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The Pharmacology of Aminoglycosides—I. Considered as a Group

Published online by Cambridge University Press:  02 January 2015

Sandra M. Norris  and
Jonathan I. Ravdin
Sandra M. Norris
Affiliation:
Department of Internal Medicine and Pharmacy
Jonathan I. Ravdin
Affiliation:
Division of Clinical Pharmacologyand Infectious Diseases, Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, Virginia
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Extract

This review of aminoglycoside pharmacology will appear in two parts. The first segment summarizes general information applicable to all agents, such as aspects of absorption, distribution, and clearance. The subsequent article will focus on specific agents currently in use in clinical practice: gentamicin, tobramycin, netilmicin, amikacin, streptomycin, and kanamycin, highlighting toxicities and pharmacokinetic-based dosing strategies.

Embedded in the history of antimicrobial agents with the discovery of streptomycin in 1944, the aminoglycosides remain a mainstay of contemporary antibiotic therapy. Noteworthy features include rapid bactericidal activity against aerobic gram-negative organisms as well as additive or synergistic activity when coadministered with beta-lactam agents. These positive attributes are offset by limited penetration into various body fluids and tissues, and dose (concentration) related renal and ototoxicity. Despite the proliferation of safer beta-lactam compounds with expanded antimicrobial spectrums, the aminoglycosides are still initial drugs of choice for most life-threatening, aerobic, gram-negative infections. Used in combination with anti-pseudomonal penicillins, the aminoglycosides are the agents of choice for empiric therapy of fever in the neutropenic host or documented tissue infection with Pseudomonas aeruginosa.

Type
Original Articles
Information
Infection Control & Hospital Epidemiology , Volume 5 , Issue 4 , April 1984 , pp. 188 - 191
Copyright
Copyright © The Society for Healthcare Epidemiology of America 1984

