Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1976 Nov;10(5):802–808. doi: 10.1128/aac.10.5.802

Combination of Bacteriostatic and Bactericidal Drugs: Lack of Significant In Vitro Antagonism Between Penicillin, Cephalothin, and Rolitetracycline

Franz D Daschner a,1
PMCID: PMC429840  PMID: 795370

Abstract

Although it is generally believed that bactericidal and bacteriostatic drugs should not be combined in vivo, in vitro experiments using the checkerboard dilution technique revealed no antagonism between penicillin/cephalothin and rolitetracycline but rather additive or synergistic activity of either drug combination in 40 to 50% of 20 Escherichia coli, and 14 Staphylococcus aureus strains. Slight antagonism occurred only between 3 and 8 h after combining penicillin/cephalothin and rolitetracycline in either bacteriostatic or bactericidal concentrations, but not after 24 h of incubation, nor was antagonism found with combinations of these drugs in bacteriostatic concentrations. Neither bacteriostatic nor bactericidal activity of penicillin/cephalothin and rolitetracycline was inhibited by pretreatment of one E. coli strain with bacteriostatic rolitetracycline or bacteriostatic penicillin/cephalothin concentrations. Penicillin and cephalothin could exert a bactericidal effect after 2-h exposure of the E. coli strain to bacteriostatic rolitetracycline concentrations. Combined action of subinhibitory penicillin and rolitetracycline concentrations resulted in more pronounced inhibition of growth than either drug alone. The higher activity of penicillin/cephalothin in combination with rolitetracycline on some E. coli and S. aureus strains might be due to a better access of rolitetracycline into bacterial cells whose cell walls have been weakened by cell wall-active, bactericidal drugs. Thus, growth of penicillin-induced spheroplasts of E. coli and stable staphylococcal L-forms was inhibited by much lower concentrations of rolitetracycline than were the corresponding parent cells with intact cell walls.

Full text

PDF
802

Selected References

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

  1. AHERN J. J., KIRBY W. M. M. Lack of interference of aureomycin with penicillin in treatment of pneumococcic pneumonia. AMA Arch Intern Med. 1953 Feb;91(2):197–203. doi: 10.1001/archinte.1953.00240140057004. [DOI] [PubMed] [Google Scholar]
  2. Brumfitt W., Percival A. Antibiotic combinations. Lancet. 1971 Feb 20;1(7695):387–389. doi: 10.1016/s0140-6736(71)92223-9. [DOI] [PubMed] [Google Scholar]
  3. Chow A. W., Patten V., Guze L. B. Comparative susceptibility of anaerobic bacteria to minocycline, doxycycline, and tetracycline. Antimicrob Agents Chemother. 1975 Jan;7(1):46–49. doi: 10.1128/aac.7.1.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. DOWLING H. F. The conditions under which the use of combinations of antibiotics is undesirable. Antibiot Chemother. 1960;8:114–125. doi: 10.1159/000386668. [DOI] [PubMed] [Google Scholar]
  5. Daschner F. D., Hövel R., Marget W. Action of gentamicin on penicillin G-induced proteus spheroplasts. Chemotherapy. 1973;18(4):235–241. doi: 10.1159/000221267. [DOI] [PubMed] [Google Scholar]
  6. Daschner F. Inhibition of cell wall synthesis by sulfonamides and trimethoprim. Chemotherapy. 1976;22(1):12–18. doi: 10.1159/000221905. [DOI] [PubMed] [Google Scholar]
  7. Dimmling T. Vergleichsstudie über drei derzeit ghebräuchliche Tetracyclinderivate zur intravenösen Anwendung (Serum- und Urinspiegel. Med Klin. 1972 Dec 8;67(49):1632–1637. [PubMed] [Google Scholar]
  8. FINLAND M., PRYLES C. V., JONES W. F., Jr Antibiotic combinations; antibacterial action of plasma of human subjects after ingestion of penicillin V or chloramphenicol or both. N Engl J Med. 1958 Apr 24;258(17):817–824. doi: 10.1056/NEJM195804242581701. [DOI] [PubMed] [Google Scholar]
  9. LEPPER M. H., DOWLING H. F. Treatment of pneumococcic meningitis with penicillin compared with penicillin plus aureomycin; studies including observations on an apparent antagonism between penicillin and aureomycin. AMA Arch Intern Med. 1951 Oct;88(4):489–494. doi: 10.1001/archinte.1951.03810100073006. [DOI] [PubMed] [Google Scholar]
  10. LEPPER M. H., JACKSON G. G., DOWLING H. F., SETO J. Comparison of results of treatment of pneumococcic infections in mice with multiple doses of aureomycin and penicillin combined compared with each drug alone. Am J Med Sci. 1953 Jun;225(6):648–656. doi: 10.1097/00000441-195306000-00009. [DOI] [PubMed] [Google Scholar]
  11. LIMSON B. M., GUEVARA R. B., Jr Efficacy of a single intravenous injection of pyrrolidinomethyltetracycline in pneumococcal pneumonia: report of 20 cases with assays of 24 hour antibiotic activity in serum. Antibiot Chemother (Northfield) 1962 Feb;12:85–90. [PubMed] [Google Scholar]
  12. Luboshitzky R., Sacks T., Michel J. Bactericidal effect of combinations of antibiotics on Klebsiella-Enterobacter-Serratia. Chemotherapy. 1973;19(6):354–366. doi: 10.1159/000221476. [DOI] [PubMed] [Google Scholar]
  13. Mouton R. P., Koelman A. The interaction patterns of combined antibacterial agents. Experiments with two agardiffusion methods. Chemotherapy. 1966;11(1):10–26. doi: 10.1159/000220434. [DOI] [PubMed] [Google Scholar]
  14. RUSSELL F. E. SYNERGISM BETWEEN SULPHONAMIDE DRUGS AND ANTIBIOTICS OF THE POLYMYXIN GROUP AGAINST PROTEUS SP. IN VITRO. J Clin Pathol. 1963 Jul;16:362–366. doi: 10.1136/jcp.16.4.362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. STROM J. The question of antagonism between penicillin and chlortetracycline, illustrated by therapeutical experiments in scarlatina. Antibiotic Med Clin Ther (New York) 1955 Jan;1(1):6–12. [PubMed] [Google Scholar]
  16. Simmons N. A. Potentiation of inhibitory activity of colistin on Pseudomonas aeruginosa by sulphamethoxazole and sulphamethizole. Br Med J. 1969 Sep 20;3(5672):693–696. doi: 10.1136/bmj.3.5672.692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Traub W. H. In vitro activity of chloramphenicol combined with cephalothin against D-Nase-positive, multiple-antibiotic resistant strains of Staphylococcus epidermidis. Chemotherapy. 1970;15(4):234–241. doi: 10.1159/000220687. [DOI] [PubMed] [Google Scholar]

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

RESOURCES