Rosaramicin, a new
macrolide antibiotic, was compared with
penicillin G in the treatment of
pneumococcal meningitis in rabbits. Animals were infected intracisternally with 10(4) colony-forming units of Streptococcus pneumoniae type III (
rosaramicin minimal inhibitory/bactericidal concentrations, 0.25/0.5 mug/ml;
penicillin G minimal inhibitory/bactericidal concentrations, 0.03/0.06 mug/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 mug/ml (range, 0.87-3.6 mug/ml). During this infusion the numbers of pneumococci in CSF decreased from 6.2 +/- 0.5 to 3.36 +/- 1.12 log(10) 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 log(10) 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, fulminant 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.