Effect of ceftriaxone-induced alterations of bacteria on neutrophil bactericidal function

Two bacterial strains (Staphylococcus aureus and Klebsiella pneumoniae) were exposed to subinhibitory concentrations of ceftriaxone. After an overnight culture in presence of 1 MIC of ceftriaxone either in broth or on solid medium S. aureus showed enlarged forms which were better phagocytosed (increase about 40%) and killed (increase about 50%) than control staphylococci. Exposure of K. pneumoniae to 0.1 MIC ceftriaxone resulted in filamentation of bacteria. When grown in the presence of 0.01 MIC, K. pneumoniae did not elongate into filaments but were significantly more phagocytosed (increase about 40%) or killed (increase about 170%) than control bacilli. The mechanism of the greater sensitivity to PMN killing of the altered S. aureus and K. pneumoniae was assessed either with phenylbutazone-treated PMN or by in-vitro exposure to crude granule extracts of PMN. The altered bacteria displayed a significant susceptibility to the non-oxidative killing mechanism while untreated bacteria were unaffected by the non-oxidative system. These data could explain the synergy observed between ceftriaxone and leucocytes in the killing of some micro-organisms.