Abstract
Serum amikacin concentrations were compared in infected renal transplant recipients that were compared in infected renal transplant recipients that were dosed using a creatinine-based nomogram (group I) or an individual computer-assisted pharmacokinetic dosing method (group II). A total of 30 treatment courses were administered. Mean postinfusion peak levels were 22 microgram/ml in group I and 23.4 microgram/ml in group II. Mean serum trough levels were 8.8 microgram/ml and 5.5 microgram/ml in groups I and II, respectively. Both peak and trough serum levels were significantly more often in the acceptable therapeutic (peak 20-32 microgram/ml) and nontoxic (through less than 10 microgram/ml) ranges in group 11 patients. Seventy-seven per cent of group II and 38% of group I peak levels were in the therapeutic range, while 87% of group II and 70% of group I trough levels were less than 10 microgram/ml. Ototoxicity developed with similar frequency in both groups and occurred significantly more often with a peak level greater than 32 microgram/ml. Declining renal function, usually as a result of allograft rejection, occurred in seven (44%) group I and only three (25%) group II patients but could not be exclusively related to amikacin in any patient. A serum trough level of greater than 10 microgram/ml was associated with an increased risk of declining renal function independent of other risk factors. Failures of aminoglycoside therapy are frequently associated with inadequate serum levels. Conversely, ototoxicity and nephrotoxicity may be related to elevated serum aminoglycoside concentrations. For these reasons, the computer-assisted pharmacokinetic dosing method should be used in septic surgical patients whose renal function is subject to sudden and unexpected changes.
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Selected References
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- Bartlett J. G. Amikacin treatment of pulmonary infections involving gentamicin-resistant gram-negative bacilli. Am J Med. 1977 Jun;62(6):945–948. doi: 10.1016/0002-9343(77)90666-0. [DOI] [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]
- Bryan L. E., Shahrabadi M. S., van den Elzen H. M. Gentamicin resistance in Pseudomonas aeruginosa: R-factor-mediated resistance. Antimicrob Agents Chemother. 1974 Aug;6(2):191–199. doi: 10.1128/aac.6.2.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cockcroft D. W., Gault M. H. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. doi: 10.1159/000180580. [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]
- Gooding P. G., Berman E., Lane A. Z., Agre K. A review of results of clinical trials with amikacin. J Infect Dis. 1976 Nov;134(Suppl):S441–S445. doi: 10.1093/infdis/135.supplement_2.s441. [DOI] [PubMed] [Google Scholar]
- Guttmann R. D. Renal transplantation (second of two parts). N Engl J Med. 1979 Nov 8;301(19):1038–1048. doi: 10.1056/NEJM197911083011905. [DOI] [PubMed] [Google Scholar]
- Haas M. J., Davies J. Enzymatic acetylation as a means of determining serum aminoglycoside concentrations. Antimicrob Agents Chemother. 1973 Oct;4(4):497–499. doi: 10.1128/aac.4.4.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hill R. B., Jr, Dahrling B. E., 2nd, Starzl T. E., Rifkind D. Death after transplantation; an analysis of sixty cases. Am J Med. 1967 Mar;42(3):327–334. doi: 10.1016/0002-9343(67)90260-4. [DOI] [PubMed] [Google Scholar]
- Lane A. Z., Wright G. E., Blair D. C. Ototoxicity and nephrotoxicity of amikacin: an overview of phase II and phase III experience in the United States. Am J Med. 1977 Jun;62(6):911–918. doi: 10.1016/0002-9343(77)90660-x. [DOI] [PubMed] [Google Scholar]
- Leonard J. M., McGee Z. A., Alford R. H. Gentamicin-resistant bacillary infection. Clinical features and amikacin therapy. Arch Intern Med. 1978 Feb;138(2):201–205. [PubMed] [Google Scholar]
- Lerner S. A., Seligsohn R., Matz G. J. Comparative clinical studies of ototoxicity and nephrotoxicity of amikacin and gentamicin. Am J Med. 1977 Jun;62(6):919–923. doi: 10.1016/0002-9343(77)90661-1. [DOI] [PubMed] [Google Scholar]