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References

1.Moellering, RC Jr: In vitro antibacterial activity of the aminoglycoside antibiotics. Rev Infect Dis 1983;5:S212–S231.CrossRefGoogle Scholar
2.Davies, JE: Resistance to aminoglycosides: Mechanism and frequency. Rev Infect Dis 1983; 5(suppl 2):S261–S266.CrossRefGoogle Scholar
3.Kunin, CM, Chalmers, TC, Leevy, CM, et al: Absorption of orally administered neomycin and kanamycin. N Engl J Med 1960;262:380–385.CrossRefGoogle ScholarPubMed
4.Last, PM, Sherlock, S: Systemic absorption of orally administered neomycin in liver disease. N Engl J Med 1960;262:385–389.CrossRefGoogle ScholarPubMed
5.Breen, KJ, Bryant, RE, Levinson, JD, et al: Neomycin absorption in man. Ann Intern Med 1972;76:211–218.CrossRefGoogle ScholarPubMed
6.Mitch, WE, Lietman, PS, Walser, M: Effects of oral neomycin and kanamycin in chronic uremic patients: I. Urea metabolism. Kidney Int 1977;11:116–122.CrossRefGoogle ScholarPubMed
7.Barza, M, Lauermann, M: Why monitor serum levels of gentamicin? Clin Pharmocokinet 1978;3:202–215.CrossRefGoogle ScholarPubMed
8.Smithivas, T, Hyams, PJ, Matalon, R, et al: The use of gentamicin in peritoneal dialysis. I. Pharmacologic results. J Infect Dis 1971;124:S77–S83.CrossRefGoogle ScholarPubMed
9.Somani, P, Shapiro, RS, Stockard, H, et al: Unidirectional absorption of gentamicin from the peritoneum during continuous ambulatory peritoneal dialysis. Clin Pharmacol Ther 1982;32:113–121.CrossRefGoogle ScholarPubMed
10.DePaepe, M, Lameire, N, Belpaire, F, et al: Peritoneal pharmacokinetics of gentamicin in man. Clin Nephrol 1983;19:107–109.Google Scholar
11.Chamberlain, G, Needham, P: The absorption of antibiotics from the bladder. J Urol 1976;116:172–173.CrossRefGoogle ScholarPubMed
12.Klastersky, J, Meunier-Carpentier, F, Kahan-Coppens, L, et al: Endotracheally administered antibiotics for gram-negative bronchopneumonia. Chest 1979;75:586–591.CrossRefGoogle ScholarPubMed
13.Odio, W, Van Leier, E, Klastersky, J: Concentrations of gentamicin in bronchial secretions after intramuscular and endotracheal administration. J Clin Pharmacol 1975;15:518–524.CrossRefGoogle ScholarPubMed
14.Stephens, D, Garey, N, Isles, A, et al: Efficacy of inhaled tobramycin in the treatment of pulmonary exacerbations in children with cystic fibrosis. Pediatric Infectious Diseases 1983;2:209–211.CrossRefGoogle ScholarPubMed
15.Briedis, DJ, Robson, HG: Cerebrospinal fluid penetration of amikacin. Antimicrob Agents Chemother 1978;13:1042–1043.CrossRefGoogle ScholarPubMed
16.Bamford, MFM, Jones, LF: Deafness and biochemical imbalance after burn treatment with topical antibiotics in young children. Arch Dis Child 1978;53:326–329.CrossRefGoogle ScholarPubMed
17.Davia, JE, Siemsen, AW, Anderson, RW: Uremia, deafness, and paralysis due to irrigating antibiotic solutions. Arch Intern Med 1970;125:135–139.CrossRefGoogle ScholarPubMed
18.Kelly, DR, Nilo, ER, Berggren, RB: Deafness after topical neomycin wound irrigation. N Engl J Med 1969;280:1338–1339.CrossRefGoogle ScholarPubMed
19.Pestka, S: Inhibitors of protein synthesis, in Weissbach, H, Pestka, S (eds): Molecular Mechanisms of Protein Synthesis. New York, Academic Press, 1977, pp 467–553.Google Scholar
20.Gyselynck, AM, Forrey, A, Cutler, R: Pharmacokinetics of gentamicin: Distribution and plasma and renal clearance. J Infect Dis 1971;124:S70–S76.CrossRefGoogle ScholarPubMed
21.Plantier, J, Forrey, AW, O'Neill, MA, et al: Pharmacokinetics of amikacin in patients with normal or impaired renal function: Radioenzymatic acetylation assay. J Infect Dis 1976;134:S323–S330.CrossRefGoogle ScholarPubMed
