Pharmacokinetic Determinants of Penicillin Cure of Gonococcal Urethritis

In a 1964 study of the pharmacokinetic determinants of penicillin cure of gonococcal urethritis, 45 male prisoner volunteers were experimentally infected with strains of Neisseria gonorrhoeae having known in vitro penicillin susceptibility. After developing urethritis, subjects received intramuscular penicillin G and had serum samples obtained serially to determine penicillin concentration. Using a multiple regression technique, we studied patient-associated parameters and parameters of the serum penicillin curves to determine the best predictors of treatment results. Cure was best predicted by the time the serum penicillin concentration remained above three to four times the penicillin minimum inhibitory concentration of the infecting strain (probability of correct classification, >0.80). Those cured had serum penicillin concentrations which remained in this range for means of 7 to 10 h. Our findings confirm principles of antimicrobial therapy derived from animal models and may have application in studying therapy of gonorrhea and other infectious diseases.