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Subpopulations of variants resistant to imipenem in Pseudomonas aeruginosa
L Nilsson1, M Nilsson, J Jendle
1Department of Clinical Bacteriology, University Hospital, Linköping, Sweden.
Abstract:
Selection and regrowth of resistant variants, which were present in low frequencies in the initial inoculum, was seen when large inocula of Pseudomonas aeruginosa were incubated with imipenem. The selective growth of resistant variants resulted in an inoculum effect, and an increase in MIC with longer incubation. When large inocula taken from strains that had been classified as sensitive in conventional MIC determinations were incubated with 4, 8 and 16 mg/l imipenem, 62%, 24% and 10%, respectively, of the strains regrew. None of the resistant variants thereby selected showed cross resistance to other beta-lactam antibiotics or aminoglycosides. In vitro evaluation of regrowth of resistant variants may be justified when choosing imipenem for therapy in the treatment of serious P. aeruginosa infections.
Insights
Large inocula of Pseudomonas aeruginosa incubated with imipenem selected for resistant variants. This inoculum effect increased imipenem
Area of Science:
- Microbiology
- Antimicrobial Resistance
- Pharmacology
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen causing serious infections.
- Imipenem is a crucial carbapenem antibiotic for treating P. aeruginosa infections.
- The inoculum effect can impact antibiotic efficacy, particularly with carbapenems.
Purpose of the Study:
- To investigate the selection and regrowth of imipenem-resistant variants of P. aeruginosa.
- To evaluate the impact of inoculum size on imipenem resistance.
- To determine if selected resistant variants exhibit cross-resistance to other antibiotics.
Main Methods:
- Incubation of large inocula of P. aeruginosa with varying concentrations of imipenem.
- Determination of minimum inhibitory concentrations (MICs) after extended incubation.
- Testing of selected resistant variants for cross-resistance to other beta-lactam and aminoglycoside antibiotics.
Main Results:
- Resistant variants were selected and regrew from large inocula of P. aeruginosa incubated with imipenem.
- An inoculum effect was observed, leading to increased MICs with longer incubation times.
- Selected resistant variants did not show cross-resistance to other tested beta-lactam or aminoglycoside antibiotics.
Conclusions:
- In vitro evaluation of resistant variant regrowth is important when considering imipenem therapy for serious P. aeruginosa infections.
- The inoculum effect highlights the need for careful consideration of dosing and bacterial load in treatment strategies.
- Understanding resistance mechanisms is crucial for optimizing antibiotic use against P. aeruginosa.