Experimental study of meropenem in the therapy of cephalosporin-susceptible and -resistant pneumococcal meningitis

Abstract

Meropenem is a carbapenem antibiotic that is highly active against the pathogens causing meningitis. Results with meropenem in the experimental rabbit model of penumococcal meningitis have been controversial, and the possible role of renal dehydropeptidase I in meropenem efficacy has been suggested. The aim of this study was to determine the efficacy of meropenem in two meningitis models and the possible influence of the animal model over results. Two strains of Streptococcus pneumoniae with different susceptibility to beta-lactams have been used in a guinea pig model and the classical rabbit meningitis model. Meropenem was bactericidal at 6 h in the guinea pig model against both strains with a reduction of >4 log ufc/ml. In the rabbit model it was bactericidal at 6 h against the susceptible strain, but against the resistant 3/8 therapeutical failures were recorded at 6 h, being bactericidal at 24 h. In conclusion, meropenem has shown bactericidal activity in both experimental models. This work emphasises the importance of an adequate election of the animal model for the appropriate development of studies of antimicrobial efficacy. We believe that guinea pig should be considered the best choice among laboratory animal species when assessing meropenem efficacy.

Treatment of bacterial meningitis: an update

“…Four randomized clinical trials in adults and children with bacterial meningitis comparing meropenem with cefotaxime or ceftriaxone demonstrated that meropenem was clinically and microbiologically comparable to cefotaxime and ceftriaxone [65][66][67][68] and no seizure activity was thought to be related to meropenem. The activity of meropenem was inconsistent in the experimental rabbit meningitis model caused by penicillinresistant or pencillin-and cephalosporin-resistant pneumococci [69,70], but showed good bactericidal effect against cephalosporin-resistant S. pneumoniae in guinea pig model [71]. The possible reason for this discrepancy may be related to the activity of renal dehydropeptidase I (DHP-1) in meropenem, which is important in bactericidal activity.…”

Quantitation of cytokine mRNA by real-time RT-PCR during a vaccination trial in a rabbit model of fascioliasis

“…Rabbits are used as models in a wide variety of studies, including for evaluation of novel antibiotic formulations as therapy against bacterial or parasitic infections (el-Bahy, 1997; Force et al, 2008), for production of high-quality antiserum, in studies of immunoglobulin structure and regulation (Kindt, 1975), in studies of B cell development (Yang et al, 2005), in studies of myxomatosis, coccidioidomicosis and trematodiasis (Clemons et al, 2007; Fouchet et al, 2008; Hussein and Khalifa, 2008; Silva et al, 2004), and in vaccination studies against parasites and viral infections (Espino and Hillyer, 2004; Palmer et al, 2006). The main goal of our laboratory is to identify Fasciola hepatica antigens with potential for use in vaccines, and we often use a rabbit model of fascioliasis to evaluate the effectiveness of these antigens.…”

Treatment of Drug-resistant Pneumococcal Meningitis

“…It is less neurotoxic with less seizure tendency compared to imipenem. An experimental study evaluated meropenem as monotherapy in meningitis caused by cephalosporinsusceptible and cephalosporin-resistant S. pneumoniae strains using two different animals, rabbits and guinea pigs [37]; bactericidal activity was excellent against the cephalosporin-susceptible strain in both animal species and against the cephalosporin-resistant strain in guinea pigs, but therapeutic failure was observed in the rabbits inoculated with the cephalosporin-resistant strain.…”