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IDSA 2026 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections - Episode 2

Empiric Risk Assessment and Carbapenemase Classification in AMR Infections

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Empiric use of novel agents should follow patient-level risk and unit-level epidemiology, while a shared vocabulary for carbapenem-resistant Enterobacterales and their carbapenemases underpins every subsequent treatment decision.

"Empiric Risk Assessment and Carbapenemase Classification in AMR Infections" examines when clinicians should reach for a novel agent before cultures return. Deciding when to start a novel agent empirically is a risk calculation, and that calculation depends on host, exposure history, and local epidemiology rather than any single rule. Dr. Haidar, a transplant infectious diseases physician, describes a spectrum of patients that runs from the stable outpatient with cystitis to the chronically critically ill patient with recurrent ventilator-associated pneumonia.

At one end, he argues, empiric coverage of a multidrug-resistant organism (MDRO) is rarely critical, although a recent rectal surveillance swab showing carbapenem-resistant Enterobacterales (CRE) can lower the threshold. At the other end, a known colonizing organism makes regimen design comparatively straightforward. Most patients, however, sit in a gray zone shaped by recent antibiotic exposure, travel to hyperendemic regions, or admission to a unit with high resistance rates.

In those cases, Dr. Haidar urges clinicians to study unit-level antibiograms rather than hospital-wide data, and to start an agent covering the likely MDRO when local rates cross a meaningful threshold. He notes that today's broader armamentarium makes early de-escalation feasible. Dr. Tamma reinforces that responsible use includes stopping or narrowing therapy as soon as the data allow.

Dr. Shields then untangles the terminology that runs through the rest of the series. He explains that CRE is a phenotypic label encompassing both non-carbapenemase-producing isolates, which typically pair ESBL or AmpC enzymes with permeability changes, and carbapenemase producers. Among the latter, he outlines the three groups most clinicians will encounter, namely KPC, NDM, and OXA-48-like enzymes, and how they differ by molecular class. The practical message is that empiric choices should follow patient-level risk, while mechanism-level vocabulary anchors every treatment decision that follows.

Up next, "Rapid Diagnostics for AMR Gram-Negative Bloodstream Infections " follows a positive blood culture from incubation to susceptibility results with Dr. Shields.

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