Abstract

Objectives

Cystic fibrosis (CF) patients are often colonized with Pseudomonas aeruginosa. During treatment, P. aeruginosa can develop subpopulations exhibiting variable in vitro antimicrobial (ABX) susceptibility patterns. Heteroresistance (HR) may underlie reported discrepancies between in vitro susceptibility results and clinical responses to various ABXs. Here, we sought to examine the presence and nature of P. aeruginosa polyclonal HR (PHR) and monoclonal HR (MHR) to ceftolozane/tazobactam in isolates originating from CF pulmonary exacerbations.

Methods

This was a single-centre, non-controlled study. Two hundred and forty-six P. aeruginosa isolates from 26 adult CF patients were included. PHR was defined as the presence of different ceftolozane/tazobactam minimum inhibitory concentration (MIC) values among P. aeruginosa isolates originating from a single patient specimen. Population analysis profiles (PAPs) were performed to assess the presence of MHR, defined as ≥4-fold change in the ceftolozane/tazobactam MIC from a single P. aeruginosa colony.

Results

Sixteen of 26 patient specimens (62%) contained PHR P. aeruginosa populations. Of these 16 patients, 6 (23%) had specimens in which PHR P. aeruginosa isolates exhibited ceftolozane/tazobactam MICs with categorical differences (i.e. susceptible versus resistant) compared to results reported as part of routine care. One isolate, PSA 1311, demonstrated MHR. Canonical ceftolozane/tazobactam resistance genes were not found in the MHR isolates (MHR PSA 1311 or PHR PSA 6130).

Conclusions

Ceftolozane/tazobactam PHR exists among P. aeruginosa isolates in this work, and approximately a quarter of these populations contained isolates with ceftolozane/tazobactam susceptibiilty interpretations different from what was reported clinically, supporting concerns surrounding the utility of traditional susceptibility testing methodology in the setting of CF specimens. Genome sequencing of isolates with acquired MHR to ceftolozane/tazobactam revealed variants of unknown significance. Future work will be centred on determining the significance of these mutations to better understand these data in clinical context.

Details

Title
Ceftolozane/tazobactam heteroresistance in cystic fibrosis-related Pseudomonas aeruginosa infections
Author
Monogue, Marguerite L 1   VIAFID ORCID Logo  ; Sanders, James M 1 ; Pybus, Christine A 2 ; Kim, Jiwoong 3 ; Zhan, Xiaowei 3   VIAFID ORCID Logo  ; Clark, Andrew E 4 ; Greenberg, David E 5 

1  Department of Pharmacy, University of Texas Southwestern Medical Center , Dallas, TX 75390 , USA 
2  Department of Microbiology, University of Texas Southwestern Medical Center , Dallas, TX 75390 , USA 
3  Department of Population and Data Sciences, Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center , Dallas, TX 75390 , USA 
4  Department of Pathology, University of Texas Southwestern Medical Center , Dallas, TX 75390 , USA 
5  Department of Internal Medicine, Infectious Diseases and Geographic Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390 , USA 
Publication year
2023
Publication date
Aug 2023
Publisher
Oxford University Press
e-ISSN
26321823
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1093/jacamr/dlad083
ProQuest document ID
3170174228
Copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.