Carbapenems are reserved as a last-line therapy for infections caused by Pseudomonas aeruginosa. However, the resistance to these antibiotics exceeds 24.2%, and in paediatric patients, infections caused by carbapenem-resistant P. aeruginosa (CR-PA) have a mortality between 25 and 38.2%. Therefore, antimicrobial agents such as ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (CT) have been developed. This study aimed to characterize CT- and CZA-non-susceptible P. aeruginosa isolates from paediatric patients in a hospital where these therapeutic agents are not yet available. Fifty-nine nonduplicate carbapenem-resistant and non-carbapenemase-producing isolates of P. aeruginosa from infected paediatric patients were analysed. Susceptibility to CT and CZA was determined with the disc diffusion method, epsilometry, and semiautomated microdilution. Sixteen isolates were selected for whole-genome sequencing. Bioinformatic analyses were used to identify acquired resistance genes and point mutations, and to determine the sequence type (ST) and clonal relationships in both local and international contexts. A total of 64.5% of the isolates were susceptible to CT and CZA. Among the resistant isolates, we identified serogroups O5, O4, O11, and O3, as well as ST348, ST389, and the high-risk clone ST309. Genes related to resistance to beta-lactams, fluoroquinolones (FQs), aminoglycosides, and other antimicrobial agents were identified. Mutations were found in the ampC gene (T105A) and in the regulatory genes ampR, mexR and nalC. All isolates carried the virulence factors exoA, phzA, algD, lecA, and lasA; 61.5% carried lasB; and 46.1%, pilA. Two major clusters were identified, one composed of ST348 and the other of ST389, which clustered with strains from China and Spain, respectively. This study reports the emergence of CT and CZA resistance in P. aeruginosa isolates from a paediatric hospital in Mexico prior to their clinical use. Genomic analyses showed alignment with global strains and revealed clonal relationships in ST348 and ST389, as well as the presence of the high-risk clone ST309. No known resistance-associated mutations were identified, suggesting pre-existing cross-resistance. Future studies integrating WGS with functional and transcriptomic approaches will be required to elucidate additional mechanisms. Not applicable.
Méndez et al. (Mon,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: