Abstract
The capabilities of two pharmacokinetic amikacin dosing methods were evaluated and compared with the standard amikacin dosage recommended by the manufacturer. Study patients participated in two consecutive prospective randomized double-blind trials of empiric antibiotic therapy for febrile episodes during granulocytopenia. Patients in study 1 received amikacin at a dosage of 15 mg/kg per day in four divided doses in combination with either ticarcillin or piperacillin. Patients in study 2 received either ticarcillin or moxalactam in combination with amikacin. Amikacin dosages in study 2 were adjusted to achieve a 1-h-postinfusion concentration of approximately 25 micrograms/ml and a trough concentration of approximately 8 micrograms/ml. Initial amikacin dosage requirements were established based on the lean body weight and estimated renal function of the patient. If amikacin serum concentrations were not within acceptable ranges, further dosage adjustments were made by using patient-specific pharmacokinetic parameters. The median 1-h-postinfusion concentration of amikacin in study 1 was 13.0 micrograms/ml, with a median trough concentration of 6.1 micrograms/ml. In study 2 the median 1-h-postinfusion concentration was 20.8 micrograms/ml, with a median trough of 6.4 micrograms/ml. Patients in study 2 required a mean dosage of 29.4 mg/kg per day. The incidence of amikacin-induced nephrotoxicity was not increased despite the substantial increase in dosage. Ototoxicity was not evaluated in study 1, but the incidence of ototoxicity in study 2 (17%) exceeded the incidence observed in a previous amikacin-plus-ticarcillin trial in which patients received 15 mg of amikacin per kg per day.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anderson E. T., Young L. S., Hewitt W. L. Simultaneous antibiotic levels in "breakthrough" gram-negative rod bacteremia. Am J Med. 1976 Oct;61(4):493–497. doi: 10.1016/0002-9343(76)90328-4. [DOI] [PubMed] [Google Scholar]
- Barza M., Brown R. B., Shen D., Gibaldi M., Weinstein L. Predictability of blood levels of gentamicin in man. J Infect Dis. 1975 Aug;132(2):165–174. doi: 10.1093/infdis/132.2.165. [DOI] [PubMed] [Google Scholar]
- Barza M., Lauermann M. Why monitor serum levels of gentamicin? Clin Pharmacokinet. 1978 May-Jun;3(3):202–215. doi: 10.2165/00003088-197803030-00002. [DOI] [PubMed] [Google Scholar]
- Bender J. F., Fortner C. L., Schimpff S. C., Grove W. R., Hahn D. M., Love L. J., Wiernik P. H. Comparative auditory toxicity of aminoglycoside antibiotics in leukopenic patients. Am J Hosp Pharm. 1979 Aug;36(8):1083–1087. [PubMed] [Google Scholar]
- Black R. E., Lau W. K., Weinstein R. J., Young L. S., Hewitt W. L. Ototoxicity of amikacin. Antimicrob Agents Chemother. 1976 Jun;9(6):956–961. doi: 10.1128/aac.9.6.956. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chiu P. J., Long J. F. Effects of hydration on gentamicin excretion and renal accumulation in furosemide-treated rats. Antimicrob Agents Chemother. 1978 Aug;14(2):214–217. doi: 10.1128/aac.14.2.214. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cipolle R. J., Seifert R. D., Zaske D. E., Strate R. G. Systematically individualizing tobramycin dosage regimens. J Clin Pharmacol. 1980 Oct;20(10):570–580. doi: 10.1002/j.1552-4604.1980.tb01672.x. [DOI] [PubMed] [Google Scholar]
- Dahlgren J. G., Anderson E. T., Hewitt W. L. Gentamicin blood levels: a guide to nephrotoxicity. Antimicrob Agents Chemother. 1975 Jul;8(1):58–62. doi: 10.1128/aac.8.1.58. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holt H. A., Broughall J. M., McCarthy M., Reeves D. S. Interactions between aminoglycoside antibiotics and carbenicillin or ticarillin. Infection. 1976;4(2):107–109. doi: 10.1007/BF01638726. [DOI] [PubMed] [Google Scholar]
- Keating M. J., Bodey G. P., Valdivieso M., Rodriguez V. A randomized comparative trial of three aminoglycosides--comparison of continuous infusions of gentamicin, amikacin and sisomicin combined with carbenicillin in the treatment of infections in neutropenic patients with malignancies. Medicine (Baltimore) 1979 Mar;58(2):159–170. doi: 10.1097/00005792-197903000-00004. [DOI] [PubMed] [Google Scholar]
- Pechere J. C., Dugal R. Clinical pharmacokinetics of aminoglycoside antibiotics. Clin Pharmacokinet. 1979 May-Jun;4(3):170–199. doi: 10.2165/00003088-197904030-00002. [DOI] [PubMed] [Google Scholar]
- Pennington J. E., Dale D. C., Reynolds H. Y., MacLowry J. D. Gentamicin sulfate pharmacokinetics: lower levels of gentamicin in blood during fever. J Infect Dis. 1975 Sep;132(3):270–275. doi: 10.1093/infdis/132.3.270. [DOI] [PubMed] [Google Scholar]
- Sarubbi F. A., Jr, Hull J. H. Amikacin serum concentrations: prediction of levels and dosage guidelines. Ann Intern Med. 1978 Nov;89(5 Pt 1):612–618. doi: 10.7326/0003-4819-89-5-612. [DOI] [PubMed] [Google Scholar]
- Sawchuk R. J., Zaske D. E., Cipolle R. J., Wargin W. A., Strate R. G. Kinetic model for gentamicin dosing with the use of individual patient parameters. Clin Pharmacol Ther. 1977 Mar;21(3):362–369. doi: 10.1002/cpt1977213362. [DOI] [PubMed] [Google Scholar]
- Schwartz S. N., Pazin G. J., Lyon J. A., Ho M., Pasculle A. W. A controlled investigation of the pharmacokinetics of gentamicin and tobramycin in obese subjects. J Infect Dis. 1978 Oct;138(4):499–505. doi: 10.1093/infdis/138.4.499. [DOI] [PubMed] [Google Scholar]
- Valdivieso M., Bodey G. P. Amikacin therapy of severe infections produced by gram-negative bacilli resistant to gentamicin. Am J Med Sci. 1977 Mar-Apr;273(2):177–184. doi: 10.1097/00000441-197703000-00007. [DOI] [PubMed] [Google Scholar]
- Wade J. C., Schimpff S. C., Newman K. A., Fortner C. L., Standiford H. C., Wiernik P. H. Piperacillin or ticarcillin plus amikacin. A double-blind prospective comparison of empiric antibiotic therapy for febrile granulocytopenic cancer patients. Am J Med. 1981 Dec;71(6):983–990. doi: 10.1016/0002-9343(81)90324-7. [DOI] [PubMed] [Google Scholar]
