Nitrofurantoin comeback for uncomplicated UTI.(Gynecology)(annual Interscience Conference on Antimicrobial Agents and Chemotherapy)

WASHINGTON -- Nitrofurantoin should be considered as a fluoroquinolonesparing agent for women with mild to moderate symptoms of uncomplicated cystitis, Dr. Thomas M. Hooton said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Nitrofurantoin, first approved in 1953 for the treatment of urinary tract infection (UTI), has been overshadowed in the last several decades, first by trimethoprim-sulfamethoxazole (TMP-SMX), and more recently by fluoroquinolones. Now the old drug's role is being reexamined in light of increasing antimicrobial resistance. "Nitrofurantoin is over 50 and still going strong," said Dr. Hooton, professor of medicine at the University of Washington, Seattle.

Guidelines issued in 1999 by the Infectious Diseases Society of America listed TMP-SMX as first-line treatment for uncomplicated, acute, symptomatic bacterial cystitis except when resistance is greater than 10%-20%, in which case fluoroquinolones should be used (Clin. Infect. Dis. 1999;29:745-58).

Nitrofurantoin, the IDSA said at the time, "may become more useful as resistance to TMP-SMX increases," but was not considered first-line due to concerns about effectiveness (85% cure rate vs. 90%-95% for other first-line agents) and safety, particularly regarding the rare but serious occurrence of acute pulmonary reaction and the even rarer peripheral neuritis.

While it's important to keep those concerns in mind, several new developments have occurred since those guidelines were issued that may shift the risk/benefit calculation, Dr. Hooton said.

One is the dramatic rise in resistance of Escherichia coli causing uncomplicated cystitis in women. In a Seattle study conducted over a 5-year period during the 1990s, E. coli resistance to TMP-SMX doubled, from 9% to 18%, while resistance to nitrofurantoin and ciprofloxacin remained unchanged, at 0%-2% for the entire study period (JAMA 1999;281:736-8).

Moreover, a safety review of published and unpublished data on nitrofurantoin revealed an extremely low rate (0.00094%) of acute pulmonary reactions and even lower rates of other major adverse events (Drugs 2001;61:353-64).