Due to its ability to acquire resistance to antimicrobial agents and its persistence on surfaces, MDR Acinetobacter baumannii evolved to become a major nosocomial pathogen, thus presenting an urgent worldwide clinical problem. Production of the carbapenem-hydrolyzing class D carbapenemases or CHDLs constitutes the major mechanism of resistance to carbapenems in A. baumannii. OXA-23 is the most prevalent CHDL found in this deadly pathogen. The Buynak laboratory has been synthesizing atypically (i.e. non-C2) substituted carbapenem antibiotics. In collaboration with Entasis and with the Rhode research group at UCF, we have recently reported improved activity (relative to meropenem) against Pseudomonas aeruginosa and Mycobacterium tuberculosis and Mycobacterium abscessus, respectively. In collaboration with the Fast research group at UT and the Palzkill group at BCM, we have also reported carbapenems with improved stability to the NDM-1 and KPC-2 carbapenemases, respectively. We now report that selected modifications of the carbapenem scaffold improve activity against carbapenem-resistant, OXA-23 producing A. baumannii. Synthesis and activity studies will be provided as well as comparisons of activity against susceptible and OXA-23 producing A. baumannii strains.

Atypically substituted carbapenem antibiotics with improved activity against OXA-23-producing Acinetobacter baumannii

2019 Spring National Meeting

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