Potential Alternative to Carbapenems for Hospital-Acquired Pneumonia?

Ceftazidime-avibactam, a new antibiotic combination, may be an effective alternative to carbapenem meropenem for the treatment of hospital-acquired pneumonia associated with antimicrobial-resistant Gram-negative pathogens, according to a recently-published study in The Lancet Infectious Diseases.

In the study, researchers assessed the efficacy and safety of ceftazidime-avibactam in patients with pneumonia originating from the hospital, including ventilator-associated pneumonia, compared with meropenem. Adult patients were randomly assigned to 2000 mg ceftazidime and 500 mg avibactam (by 2 hour intravenous infusions every 8 hours) or 1000 mg meropenem (by 30-minute intravenous infusions every 8 hours) for 7-14 days.

The researchers assessed the efficacy by clinical cure at the test-of-cure visit, 21-25 days after randomization.

Overall, 879 patients were included in the study, which was conducted between April 13, 2013 and December 11, 2015. Of these patients, 808 patients were included in the safety population, 726 were included in the clinically-modified intention-to-treat population, and 527 were included in the clinically evaluable population. Gram-negative pathogens treated in the study population included Klebsiella pneumoniae (37%) and Pseudomonas aeruginosa (30%), and 28% were ceftazidime-non-susceptible.

In the group treated with ceftazidime-avibactam, 68.6% of patients were clinically cured, compared with 73% of patients in the meropenem-treated group. Adverse events occurred in 75% of patients treated with ceftazidime-avibactam compared with74% in the meropenem group.

The researchers concluded that ceftazidime-avibactam was non-inferior to meropenem for the treatment of patients with hospital-acquired pneumonia, indicating that ceftaizidime-avibactam may serve as a potential alternative to carbapenems in some patients.

Reference

Torres A, Zhong N, Pachl J, et al. Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect Dis. 2017. DOI: http://dx.doi.org/10.1016/S1473-3099(17)30747-8.