By Gina Shaw
Obesity has been associated with treatment failure in patients receiving beta-lactam antibiotics, including novel beta-lactam/beta-lactamase inhibitor combinations. Therefore, it is important that research is done to optimize therapy regimens.
New abstracts from investigators at Wayne State University, in Detroit, presented at MAD-ID 2025, in Orlando, Fla., provide more evidence of this in two-drug combinations where the data have been lacking: meropenem-vaborbactam (M/V; Vabomere, Melinta Therapeutics) and imipenem-cilastatin-relebactam (IMI/REL; Recarbrio, Merck).
In the first study (abstract 72), investigators performed a retrospective analysis of data from two multicenter observational studies conducted in the United States between 2017 and 2024. Overall, 226 patients treated with M/V were included (nonobese, n=131; obese, n=95). In both groups, most patients were admitted to the ICU within 24 hours of the index culture collection (58%) and had lower tract respiratory infections (66%). Klebsiella pneumoniae was the most frequently targeted bacteria (41%).
Clinical success was numerically higher in the nonobese group compared with those who were obese, although this was not statistically significant (69.5% vs. 78.6%; P=0.118). However, 30-day all-cause mortality was significantly higher in the obese group (16.0% vs. 31.6%; P=0.006). After propensity weighting, obesity and pneumonia were associated with increased odds of 30-day all-cause mortality. While there was no statistically significant difference in 30-day microbiological recurrence (9/131 nonobese vs. 9/95 obese), there was a significant difference in the rate of symptoms recurring (47% in the nonobese group vs. 100% in the obese group; P=0.010).
Findings were similar in the second study (abstract 71), which assessed clinical outcomes of the newer combination IMI/REL. Overall, 151 patients participated in the study (44 obese; 107 nonobese). Most patients in both groups had lower respiratory tract infections, with the most common target being Pseudomonas aeruginosa.
“Clinical success was numerically higher among nonobese patients, 72.0% versus 65.9%, but that did not reach statistical significance,” presenting author Mohammed Al Musawa, PharmD, BCIDP, a postdoctoral fellow at Wayne State University, told Infectious Disease Special Edition. “Thirty-day all-cause mortality and 30-day microbiological recurrence were higher in the obese group without reaching significance. This may be due to the relatively small sample size of obese patients in this study population.”
Limited data exist to guide the dosing of novel beta-lactam combinations in obese patients. “We know that obesity affects the pharmacokinetics of antibiotics, including beta-lactams such as ceftazidime and tazobactam, and this study further reinforces that finding in two additional beta-lactam combinations,” Dr. Al Musawa said. “Obesity has worse outcomes in both combinations, which highlights the need for further research to optimize treatment strategies in this patient population.”
The study was funded by an investigator-initiated grant from Melinta Therapeutics.
