Evaluation of temocillin efficacy against KPC-2-producing Klebsiella pneumoniae isolates in a hollow-fibre infection model.
J Antimicrob Chemother
; 79(4): 784-789, 2024 04 02.
Article
in En
| MEDLINE
| ID: mdl-38334407
ABSTRACT
BACKGROUND:
Temocillin is an old antimicrobial that is resistant to hydrolysis by ESBLs but has variable activity against carbapenemase-producing Enterobacteriaceae. The current EUCAST susceptibility breakpoints for Enterobacterales are set at ≤16â mg/L (susceptible with increased exposure) based on a dose of 2â g q8h, but there is limited information on the efficacy of this dose against temocillin-susceptible carbapenemase-producing Klebsiella pneumoniae isolates.OBJECTIVES:
To evaluate the efficacy of this dose using a hollow-fibre infection model (HFIM) against six KPC-2-producing clinical isolates of K. pneumoniae.METHODS:
The isolates were characterized by WGS and temocillin susceptibility was determined using standard and high inoculum temocillin. Mutant frequencies were estimated and temocillin activity was tested in time-kill assays and in the HFIM. At standard conditions, three of the isolates were classified as susceptible (MICâ≤â16â mg/L) and three as resistant (MICâ>â16â mg/L). The HFIM was performed over 3â days to mimic human-like pharmacokinetics of 2â g q8h. Bacterial counts were performed by plating on Mueller-Hinton agar (MHA) and MHA containing 64â mg/L temocillin to detect resistant subpopulations.RESULTS:
All isolates showed a reduction in bacterial population of at least 3â log cfu/mL within the first 8â h of simulated treatment in the hollow-fibre assay. Regrowth was observed for the three resistant isolates and one of the susceptible ones. The MIC value for these isolates was higher by at least two dilutions compared with their initial values.CONCLUSIONS:
These data suggest that an optimized pharmacokinetic regimen may be of clinical interest for the treatment of KPC-2-producing K. pneumoniae susceptible to temocillin. These data showed activity of temocillin against KPC-2-producing K. pneumoniae susceptible to temocillin; however, a dose of 2g q8h administered over 30â min may be inadequate to prevent the emergence of resistant variants.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Penicillins
/
Klebsiella Infections
/
Carbapenem-Resistant Enterobacteriaceae
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
J Antimicrob Chemother
Year:
2024
Type:
Article
Affiliation country:
Spain