Background: Evidence-based guidelines recommend trimethoprim/sulfamethoxazole (TMP/SMX; Bactrim, Septra) as the drug of choice for treating uncomplicated cystitis in women. However, there is a perception that fluoroquinolones are more effective and safer than TMP/SMX. This may have contributed to fluoroquinolones becoming a more commonly prescribed class of antibiotic than TMP/SMX for uncomplicated urinary cystitis in the United States. This has raised concerns about the increasing rates of fluoroquinolone-resistant Escherichia coli strains. Nitrofurantoin (Furadantin) is well established as an alternative treatment, although it is less popular because its seven-day regimen is longer than the three-day course of TMP/SMX or fluoroquinolones. If an abbreviated regimen of nitrofurantoin could be demonstrated to effectively treat uncomplicated cystitis, this could increase its viability as an option for fluoroquinolone-resistant infections. Gupta and colleagues compared the effectiveness of nitrofurantoin with that of TMP/SMX in women with acute uncomplicated cystitis.

The Study: The researchers performed a prospective, randomized study of women with symptoms of acute cystitis (dysuria, frequency, and/or urgency). The participants were recruited from a university health center serving students and faculty. Pregnant or lactating women were excluded from the study, as were those with known anatomic urinary tract abnormalities or those who had used antibiotics within the preceding two weeks. Eligible women provided a clean-catch midstream urine sample for urinalysis and culture, and then were randomized to receive TMP/SMX (one double-strength tablet twice daily for three days) or nitrofurantoin (100 mg twice daily for five days). Participants returned for a follow-up visit five to nine days after the completion of therapy and again after one month to complete a questionnaire about their symptoms and to provide a urine specimen. The primary outcome was the clinical cure at the final follow-up visit. Treatment failure was defined as persistent, recurrent, or worsening symptoms, or the development of pyelonephritis.

Results: Of the 338 women ages 18 to 45 years who were enrolled in the study, 308 women with documented urinary infection on culture were available for analyses. Demographics, urinary tract infection history, and sexual history were similar between the two treatment groups. Clinical cure rates were statistically equivalent in the TMP/SMX and nitrofurantoin groups (79 and 84 percent, respectively). Similar proportions of women in both groups reported at least one adverse effect (31 and 28 percent, respectively), most commonly involving mild gastrointestinal symptoms. E. coli was responsible for 82 percent of all infections, of which 99.6 percent were microbiologically susceptible to nitrofurantoin and fluoroquinolones, and 88 percent were susceptible to TMP/SMX. Among the non-E. coli uropathogens identified, 90 percent were susceptible to nitrofurantoin, and 77 and 76 percent were susceptible to TMP/SMX and fluoroquinolones, respectively.

Conclusion: A five-day course of nitrofurantoin is clinically and microbiologically equivalent to a three-day course of TMP/SMX for the treatment of acute uncomplicated cystitis in women. Using the nitrofurantoin regimen as an alternative to fluoroquinolones could reduce the development of fluoroquinolone-resistant acute cystitis.