22.Assael, BM, Gianni, V, Marini, A, et al: Gentamicin dosage in preterm and term neonates. Arch Dis Child 1977;52:883–886.CrossRefGoogle ScholarPubMed
23.Howard, JB, McCracken, GH: Pharmacological evaluation of amikacin in neonates. Antimicrob Agents Chemother 1975;8:86–90.CrossRefGoogle ScholarPubMed
24.McCracken, GH Jr, Gay Jones, L: Gentamicin in the neonatal period. Am J Dis Child 1970;120:524–533.Google ScholarPubMed
25.Szefler, SJ, Wynn, RJ, Clarke, DF, et al: Relationship of gentamicin serum concentrations to gestational age in preterm and term neonates. J Pediatr 1980;97:312–315.CrossRefGoogle ScholarPubMed
26.Zaske, DE, Cipolle, RJ, Strate, RG, et al: Rapid gentamicin elimination in obstetric patients. Obstet Gynecol 1980;56:559–564.Google ScholarPubMed
27.Gill, MA, Kern, JW: Altered gentamicin distribution in ascitic patients. Am J Hosp Pharm 1979;36:1704–1706.Google ScholarPubMed
28.Zaske, DE, Cipolle, RJ, Solem, LD, et al: Raid individualization of gentamicin dosage regimens in 66 burn patients. Burns 1981;7:215–220.CrossRefGoogle Scholar
29.Schwartz, SN, Pazin, GJ, Lyon, JA, et al: A controlled investigation of the pharmacokinetics of gentamicin and tobramycin in obese subjects. J Infect Dis 1978;138:499–505.CrossRefGoogle ScholarPubMed
30.Bauer, LA, Blouin, RA, Griffin, WO Jr, et al: Amikacin pharmacokinetics in morbidly obese patients. Am J Hosp Pharm 1980;37:519–522.Google ScholarPubMed
31.Kaiser, AB, McGee, ZA: Aminoglycoside therapy of gram-negative bacillary meningitis. N Engl J Med 1975;293:1215–1220.CrossRefGoogle ScholarPubMed
32.Bruckner, O, Trautman, M, Kolodziejczyk, M, et al: Netilmicin in human CSF after parenteral administration in patients with slightly and severely impaired blood CSF barrier. J Antimicrob Chemother 1983;11:565–571.CrossRefGoogle ScholarPubMed
33.Strausbaugh, LJ, Mandaleris, CD, Sande, MA: Comparison of four aminoglycoside antibiotics in the therapy of experimental E. coli meningitis. J Lab Clin Med 1977;89:692–701.Google ScholarPubMed
34.Rahal, JJ Jr, Hyams, PJ, Simberkoff, MS, et al: Combined intrathecal and intramuscular gentamicin for gram-negative meningitis. N Engl J Med 1974;290:1394–1398.CrossRefGoogle ScholarPubMed
35.McCracken, GH Jr, Mize, S, Threlkeld, N: Intraventricular gentamicin therapy in gram-negative bacillary meningitis of infancy. Lancet 1980;1:787–791.Google ScholarPubMed
36.Wong, GA, Pierce, TH, Goldstein, E, et al: Penetration of antimicrobial agents into bronchial secretions. Am J Med 1975;59:219–223.CrossRefGoogle ScholarPubMed
37.Germudez, RH, Lugo, A, Ramirez-Ronda, CH, et al: Amikacin sulfate levels in human serum and bile. Antimicrob Agents Chemother 1981;19:352–354.CrossRefGoogle Scholar
38.Mendelson, J, Portnoy, J, Sigman, H: Pharmacology of gentamicin in the biliary tract of humans. Antimicrob Agents Chemother 1973;4:538–541.CrossRefGoogle ScholarPubMed
39.Pitt, HA, Roberts, RB, Johnson, WD Jr: Gentamicin levels in the human biliary tract. J Infect Dis 1973;127:299–302.CrossRefGoogle ScholarPubMed
40.Rubinstein, E, Goldfarb, J, Keren, G, et al: The penetration of gentamicin into the vitreous humor in man. Invest Ophthalmol Vis Sci 1983;24:637–639.Google ScholarPubMed
41.Gorden, TB, Cunningham, RD: Tobramycin levels in aqueous humor after subconjunctival injection in humans. Am J Ophthalmol 1982;93:107–110.CrossRefGoogle ScholarPubMed
42.Wingfield, DL, McDougal, RL, Roy, FH, et al: Ocular penetration of amikacin following intramuscular injection. Arch Ophthalmol 1983;101:117–120.CrossRefGoogle ScholarPubMed
43.Schentag, JJ, Cumbo, TJ, Jusko, WJ, et al: Gentamicin tissue accumulation and nephrotoxic reactions. JAMA 1978;240:2067–2069.CrossRefGoogle ScholarPubMed
44.Whelton, A: Intrarenal antibiotic distribution in health and disease. Kidney Int 1974;6:131–137.CrossRefGoogle ScholarPubMed
