Examining the Evidence
Does a short course of nitrofurantoin cure acute uncomplicated cystitis?
Yes. In fact, it is now the preferred treatment in women because of increasing resistance among uropathogens to trimethoprim-sulfamethoxazole (TMP-SMX) and other fluoroquinolones.
In this randomized trial, 338 women 18 to 45 years old who had acute uncomplicated urinary tract infection (UTI) were randomized to open-label treatment with nitrofurantoin (Macrobid), 100 mg twice daily for 5 days, or trimethoprim-sulfamethoxazole, one double-strength tablet twice daily for 3 days. Clinical cure 30 days after therapy was achieved in 84% of the women taking nitrofurantoin and in 79% of women taking trimethoprim-sulfamethoxazole.
This study is important because UTI is routinely treated empirically. The usual drugs prescribed for uncomplicated UTI are TMP-SMX, extended-release ciprofloxacin (Cipro), or a first- or second-generation cephalosporin. Empiric use of fluoroquinolones such as ciprofloxacin has replaced trimethoprim-sulfamethoxazole in the treatment of uncomplicated cystitis. Such replacements are inappropriate for empiric therapy, and indiscriminate use of fluoroquinolones has led to increased resistance among Staphylococcus aureus organisms.
Nor has there been proper concern about the way antibiotics alter the endogenous bacteria of the body. Overuse of antibiotics such as the β-lactams (cephalosporin and expanded-spectrum penicillins), fluoroquinolones, and macrolides has added not only to the emergence of resistant bacteria strains but also to an increase in adverse events.
Resistance to TMP-SMX ranged from 12% to 21%
In this study, the authors isolated and identified bacteria responsible for infection, and the outcome reflects the national bacterial etiology in this age group (18 to 45 years). The number one bacterium isolated in the study was Escherichia coli (82%) as the sole uropathogen (TABLE). These data confirm that E coli remains the bacterium most likely to cause acute uncomplicated UTI.
The problem is that E coli has developed resistance to the antibiotics most commonly prescribed to treat this condition. In this study, 12% of the E coli isolates were resistant to trimethoprim-sulfamethoxazole. Even more alarming, 21% of non-E coli strains were resistant to trimethoprim-sulfamethoxazole. In contrast, 99.6% of E coli isolates and 90% of non-E coli isolates were sensitive to nitrofurantoin.
Bacteria isolated from the study population (n=338)
NUMBER OF ISOLATES
Klebsiella species, Proteus mirabilis, Enterobacter species, and Streptococcus agalactiae made up the remainder of the isolates (1% to 3%).
Adverse effects did not deter use
In the trimethoprim-sulfamethoxazole group, 31% of women experienced adverse effects, as did 28% in the nitrofurantoin group. Side effects included those commonly seen with oral antibiotic therapy: nausea, diarrhea, headache, lightheadedness, and vaginal itching.
Adherence was good; only 1% of women taking trimethoprim-sulfamethoxazole and 2% of women taking nitrofurantoin discontinued the drug.
An advantage for women taking nitrofurantoin is that it is concentrated in the urine, with little uptake in tissue and other bodily fluids. Therefore, it has very little effect on the endogenous vaginal microflora and little chance of causing vaginitis.
Weaknesses of the study
This study was not blinded; therefore, clinical evaluation may have been biased.
The population involved in the study was rather homogenous—mostly white college students. A mix of races would have been more informative.
Another limitation is that the investigators chose cefotaxime (Claforan) as one of the comparative antibiotics in the microbiologic arm, but gave no reason for this choice. Cefotaxime is administered either intravenously or intramuscularly and therefore has questionable relevance to this study. The other antibiotics chosen in addition to the two study drugs were ciprofloxacin and amoxicillin-clavulanate—both commonly used to treat acute uncomplicated cystitis.
What this evidence means for clinical practice
A 5-day course of nitrofurantoin is highly effective in treating uncomplicated UTI in women. It should be the initial empiric treatment of this infection because it is effective, safe, and well tolerated.
If a 3-day course of trimethoprim-sulfamethoxazole is used, the clinician should be aware that, as E coli resistance to this agent increases, its efficacy decreases.—Sebastian Faro, MD, PhD