Meropenem-vaborbactam on par with ceftazidime-avibactam for survival in CRE infections, with an edge against resistance emergence

The likelihood of survival at 30 days among patients with carbapenem-resistant Enterobacterales (CRE) infections is similar for those who receive ceftazidime-avibactam or meropenem-vaborbactam. However, recurrent infections and the emergence of resistance are observed less frequently with the latter carbapenem/β-lactamase inhibitor combination, as suggested by a prospective observational study presented at IDWeek 2024.

The study’s primary outcome, 30-day mortality rate, was 16 percent in the full cohort of patients receiving either treatment. Following weighted regression, the adjusted odds ratio (aOR) for ceftazidime-avibactam vs meropenem-vaborbactam for mortality was 1.02 (95 percent confidence interval [CI], 0.88–1.20; p=0.76). [IDWeek 2024, abstract 314]

As an exploratory outcome, 31 percent of patients in the unadjusted full cohort had a recurrent infection with the same bacterial species by 90 days, of which 74.2 percent were receiving ceftazidime-avibactam vs 25.8 percent who were receiving meropenem-vaborbactam (p=0.23).

Among those with a recurrent infection, the emergence of resistance to the antibiotic used for the index infection was detected in isolates from two patients treated with ceftazidime-avibactam (8.7 percent) vs none from those treated with meropenem-vaborbactam (p=1.0).

“Putting it into context, the small sample-sized exploratory analysis suggests that if a patient presents again to medical care with a recurrent CRE infection, and if the isolate is susceptible to meropenem-vaborbactam, you may want to consider using that upfront,” said Dr Sara Karaba, an infectious diseases physician at the Johns Hopkins University School of Medicine, Baltimore, Maryland, US.

KPC-producing subgroup

To be eligible for inclusion, patients from five hospitals with infections due to CRE, as identified by clinical cultures, had to receive ceftazidime-avibactam or meropenem-vaborbactam for ≥3 days. Susceptibility to the agent used, assessed by broth microdilution, was required.

The full cohort (n=100) comprised 78 patients treated with ceftazidime-avibactam and 22 treated with meropenem-vaborbactam. Patients with isolates in which Klebsiella pneumoniae carbapenemase (KPC)-encoding genes were detected were analyzed as a subgroup of interest (n=73).

In this subgroup, 15.1 percent of patients in the full cohort had died by 30 days. The 30-day mortality was also similar between weighted patients treated with the two antibiotic combinations (aOR, 1.02, 95 percent CI, 0.85–1.23; p=0.81).

Higher barrier to resistance

Regarding the use of the two β-lactam/β-lactamase inhibitor combinations for CRE infections, only findings from retrospective cohorts were available in the literature prior to this study. These cohorts either estimated the clinical outcomes for the antibiotics separately, which did not permit direct comparisons within the same population, or compared the two within the same population but lacked genetic confirmation of KPC or other carbapenemases in more than half of the isolates. [Clin Infect Dis 2021;73:1664-1676; JAC Antimicrob Resist 2022;4:dlac022]

Of note, the only prior direct comparison also did not observe the emergence of resistance to meropenem-vaborbactam in patients with a recurrence of CRE infection, whereas 20 percent of those with recurrences after ceftazidime-avibactam treatment developed resistance. The authors attributed this to the higher barrier to resistance against KPC-producing Enterobacteriaceae of meropenem-vaborbactam. [Antimicrob Agents Chemother 2020;64:e02313-19]

“We did have a relatively small sample size, and this precluded our ability to make some adjustments, such as for the emergence of resistance,” cautioned Karaba before concluding by reiterating the study’s primary outcome. “Survival for patients with CRE infections, including those that are KPC-producing, was similar whether treated with ceftazidime-avibactam or meropenem-vaborbactam.”