Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1978 Nov;14(5):737–742. doi: 10.1128/aac.14.5.737

Effect of Two Cancer Chemotherapeutic Agents on the Antibacterial Activity of Three Antimicrobial Agents

Marcia R Moody 1, Maureen J Morris 1, Viola Mae Young 1, Lemuel A Moyé III 1, Stephen C Schimpff 1, Peter H Wiernik 1
PMCID: PMC352543  PMID: 103494

Abstract

Cancer chemotherapeutic agents and antibacterial antibiotics are often given concomitantly. Daunorubicin, cytosine arabinoside, and three antibiotics (gentamicin, amikacin, and ticarcillin) were tested individually and in combinations to determine their antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. These cytotoxic agents are commonly employed in the therapy of acute nonlymphocytic leukemia for remission induction therapy, and these antimicrobial agents are used in infection therapy. The maximum concentrations of the two cytotoxic drugs were chosen to be twice the known peak plasma levels of commonly employed dosage schedules. Neither of the cancer chemotherapeutic agents, alone or in combination, demonstrated bactericidal activity at the levels tested. However, in the presence of these agents, the antimicrobial activity of gentamicin and amikacin, although not that of ticarcillin, was depressed for 11 of 15 K. pneumoniae strains and 8 of 15 P. aeruginosa strains, but for none of the strains of E. coli. This level of decreased activity occasionally resulted in a minimal inhibitory concentration of the tested aminoglycoside well above the standard serum levels. Daunorubicin was more likely to antagonize gentamicin than was cytosine arabinoside.

