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Data do not support piperacillin-tazobactam for drug-resistant BSIs
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The risk for mortality was more than three times higher among patients with bloodstream infections caused by drug-resistant Escherichia coli or Klebsiella pneumoniae who received treatment with piperacillin-tazobactam compared with those who received meropenem, according to results of a randomized controlled trial.
WHO reports that E. coli and K. pneumoniae are two of the most common antibiotic-resistant pathogens found worldwide. When they enter the bloodstream, E. coli and K. pneumoniae can result in severe illness and mortality, Patrick Harris, MBBS, infectious disease physician at Princess Alexandra Hospital and postgraduate research fellow at the Center of Clinical Research at the University of Queensland, told Infectious Disease News.
“In recent decades, these bacteria have become increasingly resistant to common antibiotics, such as penicillins or cephalosporins, primarily by the acquisition of genes that encode for enzymes — beta-lactamases — that can inactivate these antibiotics and render these organisms resistant to treatment,” he said.
The prevalence of extended-spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumoniae has dramatically increased since the 1990s, according to Harris. Carbapenems, such as meropenem, are among the few remaining treatments for these strains.
“The increasing presence of ESBL-producers in our hospitals and community has resulted in a sharp rise in the use of carbapenems,” Harris said. “Excessive reliance on carbapenems may be providing selection ‘pressure’ for this emerging resistance problem. As such, there is a need to seek alternatives to carbapenems to treat serious infections caused by ESBL-producers.”
Harris and colleagues conducted a randomized controlled trial to determine whether piperacillin-tazobactam could serve as a “carbapenem-sparing” treatment option for bloodstream infections (BSIs) caused by ESBL-producing K. pneumoniae and E. coli. The researchers randomly assigned 379 patients in nine countries to receive 4.5 g of piperacillin-tazobactam every 6 hours (n = 188) or 1 g of meropenem every 8 hours (n = 191) for at least 4 days. One patient was lost to follow-up and excluded from the main analysis. The primary outcome was the difference in 30-day mortality between the groups.
The results, which were presented at the European Congress of Clinical Microbiology and Infectious Diseases, showed that most BSIs were health care associated (56.4%), originated in the urinary tract (60.9%) and were caused by E. coli (86.5%).
Overall, piperacillin-tazobactam was inferior to meropenem, Harris said. The 30-day mortality rate was 12.3% in the piperacillin-tazobactam arm vs. 3.7% in the meropenem arm, yielding a risk difference of 8.6% (95% CI, 3.4-14.5). Patients who received piperacillin-tazobactam were 3.4 (95% CI, 1.5-7.6) times more likely to die than patients who received meropenem, according to the researchers.
“These results, therefore, would not support the use of piperacillin-tazobactam for this indication,” Harris said. – by Stephanie Viguers
Reference:
Harris P, et al. Abstract O1121. Presented at: European Congress of Clinical Microbiology and Infectious Diseases; April 21-24, 2018; Madrid.
Disclosure: Harris reports no relevant financial disclosures.