Delayed bactericidal activity of beta-lactam antibiotics against Listeria monocytogenes: antagonism of chloramphenicol and rifampin.

Penicillins are considered to be the drugs of choice for the treatment of listeric meningitis, and relapse of infection is rare when treatment is given in appropriate doses for at least 14 days. Despite this, in vitro studies by others have shown that penicillins are bacteriostatic against Listeria spp. We have shown that thienamycin, penicillin G, and ampicillin are the most active beta-lactam antibiotics against Listeria spp. Of 10 strains tested, 9 were killed by less than or equal to 8 micrograms of beta-lactam antibiotics (greater than or equal to 99.9% killing) when subcultures were performed after 48, rather than 24, h of incubation. In contrast, chloramphenicol, erythromycin, doxycycline, and rifampin were bacteriostatic after 48 h of incubation. In time-kill curves, these last drugs antagonized the bactericidal action of penicillins. In view of the inefficiency of opsonization in the cerebrospinal fluid, these antagonistic combinations should probably be avoided in documented or suspected listeric meningitis.