Aztreonam-Avibactam for AMR NDM-Producing Enterobacterales

In "Aztreonam-Avibactam for AMR NDM-Producing Enterobacterales," the panel examines the first of two preferred agents for NDM producers.

Aztreonam-avibactam offers a rational, pharmacologically optimized answer to NDM-producing Enterobacterales, even though clinical efficacy data specific to these organisms remain thin. Dr. Pogue explains the logic of the combination, in which avibactam neutralizes the serine beta-lactamases that commonly accompany NDM, leaving aztreonam, a monobactam that NDM cannot effectively hydrolyze, free to act.

He describes high in vitro activity against NDM-producing Enterobacterales overall, with somewhat lower activity in E. coli, along with good coverage of coexisting ESBL, KPC, and OXA-48-like enzymes. Turning to clinical evidence, Dr. Pogue characterizes the pivotal randomized trial in complicated intra-abdominal infection and hospital-acquired pneumonia as most valuable for its safety data, because few enrolled patients had metallo-beta-lactamase producers.

He argues that the strongest support comes from observational experience with ceftazidime-avibactam given together with aztreonam, which outperformed colistin-based regimens. Dr. Tamma observes that new agents are often approved in studies that enroll few resistant organisms, leaving clinicians to build the evidence base after approval. Dr. Pogue adds that the fixed combination delivers more avibactam than the older approach.

Dr. Shields contrasts the two strategies from an implementation standpoint. He describes the logistical burden of coadministering two separate antibiotics, the difficulty of testing susceptibility to a two-drug combination, and the suboptimal avibactam exposure of the improvised regimen, all of which the formulated product resolves. He acknowledges the tradeoff that most real-world data still come from the older combination. Dr. Tamma notes that the guidance expresses a slight preference for the formulated product on practical and pharmacologic grounds, making it a reasonable default for NDM producers.

The second preferred agent comes under scrutiny in "Reassessing Cefiderocol for NDM-Producing AMR Infections," led by Dr. Haidar.