Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1985 Mar;27(3):343–349. doi: 10.1128/aac.27.3.343

Efficacy of intermittent versus continuous administration of netilmicin in a two-compartment in vitro model.

J Blaser, B B Stone, S H Zinner
PMCID: PMC176274  PMID: 3922294

Abstract

Several aminoglycoside dosage regimens were studied in a kinetic in vitro model. Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were exposed in serially placed artificial capillary units to netilmicin concentrations that changed based on human two-compartment pharmacokinetics. The same total dose per 24 h was administered as a continuous infusion (3.7 micrograms/ml) or in 1-h infusions given every 24 (24 micrograms/ml) or 8 h (8 micrograms/ml). The once daily administration showed the best response in terms of either faster killing of E. coli, K. pneumoniae, and S. aureus or greater reduction of the inocula of P. aeruginosa. After 28 h of treatment, however, all regimens reduced the nonpseudomonads by more than 99.99%, whereas all three P. aeruginosa strains regrew to greater than 10(8) CFU/ml due to selection of resistant subpopulations. In contrast to the bactericidal effect of the first dose, no killing occurred after subsequent doses if the ratio of peak drug concentration to MIC was low (less than or equal to 6). These results support the concept of administering high doses of aminoglycosides once every 24 h.

Full text

PDF
343

Selected References

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

  1. Blaser J., Rieder H., Niederer P., Lüthy R. Biological variability of multiple dose pharmacokinetics of netilmicin in man. Eur J Clin Pharmacol. 1983;24(3):399–406. doi: 10.1007/BF00610062. [DOI] [PubMed] [Google Scholar]
  2. Bodey G. P., Middleman E., Umsawadi T., Rodriguez V. Infections in cancer patients. Results with gentamicin sulfate therapy. Cancer. 1972 Jun;29(6):1697–1701. doi: 10.1002/1097-0142(197206)29:6<1697::aid-cncr2820290638>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  3. Bodey G. P., Valdivieso M., Yap B. S. The role of schedule of antibiotic therapy on the neutropenic patient. Infection. 1980;Suppl 1:75–81. doi: 10.1007/BF01644940. [DOI] [PubMed] [Google Scholar]
  4. Braveny I., Voeckl J., Machka K. Antimicrobial activity of netilmicin in comparison with gentamicin, sisomicin, tobramycin, and amikacin and their resistance patterns. Arzneimittelforschung. 1980;30(3):491–495. [PubMed] [Google Scholar]
  5. Digranes A., Dibb W. L., Ostervold B. The in vitro activity of netilmicin against 357 clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. Scand J Infect Dis Suppl. 1980;Suppl 23:30–33. [PubMed] [Google Scholar]
  6. EAGLE H., FLEISCHMAN R., LEVY M. "Continuous" vs. "discontinuous" therapy with penicillin; the effect of the interval between injections on therapeutic efficacy. N Engl J Med. 1953 Mar 19;248(12):481–488. doi: 10.1056/NEJM195303192481201. [DOI] [PubMed] [Google Scholar]
  7. Feld R., Valdivieso M., Bodey G. P., Rodriguez V. A comparative trial of sisomicin therapy by intermittent versus continuous infusion. Am J Med Sci. 1977 Sep-Oct;274(2):179–188. doi: 10.1097/00000441-197709000-00010. [DOI] [PubMed] [Google Scholar]
  8. Flick M. R., Cluff L. E. Pseudomonas bacteremia. Review of 108 cases. Am J Med. 1976 Apr;60(4):501–508. doi: 10.1016/0002-9343(76)90716-6. [DOI] [PubMed] [Google Scholar]
  9. Gerber A. U., Craig W. A. Aminoglycoside-selected subpopulations of Pseudomonas aeruginosa: characterization and virulence in normal and leukopenic mice. J Lab Clin Med. 1982 Nov;100(5):671–681. [PubMed] [Google Scholar]
