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 marcescens, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus vulgaris and Proteus mirabilis, were exposed to carbapenems (imipenem, panipenem, meropenem and biapenem) at 0.5 x MIC for 3 h, then their morphology 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 spherical or ovoid cells, except for P. aeruginosa treated with meropenem and biapenem; these latter cells had a 'bulge' midway along them and we have termed them 'oval-centred'. There was a relationship between morphology and the amount of endotoxin released following exposure to carbapenems or ceftazidime. Of all the species investigated, P. aeruginosa showed the most variable morphological changes. P. aeruginosa exposed to biapenem were longer oval-centred in shape, and released significantly more endotoxin than those exposed to imipenem, panipenem (spherical) or meropenem (shorter oval-centred cells) (P=0.030, 0.017 and 0.002, respectively). In all strains except P. aeruginosa, carbapenems induced significantly less endotoxin release than ceftazidime (P < 0.05).