Dataset Information

Susceptibility profile and β-lactamase content of global Pseudomonas aeruginosa isolates resistant to ceftolozane/tazobactam and/or imipenem/relebactam-SMART 2016-21.

ABSTRACT:

Objectives

To determine susceptibility profiles and β-lactamase content for ceftolozane/tazobactam-resistant and imipenem/relebactam-resistant Pseudomonas aeruginosa isolates collected in eight global regions during 2016-21.

Methods

Broth microdilution MICs were interpreted using CLSI breakpoints. PCR to identify β-lactamase genes or WGS was performed on selected isolate subsets.

Results

Ceftolozane/tazobactam-resistant [from 0.6% (Australia/New Zealand) to 16.7% (Eastern Europe)] and imipenem/relebactam-resistant [from 1.3% (Australia/New Zealand) to 13.6% (Latin America)] P. aeruginosa varied by geographical region. Globally, 5.9% of isolates were both ceftolozane/tazobactam resistant and imipenem/relebactam resistant; 76% of these isolates carried MBLs. Most ceftolozane/tazobactam-resistant/imipenem/relebactam-susceptible isolates carried ESBLs (44%) or did not carry non-intrinsic (acquired) β-lactamases (49%); 95% of imipenem/relebactam-resistant/ceftolozane/tazobactam-susceptible isolates did not carry non-intrinsic β-lactamases. Isolates that carried indicators of strong PDC (Pseudomonas-derived cephalosporinase) up-regulation without a mutation known to expand the spectrum of PDC, or non-intrinsic β-lactamases, showed an 8-fold increase in ceftolozane/tazobactam modal MIC; however, this rarely (3%) resulted in ceftolozane/tazobactam resistance. Isolates with a PDC mutation and an indicator for PDC upregulation were ceftolozane/tazobactam non-susceptible (MIC, ≥ 8 mg/L). MICs ranged widely (1 to >32 mg/L) for isolates with a PDC mutation and no positively identified indicator for PDC up-regulation. Imipenem/relebactam-resistant/ceftolozane/tazobactam-susceptible isolates without non-intrinsic β-lactamases frequently (91%) harboured genetic lesions implying OprD loss of function; however, this finding alone did not account for this phenotype. Among imipenem-non-susceptible isolates without non-intrinsic β-lactamases, implied OprD loss only shifted the distribution of imipenem/relebactam MICs up by 1-2 doubling dilutions, resulting in ∼10% imipenem/relebactam-resistant isolates.

Conclusions

P. aeruginosa with ceftolozane/tazobactam-resistant/imipenem/relebactam-susceptible and imipenem/relebactam-resistant/ceftolozane/tazobactam-susceptible phenotypes were uncommon and harboured diverse resistance determinants.

SUBMITTER: Karlowsky JA

PROVIDER: S-EPMC10306085 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Susceptibility profile and β-lactamase content of global <i>Pseudomonas aeruginosa</i> isolates resistant to ceftolozane/tazobactam and/or imipenem/relebactam-SMART 2016-21.

Karlowsky James A JA Lob Sibylle H SH Estabrook Mark A MA Siddiqui Fakhar F DeRyke C Andrew CA Young Katherine K Motyl Mary R MR Sahm Daniel F DF

JAC-antimicrobial resistance 20230628 3

<h4>Objectives</h4>To determine susceptibility profiles and β-lactamase content for ceftolozane/tazobactam-resistant and imipenem/relebactam-resistant <i>Pseudomonas aeruginosa</i> isolates collected in eight global regions during 2016-21.<h4>Methods</h4>Broth microdilution MICs were interpreted using CLSI breakpoints. PCR to identify β-lactamase genes or WGS was performed on selected isolate subsets.<h4>Results</h4>Ceftolozane/tazobactam-resistant [from 0.6% (Australia/New Zealand) to 16.7% (Ea ...[more]

PMID: 37388237

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