Pranita D. Tamma, MD MHS

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

"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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Overall gram-negative resistance rates have plateaued, but the carbapenemases driving carbapenem resistance have shifted, with NDM expanding alongside KPC and reshaping treatment considerations across the Enterobacterales.

Shifting AMR Gram-Negative Resistance Trends in the US

Welcome back to another Contagion Live Peer Exchange series. In "Shifting AMR Gram-Negative Resistance Trends in the US," moderator Pranita D. Tamma, MD, MHS is joined by Ryan Shields, PharmD, MS, Jason Pogue, PharmD, and Ghady Haidar, MD to open the series on antimicrobial-resistant gram-negative infections. Gram-negative resistance in the United States remains entrenched, and the most consequential recent shift lies not in overall rates but in which carbapenemases are driving carbapenem resistance. Dr. Pogue frames the landscape organism by organism, noting that 

 resistance to the familiar antipseudomonal beta-lactams has held at a stubborn baseline, with local pockets running higher at referral centers.

He adds that resistance to the novel agents, while still uncommon after more than a decade of use, now appears often enough that clinicians caring for treatment-experienced patients should not assume these drugs will remain active. Carbapenem-resistant

, he says, behaves much as it always has and should be treated as carbapenem resistant until proven otherwise.

The sharpest change, in Dr. Pogue's view, is among the Enterobacterales. Extended-spectrum beta-lactamase (ESBL) production remains the most common concern for 

, but carbapenemase-producing Enterobacterales have moved away from a near-total dominance of 

carbapenemase (KPC). Beginning around 2019 and accelerating after the COVID-19 pandemic, New Delhi metallo-beta-lactamase (NDM) producers have expanded across species, now rivaling or overtaking KPC depending on the organism.

Dr. Tamma sets the stage for the series by explaining that the panel will work through the 2026 Infectious Diseases Society of America (IDSA) guidance with a focus on mechanism-directed treatment, emerging clinical evidence, and practical implementation. She signals that NDM will return as a central theme because its treatment considerations diverge so sharply from those for KPC. For clinicians, the takeaway is that knowing which resistance mechanism circulates locally now matters as much as knowing how often resistance occurs.

Dr. Haidar explains how he weighs empiric coverage for multidrug-resistant organisms in the next episode, "Empiric Risk Assessment and Carbapenemase Classification in AMR Infections."

Pranita D. Tamma, MD MHS

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