Dosing Novel AMR Agents During Renal Replacement Therapy

This episode, "Dosing Novel AMR Agents During Renal Replacement Therapy," addresses a recurring bedside challenge for clinicians caring for the sickest patients. Getting antimicrobial exposure right in critically ill patients with fluctuating renal function is as consequential as choosing the right drug, particularly when MICs already sit close to the breakpoint. Dr. Tamma asks the two pharmacists on the panel how clinicians should approach dosing of newer agents in patients receiving continuous renal replacement therapy (CRRT).

Dr. Shields explains that cefiderocol is unusual in carrying specific CRRT dose adjustments in its label, keyed to effluent flow rate, which gives clinicians a clear framework. Aztreonam-avibactam lacks equivalent labeled guidance, but he describes preliminary ex vivo modeling presented at IDWeek suggesting that effluent rate, rather than filter type, drives clearance, and that a loading dose remains necessary.

He offers a practical principle for clinicians caught between dosing tiers, which is to round up, because CRRT is a recognized risk factor for treatment failure and resistance and beta-lactams carry a wide safety margin. Dr. Haidar urges physicians to rely on pharmacy colleagues for these decisions, recalling that older regimens for KPC often failed partly because drugs penetrated poorly to the site of infection.

Dr. Pogue adds two further considerations. He notes that cefiderocol's label also addresses augmented renal clearance, which is especially relevant when exposures against NDM producers are borderline from the outset. He also cautions that acute kidney injury in critically ill patients often resolves rapidly with resuscitation, so reducing doses too early risks underexposure during the most critical window. The shared message is that clinicians should dose aggressively at the outset in critically ill patients and partner closely with pharmacists, scaling back only once renal function has stabilized.

In "NDM E. coli Cross-Resistance and Tetracyclines in AMR Infections," Dr. Pogue explains why NDM-producing E. coli can defeat both preferred agents at once.