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Postantibiotic and bactericidal effect of imipenem against Pseudomonas aeruginosa
I Odenholt1, B Isaksson, L Nilsson
1Department of Infectious Diseases, Uppsala University, Sweden.
Abstract:
The postantibiotic effect of imipenem on Pseudomonas aeruginosa was studied at different inocula using one ATCC strain and four clinical isolates. The postantibiotic effect was measured using two different methods: viable counts and bioluminescence assay of intracellular bacterial ATP. The postantibiotic effect could be demonstrated with both methods (viable counts 1-2 h, ATP assay 3-5 h) for all strains at an inoculum of 10(6) CFU/ml. When the inoculum was raised to 10(8) CFU/ml, no postantibiotic effect could be observed with either method using routine growth conditions. This disappearance of the postantibiotic effect coincided with a loss of bactericidal effect of imipenem when high inocula were used. Improved oxygenation of the cultures restored the bactericidal and postantibiotic effects of imipenem at high inocula.
Insights
The postantibiotic effect of imipenem on Pseudomonas aeruginosa was observed at low bacterial concentrations but disappeared at high concentrations. Restoring oxygen levels in cultures revived imipenem
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- The postantibiotic effect (PAE) is crucial for understanding antibiotic efficacy.
- Pseudomonas aeruginosa infections are challenging due to antibiotic resistance.
- Imipenem is a critical antibiotic for treating severe bacterial infections.
Purpose of the Study:
- To investigate the influence of bacterial inoculum size on the postantibiotic effect of imipenem against Pseudomonas aeruginosa.
- To compare the efficacy of viable counts and ATP bioluminescence assays in measuring PAE.
- To explore factors affecting imipenem's activity at high bacterial loads.
Main Methods:
- Studied the postantibiotic effect of imipenem on *P. aeruginosa* strains (ATCC and clinical isolates).
- Utilized viable counts and intracellular bacterial ATP bioluminescence assays for PAE measurement.
- Varied bacterial inocula from 10^6 CFU/ml to 10^8 CFU/ml under routine and improved oxygenation conditions.
Main Results:
- PAE was observed at 10^6 CFU/ml (viable counts: 1-2 h; ATP assay: 3-5 h) for all strains.
- PAE and bactericidal effects were lost at 10^8 CFU/ml under routine conditions.
- Improved oxygenation restored both bactericidal and postantibiotic effects at high inocula.
Conclusions:
- Bacterial inoculum size significantly impacts imipenem's postantibiotic effect and bactericidal activity against *P. aeruginosa*.
- High bacterial loads can mask imipenem's efficacy, potentially due to reduced oxygen availability.
- Optimizing culture conditions, such as increasing oxygenation, can restore imipenem's effectiveness against *P. aeruginosa* at high bacterial concentrations.