Comparison of clinical outcomes for patients with monomicrobial vs polymicrobial Acinetobacter baumannii-calcoaceticus complex infections treated with sulbactam-durlobactam or colistin: A subset analysis from a phase 3 clinical trial
Sarah M McLeod, Alita A Miller, Khurram Rana, David Altarac, Samir H Moussa, Adam B Shapiro- Infectious Diseases
- Oncology
Abstract
Background
In a previous study, the efficacy and safety of sulbactam-durlobactam vs. colistin for the treatment of patients with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRABC) infections were evaluated in a randomized, controlled, Phase 3 trial. Both arms were dosed on a background of imipenem-cilastatin to treat co-infecting Gram-negative pathogens. Thirty-six percent of infections in the primary efficacy population were polymicrobial.
Methods
A subset analysis was performed to compare clinical and microbiological outcomes at Test of Cure (7 ± 2 days after the last dose) for patients with monomicrobial and polymicrobial CRABC infections. Minimal inhibitory concentrations of antibiotics against baseline isolates were determined by broth microdilution using CLSI methodology.
Results
28-day all-cause mortality, clinical cure and microbiological outcomes were similar for patients in the sulbactam-durlobactam treatment arm with either monomicrobial or polymicrobial ABC infections. Patients in the colistin arm with monomicrobial CRABC infections had higher mortality rates with worse clinical and microbiological outcomes compared to those with polymicrobial infections. For patients who received sulbactam-durlobactam, imipenem susceptibility of co-infecting Gram-negative pathogens trended with clinical benefit for patients with polymicrobial ABC infections. When tested in vitro, durlobactam restored imipenem susceptibility to the majority of co-infecting Gram-negative pathogens from the sulbactam-durlobactam arm. This phenotype appeared to be related to the clinical outcome in 13 of 15 evaluable cases.
Conclusions
These results suggest that the use of sulbactam-durlobactam plus a carbapenem could be an effective approach to treat polymicrobial infections that include CRABC, but additional clinical data are needed to demonstrate efficacy.