Probenecid: antibacterial action against Neisseria gonorrhoeae and interaction with benzylpenicillin

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.

Non‐Antibiotics – An Alternative for Microbial Resistance: Scope and Hope

“…[46] probenecid Neisseria spp. [45] triamiterene Streptococcus spp. [46] b-adrenergic blocker bacteria [42] Others acetyl salicylic acid active levomepromazine (Figure 4.4) [161].…”

Safety Aspects and Rational Use of Single Intramuscular Dose Ceftriaxone: Clinical Insights on the Management of Uncomplicated Gonococcal Infections

“…19 The concomitant administration of probenecid, which inhibits the renal tubular secretion of penicillin and displays synergistic in vitro antibacterial activity with penicillin, was also recommended. 20 , 21

Figure 1 Timeline of Notable Events in the Treatment of Uncomplicated Gonococcal Infections.

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“…19 The concomitant administration of probenecid, which inhibits the renal tubular secretion of penicillin and displays synergistic in vitro antibacterial activity with penicillin, was also recommended. 20,21 In 1985, in light of increasing penicillin resistance, ceftriaxone (administered as a single intramuscular dose of 250 mg) was added for the first time as a recommended treatment option. 22 The 1985 treatment guideline notably added concomitant administration of tetracycline, doxycycline, or erythromycin (the latter in those unable to receive tetracyclines) in order to provide activity against Chlamydia trachomatis, which often co-infects individuals with gonorrhea.…”