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. 2023 Jun 28;5(3):dlad080.
doi: 10.1093/jacamr/dlad080. eCollection 2023 Jun.

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

James A Karlowsky  1   2 , Sibylle H Lob  1 , Mark A Estabrook  1 , Fakhar Siddiqui  3 , C Andrew DeRyke  3 , Katherine Young  3 , Mary R Motyl  3 , Daniel F Sahm  1
Affiliations

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

James A Karlowsky et al. JAC Antimicrob Resist. .

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.

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Figures

Figure 1.
Figure 1.
Global region proportions of P. aeruginosa isolates that were ceftolozane/tazobactam resistant and imipenem/relebactam resistant, cumulative 2016–21 data. aExcludes isolates from Australia and New Zealand. AP, Asia/Pacific; ANZ, Australia/New Zealand; W EUR, Western Europe; E EUR, Eastern Europe; LA, Latin America; MEA, Middle East/Africa; US, United States of America; CAN, Canada.
Figure 2.
Figure 2.
Estimated proportion of isolates carrying carbapenemases or non-intrinsic Class A β-lactamases among P. aeruginosa isolates collected by the global SMART surveillance programme from 2016 to 2021. aIncludes 53 isolates that co-carried a GES carbapenemase (E EUR, n = 47; MEA, n = 6) and 49 isolates that co-carried KPC (AP, n = 5; LA, n = 43; USA, n = 1) among a total of 1730 MBL-positive isolates. bExcludes Australia and New Zealand. cExcludes isolates not available for molecular characterization. AP, Asia/Pacific; ANZ, Australia/New Zealand; W EUR, Western Europe; E EUR, Eastern Europe; LA, Latin America; MEA, Middle East/Africa; US, United States of America; CAN, Canada.
Figure 3.
Figure 3.
Prevalence of ceftolozane/tazobactam-resistant/imipenem/relebactam-susceptible, imipenem/relebactam-resistant/ceftolozane/tazobactam-susceptible and ceftolozane/tazobactam-resistant/imipenem/relebactam-resistant phenotypes among P. aeruginosa isolates collected by the global SMART surveillance programme from 2016 to 2021. AP, Asia/Pacific; W EUR, Western Europe; E EUR, Eastern Europe; LA, Latin America; MEA, Middle East/Africa; US/CAN, United States of America and Canada. AP includes Australia and New Zealand (ANZ) in this figure. C/T, ceftolozane/tazobactam; IMI/REL, imipenem/relebactam.
Figure 4.
Figure 4.
Non-intrinsic β-lactamases detected in molecularly characterized isolates of ceftolozane/tazobactam-resistant/imipenem/relebactam-susceptible, imipenem/relebactam-resistant/ceftolozane/tazobactam-susceptible and ceftolozane/tazobactam-resistant/imipenem/relebactam-resistant subsets of P. aeruginosa, cumulative 2016–2021 data. Intrinsic AmpC β-lactamases common to P. aeruginosa (PDC) are not shown. A representative sample of 80%–94% of isolates of each phenotype collected in each region were characterized. C/T, ceftolozane/tazobactam; IMI/REL, imipenem/relebactam; AP, Asia/Pacific; W EUR, Western Europe; E EUR, Eastern Europe; LA, Latin America; MEA, Middle East/Africa; US/CAN, United States of America and Canada. AP includes Australia and New Zealand (ANZ) in this figure.
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References

    1. Reynolds D, Kollef M. The epidemiology and pathogenesis and treatment of Pseudomonas aeruginosa infections: an update. Drugs 2021; 81: 2117–31. 10.1007/s40265-021-01635-6 - DOI - PMC - PubMed
    1. Karlowsky JA, Lob SH, Raddatz Jet al. In vitro activity of imipenem/relebactam and ceftolozane/tazobactam against clinical isolates of gram-negative bacilli with difficult-to-treat resistant phenotypes—study for monitoring antimicrobial resistance trends, United States 2015–2017. Clin Infect Dis 2021; 72: 2112–20. 10.1093/cid/ciaa381 - DOI - PubMed
    1. Karlowsky JA, Lob SH, DeRyke CAet al. In vitro activity of ceftolozane-tazobactam, imipenem-relebactam, ceftazidime-avibactam, and comparators against Pseudomonas aeruginosa isolates collected in United States hospitals according to results from the SMART surveillance program, 2018 to 2020. Antimicrob Agents Chemother 2022; 66: e00189-22. 10.1128/AAC.00189-22 - DOI - PMC - PubMed
    1. Tamma PD, Aitken SL, Bonomo RAet al. Infectious Diseases Society of America guidance on the treatment of extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Clin Infect Dis 2021; 72: 1109–16. 10.1093/cid/ciab295 - DOI - PubMed
    1. Lizza BD, Betthauser KD, Ritchie DJet al. New perspectives on antimicrobial agents: ceftolozane-tazobactam. Antimicrob Agents Chemother 2021; 65: e02318-20. 10.1128/AAC.02318-20 - DOI - PMC - PubMed

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