NDM E. coli Cross-Resistance and Tetracyclines in AMR Infections

"NDM E. coli Cross-Resistance and Tetracyclines in AMR Infections " highlights an organism-specific pitfall that can leave clinicians without an assumed salvage option. NDM-producing E. coli presents a distinct challenge because a single mechanism can undermine both preferred agents at once, leaving clinicians without the backup they may assume they have. Dr. Pogue explains that carbapenem-resistant E. coli is more likely than Klebsiella to carry NDM, and that E. coli frequently harbors insertions in penicillin-binding protein 3 (PBP3), the primary target of both aztreonam and cefiderocol.

He describes how these PBP3 changes, sometimes compounded by additional beta-lactamases, push aztreonam-avibactam MICs toward the breakpoint in E. coli, whereas they remain low in Klebsiella pneumoniae. Dr. Pogue emphasizes that it is not yet known whether this reduces clinical efficacy but argues that it warrants caution in seriously ill patients.

Dr. Shields stresses the most important practical consequence, which is that reduced susceptibility to aztreonam-avibactam in an NDM-producing E. coli signals cross-resistance to cefiderocol. Because many laboratories do not routinely test cefiderocol, he warns that clinicians should not view it as a salvage option in this setting.

The conversation then turns to the tetracycline derivatives. Dr. Haidar positions them as alternatives when novel beta-lactams are unavailable or a patient cannot tolerate beta-lactams, noting their limited clinical evidence and low plasma and urine concentrations. Dr. Pogue adds that breakpoints may overstate how many isolates are realistically treatable. Dr. Shields describes a niche for these agents as consolidation therapy in polymicrobial intra-abdominal infections after source control, and in chronic osteomyelitis, where they also ease cost and access pressures. Clinicians should recognize NDM-producing E. coli as a distinct problem and reserve tetracyclines for carefully selected scenarios.

Dr. Shields introduces a newly approved agent with a mechanism unlike any other beta-lactam in "Cefepime-Zidebactam, a Novel Option for AMR Infections."