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Antibacterial activity of meropenem against Pseudomonas aeruginosa, including antibiotic-induced morphological
M Trautmann1, M Heinemann, R Zick
1Department of Medical Microbiology and Hygiene, University Hospital Ulm, Germany.
Abstract:
The in vitro effects of meropenem on Pseudomonas aeruginosa were examined by studying (i) the inhibitory and bactericidal concentrations of meropenem versus those of imipenem for clinical isolates; (ii) changes in bacterial morphology during in vitro culture; and (iii) release of endotoxin induced by meropenem compared with that induced by other antipseudomonal compounds. Meropenem MIC90 and MBC90 values for 108 clinical isolates were 2 and 4.8 mg/l compared to 4.5 and 9.6 mg/l for imipenem. Morphological studies using phase-contrast and scanning electron microscopy showed that meropenem induced the formation of indeterminate bacterial cell forms at drug concentrations of 1-2.5 mg/l (0.5- to 1.25-fold the MIC), while spheroplasts predominated at drug levels exceeding 5 mg/l (2.5-fold the MIC). Determination of free and EDTA-releasable endotoxin activity by means of the Limulus lysate test showed that both meropenem and imipenem liberated significantly less endotoxin than did ceftazidime. Therefore, although meropenem binds to penicillin-binding proteins (PBPs) 2 and 3 (in contrast to imipenem, which binds to PBP2 only), endotoxin release should not be a cause of concern when treating systemic gram-negative infections with this drug.
Insights
Meropenem demonstrates potent inhibitory and bactericidal effects against Pseudomonas aeruginosa, inducing unique morphological changes and minimal endotoxin release compared to other antibiotics. This suggests a favorable safety profile for treating gram-negative infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Pseudomonas aeruginosa is a significant pathogen in healthcare-associated infections.
- Carbapenems are critical antibiotics for treating multidrug-resistant gram-negative bacteria.
- Understanding the in vitro activity and host response to carbapenems is crucial for effective treatment.
Purpose of the Study:
- To evaluate the in vitro efficacy of meropenem against Pseudomonas aeruginosa.
- To compare meropenem's effects on bacterial morphology and endotoxin release with imipenem.
- To assess the safety profile of meropenem concerning endotoxin liberation.
Main Methods:
- Determined meropenem and imipenem minimum inhibitory concentration (MIC90) and minimum bactericidal concentration (MBC90) for 108 clinical isolates.
- Utilized phase-contrast and scanning electron microscopy to observe bacterial morphology changes.
- Quantified endotoxin release using the Limulus lysate test.
Main Results:
- Meropenem exhibited lower MIC90 (2 mg/l) and MBC90 (4.8 mg/l) than imipenem (4.5 and 9.6 mg/l).
- Meropenem induced bacterial cell form alterations and spheroplast formation at specific concentrations.
- Both meropenem and imipenem released significantly less endotoxin than ceftazidime.
Conclusions:
- Meropenem is a potent antimicrobial agent against Pseudomonas aeruginosa in vitro.
- Meropenem's unique penicillin-binding protein interactions do not lead to excessive endotoxin release.
- Meropenem presents a favorable option for treating systemic gram-negative infections with minimal risk of endotoxin-induced complications.