Full text

PDF
737

Selected References

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

  1. Alberts D. S., Bachur N. R., Holtzman J. L. The pharmacokinetics of daunomycin in man. Clin Pharmacol Ther. 1971 Jan-Feb;12(1):96–104. doi: 10.1002/cpt197112196. [DOI] [PubMed] [Google Scholar]
  2. Bodey G. P. Infections in cancer patients. Cancer Treat Rev. 1975 Jun;2(2):89–128. doi: 10.1016/s0305-7372(75)80005-3. [DOI] [PubMed] [Google Scholar]
  3. Chabner B. A., Young R. C. Threshold methotrexate concentration for in vivo inhibition of DNA synthesis in normal and tumorous target tissues. J Clin Invest. 1973 Aug;52(8):1804–1811. doi: 10.1172/JCI107362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Coffey J. J., White C. A., Lesk A. B., Rogers W. I., Serpick A. A. Effect of allopurinol on the pharmacokinetics of 6-mercaptopurine (NSC 755) in cancer patients. Cancer Res. 1972 Jun;32(6):1283–1289. [PubMed] [Google Scholar]
  5. Dilworth J. A., Mandell G. L. Infections in patients with cancer. Semin Oncol. 1975 Dec;2(4):349–359. [PubMed] [Google Scholar]
  6. ELION G. B., SINGER S., HITCHINGS G. H. Antagonists of nucleic acid derivatives. VIII. Synergism in combinations of biochemically related antimetabolites. J Biol Chem. 1954 Jun;208(2):477–488. [PubMed] [Google Scholar]
  7. Goldschmidt M. C., Bodey G. P. Effect of chemotherapeutic agents upon microorganisms isolated from cancer patients. Antimicrob Agents Chemother. 1972 Apr;1(4):348–353. doi: 10.1128/aac.1.4.348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. HERSH E. M., BODEY G. P., NIES B. A., FREIREICH E. J. CAUSES OF DEATH IN ACUTE LEUKEMIA: A TEN-YEAR STUDY OF 414 PATIENTS FROM 1954-1963. JAMA. 1965 Jul 12;193:105–109. doi: 10.1001/jama.1965.03090020019005. [DOI] [PubMed] [Google Scholar]
  9. Hahn D. M., Schimpff S. C., Young V. M., Fortner C. L., Standiford H. C., Wiernik P. H. Amikacin and cephalothin: empiric regimen for granulocytopenic cancer patients. Antimicrob Agents Chemother. 1977 Nov;12(5):618–624. doi: 10.1128/aac.12.5.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ho D. H., Frei E., 3rd Clinical pharmacology of 1-beta-d-arabinofuranosyl cytosine. Clin Pharmacol Ther. 1971 Nov-Dec;12(6):944–954. doi: 10.1002/cpt1971126944. [DOI] [PubMed] [Google Scholar]
  11. Klastersky J., Henri A., Hensgens C., Daneau D. Gram-negative infections in cancer. Study of empiric therapy comparing carbenicillin-cephalothin with and without gentamicin. JAMA. 1974 Jan 7;227(1):45–48. doi: 10.1001/jama.227.1.45. [DOI] [PubMed] [Google Scholar]
  12. Kluge R. M., Standiford H. C., Tatem B., Young V. M., Schimpff S. C., Greene W. H., Calia F. M., Hornick R. B. The carbenicillin-gentamicin combination against Pseudomonas aeruginosa. Correlation of effect with gentamicin sensitivity. Ann Intern Med. 1974 Nov;81(5):584–587. doi: 10.7326/0003-4819-81-5-584. [DOI] [PubMed] [Google Scholar]
  13. Levine A. S., Schimpff S. C., Graw R. G., Jr, Young R. C. Hematologic malignancies and other marrow failure states: progress in the management of complicating infections. Semin Hematol. 1974 Apr;11(2):141–202. [PubMed] [Google Scholar]
  14. 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]
  15. MacLowry J. D., Jaqua M. J., Selepak S. T. Detailed methodology and implementation of a semiautomated serial dilution microtechnique for antimicrobial susceptibility testing. Appl Microbiol. 1970 Jul;20(1):46–53. doi: 10.1128/am.20.1.46-53.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Metcalfe D., Hughes W. T. Effects of methotrexate on group A beta hemolytic streptococci and streptococcal infection. Cancer. 1972 Aug;30(2):588–593. doi: 10.1002/1097-0142(197208)30:2<588::aid-cncr2820300240>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  17. Middleman E. L., Watanabe A., Kaizer H., Bodey G. P. Antibiotic combinations for infections in neutropenic patients. Evaluaton of carbenicillin plus either cephalothin or kanamycin. Cancer. 1972 Aug;30(2):573–579. doi: 10.1002/1097-0142(197208)30:2<573::aid-cncr2820300238>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  18. Phair J. P., Watanakunakorn C., Bannister T. In vitro susceptibility of Pseudomonas aeruginosa to carbenicillin and the combination of carbenicillin and gentamicin. Appl Microbiol. 1969 Sep;18(3):303–306. doi: 10.1128/am.18.3.303-306.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schimpff S. C., Young V. M., Greene W. H., Vermeulen G. D., Moody M. R., Wiernik P. H. Origin of infection in acute nonlymphocytic leukemia. Significance of hospital acquisition of potential pathogens. Ann Intern Med. 1972 Nov;77(5):707–714. doi: 10.7326/0003-4819-77-5-707. [DOI] [PubMed] [Google Scholar]
  20. Schimpff S., Satterlee W., Young V. M., Serpick A. Empiric therapy with carbenicillin and gentamicin for febrile patients with cancer and granulocytopenia. N Engl J Med. 1971 May 13;284(19):1061–1065. doi: 10.1056/NEJM197105132841904. [DOI] [PubMed] [Google Scholar]
  21. Smith C. B., Dans P. E., Wilfert J. N., Finland M. Use of gentamicin in combinations with other antibiotics. J Infect Dis. 1969 Apr-May;119(4):370–377. doi: 10.1093/infdis/119.4-5.370. [DOI] [PubMed] [Google Scholar]
  22. Sonne M., Jawetz E. Combined action of carbenicillin and gentamicin on Pseudomonas aeruginosa in vitro. Appl Microbiol. 1969 Jun;17(6):893–896. doi: 10.1128/am.17.6.893-896.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Valdivieso M., Feld R., Rodriguez V., Bodey G. P. Amikacin therapy of infections in neutropenic patients. Am J Med Sci. 1975 Nov-Dec;270(3):453–463. doi: 10.1097/00000441-197511000-00006. [DOI] [PubMed] [Google Scholar]

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

RESOURCES