Ceftazidime-avibactam tolerance and persistence among difficult-to-treat KPC-producing Klebsiella pneumoniae clinical isolates from bloodstream infections
Artikel i vetenskaplig tidskrift, 2024
Purpose: Tolerance and persistence occur “silently” in bacteria categorized as susceptible by antimicrobial susceptibility testing in clinical microbiology laboratories. They are different from resistance phenomena, not well-studied, and often remain unnoticeable. We aimed to investigate and characterize ceftazidime-avibactam (CZA) tolerance/persistence in 80 Klebsiella pneumoniae isolates from bloodstream infections. Methods: We used the Tolerance Disk Test (TDtest) to detect CZA tolerance/persistence and investigate the avibactam (AVI) influence on them, and time-kill assays with minimal duration for killing (MDK) determination to characterize/differentiate CZA tolerance from persistence, for selected isolates. Whole genome sequencing was performed for 49/80 selected isolates to investigate genes related to beta-lactam tolerance/persistence and resistance as well as phylogeny studies. Results: Tolerance/persistence to CZA was detected in 48/80 (60%) isolates, all extensively drug-resistant (XDR) or multidrug-resistant, carbapenem-resistant K. pneumoniae (CRKp), KPC producers, and previously categorized as susceptible (not resistant) to CZA. No heteroresistance was detected. CZA tolerance/persistence occurred due to ceftazidime tolerance/persistence and was not related to AVI in the CZA combination. 5/11 isolates were characterized as CZA-tolerant and 5/11 as CZA-persistent. The single (1/11) XDR and CRKp non-KPC producer was truly susceptible. All the CZA-tolerant/persistent isolates (ST11, ST258, ST340, ST437, ST16, ST17, and ST307) harbored the carbapenemase-encoding gene blaKPC−2. Mutation in only two genes (rpoS and degQ) related to beta-lactam tolerance/persistence was found in only 7/49 CZA-tolerant/persistent isolates, suggesting the presence of yet unknown beta-lactam tolerance/persistence genes. Conclusion: Among the K. pneumoniae bloodstream isolates studied, 60%, previously categorized as susceptible to CZA, were, actually, tolerant/persistent to this antibiotic, all these KPC producers.
Tolerance disk test (TDtest)
Antibiotic resistant bacteria
Minimal duration for killing (MDK)
Time-kill assays
Författare
N. Abichabki
Universidade de Sao Paulo (USP)
G. G. Gaspar
Universidade de Sao Paulo (USP)
L. R. Bortolato
Universidade de Sao Paulo (USP)
D. A.F.S. Lima
Universidade de Sao Paulo (USP)
L. N. Silva
Universidade de Sao Paulo (USP)
R. H.C. Pocente
Universidade de Sao Paulo (USP)
J. C. Ferreira
Universidade de Sao Paulo (USP)
T. C. Ogasawara
Universidade de Sao Paulo (USP)
D. Pereira
Universidade Federal do Rio Grande do Sul (UFRGS)
R. R. Guerra
Universidade Federal do Rio Grande do Sul (UFRGS)
C. Wilhelm
Universidade Federal do Rio Grande do Sul (UFRGS)
P. Barth
Universidade Federal do Rio Grande do Sul (UFRGS)
A. F. Martins
Universidade Federal do Rio Grande do Sul (UFRGS)
A. Barth
Universidade Federal do Rio Grande do Sul (UFRGS)
Gilberto U.L. Braga
Universidade de Sao Paulo (USP)
E. C.P. De Martinis
Universidade de Sao Paulo (USP)
Johan Bengtsson Palme
Chalmers, Life sciences, Systembiologi
Göteborgs universitet
CARe
F. Bellissimo-Rodrigues
Universidade de Sao Paulo (USP)
V. R. Bollela
Universidade de Sao Paulo (USP)
A. L.C. Darini
Universidade de Sao Paulo (USP)
L. N. Andrade
Universidade de Sao Paulo (USP)
European Journal of Clinical Microbiology and Infectious Diseases
0934-9723 (ISSN) 1435-4373 (eISSN)
Vol. In PressFramtidens patogener och resistensgener
Stiftelsen för Strategisk forskning (SSF) (FFL21-0174), 2022-08-01 -- 2027-12-31.
Ämneskategorier
Infektionsmedicin
Biologiska vetenskaper
DOI
10.1007/s10096-024-05005-4
PubMed
39614972