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. 1994 May;38(5):1165–1168. doi: 10.1128/aac.38.5.1165

Once-daily aminoglycoside dosing assessed by MIC reversion time with Pseudomonas aeruginosa.

J A Karlowsky 1, G G Zhanel 1, R J Davidson 1, D J Hoban 1
PMCID: PMC188170  PMID: 8067757

Abstract

A novel, in vitro, pharmacodynamic comparison of single and divided daily dosing regimens of aminoglycosides is described. Experiments were conducted to evaluate the impact of gentamicin and tobramycin concentration on the time required for the MICs for five Pseudomonas aeruginosa strains to revert to their original values (MIC reversion time [MRT]) following single and multiple 2-h aminoglycoside exposures to 8 and 24 mg/liter. Single 2-h aminoglycoside exposures to 8 mg/liter produced culture MRTs (gentamicin, 21.5 +/- 4.0 h; tobramycin, 22.3 +/- 2.8 h) that were significantly (P < 0.05) shorter than those measured following identical exposures to 24 mg/liter (gentamicin, 28.9 +/- 3.8 h; tobramycin, 26.8 +/- 3.1 h). However, three sequential 2-h exposures to 8 mg/liter, one exposure every 8 h, produced MRTs following the third exposure (gentamicin, 68.1 +/- 5.2 h; tobramycin, 77.8 +/- 7.8 h) that were significantly longer (P < 0.005) than those determined following three 2-h exposures to 24 mg/liter, one exposure every 24 h (gentamicin, 36.1 +/- 3.0 h; tobramycin, 34.5 +/- 3.0 h). In addition, the once-daily exposure regimen to 24 mg/liter consistently produced cultures with significantly (P < 0.005) higher aminoglycoside concentration/MIC ratios compared with those for cultures reexposed to 8 mg/liter once every 8 h. These data support the concept of once-daily aminoglycoside dosing.

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Selected References

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

  1. Daikos G. L., Jackson G. G., Lolans V. T., Livermore D. M. Adaptive resistance to aminoglycoside antibiotics from first-exposure down-regulation. J Infect Dis. 1990 Aug;162(2):414–420. doi: 10.1093/infdis/162.2.414. [DOI] [PubMed] [Google Scholar]
  2. Drusano G. L. Human pharmacodynamics of beta-lactams, aminoglycosides and their combination. Scand J Infect Dis Suppl. 1990;74:235–248. [PubMed] [Google Scholar]
  3. Gould I. M., Milne K., Harvey G., Jason C. Ionic binding, adaptive resistance and post-antibiotic effect of netilmicin and ciprofloxacin. J Antimicrob Chemother. 1991 Jun;27(6):741–748. doi: 10.1093/jac/27.6.741. [DOI] [PubMed] [Google Scholar]
  4. Karlowsky J. A., Zhanel G. G. Concepts on the use of liposomal antimicrobial agents: applications for aminoglycosides. Clin Infect Dis. 1992 Oct;15(4):654–667. doi: 10.1093/clind/15.4.654. [DOI] [PubMed] [Google Scholar]
  5. Karlowsky J. A., Zhanel G. G., Davidson R. J., Zieroth S. R., Hoban D. J. In vitro postantibiotic effects following multiple exposures of cefotaxime, ciprofloxacin, and gentamicin against Escherichia coli in pooled human cerebrospinal fluid and Mueller-Hinton broth. Antimicrob Agents Chemother. 1993 May;37(5):1154–1157. doi: 10.1128/aac.37.5.1154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. McGrath B. J., Marchbanks C. R., Gilbert D., Dudley M. N. In vitro postantibiotic effect following repeated exposure to imipenem, temafloxacin, and tobramycin. Antimicrob Agents Chemother. 1993 Aug;37(8):1723–1725. doi: 10.1128/aac.37.8.1723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Moore R. D., Lietman P. S., Smith C. R. Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis. 1987 Jan;155(1):93–99. doi: 10.1093/infdis/155.1.93. [DOI] [PubMed] [Google Scholar]
  8. Rotschafer J. C., Zabinski R. A., Walker K. J. Pharmacodynamic factors of antibiotic efficacy. Pharmacotherapy. 1992;12(6 Pt 2):64S–70S. [PubMed] [Google Scholar]
  9. Zhanel G. G., Ariano R. E. Once daily aminoglycoside dosing: maintained efficacy with reduced nephrotoxicity? Ren Fail. 1992;14(1):1–9. doi: 10.3109/08860229209039110. [DOI] [PubMed] [Google Scholar]
  10. Zhanel G. G., Hoban D. J., Harding G. K. The postantibiotic effect: a review of in vitro and in vivo data. DICP. 1991 Feb;25(2):153–163. doi: 10.1177/106002809102500210. [DOI] [PubMed] [Google Scholar]
  11. Zhanel G. G., Karlowsky J. A., Hoban D. J., Davidson R. J. Antimicrobial activity of subinhibitory concentrations of aminoglycosides against Pseudomonas aeruginosa as determined by the killing-curve method and the postantibiotic effect. Chemotherapy. 1991;37(2):114–121. doi: 10.1159/000238842. [DOI] [PubMed] [Google Scholar]

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