Predicting the Effect of Meropenem Against Klebsiella pneumoniae Using Minimum Inhibitory Concentrations Determined
Maria V Golikova1, Kamilla N Alieva1, Elena N Strukova1
1Department of Pharmacokinetics & Pharmacodynamics, Gause Institute of New Antibiotics, 11 Bolshaya Pirogovskaya Street, 119021 Moscow, Russia.
Abstract:
Background/Objectives: Assessing antibiotic MICs at high bacterial counts is likely to disclose hidden bacterial resistance and the inoculum effect if present and therefore also reveal potential decreased antibiotic effectiveness. In the current study, we evaluated the predictive potential of MICs determined at high bacterial inocula to evaluate meropenem effectiveness and emergence of resistance in Klebsiella pneumoniae. Methods: Nine carbapenemase-free or carbapenemase-producing K. pneumoniae strains were exposed to meropenem in an in vitro hollow-fiber infection model (HFIM). The treatment effects were correlated with simulated antibiotic ratios of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC) and to MICs determined at high inocula (AUC/MICHI). Results: Based on MICs determined at standard inocula, meropenem effects at different AUC/MIC ratios for both carbapenemase-free and carbapenemase-producing K. pneumoniae strains were stratified and could not be described by a single relationship. In contrast, when AUC/MICHI ratios were used, a single relationship with the antibiotic effect was obtained for all tested strains. Similarly, the emergence of meropenem resistance in HFIM was concordant with AUC/MICHI, but not with AUC/MIC ratios. Conclusions: MICs determined at high bacterial inocula enable the prediction of meropenem effects both for carbapenemase-free and for carbapenemase-producing K. pneumoniae strains. Also, MICs at standard and high inocula can identify carbapenemase-producing strains by revealing the inoculum effect.
Insights
Determining antibiotic minimum inhibitory concentrations (MICs) at high bacterial counts accurately predicts meropenem effectiveness and resistance in Klebsiella pneumoniae, including carbapenemase-producing strains.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Assessing antibiotic minimum inhibitory concentrations (MICs) at high bacterial counts can reveal hidden resistance and the inoculum effect.
- This approach may uncover decreased antibiotic effectiveness.
- Evaluating meropenem effectiveness and resistance emergence in Klebsiella pneumoniae requires understanding inoculum effects.
Purpose of the Study:
- To evaluate the predictive potential of MICs determined at high bacterial inocula for meropenem effectiveness.
- To assess the emergence of meropenem resistance in Klebsiella pneumoniae using high inoculum MICs.
- To compare the predictive power of standard versus high inoculum MICs in a hollow-fiber infection model.
Main Methods:
- Nine Klebsiella pneumoniae strains (carbapenemase-free and producing) were tested.
- Meropenem effectiveness was evaluated using an in vitro hollow-fiber infection model (HFIM).
- Treatment effects were correlated with area under the concentration-time curve (AUC) to MIC ratios (AUC/MIC) and high inoculum MICs (AUC/MICHI).
Main Results:
- Meropenem effects stratified by standard MICs could not be described by a single AUC/MIC relationship.
- A single relationship between antibiotic effect and AUC/MICHI was observed for all tested strains.
- Emergence of meropenem resistance in HFIM correlated with AUC/MICHI, but not AUC/MIC.
Conclusions:
- MICs determined at high bacterial inocula accurately predict meropenem effects in both carbapenemase-free and carbapenemase-producing Klebsiella pneumoniae.
- High inoculum MICs reveal the inoculum effect, aiding in the identification of carbapenemase-producing strains.
- This method enhances the prediction of antibiotic effectiveness and resistance in challenging bacterial infections.
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