Antibacterial activity of meropenem against Pseudomonas aeruginosa, including antibiotic-induced morphological changes and endotoxin-liberating effects

The in vitro effects of meropenem on Pseudomonas aeruginosa were examined b y studying (i) the inhibitory and bactericidal concentrations of meropenem versus those of imipenem for clinical isolates; (ii) changes in bacterial m orphology during in vitro culture; and (iii) release of endotoxin induced b y meropenem compared with that induced by other antipseudomonal compounds. Meropenem MIC90 and MBC90 values for 108 clinical isolates were 2 and 4.8 m g/l compared to 4.5 and 9.6 mg/l for imipenem. Morphological studies using phase-contrast and scanning electron microscopy showed that meropenem induc ed the formation of indeterminate bacterial cell forms at drug concentratio ns of 1-2.5 mg/l (0.5- to 1.25-fold the MIC), while spheroplasts predominat ed at drug levels exceeding 5 mg/l (2.5-fold the MIC). Determination of fre e and EDTA-releasable endotoxin activity by means of the Limulus lysate tes t showed that both meropenem and imipenem liberated significantly less endo toxin than did ceftazidime. Therefore, although meropenem binds to penicill in-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 treati ng systemic gram-negative infections with this drug.