45.Schentag, JJ, Jusko, WJ: Renal clearance and tissue accumulation of gentamicin. Clin Pharmacol Ther 1977;22:364–370.CrossRefGoogle ScholarPubMed
46.Scherrer, JJ, Kearns, GL, Jackson, JW: Tobramycin penetration into pericardial fluid. Am J Hosp Pharm 1981;38:1039–1040.Google ScholarPubMed
47.Riff, LJ, Jackson, GG: Pharmacology of gentamicin in man. J Infect Dis 1971;124:S98–S105.CrossRefGoogle ScholarPubMed
48.Richey, GD, Schleupner, CJ: Peritoneal fluid concentrations of gentamicin in patients with spontaneous bacterial peritonitis. Antimicrob Agents Chemother 1981;19:312–315.CrossRefGoogle ScholarPubMed
49.Gerding, DN, Hall, WH, Schierl, EA: Antibiotic concentrations in ascitic fluid of patients with ascites and bacterial peritonitis. Ann Intern Med 1977;86:708–713.CrossRefGoogle ScholarPubMed
50.Marsh, DC Jr, Matthew, EB, Perselin, RA: Transport of gentamicin into synovial fluid. JAMA 1974;228:607.CrossRefGoogle ScholarPubMed
51.Dee, TH, Koein, F: Gentamicin and tobramycin penetration into synovial fluid. Antimicrob Agents Chemother 1977;12:548–549.CrossRefGoogle ScholarPubMed
52.Flores-Mercado, F, Garcia-Mercado, JL, Estopier-Jauregui, C, et al: Clinical pharmacology of amikacin sulfate: Blood, urinary and tissue concentrations in the terminal stage of pregnancy. J Int Med Res 1977;5:292–294.CrossRefGoogle ScholarPubMed
53.Creatsas, G, Pavlatos, M, Lolis, D, et al: Ampicillin and gentamicin in the treatment of fetal intrauterine infections. J Perinat Med 1980;8:13–18.CrossRefGoogle ScholarPubMed
54.Chyo, N, Sunada, H, Nohara, S: Clinical studies of kanamycin applied in the field of obstetrics and gynecology. Asian Medical Journal 1962;5:266–275.Google Scholar
55.Malmod, S, Al-Hakiem, MHH, Landon, J, et al: Aminoglycoside antibiotics do not appear in saliva. Clin Chem 1983;29:988–989.Google Scholar
56.Alftan, O, Renkonen, OV, Sironen, A: Concentration of gentamicin in serum, urine and urological tissue in man. Acta Pathol Microbiol Scand [B] 1983; 81 (suppl 241):92–94.Google Scholar
57.Schroeder, SA, Catino, D, Toala, P, et al: Chronic Pseudomonas osteomyelitis. J Bone Joint Surg 1970;52:1611–1617.CrossRefGoogle ScholarPubMed
58.Wilson, TW, Mahon, WA, Inaba, T, et al: Elimination of tritiated gentamicin in normal human subjects and in patients with severely impaired renal function. Clin Pharmacol Ther 1973;14:815–822.CrossRefGoogle ScholarPubMed
59.Chiu, PJS, Brown, A, Miller, G, et al: Renal extraction of gentamicin in anesthetized dogs. Antimicrob Agents Chemother 1976;10:277–282.CrossRefGoogle ScholarPubMed
60.Pijck, J, Hallynck, T, Soep, H, et al: Pharmacokinetics of amikacin in patients with renal insufficiency: Relation of half-life and creatinine clearance. J Infect Dis 1976;134:S331–S341.CrossRefGoogle ScholarPubMed
61.McHenry, MC, Gavan, TL, Gifford, RW, et al: Gentamicin dosages for renal insufficiency. Adjustments based on endogenous creatinine clearance and serum creatinine concentration. Ann Intern Med 1971;74:192–197.CrossRefGoogle ScholarPubMed
62.Greenblatt, DJ, Koch-Weser, J: Clinical pharmacokinetics (second of two parts). N Engl J Med 1975;293:964–970.CrossRefGoogle ScholarPubMed
63.Sarubbi, FA, Hull, JH: Amikacin serum concentrations: Prediction of levels and dosage guidelines. Ann Intern Med 1978;89:612–618.CrossRefGoogle ScholarPubMed
64.Chan, RA, Benner, EJ, Hoeprich, RD: Gentamicin therapy in renal failure: A nomogram for dosage. Ann Intern Med 1978;76:775–778.Google Scholar
65.Sawchuk, RJ, Zaske, DE: Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: Gentamicin in burn patients. J Pharmacokinet Biopharm 1976;4:183–195.CrossRefGoogle ScholarPubMed