NEW YORK (Reuters Health) – While carbapenems are the drugs of choice for treating infections due to Enterobacteriaceae that produce extended-spectrum beta-lactamases, treatment with combination beta-lactam/beta-lactamase inhibitor antibiotics (BLBLI) appears to be equally effective, according to a Spanish study.

“These results suggest that BLBLI, if active in vitro, should be considered a reasonable alternative to carbapenems for treating such infections under certain conditions,” comment the authors of the report in Clinical Infectious Diseases online November 4.

Dr. Jesus Rodriguez-Bano, with Hospital Universitario Virgen Macarena in Seville, and colleagues point out that extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) are now a frequent cause of infection in the community and in healthcare centers, and the increased use of carbapenems may be leading to the spread of carbapenemase-producing organisms.

The team notes that extended-spectrum beta-lactamases are inhibited by beta-lactam inhibitors, and that BLBLIs such as amoxicillin-clavulanate or piperacillin-tazobactam remain active against ESBL-producing E. coli in many areas.

To investigate the efficacy of these combinations, the authors compared outcomes of patients with bloodstream infections caused by ESBL-producing E. coli who had been treated with intravenous BLBLI or carbapenems. One cohort of 103 patients had been treated empirically (BLBLI, 72; carbapenem, 31), while another group of 174 patients had received definitive therapy (BLBLI, 54; carbapenem, 120).

The investigators found that the 30-day mortality rate with a BLBLI versus a carbapenem was 9.7% vs 19.4% in the empiric group and 9.3% vs 16.7% in the definitive group. On multivariate analysis, these rates were not statistically different.

In addition, length of hospital stay was not affected by treatment with a BLBLI or a carbapenem, Dr. Rodriguez-Bano and colleagues report.

“In conclusion,” they write, “our results suggest that AMC (amoxicillin-clavulanate) or PTZ (piperacillin-tazobactam), if used at adequate dosages, are suitable options for the definitive therapy of susceptible ESBL-E. coli strains causing bloodstream infections,” which could help prevent overuse of carbapenems.

Two editorialists comment that clinicians in the United States and elsewhere “may be able to use these data to spare the use of carbapenems for the treatment of infections caused by ESBL-producing E. coli, but this will not be easy.”

For one thing, susceptibility testing of ESBL-producing E. coli for piperacillin/tazobactam resistance often has to be done manually. For another, amoxicillin/clavulanate is not available in parenteral formulation in the US, so “ its role may be limited to ‘step-down’ oral therapy in selected cases,” Dr. Federico Perez and Dr. Robert A. Bonomo, with the Louis Stokes Cleveland VA Medical Center, Ohio, point out.

Reference:

?-Lactam/?-Lactam Inhibitor Combinations for the Treatment of Bacteremia Due to Extended-Spectrum ?-Lactamase–Producing Escherichia coli: A Post Hoc Analysis of Prospective Cohorts

Reference:

Can We Really Use ß-Lactam/ß-Lactam Inhibitor Combinations for the Treatment of Infections Caused by Extended-Spectrum ß-Lactamase–Producing Bacteria?

Clin Infect Dis 2011.