Rosamicin: Evaluation In Vitro and Comparison with Erythromycin and Lincomycin

The in vitro activity of rosamicin was determined against 231 strains of anaerobic bacteria and compared with the activity of erythromycin against the same strains. Rosamicin and erythromycin had similar activity against strains of Peptostreptococcus and gram-positive nonsporeforming bacilli. Rosamicin was somewhat more active against strains of Peptococcus, Clostridium , and gram-negative anaerobes. All strains of Bacteroides fragilis tested were inhibited by 4 μg of rosamicin or less per ml, whereas only 76% of them were inhibited by this concentration of erythromycin. Rosamicin was distinctly more active against Fusobacterium nucleatum . Because of its in vitro activity, further investigation of the pharmacology of this drug is warranted.

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confidence: 99%

Rosamicin: In Vitro Activity Against Anaerobes and Comparison with Erythromycin

Sutter

Finegold²

1976

“…Rosaramicin is a broad-spectrum macrolide antibiotic, similar to erythromycin (1,10). The antibiotic is isolated from fermentation broth of Micromonospora rosaria (11).…”

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confidence: 99%

Pharmacokinetics and metabolism of rosaramicin in humans

Lin¹,

Chung²,

Gural³

et al. 1984

The pharmacokinetics of rosaramicin was studied in subjects receiving 500 mg of the drug (i) by 1-h intravenous infusion, (ii) in solution orally, or (iii) as tablets orally. After intravenous administration, the rosaramicin levels in serum declined rapidly with t112S of 0.27 h for the distribution phase and 3.28 h for the elimination phase. The apparent volume of distribution was 3.78 liter/kg, and the total body clearance was 13.41 ml/min per kg, indicating extensive tissue distribution or metabolism or both. Similar pharmacokinetic data were obtained after oral administration of the drug in solution or tablets and after intravenous dosing. The absolute bioavailability of the drug administered orally, in either tablets or solution, was 32 to 39%. The metabolism and excretion of [14C]rosaramicin administered orally were also evaluated in volunteers. The serum area under the curve (oo) of unchanged rosaramicin was 19% of that of total radioactivity, indicating extensive metabolism of the drug. About 7.0% of the radioactivity was recovered in the urine, and 86.7% was recovered in the feces. Only a small amount of unchanged rosaramicin was present in the urine (7 to 9% of urinary radioactivity), but none was present in the feces. The major metabolite, 20-bis-ureidorosaramicin, represented 17 to 38% of the radioactivity in the urine and 26 to 29% of the radioactivity in the feces.Rosaramicin is a broad-spectrum macrolide antibiotic, similar to erythromycin (1, 10). The antibiotic is isolated from fermentation broth of Micromonospora rosaria (11). Rosaramicin has been shown to have good in vitro activity against gram-positive aerobes and anaerobes. In addition, rosaramicin has been shown to have greater in vitro activity than erythromycin against a variety of gram-negative organisms and anaerobes, including Bacteroides and Mvcoplasma species (12). This paper describes the pharmacokinetics of rosaramicin in subjects receiving 500-mg doses by (i) 1-h intravenous infusion, (ii) solution orally, or (iii) tablets orally. The metabolism and excretion of ['4C]rosaramicin after oral administration of a 500-mg dose of [14C]rosaramicin were also evaluated. MATERIALS AND METHODSCompound. For the pharmacokinetic study, a rosaramicin solution (100 mg/ml) for oral administration was obtained by adding 3 ml of sterile water to the sterile vial containing rosaramicin sodium dihydrogen phosphate, lyophilized powder (equivalent to 300 mg of rosaramicin base). The rosaramicin solution (2.5 mg/ml) for intravenous infusion was obtained by adding 12 ml of the oral solution to 468 ml of saline. The 250-mg rosaramicin tablets were manufactured by Schering Corp.For the metabolic study, 5-[14C]rosaramicin (Fig. 1) inverse isotope dilution technique and high-pressure liquid chromatography (HPLC), was greater than 95%.Administration of rosaramicin. Twelve healthy male volunteers participated in the pharmacokinetic study of single blind three-way crossover design. After an 8-h fast, each subject received 500 mg of rosaramicin as (i) two 250-mg...

“…This agent is active in vitro against S. pneumoniae and the other species of bacteria most often associated with bacterial meningitis (6,13). Rosaramicin should penetrate well into the central nervous system because, like chloramphenicol, it is highly soluble in lipid solvents (20).…”

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confidence: 99%

Rosaramicin Versus Penicillin G in Experimental Pneumococcal Meningitis

Nolan¹,

Monson²,

Ulmer³

1979

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.