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. 1993 Apr;37(4):914–917. doi: 10.1128/aac.37.4.914

Kill kinetics and regrowth patterns of Escherichia coli exposed to gentamicin concentration-time profiles simulating in vivo bolus and infusion dosing.

E B Bastone 1, S C Li 1, L L Ioannides-Demos 1, W J Spicer 1, A J McLean 1
PMCID: PMC187813  PMID: 8494392

Abstract

The relative influence of peak concentration (Cmax) versus the area under the antibiotic concentration-time curve (AUC) on the bactericidal effect of gentamicin against Escherichia coli NCTC 10418 was studied. Bacteria in the lag phase were exposed to an in vitro gentamicin concentration series which mirrored the concentrations determined in patients after 80-mg intravenous bolus (1 min) and 80-mg intravenous infusion (30 min) doses. Bacterial viable cell counts and gentamicin concentrations were measured before and during antibiotic exposure. Both the Cmax and AUC were shown to be factors determining antibacterial activity; however, the Cmax was an independent determinant of effect. These findings indicate that bolus intravenous dosing with gentamicin could maximize bactericidal activity. Increased efficacy could result at any given daily antibiotic dose if delivered via bolus with long intervals (12 to 24 h) between doses if appropriate precautions to avoid toxicity are taken.

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Selected References

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

  1. Bailey R. R., Lynn K. L. Letter: Serum levels of gentamicin after intravenous bolus injection. Lancet. 1974 Apr 20;1(7860):730–730. doi: 10.1016/s0140-6736(74)92929-8. [DOI] [PubMed] [Google Scholar]
  2. Blaser J., Stone B. B., Groner M. C., Zinner S. H. Comparative study with enoxacin and netilmicin in a pharmacodynamic model to determine importance of ratio of antibiotic peak concentration to MIC for bactericidal activity and emergence of resistance. Antimicrob Agents Chemother. 1987 Jul;31(7):1054–1060. doi: 10.1128/aac.31.7.1054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bosch D. E., Williams D. N. Comparison of serum aminoglycoside concentrations produced by two infusion methods. Clin Pharm. 1990 Oct;9(10):777–780. [PubMed] [Google Scholar]
  4. Dobbs S. M., Mawer G. E. Intravenous injection of gentamicin and tobramycin without impairment of hearing. J Infect Dis. 1976 Aug;134 (Suppl):S114–S117. doi: 10.1093/infdis/134.supplement_1.s114. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. EAGLE H., FLEISCHMAN R., MUSSELMAN A. D. Effect of schedule of administration on the therapeutic efficacy of penicillin; importance of the aggregate time penicillin remains at effectively bactericidal levels. Am J Med. 1950 Sep;9(3):280–299. doi: 10.1016/0002-9343(50)90425-6. [DOI] [PubMed] [Google Scholar]
  7. Gerber A. U., Brugger H. P., Feller C., Stritzko T., Stalder B. Antibiotic therapy of infections due to Pseudomonas aeruginosa in normal and granulocytopenic mice: comparison of murine and human pharmacokinetics. J Infect Dis. 1986 Jan;153(1):90–97. doi: 10.1093/infdis/153.1.90. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Gilbert D. N. Once-daily aminoglycoside therapy. Antimicrob Agents Chemother. 1991 Mar;35(3):399–405. doi: 10.1128/aac.35.3.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Guggenbichler J. P., Semenitz E., König P. Kill kinetics and regrowth pattern of bacteria exposed to antibiotic concentrations simulating those observed in vivo. J Antimicrob Chemother. 1985 Jan;15 (Suppl A):139–146. doi: 10.1093/jac/15.suppl_a.139. [DOI] [PubMed] [Google Scholar]
  13. Klastersky J., Thys J. P., Mombelli G. Comparative studies of intermittent and continuous administration of aminoglycosides in the treatment of bronchopulmonary infections due to gram-negative bacteria. Rev Infect Dis. 1981 Jan-Feb;3(1):74–83. doi: 10.1093/clinids/3.1.74. [DOI] [PubMed] [Google Scholar]
  14. LeBel M., Spino M. Pulse dosing versus continuous infusion of antibiotics. Pharmacokinetic-pharmacodynamic considerations. Clin Pharmacokinet. 1988 Feb;14(2):71–95. doi: 10.2165/00003088-198814020-00002. [DOI] [PubMed] [Google Scholar]
  15. MILLER A. K., WILMER D. L., VERWEY W. F. Effect of penicillin dosage schedule on treatment of experimental typhoid infections in mice. Proc Soc Exp Biol Med. 1950 May;74(1):62–64. doi: 10.3181/00379727-74-17810. [DOI] [PubMed] [Google Scholar]
  16. Mendelson J., Portnoy J., Dick V., Black M. Safety of the bolus administration of gentamicin. Antimicrob Agents Chemother. 1976 Apr;9(4):633–638. doi: 10.1128/aac.9.4.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mendelson J., Portnoy J., Sigman H. Pharmacology of gentamicin in the biliary tract of humans. Antimicrob Agents Chemother. 1973 Nov;4(5):538–541. doi: 10.1128/aac.4.5.538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Meunier F., Van der Auwera P., Schmitt H., de Maertelaer V., Klastersky J. Pharmacokinetics of gentamicin after i.v. infusion or iv bolus. J Antimicrob Chemother. 1987 Feb;19(2):225–231. doi: 10.1093/jac/19.2.225. [DOI] [PubMed] [Google Scholar]
  19. Tulkens P. M. Efficacy and safety of aminoglycosides once-a-day: experimental and clinical data. Scand J Infect Dis Suppl. 1990;74:249–257. [PubMed] [Google Scholar]
  20. White C. A., Toothaker R. D., Smith A. L., Slattery J. T. In vitro evaluation of the determinants of bactericidal activity of ampicillin dosing regimens against Escherichia coli. Antimicrob Agents Chemother. 1989 Jul;33(7):1046–1051. doi: 10.1128/aac.33.7.1046. [DOI] [PMC free article] [PubMed] [Google Scholar]

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