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The postantibiotic effect of imipenem: relationship with drug concentration, duration of exposure, and MIC
W J Munckhof1, D Olden, J D Turnidge
1Department of Infectious Diseases and Clinical Epidemiology, Monash Medical Centre, Melbourne, Victoria, Australia.
Abstract:
The postantibiotic effect (PAE) of imipenem against Escherichia coli was measured at a wide variety of drug concentrations and times of exposure. We observed that the area under the concentration-time curve of drug exposure (AUC), the product of time of exposure and concentration of drug, is a much better predictor of the duration of the PAE than either parameter alone. We also measured the PAE of imipenem against strains of gram-positive and gram-negative bacteria for which MICs varied widely. The E50, the AUC required to produce 50% of the maximum PAE, is correlated with the MIC and is independent of species. This may explain why the duration of the PAE differs for bacteria of the same species for which MICs are different.
Insights
The area under the concentration-time curve (AUC) of imipenem exposure better predicts the postantibiotic effect (PAE) duration than concentration or time alone. AUC also correlates with the minimum inhibitory concentration (MIC), explaining varied PAE durations.
Area of Science:
- Pharmacology
- Microbiology
- Antibiotic Resistance
Background:
- The postantibiotic effect (PAE) is a crucial factor in determining antibiotic efficacy.
- Understanding factors influencing PAE duration is vital for optimizing antimicrobial therapy.
- Imipenem is a broad-spectrum carbapenem antibiotic used against various bacterial infections.
Purpose of the Study:
- To investigate the relationship between imipenem exposure parameters and the resulting postantibiotic effect (PAE) against Escherichia coli.
- To determine the predictive value of the area under the concentration-time curve (AUC) for PAE duration.
- To assess the correlation between AUC, minimum inhibitory concentration (MIC), and PAE across different bacterial species.
Main Methods:
- Measurement of imipenem's PAE against Escherichia coli at various drug concentrations and exposure times.
- Calculation of the area under the concentration-time curve (AUC) as a composite measure of drug exposure.
- Evaluation of PAE in gram-positive and gram-negative bacteria with differing MICs.
Main Results:
- The area under the concentration-time curve (AUC) was found to be a superior predictor of postantibiotic effect (PAE) duration compared to drug concentration or exposure time individually.
- The E50, defined as the AUC required to achieve 50% of the maximal PAE, demonstrated a correlation with the minimum inhibitory concentration (MIC).
- This correlation between E50 and MIC was independent of bacterial species, suggesting a conserved relationship.
Conclusions:
- Area under the concentration-time curve (AUC) is a key determinant of postantibiotic effect (PAE) duration for imipenem.
- The correlation between AUC and MIC provides a framework for understanding inter-species variations in PAE.
- This finding may elucidate why PAE duration varies among bacteria with different MICs, even within the same species.