Evaluation of antimicrobial regimens in a guinea-pig model of meningitis caused by Pseudomonas aeruginosa

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 μl of a solution containing106 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/8 h, meropenem 200 mg/kg/8 h, tobramycin 30 mg/kg/24 h. 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 5 log10 CFU and mean WBC was 16,000/-l. All control animals died in 24 h with a 12% increase in cerebral edema. All blood-cultures were negative. Ceftazidime, ceftazidime + tobramycin and meropenem reduced the CSF bacterial concentration at 8 h by 2.5 log10. 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.