Susceptibility profile and β-lactamase content of global <i>Pseudomonas aeruginosa</i> isolates resistant to ceftolozane/tazobactam and/or imipenem/relebactam—SMART 2016–21
Why this work is in the frame
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Bibliographic record
Abstract
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 &gt;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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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it