title: Evaluation of antimicrobial regimens in a guinea-pig model of meningitis caused by Pseudomonas aeruginosa.
abstract: To compare the efficacy of meropenem, ceftazidime, tobramycin and ceftazidime+tobramycin in a guinea-pig model of P. aeruginosa meningitis. After anesthesia, the atlanto-occipital membrane was punctured with a butterfly needle and 100 microl of a solution containing 10(6)CFU/ml of P. aeruginosa were injected directly into the cisterna magna. Four h later, therapy was initiated with saline or antibiotics given im for 48 h in doses that obtained CSF levels as in human meningitis: ceftazidime 200 mg/kg/8h, meropenem 200 mg/kg/8h, tobramycin 30 mg/kg/24h. Tobramycin was also given intracisternally. Animals were sacrificed at different time points. CSF and blood samples were collected and a meningeal swab was performed. Four hours after inoculation, bacterial concentration in CSF was 4 to 5log10CFU and mean WBC was 16,000/-l. All control animals died in 24h with a 12% increase in cerebral edema. All blood-cultures were negative. Ceftazidime, ceftazidime+tobramycin and meropenem reduced the CSF bacterial concentration at 8h by 2.5log10. At 48 h all CSF cultures were sterile but meningeal swab cultures remained positive in 30%. Our results suggest that meropenem may be at least as effective as ceftazidime and that the addition of tobramycin to ceftazidime may improve its efficacy.
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL, Hospital Universitari de Bellvitge, University of Barcelona, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: José Maria
authors.initials: JM
authors.lastname: Maiques
authors.forename: Alejandro
authors.initials: A
authors.lastname: Doménech
authors.forename: Carmen
authors.initials: C
authors.lastname: Cabellos
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernández
authors.forename: Sandra
authors.initials: S
authors.lastname: Ribes
authors.forename: Fe
authors.initials: F
authors.lastname: Tubau
authors.forename: Francesc
authors.initials: F
authors.lastname: Gudiol
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Viladrich
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008581:Meningitis / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000254:growth & development*
chemical_list: D000890:Anti-Infective Agents