Federal Grant Award Summary

The National Institute of Allergy and Infectious Diseases (NIAID) awarded The Children's Hospital of Philadelphia Research Institute a $448,292 Project Grant (CFDA 93.855: Allergy and Infectious Diseases Research) on July 16, 2026, with completion scheduled for June 30, 2028. This award funds investigative research using a hollow fiber infection model to examine the efficacy of ceftazidime-avibactam (CAZ-AVI) in combination with meropenem for preventing and treating infections caused by mutant KPC-producing Enterobacterales. The research addresses a critical clinical gap: while CAZ-AVI resistance emerges in approximately 15% of KPC-producing isolates during treatment, concurrent mutations in the KPC enzyme's omega-loop region paradoxically reduce carbapenem minimum inhibitory concentrations (MICs), potentially restoring meropenem susceptibility. The study will determine whether reduced carbapenem MICs render carbapenems clinically effective against mutant KPC infections—a vital question given that CAZ-AVI is frequently the only available KPC-active beta-lactam in many hospital formularies and that multiple beta-lactam/beta-lactamase inhibitor combinations under development face similar resistance risks.

This research has direct clinical applicability for treating KPC-producing infections, which carry upwards of 40% mortality rates and represent a significant public health threat. By elucidating whether carbapenem therapy can effectively address CAZ-AVI-resistant mutant KPC infections, the findings will inform treatment protocols and antimicrobial stewardship strategies for this high-consequence drug-resistant pathogen. The work is conducted at the awardee's Philadelphia, Pennsylvania facility under the investigator-initiated Project Grant mechanism, which represents the predominant funding structure within the NIAID portfolio.