Factors influencing the therapy of experimental Proteus mirabilis meningitis in rabbits

Abstract

The therapy of Proteus mirabilis meningitis with gentamicin alone and in combination with chloramphenicol was studied in a rabbit model. Antibiotics were administered for 8 hr. Samples of serum and cerebrospinal fluid (CSF) obtained simultaneously were assayed at 2-hr intervals for antibiotic concentration and counts of bacteria in CSF. The percentage of penetration ([concentration in CSF divided by concentration in serum] x 100%) of gentamicin ranged from 14% to 23%, but very large dosages were required to kill bacteria in the CSF. Although the minimal bactericidal concentration (MBC) of gentamicin was 1 microgram/ml, killing in vivo occurred only when concentrations in CSF were 10--30 times the MBC. The high concentration required for bactericidal activity in vivo may be explained by the reduced pH of infected CSF (mean pH, 6.98; range, 6.69--7.18). The bactericidal action of gentamicin was abolished by the simultaneous administration of chloramphenicol. Titers of bacteria in CSF were reduced 2.60 log10 (mean) with gentamicin therapy vs. 0.92 log10 (mean) with combination (P less than 0.01).