Beta-Lactam Therapy of Urinary Tract Infection Fails Again

By Stan Deresinski, MD, FACP, FIDSA, Clinical Professor of Medicine, Stanford University, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.

Source: Hooton TM, Roberts PL, Stapleton AE. Cefpodoxime vs ciprofloxacin forshort-course treatment of acute uncomplicated cystitis: a randomized trial. JAMA 2012;307:583-9.

The increasing prevalence of antibiotic resistance in urinary pathogens has led Hooton and colleagues to examine the efficacy of a relatively broad spectrum orally administered cephalosporin in the treatment of uncomplicated cystitis. They randomized 300 women ages 18 to 50 years to receive, for 3 days, either ciprofloxacin (500 mg twice daily) or cefpodoxime proxetil (100 mg twice daily) in a double blind fashion. Three-fourths of infections were due to Escherichia coli, while Staphylococcus saprophyticus, Klebsiella species, Proteus mirabilis, and Streptococcus agalactiae each accounted for 1%-3%. Four percent of isolates were nonsusceptible to ciprofloxacin while 8% were nonsusceptible to cefpodoxime.

In an intent-to-treat analysis, the clinical cure rate at 30 days was 93% (139/150) among ciprofloxacin recipients and 82% (123/150) among cefpodoxime recipients; the difference of 11% (95% CI, 3% - 18%) thus failing to meet the preset criterion for noninferiority requiring that the upper limit of the confidence interval be <10%. Ciprofloxacin therapy was associated with a 96% (123/128) microbiological eradication rate while this was achieved in only 81% (104/129) of those given cefpodoxime for a difference of 15% (95% CI, 8%-23%). Ciprofloxacin was also significantly more successful at eliminating vaginal colonization with E. coli.

Commentary

The current IDSA recommendations for antibiotic choice in the empiric treatment of uncomplicated cystitis include the following options: nitrofurantoin, trimethoprim-sulfamethoxazole (if local resistant rates do not exceed 20%), fosfomycin, and pivmecillinam. The last is not available in North America and comes with a warning regarding lower efficacy than some other choices, as well as avoidance if early pyelonephritis is suspected. Fluoroquinolones are to be considered alternative therapies, both because of fear of "collateral damage" and a desire to preserve their efficacy.

β-lactam antibiotics have previously demonstrated efficacy that is inferior to comparators in clinical trials. As a consequence the IDSA guideline1 states the following: "β-lactam agents, including amoxicillin-clavulanate, cefdinir, cefaclor, and cefpodoxime-proxetil, in 3–7-day regimens are appropriate choices for therapy when other recommended agents cannot be used. Other β-lactams, such as cephalexin, are less well studied but may also be appropriate in certain settings (B-III). The β-lactams generally have inferior efficacy and more adverse effects, compared with other UTI antimicrobials (B-I). For these reasons, β-lactams other than pivmecillinam should be used with caution for uncomplicated cystitis. Amoxicillin or ampicillin should not be used for empirical treatment given the relatively poor efficacy, as discussed in the 1999 guidelines and the very high prevalence of antimicrobial resistance to these agents worldwide."

This study by Hooton and colleagues confirms that cefpodoxime should only be prescribed for the treatment of cystitis when more effective recommended antibiotics cannot be used.

Reference

  1. Gupta K, et al; Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52:e103-20.