Postantibiotic effect and host-bacteria interactions.

Suppression of bacterial growth that persists after short exposure of bacteria to antimicro-bial agents, called the postantibiotic effect (PAE), has been observed both in vitro and in vivo. Duration, and even presence or absence of PAE depends upon the organism, the antimicrobial agent and the environmental conditions used for measuring the effect (Craig, 1991). The most important factors contributing to PAE include concentration, exposure time and mode of action of the tested drug, type of organism, inoculum size, and type of growth medium, and growth phase (see Craig & Gudmundsson, 1991). Despite the recognition of PAE many years ago by Bigger (1944), and then by Eagle, Fleischman & Musselman (1950), the mechanism by which it occurs remains to be elucidated. Possible mechanisms include non-lethal damage induced by the antimicrobial agent and drug persistence at the binding site (Craig & Gudmundsson, 1991). PAEs are multiple, including delayed recovery of proteins with and without enzyme activities, prolonged changes in cell morphology, metabolic alteration, modifications of generation times, susceptibility to phagocytosis and altered susceptibility to antibiotics after re-exposure. Many of these effects are probably linked (Mackenzie & Gould, 1993). Altered susceptibility to polymorphonuclear (PMN) cells during the PAE phase is known as the post antibiotic leucocyte effect (PALE) 1991). PALE was found to be both strain-and drug-dependent. In Escherichia coli aminogly-cosides and macrolides (protein synthesis inhibitors) displayed greater PALE than the cell-wall acting /?-lactam antibiotics (McDon-ald et al., 1983). Erythromycin increased the susceptibility of Streptococcus pneumoniae to the bactericidal activity of human PMNs but decreased that of E. coli. Exposure to roxithromycin increased opsonization and phagocytosis in S. pneumoniae but not in Streptococcus pyogenes (Gemmell & McLeod, 1992). Erythromycin and to a lesser extent azithromycin increased the susceptibility of streptococci to the killing activity of human PMNs not only during the PAE phase but also after recovery (Ramadan et al., 1994). Erythromycin and roxithromycin but not azithromycin altered opsonization and increased the susceptibility of Staphylococcus aureus to phagocytosis by human PMNs (Pascual et al., 1990). A short exposure to vancomycin increased the susceptibility of Enterococcus faecalis to PMNs (Bayer & Tu, 1990). The combination of ampicillan/sulbac-tam enhanced the suscepbility of Staphylococcus aureus to phagocytosis by PMNs, in contrast, and probably due to low intracellular penetration of /?-lactams, the same combination displayed no significant antimicrobial effect against the bacterium when 'it was intracellularly located, within the PMNs (Pascual et al., 1991). Short exposure of …