AN IN-VITRO STUDY OF CARBAPENEM-INDUCED MORPHOLOGICAL-CHANGES AND ENDOTOXIN RELEASE IN CLINICAL ISOLATES OF GRAM-NEGATIVE BACILLI

One hundred clinical isolates, including Escherichia coli, Serratia ma rcescens, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus vulga ris and Proteus mirabilis, were exposed to carbapenems (imipenem, pani penem, meropenem and biapenem) at 0.5 x MIC for 3 h, then their morpho logy was examined and endotoxin release determined. Ceftazidime, which induces filament formation, was used as a control. Scanning electron microscopy showed that these carbapenems induced formation of spherica l or ovoid cells, except for P. aeruginosa treated with meropenem and biapenem; these latter cells had a 'bulge' midway along them and we ha ve termed them 'oval-centred'. There was a relationship between morpho logy and the amount of endotoxin released following exposure to carbap enems or ceftazidime. Of all the species investigated, P. aeruginosa s howed the most variable morphological changes. P. aeruginosa exposed t o biapenem were longer oval-centred in shape, and released significant ly more endotoxin than those exposed to imipenem, panipenem (spherical ) or meropenem (shorter oval-centred cells) (P = 0.030, 0.017 and 0.00 2, respectively). In all strains except P. aeruginosa, carbapenems ind uced significantly less endotoxin release than ceftazidime (P < 0.05).