By 30 days, 23 of those randomized to the combination therapy (12.3%) and seven (3.7%) of those randomized to meropenem had died – a significant 8.6% difference. This translated to more than a threefold increase in the risk of death for those taking the combination (RR 3.4; P = .002). The number needed to harm was just 12.
All of the secondary endpoints also favored meropenem, although the differences were not statistically significant. Patients taking meropenem experienced clinical and microbiological improvement a mean of 1 day sooner (2 vs. 3 days). Microbiological relapse occurred in 2% of those taking meropenem compared with 4.8% of those taking PTZ. The meropenem group was also less likely to develop a multidrug resistant organism or C. difficile infection (4.2% vs. 8%).
The investigators performed several subgroup analyses looking for other trends in 30-day mortality. The difference remained significant no matter how the groups were analyzed.
“Patients with urinary tract infections had a slightly lower risk of mortality, but even after adjusting for risk in several multivariate regression models, the increased risk of 30-day mortality remained,” Dr. Harris said.
The Australasian Society for Antimicrobials and the International Society for Chemotherapy funded the work. Dr. Harris reported having no financial declarations.