MedWire News: A 3-day regimen of cefpodoxime does not meet criteria for noninferiority to ciprofloxacin in achieving clinical cure in women with acute uncomplicated cystitis, show study findings.
"Cefpodoxime demonstrated significantly poorer activity than ciprofloxacin in eradicating E. coli from the vaginal flora in this study," say Thomas Hooton (University of Miami, Florida, USA) and colleagues.
Although fluoroquinolones such as ciproflaxacin remain the most reliable urinary antimicrobial, resistance rates have increased and there is now a need for fluoroquinolone-sparing antimicrobials, explains the team in JAMA.
The researchers therefore conducted a study to assess whether cefpodoxime, an oral third-generation cephalosporin, would have clinically acceptable efficacy and tolerance compared with ciprofloxacin in a study including 300 women, aged 18 to 55 years, with acute uncomplicated cystitis. A noninferiority margin of 10% was considered to be clinically acceptable.
After undergoing a midstream urine specimen collection to evaluate bacteriuria and pyuria, and a vaginal swab to evaluate bacterial colonization, the women were randomly assigned to receive ciprofloxacin 250 mg or cefpodoxime proxetil 100 mg twice daily for 3 days.
Patients attended follow-up visits at 5 to 9 and 28 to 30 days after completion of therapy. They were asked to return to the clinic if their symptoms did not resolve or if they had recurrent symptoms of acute cystitis.
At each return visit, a questionnaire regarding urinary tract infection symptoms was administered, and urine and vaginal specimens were collected.
The primary study outcome was clinical cure at the 30-day follow-up visit (no further requirement for antimicrobial treatment versus not responded to treatment), and the secondary outcomes were clinical and microbiologic cure at the first follow-up visit, and vaginal E. coli colonization at each follow-up visit.
Microbiologic cure was defined as having less than 105 colony-forming units per milliliter of all uropathogens and at least a 10-fold decrease in colony count of the causative uropathogen compared with the urine count at enrollment.
The researchers report that, with intention-to-treat analysis in which patients lost to the 30-day follow up (n=33) were considered as clinically cured, the overall clinical cure rate was 93% for ciprofloxacin compared with 82% for cefpodoxime (noninferiority margin of 11%).
In an alternative intention-to-treat analysis, where patients lost to follow-up were considered to have not responded to treatment, the clinical cure rate was 83% for ciprofloxacin compared with 71% for cefpodoxime (noninferiority margin of 12%).
The researchers also report that the microbiologic cure at the first follow-up visit was 96% for ciprofloxacin compared with 81% for cefpodoxime.
Vaginal E. coli colonization was present in 82% of the women in both groups at enrollment. At the first follow-up visit, 16% of those given ciprofloxacin had vaginal E. coli compared with 40% of those treated with cefpodoxime, and the between-group difference persisted at the 30-day follow-up (29 vs 40%).
"Our findings failed to demonstrate clinical noninferiority for 100 mg cefpodoxime twice daily for 3 days compared with 250 mg of ciprofloxacin twice daily for 3 days," write Hooton et al.
The team concludes that, along with concerns about possible adverse ecologic effects that have been associated with other broad-spectrum cephalosporins, the results do not support the use of cefpodoxime as a first-line fluoroquinolone-sparing antimicrobial for acute uncomplicated cystitis.
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