Approach

Oral antibiotics are the mainstay of treatment of urinary tract infection (UTI).

Choice of antibiotic should be guided by past infections and associated antibiotic susceptibility data from the past 6 months, antibiotic exposures within the past 30 days, and local antimicrobial resistance patterns. This includes the possibility of infection with extended-spectrum beta-lactamase (ESBL)-producing organisms, namely Escherichia coli and Klebsiella pneumoniae.[11]

Treatment rationale is based upon whether the UTI is complicated or uncomplicated. Complicated cases include patients with any of the following: anatomic or functional abnormalities within the urinary tract, male sex, pregnancy, immunosuppression (e.g., renal transplant), diabetes, incomplete voiding, indwelling urinary catheter, recent instrumentation, healthcare-associated infection, or history of infection with ESBL-producing organisms or other multidrug resistant organisms.[1]​ Such patients require a longer and more aggressive treatment course. 

Uncomplicated acute cystitis

The first-line treatment for uncomplicated acute cystitis is nitrofurantoin for 3 to 5 days or trimethoprim/sulfamethoxazole (TMP/SMX) for 3 days.[1][43][44]​​​​ These agents have similar efficacy; however, TMP/SMX should not be used as first-line treatment if local resistance rates of uropathogens causing uncomplicated cystitis exceeds 20%.[1]​​[43] Nitrofurantoin and TMP/SMX are active against multiple antibiotic-resistant bacteria, including ESBL-producing organisms.[11]​ Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency should not use nitrofurantoin because of the risk of developing hemolytic anemia.

European Association of Urology (EAU) guidelines recommend fosfomycin as a first-line alternative for uncomplicated acute cystitis. EAU also recommend pivmecillinam first line; however, it is not available in the US.[1]​ Fosfomycin is active against cystitis caused by ESBL-producing E coli.[11]​ One meta-analysis found fosfomycin had similar efficacy to other antibiotics in uncomplicated acute cystitis.[45] However, one study comparing a 5-day course of nitrofurantoin to a single dose of fosfomycin found nitrofurantoin led to higher clinical and microbiologic resolution.[46] Other alternatives, such as cephalosporins or aminopenicillins, are not recommended for empiric therapy, except in selected cases.[1][43]​​​ Compared with nitrofurantoin, TMP/SMX, or fosfomycin, beta-lactam agents have higher risk of ecological collateral damage (selection of drug-resistant organisms, colonization or infection with multidrug-resistant organisms, higher risk of subsequent infections such as Clostridium difficile).[34] Fluoroquinolones are not suitable for antimicrobial therapy in uncomplicated cystitis because of negative ecological effects and should be reserved for complicated and/or severe infection.[1][43]

When comparing different strategies in the management of uncomplicated UTI (empiric antibiotic treatment, delayed prescribing and targeted prescribing based on midstream urine results), all have been shown to achieve similar symptom control.[32] Antibiotics have shown to be superior to placebo.[47]

If the patient does not begin to improve with 2-3 days of therapy, further evaluation is indicated. If not already done, diagnosis should be confirmed by urinalysis and, prior to switching antibiotics, a urine culture should be obtained to help guide subsequent therapy.

If a patient has a previous history of cystitis and this is a recurrent episode, patient-initiated therapy for this and possible future episodes may be considered. This is where the antibiotic prescription is given to the woman in advance of symptoms with detailed instructions on usage. Patient information brochures have been shown to help in this regard.[48]

Phenazopyridine may be used for symptomatic relief as an adjunct to antibiotic therapy. Note that it can cause hemolysis in patients with G6PD deficiency.

