Treating KPC and OXA-48-Like Carbapenemase Producers

In "Treating KPC and OXA-48-Like Carbapenemase Producers," the panel steps back from NDM to review therapy for the serine carbapenemases. Treatment of Klebsiella pneumoniae carbapenemase (KPC) producers has changed little since earlier versions of the guidance, and the panel argues that this stability reflects reliable options rather than stagnation. After an extended focus on NDM, Dr. Tamma asks Dr. Pogue to review the preferred agents for KPC and OXA-48-like producers and to note anything new that has shaped his practice.

Dr. Pogue explains that the therapeutic conversation for KPC centers on ceftazidime-avibactam and meropenem-vaborbactam, both designed with this enzyme in mind. He notes that many pharmacokinetic-pharmacodynamic specialists believe meropenem-vaborbactam has characteristics that could reduce resistance emergence or improve outcomes, but acknowledges that comparative studies have not yet demonstrated a clear difference. The guidance therefore slightly favors meropenem-vaborbactam while treating both agents as reasonable, and he expects institutional preference to guide selection until larger datasets arrive.

Turning to OXA-48-like enzymes, Dr. Pogue describes them as relatively uncommon in the United States and frequently found alongside NDM in isolates producing two carbapenemases. When they do appear, he says, the preference for ceftazidime-avibactam is clear, because avibactam is distinctive in its ability to inhibit these enzymes and ceftazidime is only weakly hydrolyzed by them. The panel also addresses imipenem-relebactam, which Dr. Pogue notes was never a favored KPC option despite its in vitro activity, partly because the other agents arrived first or offered pharmacologic advantages. Its withdrawal from the US market has made the question moot domestically, although Dr. Shields reminds international viewers that it remains available elsewhere and that local access will shape how guidance recommendations apply. For KPC infections, clinicians can rely on the established agents while watching for comparative data.

Dr. Shields leads the discussion of the most mechanistically complex pathogen in the series in "Treating Difficult-to-Treat Resistant Pseudomonas aeruginosa."