Antibacterial Activity of Meropenem against Pseudomonas aeruginosa, Including Antibiotic-Induced Morphological Changes and Endotoxin-Liberating Effects |
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Authors: | M Trautmann M Heinemann R Zick A Möricke M Seidelmann D Berger |
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Institution: | Department of Medical Microbiology and Hygiene, University Hospital Ulm, Steinh?velstra?e 9, D-89075 Ulm, Germany, DE Department of General Surgery, University of Ulm, Steinh?velstra?e 9, D-89075 Ulm, Germany, DE
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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. |
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