Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

uncomplicated urinary tract infection (UTI): nonpregnant

1st line – antibiotic therapy

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ACUTE
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uncomplicated urinary tract infection (UTI): nonpregnant
1st line – 

antibiotic therapy

Although adverse reactions to the antibiotics and the promotion of antibiotic resistance are possible, these regimens are generally well tolerated and effective so the risk/benefit analysis is clearly in favor of treating these infections.

Trimethoprim/sulfamethoxazole (TMP/SMX) (or trimethoprim alone) and nitrofurantoin have similar efficacy; however, TMP/SMX (or trimethoprim alone) should not be used as first-line treatment if local resistance rates of uropathogens causing uncomplicated cystitis exceed 20%.[1][43] Nitrofurantoin and TMP/SMX are active against multiple antibiotic-resistant bacteria, including extended-spectrum beta-lactamase (ESBL)-producing enterobacterales such as Escherichia coli and Klebsiella pneumoniae.[11]​ 

European Association of Urology guidelines recommend fosfomycin as a first-line alternative for uncomplicated acute cystitis.[1] There is sufficient evidence to suggest that a single dose of fosfomycin has noninferior efficacy compared with 3 days of therapy with either a fluoroquinolone or TMP/SMX.[43][45][56]​​ Fosfomycin is active against cystitis caused by ESBL-producing E coli.[11]

Other alternatives, such as cephalosporins or aminopenicillins, are not recommended for empiric therapy, except in selected cases.[1][43]​​​ 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]

Patients with glucose-6-phosphate dehydrogenase deficiency should not use nitrofurantoin because of the risk of developing hemolytic anemia.

Primary options

nitrofurantoin: 100 mg orally (extended-release) twice daily for 3-5 days; 50-100 mg orally (immediate-release) four times daily for 3-5 days

OR

sulfamethoxazole/trimethoprim: 160 mg orally twice daily for 3 days

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OR

fosfomycin tromethamine: 3 g orally as a single dose

Consider – symptomatic relief of dysuria

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ACUTE
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uncomplicated urinary tract infection (UTI): nonpregnant
Consider – 

symptomatic relief of dysuria

Treatment recommended for SOME patients in selected patient group

Phenazopyridine may be used for symptomatic relief for dysuria as an adjunct to antibiotic therapy.

Patients with glucose-6-phosphate dehydrogenase deficiency should not use phenazopyridine because of the risk of developing hemolytic anemia.

Primary options

phenazopyridine: 200 mg orally three times daily for 2 days when required

complicated UTI: nonpregnant

1st line – antibiotic therapy

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ACUTE
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complicated UTI: nonpregnant
1st line – 

antibiotic therapy

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 extended spectrum beta-lactamase (ESBL)-producing organisms or other multi-drug resistant organisms.[1]​ Such patients require a longer and more aggressive treatment course. 

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.

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 if the patient has used a fluoroquinolone within the last 6 months.[1][49]​​ The fluoroquinolones levofloxacin and ciprofloxacin are active against ESBL-producing enterobacterales such as Escherichia coli and Klebsiella pneumoniae.[11]​ In cases of fluoroquinolone allergy or resistance, a third-generation cephalosporin (such as cefpodoxime) would be an appropriate first choice.

Fluoroquinolones have been associated with serious, disabling, and potentially irreversible adverse effects, including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.[57]​ Warnings have also been issued about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[58][59]​​​ 

Patients with a complicated UTI with systemic symptoms requiring hospitalization should be initially treated with: intravenous antibiotics such as 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]

In addition, the patient should be further investigated for management of any associated complicating factor as appropriate.

Primary options

levofloxacin: 250 mg orally once daily for 7-14 days

OR

ciprofloxacin: 250-500 mg orally twice daily for 7-14 days

Secondary options

cefpodoxime proxetil: 100 mg orally twice daily for 7 days

OR

ampicillin: 500 mg intravenously every 6 hours

and

gentamicin: 3-5 mg/kg/day intravenously given in divided doses every 8 hours

OR

cefuroxime sodium: 750-1500 mg intravenously every 8 hours

and

gentamicin: 3-5 mg/kg/day intravenously given in divided doses every 8 hours

OR

ceftriaxone: 1-2 g intravenously every 24 hours

Consider – symptomatic relief of dysuria

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ACUTE
|
complicated UTI: nonpregnant
Consider – 

symptomatic relief of dysuria

Treatment recommended for SOME patients in selected patient group

Phenazopyridine may be used for symptomatic relief for dysuria as an adjunct to antibiotic therapy.

Patients with glucose-6-phosphate dehydrogenase deficiency should not use phenazopyridine because of the risk of developing hemolytic anemia.

Primary options

phenazopyridine: 200 mg orally three times daily for 2 days when required

uncomplicated or complicated UTI: pregnant

1st line – antibiotic therapy

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ACUTE
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uncomplicated or complicated UTI: pregnant
1st line – 

antibiotic therapy

Pregnancy is a complicating factor in the treatment of acute cystitis. The presence of UTI in pregnant individuals is associated with potential adverse pregnancy outcomes, including preterm labor and low birth weight.[40]​ Development of pyelonephritis in pregnancy can lead to loss of pregnancy.[41]​​

Culture and sensitivity are indicated to guide treatment as antibiotic choices are limited in pregnancy.[1][40]

Fluoroquinolones, tetracyclines, and trimethoprim/sulfamethoxazole are generally not recommended in pregnancy, so the first-line antibiotic is nitrofurantoin or fosfomycin.​ Nitrofurantoin should be avoided at the end of pregnancy due to a theoretical risk of hemolytic anemia in the newborn.[50] Penicillins and cephalosporins may also be considered. Amoxicillin should only be used if culture results are available and susceptible.

Primary options

nitrofurantoin: 100 mg orally (extended-release) twice daily for 3-5 days; 50-100 mg orally (immediate-release) four times daily for 3-5 days

OR

fosfomycin tromethamine: 3 g orally as a single dose

Secondary options

cephalexin: 500 mg orally twice daily for 7 days

OR

amoxicillin: 500 mg orally three times a day for 7 days

ONGOING

​​at risk of chronic recurrent UTI

1st line – antibiotic prophylaxis ± supportive measures

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ONGOING
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​​at risk of chronic recurrent UTI
1st line – 

antibiotic prophylaxis ± supportive measures

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

Patients with chronic recurrent UTIs are offered antibiotic prophylaxis taken either daily or postcoitally. 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 trimethoprim/sulfamethoxazole, trimethoprim alone, fosfomycin, and nitrofurantoin.[1][8][60]​​​​​ Caution should be applied when using nitrofurantoin long-term due to the risk of lung injury.[51]

Urination after coitus may be useful. 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]

Primary options

sulfamethoxazole/trimethoprim: 40 mg orally once daily or three times weekly; 40-80 mg orally post-coitally

More

OR

nitrofurantoin: 50-100 mg orally (immediate-release) once daily or post-coitally

OR

trimethoprim: 100 mg orally once daily

OR

fosfomycin tromethamine: 3 g orally every 10 days

Secondary options

methenamine hippurate: 1 g orally twice daily

Consider – vaginal estrogen

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ONGOING
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​​at risk of chronic recurrent UTI
Consider – 

vaginal estrogen

Treatment recommended for SOME patients in selected patient group

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 postmenopausual 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]​​ There are many different types and formulations of vaginal estrogen available; consult local formulary.

Consider – patient-initiated therapy

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ONGOING
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​​at risk of chronic recurrent UTI
Consider – 

patient-initiated therapy

Treatment recommended for SOME patients in selected patient group

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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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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