Studies on T-2636 antibiotics. IV. In vitro and in vivo antibacterial activity of T-2636 antibiotics.

Abstract

T-2636 C shows a strong in vitro antimicrobial activity against a variety of Gram-positive bacteria, Neisseria gonorrhoeae and Vibrio cholerae, while T-2636 A, D and F are relatively weak in this respect. T-2636 A and C are more active in vitro at pH 6.0 than at pH 9.0. The antibacterial in vitro activity is enhanced by decrease in bacterial inoculum size. Presence of horse serum in the mediumresults in the decreased activity. The development of resistance of the sensitive bacteria to T-2636 C is demonstrated by exposure according to the serial transfer method. In the cross resistance test using Staphylococcus aureus which had been maderesistant to T-2636 C or macrolide antibiotics in vitro, T-2636 C show a weak activity against microorganisms resistant to spiramycin and triacetyl-oleandomycin, but T-2636 C resistant S. aureus was sensitive to macrolide antibiotics. T-2636Cis effective against staphylococci, isolated from patients, at the similar concentration against the standard laboratory staphylococci. T-2636 demonstrated also bacteriostatic activity. The primary active site of T-2636 C on S. aureus is inhibition of the protein synthesis. T-2636 A and C are effective against experimental infections in mice by S. aureus and Streptococcus pyogenes, when administered intraperitoneally or orally. But T-2636 A was less effective by subcutaneous route.