MADRID – A study designed to test the benefit of piperacillin-tazobactam in cephalosporin-resistant bloodstream infections has showed just the opposite: The combination can be fatal for these patients, conferring a threefold increased risk of death compared with meropenem.
The piperacillin-tazobactam combination (PTZ) was associated with a significantly higher 30-day mortality than that of meropenem (12.3% vs. 3.7%; RR 3.4),, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
The number needed to harm with PTZ treatment was 12, said Dr. Harris of the University of Queensland, Australia.
“This was really not the result we wanted. We were expecting to show noninferiority, but the answer we did get was quite compelling. We have to say that in patients with these kinds of bloodstream infections, the use of piperacillin-tazobactam is definitely not supported.”
The signal came on strongly and quickly in the 32-country, he said. An independent data safety monitoring board stopped the study at 75% recruitment after reviewing the alarming interim results last summer.
The trial was designed to test a seemingly sound hypothesis. PTZ is an effective weapon against increasingly extended spectrum beta-lactamase–producing (ESBL) Escherichia coli and Klebsiella infections. These have long been treated with carbapenems, including meropenem, but the widespread global use of that class is putting heavy environmental pressure on these bacteria and creating carbapenem resistance, Dr. Harris said.
“Carbapenems have for many years been the top therapy for these infections, but it may well be a strong selection driver for carbapenem resistance in Gram negative bacilli. We should be thinking about carbapenem-sparing therapy, and it seemed that piperacillin-tazobactam could be useful here.”