Background: As one of the “ESKAPE” pathogens, P. aeruginosa is recognised globally as a serious concern for public health, primarily due to its virulence, multidrug (MDR) and pandrug resistance potential, and association with poor clinical outcomes. Compared to international cohorts, our understanding of P. aeruginosa infections in Australians with bronchiectasis is relatively poor, with very little known about population diversity, antimicrobial resistance (AMR), or persistence and transmission dynamics.
Methods: Forty-three P. aeruginosa isolates were obtained from 14 Australians with bronchiectasis that participated in the Bronchiectasis and Low-dose Erythromycin Study (BLESS). Isolates were subjected to antimicrobial susceptibility profiling using disc diffusion and broth micro-dilution. All isolates were whole-genome sequenced (WGS) and characterised using comparative genomics, along with in silico identification of AMR-conferring variants using our P. aeruginosa ARDaP-compatible AMR database(1).
Results: WGS identified persistent P. aeruginosa infection in 6/10(60%) participants with multiple samples, multi-lineage infections in 2/10 participants, and potential infection transmission between patients on two occasions. Using multi-locus sequence typing, 16 sequence types (ST) were identified, three of which are novel, indicating likely under-sampling of P. aeruginosa from Australian bronchiectasis cohorts. The highest levels of AMR were seen for ST1097 and ST915, both rarely reported, followed by the more common ST274. We identified moderate AMR rates, with 4/43(9%) isolates classified as MDR; that is, AMR towards three or more antibiotic classes. Ciprofloxacin AMR was most common, being identified in 33% of strains, followed by AMR towards ceftazidime-avibactam (16%), piperacillin-tazobactam (14%), cefepime (14%), aztreonam (14%), meropenem (7%) and imipenem (5%). No AMR was seen towards tobramycin, amikacin, or colistin. In silico analysis identified several chromosomal AMR determinants that have previously been associated with AMR. Importantly, no high-risk mobile genetic elements, such as the blaVIM carbapenemase, were identified.
Conclusions: Our findings shed much-needed light on the diversity, transmission dynamics, prevalence, and genomic basis of AMR in P. aeruginosa from Australians with bronchiectasis. Our work highlights the importance of infection control to prevent patient-to-patient spread of AMR and MDR clones, and the need for accurate antimicrobial susceptibility profiling of P. aeruginosa to effectively eradicate infections, prevent persistence, and reduce patient morbidity and mortality.