Three studies map how superbugs evade antibiotics and spread to vulnerable patients
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To defeat multidrug-resistant superbugs, bacterial defenses must be confronted wherever they may emerge, from basic genetic mutations in a laboratory to complex real-world transmission in hospital rooms. A new trio of studies published in Antimicrobial Agents and Chemotherapy and researched by the laboratory of Barry N. Kreiswirth, Ph.D., at the Hackensack Meridian Center for Discovery and Innovation (CDI) demonstrates how an integrated approach might yet expose and overcome these diverse survival mechanisms.
The Kreiswirth Lab continues to focus on different aspects of antimicrobial resistance (AMR), and Kreiswirth himself has driven or collaborated on these AAC studies.
"These studies collectively show how we are tracking and better understanding the many forms of drug resistance that bacterial pathogens evolve, given the opportunity," said Kreiswirth, a member of the CDI and professor at the Hackensack Meridian School of Medicine.
The three papers, published together, explore bacterial resistance across three distinct dimensions.
In the first paper, the team used high-density transposon sequencing (TnSeq) to map genes governing susceptibility in carbapenem-resistant Klebsiella pneumoniae. The scientists, led by Zhichen Zhu, Ph.D., Liang Chen, Ph.D., of the University at Buffalo, and Kreiswirth, discovered that when superbugs alter their outer surface to evade viral phages, they pay an evolutionary price: Losing these surface receptors resensitizes the bacteria to last-line antibiotics like meropenem, colistin and cefiderocol.
The second publication shows how cefiderocol—a novel siderophore cephalosporin that exploits bacterial iron uptake channels—can be evaded by so-called "superbugs." The team identified a multilayered defense network involving cell envelope homeostasis and blaKPC-3 β-lactamases. Deleting blaKPC-3 in resistant strains reduced drug minimum inhibitory concentrations fourfold, showing how low intracellular drug levels allow even modest enzyme activity to drive high-level resistance. The lead authors are Kevin J. Rome, Ph.D., Austin J. Terlecky and Kreiswirth.
The third paper documented how the CDI team and colleagues tracked 159 acute leukemia and myelodysplastic syndrome patients undergoing chemotherapy. The researchers found that 20% of patients colonized with extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) developed matching bloodstream infections during neutropenia. Whole-genome sequencing confirmed a 100% match between colonizing and bloodstream strains, proving that targeted screening can effectively guide prophylactic antibiotics while preventing unnecessary overuse. This prospective study was led by Kate Stoeckle, M.D., Michael J. Satlin, M.D., Lars F. Westblade, Ph.D., all of Weill Cornell Medicine, Chen and Kreiswirth.
"By bridging molecular genetics, genomics and clinical epidemiology, Kreiswirth and his lab continue to uncover the underlying rules of bacterial survival—which are pointing the way toward better clinical outcomes," said David Perlin, chief scientific officer and executive vice president of the CDI.
Publication details
Zhichen Zhu et al, Genome-wide transposon screening uncovers phage resistance mechanisms and bidirectional effects on antibiotic susceptibility in carbapenem-resistant Klebsiella pneumoniae, Antimicrobial Agents and Chemotherapy (2026). DOI: 10.1128/aac.00506-26
Kevin J. Rome et al, Intrinsic resistance networks shape cefiderocol susceptibility in ST258 Klebsiella pneumoniae, Antimicrobial Agents and Chemotherapy (2026). DOI: 10.1128/aac.00197-26
Kate Stoeckle et al, Colonization with extended-spectrum and AmpC β-lactamase-producing Enterobacterales and bacteremia risk in patients with acute leukemia who receive induction chemotherapy without fluoroquinolone prophylaxis, Antimicrobial Agents and Chemotherapy (2026). DOI: 10.1128/aac.01738-25
Journal information: Antimicrobial Agents and Chemotherapy
Clinical categories
Infectious diseasesLaboratory medicineClinical pharmacology Provided by Hackensack Meridian Health Who's behind this story?
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