  10. Gerber A. U., Craig W. A., Brugger H. P., Feller C., Vastola A. P., Brandel J. Impact of dosing intervals on activity of gentamicin and ticarcillin against Pseudomonas aeruginosa in granulocytopenic mice. J Infect Dis. 1983 May;147(5):910–917. doi: 10.1093/infdis/147.5.910. [DOI] [PubMed] [Google Scholar]
  11. Gerber A. U., Vastola A. P., Brandel J., Craig W. A. Selection of aminoglycoside-resistant variants of Pseudomonas aeruginosa in an in vivo model. J Infect Dis. 1982 Nov;146(5):691–697. doi: 10.1093/infdis/146.5.691. [DOI] [PubMed] [Google Scholar]
  12. Gerber A. U., Wiprächtiger P., Stettler-Spichiger U., Lebek G. Constant infusions vs. intermittent doses of gentamicin against Pseudomonas aeruginosa in vitro. J Infect Dis. 1982 Apr;145(4):554–560. doi: 10.1093/infdis/145.4.554. [DOI] [PubMed] [Google Scholar]
  13. Grasso S., Meinardi G., de Carneri I., Tamassia V. New in vitro model to study the effect of antibiotic concentration and rate of elimination on antibacterial activity. Antimicrob Agents Chemother. 1978 Apr;13(4):570–576. doi: 10.1128/aac.13.4.570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lerner A. M., Reyes M. P., Cone L. A., Blair D. C., Jansen W., Wright G. E., Lorber R. R. Randomised, controlled trial of the comparative efficacy, auditory toxicity, and nephrotoxicity of tobramycin and netilmicin. Lancet. 1983 May 21;1(8334):1123–1126. doi: 10.1016/s0140-6736(83)92864-7. [DOI] [PubMed] [Google Scholar]
  15. Murakawa T., Sakamoto H., Hirose T., Nishida M. New in vitro kinetic model for evaluating bactericidal efficacy of antibiotics. Antimicrob Agents Chemother. 1980 Sep;18(3):377–381. doi: 10.1128/aac.18.3.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Powell S. H., Thompson W. L., Luthe M. A., Stern R. C., Grossniklaus D. A., Bloxham D. D., Groden D. L., Jacobs M. R., DiScenna A. O., Cash H. A. Once-daily vs. continuous aminoglycoside dosing: efficacy and toxicity in animal and clinical studies of gentamicin, netilmicin, and tobramycin. J Infect Dis. 1983 May;147(5):918–932. doi: 10.1093/infdis/147.5.918. [DOI] [PubMed] [Google Scholar]
  17. Schneider P., Tosch W., Maurer M., Zak O. Antibacterial effects of cefroxadine, cephalexin and cephradine in a new in vitro pharmacokinetic model. J Antibiot (Tokyo) 1982 Jul;35(7):843–849. doi: 10.7164/antibiotics.35.843. [DOI] [PubMed] [Google Scholar]
  18. Toothaker R. D., Welling P. G., Craig W. A. An in vitro model for the study of antibacterial dosage regimen design. J Pharm Sci. 1982 Aug;71(8):861–864. doi: 10.1002/jps.2600710805. [DOI] [PubMed] [Google Scholar]
  19. Van Etta L. L., Peterson L. R., Fasching C. E., Gerding D. N. Effect of the ratio of surface area to volume on the penetration of antibiotics in to extravascular spaces in an in vitro model. J Infect Dis. 1982 Sep;146(3):423–428. doi: 10.1093/infdis/146.3.423. [DOI] [PubMed] [Google Scholar]
  20. Woolfrey B. F., Fox J. M., Quall C. O. Comparison of minimum inhibitory concentration values determined by three antimicrobic dilution methods for Pseudomonas aeruginosa. Am J Clin Pathol. 1981 Jan;75(1):39–44. doi: 10.1093/ajcp/75.1.39. [DOI] [PubMed] [Google Scholar]
  21. Zinner S. H., Husson M., Klastersky J. An artificial capillary in vitro kinetic model of antibiotic bactericidal activity. J Infect Dis. 1981 Dec;144(6):583–587. doi: 10.1093/infdis/144.6.583. [DOI] [PubMed] [Google Scholar]

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

RESOURCES