Antagonism, determined by isobolograms constructed from data from combinations of ampicillin and chloramphenicol at or below the minimal inhibitory or bactericidal concentrations, was observed against 13 clinical isolates of meningococcus and against one isolate of pneumococcus. Synergy occurred against six strains of pneumococcus and three of meningococcus. Additive effects were noted against 14 isolates of pneumococcus and 5 of meningococcus. There was no relationship between the minimal inhibitory or bactericidal concentrations for the isolates and the occurrence of antagonistic, additive, or synergistic effects. These data indicate that ampicillin and chloramphenicol may be antagonistic in vitro against some strains of pneumococcus or meningococcus.The combination of ampicillin or penicillin with chloramphenicol has been recommended as initial antibiotic therapy for patients with suspected bacterial meningitis because of the emergence of ampicillin-resistant Haemophilus influenzae type b strains (2). This recommendation was supported by data from a recent in vitro study (6) which showed that ampicillin and chloramphenicol were not antagonistic against H. influenzae type b. However, limited information (1, 7-9) is available about the interaction of these antibiotics against Streptococcus pneumoniae (pneumococcus) or Neisseria meningitidis (meningococcus), the-other two common causes of childhood meningitis.The present study was done to examine the in vitro effect of ampicillin and chloramphenicol against isolates of S. pneumoniae and N. meningitidis.
MATERIALS AND METHODSBacterial isolates. A total of 21 strains of S. pneumoniae and 21 strains of N. meningitidis were isolated from patients or were obtained from Clyde Thornsberry (Center for Disease Control). The pneumococci were isolated from either blood (12 strains) or cerebrospinal fluid (9 strains). Capsular typing was not done on the pneumococcal strains. The meningococci were isolated from cerebrospinal fluid (13 strains), blood (2 strains), throat culture (2 strains), brain, spleen, or eye culture (1 strain each), and an unknown source (1 strain). Of the meningococci 13 strains were group B and 8 were group C.Media. Studies were done by using Mueller-Hinton broth to grow the meningococci and Todd-Hewitt broth supplemented with 5% human serum to grow the pneumococci. Bacterial colony counts of the meningococci or pneumococci were determined by plating 0.1-ml samples from serial 10-fold dilutions of broth cultures onto the surface of chocolate agar plates containing 1% IsoVitaleX (Baltimore Biological Laboratory) or plates containing 5% sheep blood, respectively (5).Studies of antimicrobial interaction. The 42 strains were tested in duplicate for their susceptibility to ampicillin and chloramphenicol, separately and in combination, by using a microtiter apparatus (Cooke Engineering Co., Alexandria, Va.).Tests were done in microtiter plates by using a modification of a previously described procedure (6). Final concentrations of ampicillin increased in 0.0...