ss-Lactam Antibiotic-Induced Release of Free Endotoxin: In Vitro Comparison of Penicillin-Binding Protein (PBP) 2-Specific Imipenem and PBP 3-Specific Ceftazidime
The relative effects of two ß-Iactam antibiotics, penicillin-binding protein (PBP) 2-specific imipenem and PBP 3-specific ceftazidime, upon in vitro induction of lipopolysaccharide(LPS) release were investigated against smooth- and rough-LPS mutant isolates of Pseudomonas aeruginosa. Free LPS liberated from both isolates are 10- to 40-fold higher for ceftazidime-exposed cultures than control or imipenem-treated cultures after 4–8 h at 35°C despite equivalentMICs. Lethalities of filtrates in micecorrelated with in vitro endotoxin assay results. Sub-MIC levelsof ceftazidime induced filamentation and LPS release without significant bacterial lysis. Amounts released not only matched the quantities achieved at inhibitory concentrations (e.g., 1-,2-, and 50-times MIC) of ceftazidime but significantlyexceeded levels of LPS liberated by exposure to imipenem, ⩽100 times its MIC. Sub-MIC levelsofimipenem released relativelysmall amounts of free LPS while reducing colony counts ∼2 logs more than equivalent amounts of ceftazidime after 2 h. Data suggest that ceftazidime-inducedfilamentation releases larger quantities ofbioreactive LPS than nonfilamentous fast-lysing imipenem.