Tissue fluid penetration and anti-treponemal activity of trospectomycin (a new spectinomycin analog) in the rabbit syphilis model.

The antitreponemal activity of trospectomycin (a novel 6'-propyl analog of spectinomycin) was correlated with concentrations in serum and tissue chamber fluid in a cutaneously-infected rabbit model of syphilis. After single-dose intramuscular (im) injections of trospectomycin, spectinomycin hydrochloride, and aqueous procaine penicillin G(APPG), concentrations of the drugs in paired specimens of serum and tissue fluid were determined and correlated with response of Treponema pallidum-infected lesions. Lesions responded most rapidly in APPG-treated animals. Rapid response correlated with more prolonged levels of APPG in both serum and tissue fluid. Trospectomycin, when given in single doses exceeding 40 mg/kg, surpassed penicillin in peak serum levels (greater than 60 micrograms/ml at 1 hr) but not in duration of activity. Higher and prolonged concentrations of trospectomycin in tissue fluid correlated with more effective clearance of treponemes from cutaneous lesions. Animals treated with less than 40 mg of trospectomycin/kg or with 20-80 mg/kg of the parent compound (spectinomycin hydrochloride) had cutaneous lesions that were persistently darkfield-positive, as confirmed by three or more consecutive smears.