Oral antimicrobial options for acute simple cystitis

	Dose	Duration	Comment
First-line options
Nitrofurantoin monohydrate/macrocrystals (Macrobid)^*	100 mg orally twice daily	Females: 5 days^¶ Males: 7 days	Retains activity against some MDR organisms Avoid if: Concern for early pyelonephritis CrCl <30 mL/minute
Trimethoprim-sulfamethoxazole^Δ	One double-strength tablet (160 mg/800 mg) orally twice daily	Females: 3 days^¶ Males: 7 days	Useful for males with concern for possible prostatitis Avoid if: Regional prevalence of resistance known to be >20%
Fosfomycin	3 g of powder mixed in water and administered orally	Single dose^¶	Retains activity against some MDR organisms Avoid if: Concern for early pyelonephritis
Pivmecillinam	185 mg pivmecillinam base orally three times daily^◊ or 400 mg pivmecillinam HCl orally three times daily^◊	Females: 3 to 7 days^¶ for the 185 mg base dose; 3 to 5 days for the 400 mg HCl dose Males: 7 days	Retains activity against some MDR organisms Avoid if: Concern for early pyelonephritis Not well studied in males
Alternatives: Other beta-lactams
Amoxicillin-clavulanate	500 mg orally twice daily	Females: 5 to 7 days^¶ Males: 7 days	Dose is based on amoxicillin component
Cefadroxil	500 mg orally twice daily	Females: 5 to 7 days^¶ Males: 7 days
Cefpodoxime	100 mg orally twice daily	Females: 5 to 7 days^¶ Males: 7 days
Cephalexin	500 mg orally twice daily^§	Females: 5 to 7 days^¶ Males: 7 days
Cefdinir	300 mg orally twice daily	Females: 5 to 7 days^¶ Males: 7 days	Does not achieve high urinary concentrations but may be sufficient to treat cystitis with susceptible organisms
Alternatives: Fluoroquinolones
Ciprofloxacin	250 mg orally twice daily or 500 mg extended release orally once daily	Females: 3 days^¶ Males: 5 days	Useful for males with concern for possible prostatitis^¥ Extended-release formulation not available in the United States
Levofloxacin	250 mg orally once daily	Females: 3 days^¶ Males: 5 days	Useful for males with concern for possible prostatitis^¥

These options for oral antimicrobial therapy of acute simple cystitis apply to adults and adolescents of all ages. Doses listed are for individuals with normal kidney function; dose adjustments may be needed for individuals with kidney impairment.

First-line options strike a favorable balance between efficacy and adverse effects (including the risk of selecting for resistant organisms). The choice among them should be individualized to patient circumstances (allergy, tolerability, expected adherence), local community resistance prevalence, availability, cost, and patient and provider threshold for failure. If the patient has taken one of the agents in the preceding three months, a different one should be selected. Beta-lactams are second-line agents because they are less effective and have more potential adverse effects. Although fluoroquinolones are very effective, associated adverse effects and increasing resistance rates mitigate their utility; we only use them if other agents cannot be used or in males with concern for possible prostatitis.

CrCl: creatinine clearance; ESBL: extended-spectrum beta-lactamase; FDA: US Food and Drug Administration; HCl: hydrochloride; MDR: multidrug-resistant.

* Nitrofurantoin is also available as nitrofurantoin macrocrystals (Macrodantin), which is dosed differently. Refer to the drug information monograph for nitrofurantoin included within UpToDate.

¶ For females with urinary tract abnormalities, immunocompromising conditions, or poorly controlled diabetes mellitus, it is reasonable to use a longer duration of therapy (eg, 7 days). If a longer duration of fosfomycin is needed (ie, more than a single dose), additional doses are administered every 2 to 3 days for up to 3 doses.

Δ Trimethoprim 100 mg orally twice daily for 3 days is a potential option for individuals who have a sulfonamide (but not trimethoprim) allergy if regional prevalence of resistance is known to be <20%.

◊ The dosing for pivmecillinam varies by region, and overall, there is no evidence clearly demonstrating that one regimen is superior to the other. Also, depending on country, the dose is expressed as either pivmecillinam base or pivmecillinam HCl salt; 185 mg pivemecillinam base is equivalent to 200 mg pivmecillinam HCl. In the United States, the FDA-approved dose is 185 mg pivmecillinam base three times daily. In some European countries, the recommended dose is 400 mg pivemecillinam HCl three times daily. We generally use the FDA-approved dose; however, for directed therapy of MDR organisms (eg, ESBL-producing isolates that are susceptible to pivmecillinam), it is reasonable to use the higher dose.

§ Cephalexin can also be dosed at 250 mg orally every 6 hours.

¥ For males who have more severe cystitis symptoms or concern about early involvement of the prostate (eg, recurrent UTI with the same pathogen, equivocal prostatic tenderness), we use higher doses of fluoroquinolones (ciprofloxacin 500 mg orally twice daily or 1000 mg extended release once daily, or levofloxacin 750 mg orally once daily).

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Oral antimicrobial options for acute simple cystitis