Pharmacokinetic and bacteriological correlations between antimicrobial therapy of experimental meningitis in rabbits and meningitis in humans: a review

Abstract

Animal models of bacterial meningitis have been developed to study antimicrobial pharmacokinetics and efficacy for eliminating bacteria from cerebrospinal fluid (CSF) and to study pathophysiology. The correlation between observations in the rabbit model and in paediatric patients with meningitis was evaluated. When dosages of the beta-lactam or aminoglycosidic antibiotics which will produce serum concentrations approximating those in the human were given to rabbits, the degree of penetration of antibiotics into CSF and the bactericidal activity in CSF were comparable in rabbits and humans. Differing rates of elimination of Gram-negative enteric bacteria from rabbit CSF correlated directly with the bactericidal titres. However, in children with meningitis, this correlation was not found. Instead, it appeared that there was a critical level of bactericidal activity of 1:8 at which optimal killing of bacteria occurred. Increasing the bactericidal activity beyond that point did not accelerate elimination of bacteria from CSF. It is concluded that the rabbit model of bacterial meningitis is useful for predicting pharmacokinetics and activity of new antibiotics in CSF, but not for predicting differing degrees of effectiveness among antibiotics.