are wanting, however. In one study of 463 patients and 121 age-matched controls, 70% of patients were found to harbor at least one organism in a postprostatic massage specimen, and uropathogens such as E. coli were isolated from 8% of patients and 8.3% of controls. In another study, gram-positive organisms were isolated from 6% of 470 men after prostatic massage, but 97% of these organisms were not confirmed on second culture, suggesting contamination or colonization.

Despite this uncertainty, chronic bacterial prostatitis does respond to appropriate antimicrobial treatment, although relapse after treatment is common. Ciprofloxacin is the first choice for antimicrobial treatment of chronic bacterial prostatitis when susceptible organisms are isolated. These agents penetrate well into the prostate and seminal fluid, and they remain active in the acidic environment of the prostate. Cure rates at 6 months after a 4-week course are 75% to 89%, ^, although late relapses may still occur. Trimethoprim/sulfamethoxazole (TMP-SMX) is often the first alternative therapy used: It appears to have excellent prostatic penetration, particularly the trimethoprim component. Data supporting its therapeutic use are sparse, however, coming mainly come from older studies with smaller numbers of patients and longer (90-day) treatment courses. Doxycycline and macrolides are considered second-line drugs but are preferred for gram-positive infections. Men who present for the first time with CPPS and with evidence of inflammation (i.e., leukocytes) in expressed prostatic secretions, but in whom cultures are negative, should be prescribed a 4-week trial of antimicrobial therapy if they have not previously received a prolonged antimicrobial course. ^, In reported case series, up to 10% of men with such findings show response to antimicrobial therapy despite negative culture results; however, comparative clinical trials in treatment-naïve men with negative culture results have not been reported. If symptoms persist or recur after this 4-week antimicrobial trial, and if results of postprostatic massage cultures remain negative, further antimicrobial therapy is not indicated and patients may be referred for perineal physical therapy. ^{, ,}

The prevalence of bacteriuria among sexually active young women ranges from 3% to 5% but is <1% among age-matched controls who are not sexually active. Bacteriuria is present in 5% to 10% of healthy postmenopausal women and in 20% of women older than 80 years living in the community. Asymptomatic bacteriuria is uncommon in younger men, but the prevalence increases in men older than 65 years, presumably concurrently with age-related prostate hypertrophy. Bacteriuria occurs in 10% of healthy men older than 80 years living in the community. Among residents of nursing homes who do not have indwelling catheters, 20% to 50% of women and 15% to 40% of men are bacteriuric. The prevalence among persons with long-term indwelling catheters is 100%. Among spinal cord–injured patients with impaired voiding and no indwelling catheter, the prevalence of bacteriuria is 50%, regardless of the method used for bladder emptying.

Patients with an increased prevalence of ASB also have a higher incidence of symptomatic UTI—yet this higher frequency is not attributable to bacteriuria. The same biological determinants promote both asymptomatic and symptomatic infection. Bacteriuria in healthy young women is usually transient, but up to 8% have acute cystitis within 1 week of initial identification of a positive urine culture result. In women with diabetes and female or male residents of nursing homes, persistent bacteriuria for months or years, frequently with the same strain, is often observed. No long-term negative outcomes have been attributed to asymptomatic bacteriuria. ^, Bacteriuric individuals are not at increased risk of hypertension or chronic renal failure, and survival is similar to that for persons without bacteriuria.

Harmful short-term outcomes attributable to asymptomatic bacteriuria have been recognized in only two distinct populations: pregnant women and patients who undergo traumatic genitourinary procedures. The prevalence of bacteriuria during early pregnancy is 3% to 7%, similar to that among age-matched nonpregnant women. The physiologic changes that accompany the increased progesterone levels in pregnancy include smooth muscle relaxation and decreased peristalsis, which result in dilation of the renal pelvis and ureters. In later pregnancy, ureteric obstruction may result from pressure of the uterus at the pelvic brim. Earlier studies reported that in 20% to 35% of pregnant women with untreated bacteriuria, acute pyelonephritis developed later in pregnancy, usually at the end of the second trimester or early in the third trimester; this incidence of pyelonephritis was 20-fold to 30-fold higher among untreated women with bacteriuria than among women whose initial screening urine cultures yielded negative results or in whom bacteriuria was treated. In these earlier studies, acute pyelonephritis in later pregnancy was associated with premature delivery and poorer fetal outcomes.

A 2015 randomized trial from the Netherlands, however, where screening for ASB in pregnancy is not part of routine care, calls into question the incidence and outcomes reported in earlier studies. While pyelonephritis occurred more frequently in pregnant participants with untreated ASB than in those without ASB or with treated ASB, it occurred in only 2.4% of women—much less than the 20% to 35% reported in earlier studies—and its occurrence did not lead to adverse fetal outcomes.

The second group of bacteriuric patients at risk are those who undergo traumatic urologic procedures. If bacteriuria remains untreated, bacteremia develops in up to 60% after the procedure and in 5% to 10% progresses to severe sepsis or septic shock.

