Antagonism of ampicillin and chloramphenicol for meningeal isolates of group B streptococci

Abstract

The increasing prevalence of ampicillin-resistant Haemophilus influenzae type b has led to the recomxniendation that ampicillin and chloramphenicol be given as the initial therapy for suspected bacterial meningitis in infants and children. However, during the first 2 months of life, H. influenzae type b is a rare cause of meningitis, whereas group B streptococcus is the most frequently isolated agent. Since ampicillin and chloramphenicol have been shown to be antagonistic for other streptococci, an in vitro study of their effect on group B streptococci was performed. The effect of ampicillin and chloramphenicol, alone and in combination, on 18 meningeal isolates was determined for 2 different inocula of group B streptococci, using microtiter broth dilution and growth kinetic assays. Isoboles, fractional lethal concentration indices, or both indicated antagonism for all strains. Growth kinetic assays for two representative strains demonstrated inhibition of the early bactericidal activity of ampicillin by chloramphenicol. These findings of in vitro antagonism suggest that this combination may be contraindicated for the treatment of infants with group B streptococcal meningitis.Because of the emergence of ampicillin-resistant Haemophilus influenzae type b strains, a combination of ampicillin with chloramphenicol has been recommended since 1974 as initial antibiotic therapy for bacterial meningitis beyond the neonatal period (2). This recommendation may lead to the occasional treatment of infants less than 2 months of age with this combination, although H. influenzae type b is infrequently isolated from infants in this age group with meningitis (1,15,19,20).In vitro and some in vivo studies have indicated that chloramphenicol in combination with a penicillin is antagonistic for some bacterial species. For example, interference with the early bactericidal effect of penicillin was reported by Wallace et al. (17) in an animal model of pneumococcal meningitis. Similarly, Mathies et al. (13) observed an increased case-fatality ratio among children and adults with bacterial meningitis who were treated with the combination of ampicillin, chloramphenicol, and streptomycin compared with those who were treated with ampicillin alone.Because group B streptococci (GBS) are the single most frequent agents isolated in our medical center from infants less than 2 months of age with bacterial meningitis (1), we believed it important to evaluate the in vitro effect of ampicillin and chloramphenicol against several meningeal isolates. MATERIALS AND METHODSBacterial isolates. Eighteen cerebrospinal fluid (CSF) isolates of GBS from infants <2 months of age were serotyped by the capillary precipitin method of McCarty and Lancefield (14). The serotype distribution of these strains was representative of that reported among neonatal meningeal isolates (18)

Susceptibility of group B streptococci to 16 beta-lactam antibiotics, including new penicillin and cephalosporin derivatives

“…The penicillin MICs obtained in this study agree with those reported by Baker et al (2) Penicillin tolerance has been described in 4% of strains of group B streptococci (15). Tolerant strains had MICs of penicillin that were similar to those of nontolerant strains (mean MIC, 0.04 ,ug/ml), but MBCs of penicillin G were 0.3 to 1.25 pg/ml (mean, 0.6 ,ug/ml) for tolerant strains as compared with 0.04 to 0.3 ,ug/ml (mean, 0.08 jig/ml) for nontolerant strains (8).…”

“…Despite the availability of new and effective antimicrobial agents for the treatment of lifethreatening bacterial infections, neonatal meningitis continues to be associated with an unacceptable mortality and morbidity rate (11 (15). Penicillin-treated group B streptococci, however, show increased susceptibility to the bactericidal activity of human polymorphonuclear leukocytes (5).…”

Paradox between the responses of Escherichia coli K1 to ampicillin and chloramphenicol in vitro and in vivo

“…The activity of combinations of penicillin and chloramphenicol is a subject of considerable debate. In vitro, such combinations have been shown to be antagonistic, indifferent, or synergistic against several gram-negative and gram-positive organisms (6,12,14,20,26,30). The in vivo effects of such combinations in experimental infections have been related to drug administration: antagonism occurred when chloramphenicol was given before but not after penicillin administration (15,29).…”

Cefotaxime diffusion into cerebrospinal fluid of children with meningitis

“…Chloramphenicol is potentially toxic and produces unpredictable blood levels (13,14), and chloramphenicolresistant isolates of H. influenzae are now recognized. In addition, the combination of ampicillin and chloramphenicol may be antagonistic against some enteric gram-negative rods and group B streptococci, both of which are major pathogens in neonatal meningitis (2,18).…”