Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1984 Jun;25(6):676–682. doi: 10.1128/aac.25.6.676

Probenecid: antibacterial action against Neisseria gonorrhoeae and interaction with benzylpenicillin.

B W Catlin
PMCID: PMC185621  PMID: 6430225

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.

Full text

PDF
676

Images in this article

678Image
on p.678
678Image
on p.678

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benedict R. G., Schmidt W. H., Coghill R. D. The Stability of Penicillin in Aqueous Solution. J Bacteriol. 1946 Mar;51(3):291–292. [PMC free article] [PubMed] [Google Scholar]
  2. Bryson V., Szybalski W. Microbial Selection. Science. 1952 Jul 18;116(3003):45–51. doi: 10.1126/science.116.3003.45. [DOI] [PubMed] [Google Scholar]
  3. Carifo K., Catlin B. W. Neisseria gonorrhoeae auxotyping: differentiation of clinical isolates based on growth responses on chemically defined media. Appl Microbiol. 1973 Sep;26(3):223–230. doi: 10.1128/am.26.3.223-230.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Catlin B. W., Pace P. J. Auxotypes and penicillin susceptibilities of Neisseria gonorrhoeae isolated from patients with gonorrhea involving two or more sites. Antimicrob Agents Chemother. 1977 Aug;12(2):147–156. doi: 10.1128/aac.12.2.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cunningham R. F., Israili Z. H., Dayton P. G. Clinical pharmacokinetics of probenecid. Clin Pharmacokinet. 1981 Mar-Apr;6(2):135–151. doi: 10.2165/00003088-198106020-00004. [DOI] [PubMed] [Google Scholar]
  6. DiPiro J. T., Taylor A. T., Steele J. C., Jr Lack of influence of commonly used drugs on bioassay indicator organisms. Antimicrob Agents Chemother. 1983 May;23(5):703–705. doi: 10.1128/aac.23.5.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dougherty T. J., Koller A. E., Tomasz A. Penicillin-binding proteins of penicillin-susceptible and intrinsically resistant Neisseria gonorrhoeae. Antimicrob Agents Chemother. 1980 Nov;18(5):730–737. doi: 10.1128/aac.18.5.730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Evans A. J., Morrison G. D., Price D. J. Prolonged use of the Greenland method of treatment of gonorrhoea. Br J Vener Dis. 1980 Apr;56(2):88–91. doi: 10.1136/sti.56.2.88. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Guinan M. E., Biddle J., Thornsberry C., Reynolds G., Zaidi A., Wiesner P. The National Gonorrhea Therapy Monitoring Study: I. Review of treatment results and of in-vitro antibiotic susceptibility, 1972-1978. Sex Transm Dis. 1979 Apr-Jun;6(2 Suppl):93–102. [PubMed] [Google Scholar]
  10. Gwynn M. N., Webb T. L., Rolinson G. N. Regrowth of Pseudomonas aeruginosa and other bacteria after the bactericidal action of carbenicillin and other beta-lactam antibiotics. J Infect Dis. 1981 Sep;144(3):263–269. doi: 10.1093/infdis/144.3.263. [DOI] [PubMed] [Google Scholar]
  11. Hendry A. T., Stewart I. O. Auxanographic grouping and typing of Neisseria gonorrhoeae. Can J Microbiol. 1979 Apr;25(4):512–521. doi: 10.1139/m79-075. [DOI] [PubMed] [Google Scholar]
  12. Hilton A. L. PAM plus probenecid and procaine penicillin plus probenecid in gonorrhoea. Br J Vener Dis. 1971 Apr;47(2):107–110. doi: 10.1136/sti.47.2.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Holmes K. K., Johnson D. W., Floyd T. M. Studies of venereal disease. I. Probenecid-procaine penicillin G combination and tetracycline hydrochloride in the treatment of "penicillin-resistant" gonorrhea in men. JAMA. 1967 Nov 6;202(6):461–473. doi: 10.1001/jama.202.6.461. [DOI] [PubMed] [Google Scholar]
  14. Jaffe H. W., Zaidi A. A., Thornsberry C., Reynolds G. H., Wiesner P. J. Trends and seasonality of antibiotic resistance of Neisseria gonorrhoeae. J Infect Dis. 1977 Nov;136(5):684–688. doi: 10.1093/infdis/136.5.684. [DOI] [PubMed] [Google Scholar]
  15. Kim K. S., Anthony B. F. Use of penicillin-gradient and replicate plates for the demonstration of tolerance to penicillin in streptococci. J Infect Dis. 1983 Sep;148(3):488–491. doi: 10.1093/infdis/148.3.488. [DOI] [PubMed] [Google Scholar]
  16. Lesiński J., Dzierzanowska D., Szymczak M., Linda H., Wiśniewska C., Nawara A., Winogrodzka A. Treatment of gonorrhoea with procaine penicillin plus probenecid. Br J Vener Dis. 1973 Aug;49(4):358–361. doi: 10.1136/sti.49.4.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lysko P. G., Morse S. A. Neisseria gonorrhoeae cell envelope: permeability to hydrophobic molecules. J Bacteriol. 1981 Feb;145(2):946–952. doi: 10.1128/jb.145.2.946-952.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Olsen G. A. Consumption of antibiotics in Greenland, 1964-70. IV. Changes in the sensitivity of N. gonorrhoeae to antibiotics. Br J Vener Dis. 1973 Feb;49(1):33–41. doi: 10.1136/sti.49.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Olsen G. A., Lomholt G. Gonorrhoea treated by a combination of probenecid and sodium penicillin G. Br J Vener Dis. 1969 Jun;45(2):144–148. doi: 10.1136/sti.45.2.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Swanson J. Colony opacity and protein II compositions of gonococci. Infect Immun. 1982 Jul;37(1):359–368. doi: 10.1128/iai.37.1.359-368.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Swanson J. Studies on gonococcus infection. XII. Colony color and opacity varienats of gonococci. Infect Immun. 1978 Jan;19(1):320–331. doi: 10.1128/iai.19.1.320-331.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Taylor P. C., Schoenknecht F. D., Sherris J. C., Linner E. C. Determination of minimum bactericidal concentrations of oxacillin for Staphylococcus aureus: influence and significance of technical factors. Antimicrob Agents Chemother. 1983 Jan;23(1):142–150. doi: 10.1128/aac.23.1.142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Totten P. A., Holmes K. K., Handsfield H. H., Knapp J. S., Perine P. L., Falkow S. DNA hybridization technique for the detection of Neisseria gonorrhoeae in men with urethritis. J Infect Dis. 1983 Sep;148(3):462–471. doi: 10.1093/infdis/148.3.462. [DOI] [PubMed] [Google Scholar]
  24. Wigfield A. S., Selkon J. B., Rich G. E. Single-session treatment of uncomplicated gonorrhoea in men, using penicillin combined with cotrimoxazole. Controlled trial comparing four different treatment schedules with observations on antibiotic sensitivities of gonococci and a review of the literature. Br J Vener Dis. 1973 Jun;49(3):277–290. doi: 10.1136/sti.49.3.277. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES