According to a study published in the February 8 issue of JAMA, cefpodoxime, an antibiotic used as a short-term therapy in women with uncomplicated bladder infection (cystitis), failed to meet criteria for non-inferiority in comparison to ciprofloxacin. There have been concerns that ciprofloxacin, classed as a fluoroquinolone antibiotic, is overused, resulting in an increase in resistance rates. The criteria for non-inferiority were defined as cefpodoxime’s efficacy lying within a pre-specified margin of 10% of ciprofloxacin’s efficacy.
Fluoroquinolones have high efficacy rates and very low adverse events as a 3-day regimen recommended for the treatment of uncomplicated cystitis, but there have been increasing reports of antimicrobial resistance amongst fluoroquinolones. The researchers state in their background information that to prevent further emergence of fluoroquinolone resistance, there are calls to restrict the use of fluoroquinolones to specific instances of uncomplicated cystitis when other first-line urinary tract infection (UTI) antimicrobials are unsuitable.
The researchers say that:
“Cefpodoxime, with its broad spectrum of antimicrobial activity, would provide a useful alternative to fluoroquinolones for the treatment of cystitis if demonstrated to be similar in efficacy to fluoroquinolones and without adverse ecological effects (such as the selection of drug-resistant organisms).”
Thomas M. Hooton, M.D., of the University of Miami and his team decided to perform a clinical trial to evaluate cefpodoxime’s clinical efficacy and tolerance compared with ciprofloxacin in 300 women aged between 18 to 55 years with acute uncomplicated cystitis. The study period was from 2005 to 2009, with outcomes evaluated at 5 to 9 days and 28 to 30 days after treatment was completed.
Intent-to-treat and per-protocol analyses were conducted, however 15 women of the 150 in the ciprofloxacin group and 17 women of the 150 in the cefpodoxime group were lost to follow-up. The researchers randomized the patients to receive either 250 mg of ciprofloxacin orally twice a-day for 3 days or 100 mg of cefpodoxime proxetil orally twice a-day for 3 days.
The overall clinical cure was defined as not needing antimicrobial treatment during follow-up until the 30-day follow-up visit. Researchers speculated that cefpodoxime would prove noninferior to ciprofloxacin by a 10 percent margin before data was collected.
They found that the overall clinical cure rate with the intent-to-treat approach in which they accounted for the number of lost patients to follow-up was 93% in 139 of the 150 patients in the ciprofloxacin group compared with 82% in 123 of the 150 patients in the cefpodoxime group.
The non-inferiority test proved to be statistically unimportant. The researchers performed an alternative intent-to-treat analysis in which patients lost to follow-up were considered as non-responsive to treatment, which revealed a clinical cure rate of 83% in 124 of 150 patients in the ciprofloxacin group compared with 71% in 106 of 150 patients in the cefpodoxime group.
The overall clinical cure rate amongst those women in the ciprofloxaxin group who reported to have had no previous UTI in the year prior to enrollment was 96% and 83% in the cefpodoxime group, a marginal difference that was not observed amongst those who reported 1 or more UTIs in the year before enrollment.
The results of the clinical cure rate at the first follow up, which was on average 5 days following treatment, was 93% for ciprofloxacin compared with 88% for cefpodoxime, whilst the microbiological cure rate at the first average follow-up visit at 5 days after treatment was 96% in the ciprofloxacin group compared with 81% in the cefpodoxime group.
The researchers found at first follow-up, that 16% of women in the ciprofloxacin group had vaginal E coli colonization, a presence of organisms on some surface or in some bodily fluid that are symptom-free, compared with 40% in the cefpodoxime group. According to the researchers, the differential effect of the two drugs on vaginal E coli colonization may have impacted on the difference in clinical outcomes.
They comment: “Among women with uncomplicated cystitis, a 3-day regimen of cefpodoxime compared with ciprofloxacin did not meet criteria for non-inferiority for achieving clinical cure,” adding that this result together with concerns regarding potential ecological adverse effects linked to other broad-spectrum β-lactams, a class of antimicrobials that includes cefpodoxime, do not recommend using cefpodoxime as a first-line fluoroquinolone-sparing antimicrobial for acute uncomplicated cystitis.
Written by Petra Rattue