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. 1997 Nov;41(11):2586–2588. doi: 10.1128/aac.41.11.2586

In vitro synergistic activities of tobramycin and selected beta-lactams against 75 gram-negative clinical isolates.

R C Owens Jr 1, M A Banevicius 1, D P Nicolau 1, C H Nightingale 1, R Quintiliani 1
PMCID: PMC164171  PMID: 9371376

Abstract

The microdilution checkerboard technique was utilized to distinguish synergistic activity between tobramycin and four beta-lactams: piperacillin-tazobactam, ticarcillin-clavulanate, ceftazidime, and ceftriaxone. Beta-lactam-aminoglycoside combinations were tested against 75 clinical isolates of Pseudomonas aeruginosa, Acinetobacter baumanii, Citrobacterfreundii, Serratia marcescens, and Enterobacter cloacae. Despite in vitro susceptibilities, all isolates demonstrated either synergism or indifference; no antagonism was observed. Against pathogenic gram-negative nosocomial isolates, a greater percentage of synergy was consistently observed with combination regimens containing tobramycin and piperacillin-tazobactam or ticarcillin-clavulanate than with the cephalosporin-containing regimens.

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Selected References

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  1. Andriole V. T. Antibiotic synergy in experimental infection with Pseudomonas. II. The effect of carbenicillin, cephalothin, or cephanone combined with tobramycin or gentamicin. J Infect Dis. 1974 Feb;129(2):124–133. doi: 10.1093/infdis/129.2.124. [DOI] [PubMed] [Google Scholar]
  2. Andriole V. T. Synergy of carbenicillin and gentamicin in experimental infection with Pseudomonas. J Infect Dis. 1971 Dec;124 (Suppl):S46–S55. doi: 10.1093/infdis/124.supplement_1.s46. [DOI] [PubMed] [Google Scholar]
  3. Archer G., Fekety F. R., Jr Experimental endocarditis due to Pseudomonas aeruginosa. II. Therapy with carbenicillin and gentamicin. J Infect Dis. 1977 Sep;136(3):327–335. doi: 10.1093/infdis/136.3.327. [DOI] [PubMed] [Google Scholar]
  4. Barriere S. L. Bacterial resistance to beta-lactams, and its prevention with combination antimicrobial therapy. Pharmacotherapy. 1992;12(5):397–402. [PubMed] [Google Scholar]
  5. Bodey G. P., Feld R., Burgess M. A. Beta-lactam antibiotics alone or in combination with gentamicin for therapy of gram-negative bacillary infections in neutropenic patients. Am J Med Sci. 1976 Mar-Apr;271(2):179–186. doi: 10.1097/00000441-197603000-00006. [DOI] [PubMed] [Google Scholar]
  6. Bodey G. P., Jadeja L., Elting L. Pseudomonas bacteremia. Retrospective analysis of 410 episodes. Arch Intern Med. 1985 Sep;145(9):1621–1629. doi: 10.1001/archinte.145.9.1621. [DOI] [PubMed] [Google Scholar]
  7. Durack D. T., Pelletier L. L., Petersdorf R. G. Chemotherapy of experimental streptococcal endocarditis. II. Synergism between penicillin and streptomycin against penicillin-sensitive streptococci. J Clin Invest. 1974 Mar;53(3):829–833. doi: 10.1172/JCI107622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Gribble M. J., Chow A. W., Naiman S. C., Smith J. A., Bowie W. R., Sacks S. L., Grossman L., Buskard N., Growe G. H., Plenderleith L. H. Prospective randomized trial of piperacillin monotherapy versus carboxypenicillin-aminoglycoside combination regimens in the empirical treatment of serious bacterial infections. Antimicrob Agents Chemother. 1983 Sep;24(3):388–393. doi: 10.1128/aac.24.3.388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hallander H. O., Dornbusch K., Gezelius L., Jacobson K., Karlsson I. Synergism between aminoglycosides and cephalosporins with antipseudomonal activity: interaction index and killing curve method. Antimicrob Agents Chemother. 1982 Nov;22(5):743–752. doi: 10.1128/aac.22.5.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hilf M., Yu V. L., Sharp J., Zuravleff J. J., Korvick J. A., Muder R. R. Antibiotic therapy for Pseudomonas aeruginosa bacteremia: outcome correlations in a prospective study of 200 patients. Am J Med. 1989 Nov;87(5):540–546. doi: 10.1016/s0002-9343(89)80611-4. [DOI] [PubMed] [Google Scholar]
  12. Klastersky J., Cappel R., Daneau D. Clinical significance of in vitro synergism between antibiotics in gram-negative infections. Antimicrob Agents Chemother. 1972 Dec;2(6):470–475. doi: 10.1128/aac.2.6.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Korvick J. A., Yu V. L. Antimicrobial agent therapy for Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1991 Nov;35(11):2167–2172. doi: 10.1128/aac.35.11.2167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Moellering R. C., Jr Antimicrobial synergism--an elusive concept. J Infect Dis. 1979 Oct;140(4):639–641. doi: 10.1093/infdis/140.4.639. [DOI] [PubMed] [Google Scholar]
  16. Rand K. H., Houck H. J., Brown P., Bennett D. Reproducibility of the microdilution checkerboard method for antibiotic synergy. Antimicrob Agents Chemother. 1993 Mar;37(3):613–615. doi: 10.1128/aac.37.3.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Reyes M. P., El-Khatib M. R., Brown W. J., Smith F., Lerner A. M. Synergy between carbenicillin and an aminoglycoside (gentamicin or tobramycin) against Pseudomonas aeruginosa isolated from patients with endocarditis and sensitivity of isolates to normal human serum. J Infect Dis. 1979 Aug;140(2):192–202. doi: 10.1093/infdis/140.2.192. [DOI] [PubMed] [Google Scholar]
  18. Sande M. A., Irvin R. G. Penicillin-aminoglycoside synergy in experimental Streptococcus viridans endocarditis. J Infect Dis. 1974 May;129(5):572–576. doi: 10.1093/infdis/129.5.572. [DOI] [PubMed] [Google Scholar]
  19. Sanders C. C., Sanders W. E., Jr Emergence of resistance during therapy with the newer beta-lactam antibiotics: role of inducible beta-lactamases and implications for the future. Rev Infect Dis. 1983 Jul-Aug;5(4):639–648. doi: 10.1093/clinids/5.4.639. [DOI] [PubMed] [Google Scholar]
  20. Scheld W. M., Fletcher D. D., Fink F. N., Sande M. A. Response to therapy in an experimental rabbit model of meningitis due to Listeria monocytogenes. J Infect Dis. 1979 Sep;140(3):287–294. doi: 10.1093/infdis/140.3.287. [DOI] [PubMed] [Google Scholar]
  21. Wilson W. R., Geraci J. E., Wilkowske C. J., Washington J. A., 2nd Short-term intramuscular therapy with procaine penicillin plus streptomycin for infective endocarditis due to viridans streptococci. Circulation. 1978 Jun;57(6):1158–1161. doi: 10.1161/01.cir.57.6.1158. [DOI] [PubMed] [Google Scholar]
  22. Wilson W. R., Thompson R. L., Wilkowske C. J., Washington J. A., 2nd, Giuliani E. R., Geraci J. E. Short-term therapy for streptococcal infective endocarditis. Combined intramuscular administration of penicillin and streptomycin. JAMA. 1981 Jan 23;245(4):360–363. [PubMed] [Google Scholar]

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