β-lactam/β-lactamase inhibitor combination noninferior to piperacillin/tazobactam for pneumonia

In the treatment of adults with hospital-associated (HABP) or ventilator-associated bacterial pneumonia (VABP), the β-lactam/β-lactamase inhibitor combination imipenem/cilastatin/relebactam appears to be as good as piperacillin/tazobactam, with similar safety profiles, according to a phase III trial.

The trial included 270 critically ill adult patients with HABP/VABP enrolled across 53 sites in eight countries, including China (n=204), Brazil (n=3), France (n=8), Mexico (n=9), Philippines (n=8), Russia (n=12), Romania (n=7), and Ukraine (n=2). These patients were randomly assigned to treatment with either intravenous imipenem/cilastatin/relebactam 500 mg/250 mg (n=134) or piperacillin/tazobactam 4,000 mg/500 mg (n=136) every 6 h for 7–14 days.

The primary endpoint was 28-day all-cause mortality. Secondary endpoints included clinical response, microbiological response, and adverse event (AE) incidence.

The mean patient age was 57.6 years, and the majority were men (73.3 percent). Of the patients, 55.6 percent had nonventilated HABP, 15.2 percent had ventilated HABP, and 29.3 percent had VABP. More than half of the patients in each treatment group had an APACHE II score of ≥15 (54.5 percent in the imipenem/cilastatin/relebactam group; 55.1 percent in the piperacillin/tazobactam group).

Imipenem/cilastatin/relebactam showed noninferiority to piperacillin/tazobactam in terms of 28-day all-cause mortality (11.2 percent vs 5.9 percent; adjusted difference, 5.2 percent, 95 percent confidence interval, −1.5 to 12.4). Favourable clinical and microbiological responses were similar between the two treatment groups.

AEs leading to death were largely in line with patients’ pre-existing or underlying illness.