Use instead of fluoroquinolones when TMP/SMX is not an option for acute uncomplicated cases.


Five-day courses of nitrofurantoin are equivalent clinically and microbiologically to three-day courses of trimethoprim-sulfamethoxazole (TMP/SMX) for treating acute uncomplicated cystitis in women, researchers say.

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The finding, which was published in Archives of Internal Medicine (2007;167:2207-2212), could enable clinicians to prevent further emergence of microbial resistance to fluoroquinolones, which frequently are used as an alternative to TMP/SMX when the latter cannot be used because of resistance or allergy.

Evidence-based guidelines from the Infectious Diseases Society of America concluded that a three-day course of TMP/SMX is the preferred regimen for acute uncomplicated cystitis because of its high efficacy and minimal adverse effects, the researchers noted. Resistance to TMP/SMX, however, is now present in more than 20% of women with acute cystitis in many locales, making the use of an alternative drug necessary.


Nitrofurantoin has been used for more than 50 years for uncomplicated cystitis, the investigators observed. Although it remains active against most uropathogens, its popularity is hindered by a recommended seven-day dosing regimen and concerns about efficacy and tolerance, they noted. Few studies have evaluated the efficacy and tolerance of the drug, especially in a regimen shorter than seven days.


Kalpana Gupta, MD, MPH, and her colleagues at the University of Washington in Seattle randomly assigned 338 women (aged 18-45 years) with acute uncomplicated cystitis to receive either nitrofurantoin 100 mg twice daily for five days or one double-strength TMP/SMX tablet twice daily for three days. Clinical cure was achieved in 79% of the TMP/SMX and 84% of the nitrofurantoin recipients, according to the investigators. Clinical and microbiological cure rates at the first follow-up visit were equivalent, the researchers noted. They concluded that a five-day course of nitrofurantoin “should be considered an effective fluoroquinolone-sparing alternative for the treatment of acute cystitis in women.”


Dr. Gupta, who is now at Boston University and the VA Hospital in Boston, noted that increasing rates of fluoroquinolone resistance are being reported worldwide, including in some regions of the United States. To prevent further emergence of fluoroquinolone resistance, many experts recommend limiting the use of these agents to more serious infections, with fluoroquinolone-sparing drugs being preferred as second-line therapy for UTI when TMP/SMX cannot be used.


Although this particular study was not designed to evaluate a three-day regimen of nitrofurantoin, it demonstrated that most women (98%) experienced microbiological cure after three days of therapy, according to the investigators.