Complicated acute cystitis

In patients with suspected complicated acute cystitis, the diagnosis should be confirmed with a urinalysis and urine culture. Antibiotics should be started, and the treatment strategy can later be modified if necessary based on the culture and sensitivity results.[1]

Fluoroquinolones are generally indicated as first-line therapy for complicated acute cystitis. However, a fluoroquinolone can only be recommended for empiric treatment provided local resistance patterns are less than 10%; the patient is not seriously ill and the whole treatment can be given orally; or the patient has an anaphylaxis for beta-lactam antimicrobials.[1] Due to their high use in some urological patients, fluoroquinolones are less likely to be successful in this specific cohort and therefore are not recommended first line for empiric treatment if the patient has used a fluoroquinolone within the last 6 months.[1][49]​​ In cases of fluoroquinolone allergy or resistance, a third-generation cephalosporin (such as cefpodoxime) would be an appropriate first choice.

Patients with a complicated UTI with systemic symptoms requiring hospitalization should be initially treated with intravenous antibiotics. These include amoxicillin plus an aminoglycoside, a second-generation cephalosporin plus an aminoglycoside, or a third-generation cephalosporin.[1] With improvement, the patient's regimen can be changed to an oral antimicrobial to which the organism is susceptive to complete the course of therapy.[43]

Phenazopyridine may be used for symptomatic relief as an adjunct to antibiotic therapy. Note that it can cause hemolysis in patients with G6PD deficiency.

Acute cystitis in pregnancy

In those whose infection is complicated by pregnancy, fluoroquinolones, tetracyclines, and trimethoprim/sulfamethoxazole are generally not recommended. Therefore, for these patients the first-line antibiotic is nitrofurantoin or fosfomycin.[1]​ Nitrofurantoin should be avoided at the end of pregnancy due to a theoretical risk of hemolytic anemia in the newborn.[50] Alternatives include cephalosporins and penicillins.[1]

Recurrent cystitis

A recurrent UTI may be complicated or uncomplicated, and is defined as at least 3 cases per year or 2 cases with 6 months.[1]​

Patients with chronic recurrent UTIs are offered antibiotic prophylaxis taken either daily or postcoitally. As for acute UTI, choice of antibiotic should be guided by past infections and associated antibiotic susceptibility data from the past 6 months, antibiotic exposures within the past 30 days, and local antimicrobial resistance patterns.[11]​ Options include TMP/SMX, trimethoprim alone, fosfomycin, and nitrofurantoin.[1][8]​​​​ Caution should be applied when using nitrofurantoin long-term due to the risk of lung injury.[51]

Urination after coitus, increased water intake, and a course of probiotics may also be beneficial in preventing recurrent cystitis; however, high-quality evidence is limited.​[29]

Methenamine hippurate functions as a urinary antiseptic as it is converted to ammonia and formaldehyde in the acidic environment of the lower urinary tract. In one open-label randomized trial, methenamine hippurate demonstrated noninferiority to antibiotic prophylaxis over a 12-month period, with an acceptable safety profile.[52]​ Further studies are recommended; however, methenamine hippurate may be considered in some patients according to their individual preferences and antibiotic stewardship initiatives.​[52]​​​​[53]

One systematic review and meta-analysis of randomized and quasi-randomized trials found that daily high doses of cranberry, often in the form of pills or concentrates, reduced rates of symptomatic, culture-verified UTIs in nonpregnant women with recurrent UTIs (and no underlying urological abnormality).[54]​ Cranberry products may be recommended for recurrent UTI prevention; however, there is no clear clinical evidence regarding the appropriate dose and treatment duration.[1]

In postmenopausal women, estrogen levels decline leading to vaginal atrophy and increased risk of recurrent UTI. Vaginal estrogen replacement may potentially reduce risk of recurrent UTI in postmenopausal women. Evidence is strongest for topical estrogen in the form of a cream or pessary.[1]​ The lowest effective dose of vaginal estrogen should be used.[55]

Patient-initiated therapy for possible future episodes may also be considered. This is where the antibiotic prescription is given to the woman in advance of symptoms with detailed instructions on usage. Patient information brochures have been shown to help in this regard.[48]

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