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 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.
Maiques
José Maria
JM
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.
Doménech
Alejandro
A
Cabellos
Carmen
C
Fernández
Antonio
A
Ribes
Sandra
S
Tubau
Fe
F
Gudiol
Francesc
F
Viladrich
Pedro F
PF
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*
D000890:Anti-Infective Agents