- Meyer R. D., Lewis R. P., Carmalt E. D., Finegold S. M. Amikacin therapy for serious gram-negative bacillary infections. Ann Intern Med. 1975 Dec;83(6):790–800. doi: 10.7326/0003-4819-83-6-790. [DOI] [PubMed] [Google Scholar]
- Meyer R. D., Lewis R. P., Finegold S. M. Amikacin therapy for gram-negative septicemia. Am J Med. 1977 Jun;62(6):930–935. doi: 10.1016/0002-9343(77)90663-5. [DOI] [PubMed] [Google Scholar]
- Murphy J. F., McDonald F. D., Dawson M., Reite A., Turcotte J., Fekety F. R., Jr Factors affecting the frequency infection in renal transplant recipients. Arch Intern Med. 1976 Jun;136(6):670–677. [PubMed] [Google Scholar]
- Myerowitz R. L., Medeiros A. A., O'Brien T. F. Bacterial infection in renal homotransplant recipients. A study of fifty-three bacteremic episodes. Am J Med. 1972 Sep;53(3):308–314. doi: 10.1016/0002-9343(72)90173-8. [DOI] [PubMed] [Google Scholar]
- Nielsen H. E., Korsager B. Bacteremia after renal transplantation. Scand J Infect Dis. 1977;9(2):111–117. doi: 10.3109/inf.1977.9.issue-2.10. [DOI] [PubMed] [Google Scholar]
- Noone P., Beale D. F., Pollock S. S., Perera M. R., Amirak I. D., Fernando O. N., Moorhead J. F. Monitoring aminoglycoside use in patients with severely impaired renal function. Br Med J. 1978 Aug 12;2(6135):470–473. doi: 10.1136/bmj.2.6135.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pollock A. A., Berger S. A., Richmond A. S., Simberkoff M. S., Rahal J. J., Jr Amikacin therapy for serious gram-negative infection. JAMA. 1977 Feb 7;237(6):562–564. [PubMed] [Google Scholar]
- Price K. E., DeFuria M. D., Pursiano T. A. Amikacin, an aminoglycoside with marked activity against antibiotic-resistant clinical isolates. J Infect Dis. 1976 Nov;134(Suppl):S249–S261. doi: 10.1093/infdis/135.supplement_2.s249. [DOI] [PubMed] [Google Scholar]
- Price K. E., Pursiano T. A., DeFuria M. D. Activity of BB-K8 (amikacin) against clinical isolates resistant to one or more aminoglycoside antibiotics. Antimicrob Agents Chemother. 1974 Feb;5(2):143–152. doi: 10.1128/aac.5.2.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruckdeschel J. C., Schimpff S. C., Smyth A. C., Mardiney M. R., Jr Herpes zoster and impaired cell-associated immunity to the varicella-zoster virus in patients with Hodgkin's disease. Am J Med. 1977 Jan;62(1):77–85. doi: 10.1016/0002-9343(77)90352-7. [DOI] [PubMed] [Google Scholar]
- SPANGLER A. S., JACKSON J. H., FIUMARA N. J., WARTHIN T. A. SYPHILIS WITH A NEGATIVE BLOOD TEST REACTION. JAMA. 1964 Jul 13;189:87–90. doi: 10.1001/jama.1964.03070020015003. [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]
- Sawchuk R. J., Zaske D. E. Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: gentamicin in burn patients. J Pharmacokinet Biopharm. 1976 Apr;4(2):183–195. doi: 10.1007/BF01086153. [DOI] [PubMed] [Google Scholar]
- Smith C. R., Baughman K. L., Edwards C. Q., Rogers J. F., Lietman P. S. Controlled comparison of amikacin and gentamicin. N Engl J Med. 1977 Feb 17;296(7):349–353. doi: 10.1056/NEJM197702172960701. [DOI] [PubMed] [Google Scholar]
- Smith C. R., Maxwell R. R., Edwards C. Q., Rogers J. F., Lietman P. S. Nephrotoxicity induced by gentamicin and amikacin. Johns Hopkins Med J. 1978 Mar;142(3):85–90. [PubMed] [Google Scholar]
- Tally F. P., Louie T. J., O'Keefe P., Gorbach S. L., Bartlett J. G. Amikacin therapy for severe gram-negative sepsis: efficacy in infections involving gentamicin-resistant organisms. J Infect Dis. 1976 Nov;134(Suppl):S428–S432. doi: 10.1093/infdis/135.supplement_2.s428. [DOI] [PubMed] [Google Scholar]
- Tally F. P., Louie T. J., Weinstein W. M., Bartlett J. G., Gorbach S. L. Amikacin therapy for severe gram-negative sepsis. Emphasis on infections with gentamicin-resistant organisms. Ann Intern Med. 1975 Oct;83(4):484–488. doi: 10.7326/0003-4819-83-4-484. [DOI] [PubMed] [Google Scholar]
- Tapia H. R., Holley K. E., Woods J. E., Johnson W. J. Causes of death after renal transplantation. Arch Intern Med. 1973 Feb;131(2):204–210. [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]
- Zaske D. E., Sawchuk R. J., Strate R. G. The necessity of increased doses of amikacin in burn patients. Surgery. 1978 Nov;84(5):603–608. [PubMed] [Google Scholar]