Open AccessIn vitro and in vivo evaluation of A-56268 (TE-031), a new macrolide
Author(s) -
Prabhavathi Fernandes,
Robert T. Bailer,
R. N. Swanson,
Charles W. Hanson,
Edith McDonald,
N. Ramer,
Dwight J. Hardy,
N. L. Shipkowitz,
R. R. Bower,
E Gade
Publication year - 1986
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.30.6.865
Subject(s) - erythromycin , microbiology and biotechnology , streptococcus pneumoniae , streptococcus pyogenes , in vivo , staphylococcus epidermidis , staphylococcus aureus , haemophilus influenzae , propionibacterium acnes , antibacterial agent , serial dilution , chemistry , biology , antibiotics , medicine , bacteria , genetics , alternative medicine , pathology
The in vitro and in vivo antibacterial activity of A-56268 (TE-031), the 6-O-methyl derivative of erythromycin, was compared with those of erythromycin and other reference drugs. A-56268 had the same spectrum of antibacterial activity as erythromycin. A-56268 was generally 1 log2 dilution more potent or equal to erythromycin against all organisms except haemophilus influenzae and Propionibacterium acnes, for which A-56268 was 1 log2 dilution and 3 log2 dilutions, respectively, less potent. The MBC of A-56268 and erythromycin was not significantly different from the MIC against Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus epidermidis, and H. influenzae but was more than 2 log2 dilutions higher than the MICs for some Staphylococcus aureus strains. Human serum at a concentration of 50% did not change the in vitro potency of A-56268 or erythromycin. A-56268 was similar to erythromycin in being more active at pH 8.0 than at the physiologic pH of 7.3. The activity of A-56268 was synergistic with sulfamethoxazole against 4 of 12 strains of H. influenzae. In mouse protection tests, when administered orally A-56268 was more potent than erythromycin against H. influenzae, S. pyogenes, S. pneumoniae, and S. aureus. After subcutaneous administration the potencies of A-56268 and erythromycin were not statistically different from each other. A-56268 was more potent than erythromycin against Legionella infection in guinea pigs. The concentration of A-56268 in the serum and lung was higher than that of erythromycin after intraperitoneal administration. In A-56268 in the serum and lung was higher than that of erythromycin after intraperitoneal administration. In mice, the peak levels in serum of A-56268 and erythromycin were similar after subcutaneous administration and seven times higher for A-56268 after oral administration. The serum half-life of A-56268 was approximately twice that of erythromycin after administration by both routes.