Authors
Stefano Mancini, Linda Mueller, Silvio D Brugger, Helena M B Seth-Smith, Peter M Keller, Natalia Kolesnik-Goldmann, Muhammad Ali Syed, Tim Roloff, Oliver Nolte
Published in
Microbiology spectrum. Pages e0223526. Sep 23, 2026. Epub Sep 23, 2026.
Abstract
Pseudomonas aeruginosa can develop carbapenem resistance through chromosomal mechanisms and/or by acquiring plasmid-mediated carbapenemases, including the most prevalent metallo-β-lactamases (MBLs) and/or extended-spectrum β-lactamases (ESBLs). Conventional β-lactam susceptibility testing does not reliably discriminate MBL/ESBL-producing carbapenem-resistant P. aeruginosa (MBL/ESBL-CRPA) from non-carbapenemase-producing isolates, here referred to as AmpC-hyperproducers. However, these groups exhibit distinct susceptibility patterns to novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations, including ceftolozane/tazobactam (C/T), ceftazidime/avibactam (C/A), imipenem/relebactam (I/R), and meropenem/vaborbactam (M/V). We investigated potential screening cut-offs for detecting MBL/ESBL production in CRPA using the VITEK-2 AST-N443 and Phoenix NMIC-486 cards. Antimicrobial susceptibility testing was performed using the VITEK-2 AST-N443 and Phoenix NMIC-486 cards on 135 whole-genome-sequenced international CRPA isolates resistant by disc diffusion to ceftazidime, cefepime, imipenem, and/or meropenem. The collection included 71 MBL-producing isolates, of which nine co-produced ESBLs, as well as one KPC-2-, one GES-5-, and twelve ESBL-only producers. The remaining 50 represented AmpC-hyperproducers. MIC distributions were analyzed to identify discriminatory screening cut-offs. C/T was the most discriminatory BL/BLI combination for differentiating MBL/ESBL-CRPA from AmpC-hyperproducers. For the VITEK-2 AST-N443, a C/T MIC ≥32 mg/L achieved 100% sensitivity for MBL±ESBL detection (71/71) and 91.7% sensitivity for ESBL-only producers (11/12), with 82% specificity (41/50). For the Phoenix NMIC-486, a C/T MIC >8 mg/L achieved 100% sensitivity for both MBL and ESBL detection, with 80% specificity (40/50). Combining additional BL/BLI agents did not further improve specificity. Elevated C/T MICs represent reliable phenotypic screening markers for MBL and ESBL production in CRPA using both the VITEK-2 AST-N443 and Phoenix NMIC-486 systems.IMPORTANCERapid identification of the underlying resistance mechanism in carbapenem-resistant Pseudomonas aeruginosa (CRPA) is essential for effective treatment and infection control. Differentiating high-level resistance acquired via plasmid-borne carbapenemases and/or extended-spectrum β-lactamases (ESBLs) from resistance driven by intrinsic mechanisms, including AmpC-type β-lactamase hyperproduction, remains challenging because conventional antimicrobial susceptibility testing (AST) using classic β-lactams cannot reliably separate these phenotypes. This distinction is relevant because many recently introduced β-lactam/β-lactamase inhibitor combinations are inactive against metallo-β-lactamase (MBL) carbapenemase-producing isolates but may remain active against strains in which resistance is driven by intrinsic mechanisms. Detection of acquired carbapenemases may also trigger enhanced infection-control measures and epidemiological investigations. Our study identifies reliable screening cut-offs for MBL- and ESBL-production in CRPA using standard VITEK 2 and Phoenix automated AST panels. This readily available approach may accelerate detection, support routine laboratory workflows, reduce unnecessary confirmatory testing, and facilitate earlier targeted therapy and infection-control interventions in laboratories using these systems worldwide without requiring additional specialized testing or infrastructure.
PMID:
42775889
Bibliographic data and abstract were imported from PubMed on 23 Sep 2026.
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