E. coli is isolated from 80% of healthy women with asymptomatic bacteriuria. Most of the remaining bacterial strains are reported to be K. pneumoniae, Enterococcus species, and coagulase-negative staphylococci, but isolation of the latter two may be a result of urine sample contamination from the distal urethra. For men older than 65 years of age, coagulase-negative staphylococci are isolated most frequently, followed by E. coli and Enterococcus species. In patients with underlying genitourinary abnormalities, a wider variety of organisms are isolated. E. coli and other organisms associated with ASB are characterized by the relative absence of or lack of expression of recognized virulence factors. Some strains that are strongly adherent but unable to stimulate an epithelial cell IL-6 cytokine response have been described. These relatively avirulent E. coli strains may originate from nonvirulent commensal strains or evolve from virulent strains by attenuation of virulence genes. ^, Other organisms frequently isolated, such as coagulase-negative staphylococci and Enterococcus species, are relatively nonpathogenic and seldom associated with symptomatic infection. Biofilm formation results in polymicrobial bacteriuria in patients with chronic indwelling catheters.

The genetic and behavioral risk factors and genitourinary abnormalities associated with ASB are similar to those described for uncomplicated and complicated symptomatic UTI. For younger women, behavioral risks are sexual activity and spermicide use. Bacteriuric women older than 80 years who reside in the community are characterized by reduced mobility, urinary incontinence, and receiving estrogen treatment; and men older than 80 years with bacteriuria are characterized by prostate disease, history of stroke, and residence in supervised housing. Functional impairment is the major risk factor associated with asymptomatic bacteriuria in the long-term care facility population without indwelling catheters. Higher residual urine volume is not associated with increased bacteriuria in elderly populations but has been associated with bacteriuria in patients referred to an ambulatory urology clinic.

The criterion for identification of ASB is an organism quantitative count of ≥10 ⁵ CFU/mL in a urine culture. For women, two consecutive urine specimens with similar culture results are recommended, but a single specimen is sufficient for men. When an initial urine culture in a young woman yields positive results, a second positive result in a specimen obtained within 2 weeks confirms bacteriuria in 85% to 90% of women. If the second specimen result is negative, the initial positive culture result may have been contaminated; however, bacteriuria may also have resolved spontaneously. If a voided specimen has a low quantitative count of a single potential uropathogen, and if it is essential to rule out bacteriuria, a second urine specimen should be collected as a first morning void.

Pyuria usually accompanies bacteriuria, but there is variability in the frequency of pyuria observed in different populations. Pyuria is present in only 50% of bacteriuric pregnant women; therefore screening for pyuria is not a reliable method to rule out bacteriuria in pregnancy. Pyuria is present in about 75% of diabetic women with bacteriuria, in 90% of bacteriuric patients undergoing hemodialysis, and in >90% of elderly persons with bacteriuria. Pyuria also occurs in 30% to 70% of bacteriuric patients with short-term indwelling catheters and in 100% of those with long-term indwelling catheters. Some other biomarkers have been explored to be used in differentiating asymptomatic from symptomatic infection, particularly in the nursing home population. Urinary IL-6 has some association with symptomatic infection but has not been shown, to date, to have clinical utility. ^,

Screening for and treatment of ASB is recommended only for pregnant women or for patients who will undergo a traumatic genitourinary tract procedure. For other patients, treatment does not improve short- or long-term clinical outcomes, whereas negative consequences such as reinfection with organisms of increased antimicrobial resistance and adverse drug effects occur. ^, In girls and women, an increased frequency of symptomatic infection has been reported after treatment of asymptomatic bacteriuria. ^, This finding may be attributable to alteration of vaginal flora by antimicrobial therapy or replacement of a benign organism in the urine by a more virulent organism. Studies suggest no benefits of treatment of asymptomatic bacteriuria for patients with complicated infection including renal transplant recipients. Treatment of patients with asymptomatic bacteriuria is identified as a major contributor to inappropriate antimicrobial use and is an important target for intervention in antimicrobial stewardship programs. ^,

Current recommendations are that pregnant women be screened for bacteriuria by urine culture at the end of the first trimester and treated once (without follow-up surveillance cultures) if bacteriuria is found. Preferred regimens include a 5- or 7-day course of nitrofurantoin or a 7-day course of amoxicillin, amoxicillin/clavulanic acid, or a cephalosporin. The specific regimen is chosen on the basis of the organism isolated and the patient’s tolerance. Shorter antimicrobial courses are sometimes prescribed, but these abbreviated courses are likely less effective. TMP/SMX should be avoided, especially in the first trimester, and fluoroquinolones are contraindicated during pregnancy.

Initiation of effective antimicrobial treatment immediately before a traumatic urologic procedure prevents bacteremia and sepsis in a bacteriuric patient. ^, Conceptually, this approach is surgical prophylaxis rather than treatment of asymptomatic bacteriuria. A single dose of an antimicrobial agent is usually adequate, although some guidelines recommend that the antimicrobial agent be continued after transurethral resection of the prostate until the indwelling catheter is removed. Antimicrobial agents are not recommended for minor urologic procedures, such as cystoscopy and urodynamic studies or before replacement of a long-term urethral catheter, as the risk of bacteremia and sepsis with these interventions is low and clinical outcomes are not improved with prophylactic antimicrobial agents. ^{, ,}