Bactericidal versus Bacteriostatic Antibiotic Therapy

/Ag/ml; strain2-MIC 1 ,g/ml, MBC 2 ,g/ml. Animals were treated with either ampicillin or chloramphenicol in dosages that achieved a peak bactericidal effect in cerebrospinal fluid (CSF) for ampicillin against both strains. Two different dosages were used for chloramphenicol. The first dosage achieved a peak CSF concentration of 4.4±1.1 gg/ml that produced a bacteriostatic effect against strainI and bactericidal effect against strain2. The second dosage achieved a bactericidal effect against both strains (mean peak CSF concentration 30.0 Ag/ml). All animals were treated intramuscularly three times a day for 5 d. CSF was sampled daily and 3 d after discontinuation of therapy for quantitative bacterial cultures. Results demonstrate Portions of this work were presented at the Annual Meeting of the American Federation for Clinical Research, Wash., D.C., May 1979, and was published in abstract form in 1979. Clin. Res. 27: 355a. (Abstr.) Dr. Scheld is the recipient of the Clinical Investigator Award 1-K08-AI00517-01 from the National Institute of Allergy and Infectious Diseases. Address all correspondence to Dr. W. M. Scheld, Division of Infectious Diseases, University of Virginia School of Medicine, Charlottesville, VA 22908. Received for publication 28 June 1982 and in revised form 9 November 1982. that only antimicrobial therapy that achieved a bactericidal effect in CSF was associated with cure. Over 90% of animals treated with one of the bactericidal regimens (i.e., animals in which the bacterial counts in CSF dropped >5 log10 colony-forming units [cfu]/ ml after 48 h) had sterile CSF after 5 d of treatment. On the other hand, the regimen that achieved bacteriostatic concentrations (CSF drug concentrations between the MIC and MBC) produced a drop of 2.4 log10 cfu/ml by 48 h; however, none of the animals that survived had sterile CSF after 5 d. These studies clearly demonstrate in a strictly controlled manner that maximally effective antimicrobial therapy of experimental pneumococcal meningitis depends on achieving a bactericidal effect in CSF.