Rosaramicin Versus Penicillin G in Experimental Pneumococcal Meningitis

Abstract

Rosaramicin, a new macrolide antibiotic, was compared with penicillin G in the treatment of pneumococcal meningitis in rabbits. Animals were infected intracistemally with 104 colony-forming units of Streptococcus pneumoniae type III (rosaramicin minimal inhibitory/bactericidal concentrations, 0.25/0.5 ,ug/ml; penicillin G miniimal inhibitory/bactericidal concentrations, 0.03/0.06 pug/ml). Treatment was instituted 96 h later. Infusion of rosaramicin at 25 mg/kg per h intravenously for 8 h produced a peak cerebrospinal fluid (CSF) drug concentration of 1.54 pug/ml (range, 0.87-3.6 pug/ml). During this infusion the numbers of pneumococci in CSF decreased from 6.2 ± 0.5 to 3.36 ± 1.12 logio colony-forming units per ml. Penicillin G, infused at 30 mg/kg per h for 8 h, reached a similar concentration in CSF but caused a greater reduction (P < 0.01) in CSF bacteria, from 6.4 ± 0.36 to 1.3 ± 0.67 logio colony-forming units per ml. Penicillin G, at 100 mg/kg per day intramuscularly for 5 days, cured 7 of 10 rabbits with pneumococcal meningitis. A higher dose, 300 mg/kg per day for 5 days, was no more efficacious: 11 of 14 rabbits were cured. Rosaramicin at 100 mg/kg per day intramuscularly for 5 days cured only 5 of 15 rabbits with meningitis, but a higher dosage regimen of that drug (250 mg/kg per day intramuscularly) produced acute, fuhminant enterocecitis and death within 48 h in seven of eight rabbits. No cytotoxin was detected in the feces of one rabbit with acute enterocecitis. Thus the efficacy of rosaramicin in experimental pneumococcal meningitis, measured by bacterial clearance from CSF and by treatment outcome, was less than that of penicillin G. In addition, high-dose parenteral rosaramicin caused acute, fulminant enterocecitis in a high proportion of treated rabbits.

Bactericidal versus Bacteriostatic Antibiotic Therapy of Experimental Pneumococcal Meningitis in Rabbits

“…The CSF pneumococcal concentrations in the present experiments, before therapy, were in the range of log1o 4.0->8.0 cfu/ml, similar to previously reported studies with experimental meningitis (27). In addition, concentrations regularly exceeded 108 cfu/ml CSF at the time of death in untreated animals, as noted in other studies (12,27,28,(31)(32)(33)(34). These bacterial concentrations likely reflect inefficient host defense mechanisms at the site of infection.…”