TOLYPOMYCIN, A NEW ANTIBIOTIC. V: IN VITRO AND IN VIVO ANTIMICROBIAL ACTIVITY

Tolypomycin-Y and R show a strong in vitro antibacterial activity against Gram-positive bacteria and Neisseria gonorrhoeae. These antibiotics also inhibit the growth of Gram-negative bacteria to some extent. The antibacterial activities are not influenced by the presence of horse serum in the medium. They are approximately 10-30 times more active at pH 6.0 than at pH 9.0. An enhancement of in vitro activity is observed when the bacterial inoculum size is decreased. The rather rapid development of resistance to tolypomycins is shown in the sensitive bacteria by the serial transfer method. The appearance frequencies of one-step resistant strain of Staphylococcus aureus to 1-100mcg/ml of these antibiotics are 2.3-5.8×10-6. Cross resistance is observed between tolypomycins and rifampicin, but it is not observed between tolypomycins and several other antibiotics tested. These antibiotics are effective against staphylococci isolated from patients at concentrations similar to those needed for the standard laboratory staphylococci. Tolypomycins were demonstrated to have bactericidal activity. Tolypomycins administered by subcutaneous, intraperitoneal and intravenous routes, are effective against experimental infections in mice caused by Staphylococcus aureus, Streptococcus pyogenes and Diplococcus pneumoniae type I. In addition, some activity is also shown by oral route.