title: 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.
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Force
authors.forename: F
authors.initials: F
authors.lastname: Taberner
authors.forename: C
authors.initials: C
authors.lastname: Cabellos
authors.forename: S
authors.initials: S
authors.lastname: Ribes
authors.forename: A
authors.initials: A
authors.lastname: Domenech
authors.forename: F
authors.initials: F
authors.lastname: Tubau
authors.forename: P F
authors.initials: PF
authors.lastname: Viladrich
authors.forename: F
authors.initials: F
authors.lastname: Gudiol
mesh_terms: D000818:Animals; D018550:Cephalosporin Resistance / Q000502:physiology; D002511:Cephalosporins / Q000494:pharmacology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D016920:Meningitis, Bacterial / Q000188:drug therapy*; D008586:Meningitis, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D013845:Thienamycins / Q000627:therapeutic use*
chemical_list: D002511:Cephalosporins; D013845:Thienamycins; D000077731:Meropenem