Real-World Performance of Susceptibility Testing for Ceftolozane/Tazobactam against Non-Carbapenemase- Producing Carbapenem-Resistant Pseudomonas aeruginosa

Lina Rivas, Manuel Alcalde-Rico, José R.W. Martínez, María Victoria Moreno, Pamela Rojas, Aniela Wozniak, Patricia García, Jorge Olivares-Pacheco, William R. Miller, Cesar A. Arias, Ayesha Khan, José M. Munita

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Ceftolozane/tazbactam (C/T) is a potent anti-pseudomonal agent that has clinical utility against infections caused by non-carbapenemase, producing-carbapenem-resistant Pseudomonas aeruginosa (non-CP-CR-PA). Accurate, precise, and reliable antimicrobial susceptibility testing (AST) is crucial to guide clinical decisions. However, studies assessing the performance of different AST methods against non-CP-CR-PA (the main clinical niche for C/T), are lacking. Here, we evaluated performance of gradient strips (Etest and MIC test strip [MTS], and disk diffusion [DD]) using CLSI breakpoints. Additionally, we assessed the performance of DD using EUCAST breakpoints. For all susceptibility tests, we used a collection of 97 non-CP-CR-PA clinical isolates recovered from 11 Chilean hospitals. Both gradient strips and DD had acceptable performance when using CLSI breakpoints, yielding a categorical agreement (CA) of >90% and 92%, respectively. In contrast, DD using EUCAST breakpoints performed suboptimally (CA 81%). MTS yielded a higher essential agreement (EA, >90%) than Etest (84%). Importantly, the performance of all methods varied significantly when the isolates were stratified by their degree of susceptibility to other anti-pseudomonal β-lactams. All methods had 100% CA when testing isolates that were pan-susceptible to all β-lactams (Pan-β-S). However, the CA markedly decreased when testing isolates resistant to all β-lactams (Pan-β-R). Indeed, the CA was 81% for Etest (six errors), 78% for MTS (seven errors), and 78% and 56% for DD when using CLSI (seven errors) or EUCAST breakpoints (14 errors), respectively. Our results suggest that all manual AST methods have strikingly decreased performance in the context of Pan-β-R P. aeruginosa with potentially major clinical implications.

Original languageEnglish (US)
Article numbere01657-21
Pages (from-to)e0165721
JournalAntimicrobial Agents and Chemotherapy
Issue number1
StatePublished - Jan 18 2022


  • Antibiotic resistance
  • Antimicrobial activity
  • Beta-lactams
  • Bloodstream infections
  • Carbapenem-resistant P. aeruginosa
  • Ceftolozane/tazobactam
  • Gram-negative bacteria
  • Infectious disease
  • Multidrug resistance
  • Non-carbapenemase-producing
  • Pseudomonas
  • Pseudomonas aeruginosa
  • Susceptibility testing
  • Carbapenems/pharmacology
  • Humans
  • Anti-Bacterial Agents/pharmacology
  • Microbial Sensitivity Tests
  • Cephalosporins/pharmacology
  • Tazobactam/pharmacology
  • Pseudomonas Infections/drug therapy

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Infectious Diseases
  • Pharmacology


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