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Studies on the postantibiotic effect and the postantibiotic sub-MIC effect of meropenem
1Department of Infectious Diseases, Uppsala University Hospital, Sweden.
Abstract:
The postantibiotic effect (PAE), the postantibiotic sub-MIC effect (PA SME) and the sub-MIC effect (SME) of a new carbapenem, meropenem, were determined for different strains of Escherichia coli and Pseudomonas aeruginosa. A PAE was induced by 10 x MIC of meropenem for 2 h. After induction, the antibiotic was eliminated by washing and dilution. The strains in the postantibiotic exposure phase and the controls were then exposed to no antibiotic or to different sub-MICs concentrations (0.1-0.6 x MIC) of meropenem. The growth curves were followed for 24 h with viable counts and/or measured by continuous monitoring of optical density in a BioScreen C apparatus. Zero or very low values for the PAE were seen in the strains studied. However, a long PA SME and SME were seen for P. aeruginosa when determined by both methods, which at 0.3 x MIC gave comparable results. At lower concentrations the PA SMEs measured with BioScreen C were shorter, probably due to differences in the definition between the two methods. The BioScreen C method was less laborious than viable counting. However, one disadvantage of the BioScreen C method was that manual viable counting still had to be used to determine bacterial killing. No PA SME or SME against E. coli was observed, and the increased sensitivity of P. aeruginosa to sub-MICs of carbapenems remains unexplained.
Insights
Meropenem showed minimal postantibiotic effect (PAE) against E. coli and P. aeruginosa. However, significant postantibiotic sub-MIC effects (PA SME) and sub-MIC effects (SME) were observed in P. aeruginosa, indicating potential for carbapenem activity at sub-inhibitory concentrations.
Area of Science:
- Microbiology
- Pharmacology
- Antimicrobial Resistance
Background:
- The postantibiotic effect (PAE), postantibiotic sub-MIC effect (PA SME), and sub-MIC effect (SME) are crucial parameters for evaluating antibiotic efficacy.
- Meropenem is a carbapenem antibiotic used to treat serious bacterial infections.
- Understanding the effects of sub-inhibitory concentrations of antibiotics is important for managing antimicrobial resistance.
Purpose of the Study:
- To determine the PAE, PA SME, and SME of meropenem against Escherichia coli and Pseudomonas aeruginosa.
- To compare the efficacy of meropenem at different sub-inhibitory concentrations.
- To evaluate the utility of BioScreen C for measuring these effects.
Main Methods:
- Induction of PAE using 10x MIC of meropenem for 2 hours.
- Exposure to various sub-MICs (0.1-0.6x MIC) of meropenem.
- Monitoring bacterial growth curves for 24 hours using viable counts and BioScreen C optical density measurements.
Main Results:
- Meropenem exhibited zero or very low PAE against both E. coli and P. aeruginosa.
- A notable PA SME and SME were observed for P. aeruginosa, particularly at 0.3x MIC.
- No significant PA SME or SME was found for E. coli, and the enhanced sensitivity of P. aeruginosa remains unexplained.
Conclusions:
- Meropenem demonstrates limited postantibiotic effect but significant sub-inhibitory effects on P. aeruginosa.
- The BioScreen C method is a less laborious alternative to viable counting for these measurements, though manual counts are still needed for bacterial killing.
- Further research is needed to elucidate the mechanisms behind P. aeruginosa's increased sensitivity to sub-MIC carbapenems.