Probenecid: antibacterial action against Neisseria gonorrhoeae and interaction with benzylpenicillin

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Abstract
Neisseria gonorrhoeae strains were used in an investigation of the antibacterial action of probenecid and its interaction with benzylpenicillin. The growth of 112 routine isolates was inhibited by probenecid at concentrations of 100 to 500 micrograms/ml incorporated in agar. Additive or synergistic effects of benzylpenicillin-probenecid combinations were graphically illustrated in gradient plates. In agar dilution tests with a resistant gonococcal strain, the MICs of benzylpenicillin alone and probenecid alone were 0.8 and 500 micrograms/ml, respectively; in contrast, the MICs of combinations of benzylpenicillin and probenecid were 0.45 and 75 micrograms/ml and 0.3 and 150 micrograms/ml, respectively. High concentrations of probenecid in broth were bactericidal. Probenecid alone at 50 to 100 micrograms/ml had little antibacterial effect, but in combination with an appropriate concentration of benzylpenicillin, it produced reductions of CFU in 6 h that were 100 to 300 times that produced by benzylpenicillin alone. Thus, in addition to its well-known pharmacological effects, probenecid potentiates the in vitro action of benzylpenicillin for gonococci. I suggest that synergism contributes to the beneficial effect of the benzylpenicillin-probenecid regimen for the treatment of gonorrhea. Furthermore, synergism may explain the reduction in the ratio of partially benzylpenicillin-resistant N. gonorrhoeae strains to benzylpenicillin-susceptible strains that occurred in the United States between 1972 and 1978.