Bactericidal and Bacteriostatic Action of Chloramphenicol Against Meningeal Pathogens

Abstract

The bacteriostatic and bactericidal effects of chloramphenicol, ampicillin, tetracycline, and sulfisoxazole were compared against several potential meningeal pathogens. Chloramphenicol is bactericidal at clinically achievable concentrations against Haemophilus influenzae, Streptococcuspneumoniae, and Neisseria meningitidis. It is bacteriostatic against gram-negative bacilli of the farnily Enterobacteriaceae and against Staphylococcus aureus. Chloramphenicol has proven highly efficacious in the treatment of bacterial meningitis caused by those organisms against which it is bactericidal at low concentrations. Because leukocytic phagocytosis in the subarachnoid space is inefficient, we propose that bactericidal activity in cerebrospinal fluid is important for optimal therapy of bacterial meningitis. Chloramphenicol does not provide such activity in meningitis caused by enteric gram-negative bacilli.Chloramphenicol has assumed an increasingly important role in the therapy of pyogenic meningitis. It is considered the drug of choice for meningitis due to ampicillin-resistant Haemophilus influenzae and for pneumococcal and meningococcal meningitis in patients allergic to penicillin. Recently, enteric gram-negative bacfilary meningitis has been noted more frequently among adults undergoing neurosurgical procedures and in those with debilitating disease (7). Antibiotic susceptibility of these pathogens is often limited to chloramphenicol and aminoglycosides. When chloramphenicol susceptibility is known, this drug has been favored as the treatment of choice because of its greater penetrability from serum to cerebrospinal fluid (11 and an inoculum of 105 organisms per ml. One-half milliliter of inoculum was added to 0.5 ml of each antibiotic dilution, and the suspensions were incubated for 18 h at 370C. The minimal inhibitory concentration (MIC) was defined as the lowest concentration of antibiotic preventing visible turbidity. All clear tubes were subcultured with a calibrated loop (0.01 ml) onto antibiotic-free agar for 18 h at 37°C. The minimal bactericidal concentration (MBC) was defined as that yielding growth of fewer than five colonies (>99% killing). Supplement C (2.5%, Difco) was added for determination of H. influenzae susceptibility. Quantitative studies of bacterial killing rates were performed with 2-mi suspensions containing 105 organisms per ml. Aliquots of 0.1 ml were removed at timed intervals, and colony-forming units were counted by the standard plate dilution technique. RESULTSEleven strains of H. influenzae, 10 strains of S. pneumoniae, and 10 strains ofN. meningitidis were tested for their bacteriostatic and bactericidal susceptibility to chloramphenicol, ampicillin, and tetracycline. Susceptibility of the N. meningitidis strains to sulfisoxazole was also tested.Against H. influenzae, the MIC of chloramphenicol was at least twofold lower than that of ampicillin for 10 of 11 strains. The MBC of chloramphenicol was at least twofold lower than that of ampicillin for six strains and equal to that of ampic...

In vitro activities of trimethoprim and sulfamethoxazole against Listeria monocytogenes

“…In general, the use of bactericidal antimicrobial agents appears to be desirable (and often necessary) in the therapy of bacterial meningitis (24). In meningitis, despite the presence of abundant phagocytic cells in the cerebrospinal fluid, opsonization is impaired due to the relatively low concentration of complement present (7,11,31).…”

Tests for bactericidal effects of antimicrobial agents: technical performance and clinical relevance

“…While the utility of assessing the bactericidal activity of particular drugs for individual patients with these types of infections is controversial, knowing whether an agent or class of agents is considered bactericidal against a particular microorganism(s) may be important. For example, Rahal and Simberkoff (89) showed that chloramphenicol is bactericidal against such meningeal pathogens as H. influenzae, Streptococcus pneumoniae, and Neisseria meningitidis, whereas it is only bacteriostatic against members of the family Enterobacteniaceae and S. aureus. The classes of commonly used antimicrobial agents that are considered bactericidal include penicillins, cephalosporins, and related compounds; vancomycin and related compounds; aminoglycosides; quinolones; rifampin; metronidazole; bacitracin; polymyxin; and colistimethate.…”

Antibiotic-Free Selection for Bio-Production: Moving Towards a New "Gold Standard"

“…The spectra of activity of this antibiotic being variable between true bactericidal and bacteriostatic effect according to the gram character or nature of the bacterial strain considered (Rahal and Simberkoff 1979).…”