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DRUG RECORD


AMINOGLYCOSIDES

OVERVIEW
Aminoglycosides

 

The aminoglycosides are natural products and semisynthetic derivatives from a variety of actinomycetes.  The first aminoglycoside used in clinical practice was streptomycin which was derived from Streptomyces griseus and was the first effective agent against mycobacterium tuberculosis.  The discovery and characterization of the antibacterial activity of streptomycin led to the award of the Nobel Prize in Medicine to Waksman and his coworkers.  Currently available aminoglycosides are used primarily to treat severe aerobic gram negative bacterial infections, usually in combination with penicillins or cephalosporins.  Aminoglycosides have a common structure of two or more amino sugars joined in glycosidic linkage to a hexose nucleus.  The aminoglycosides are believed to act by binding to ribosomes of bacteria and blocking protein synthesis.  Aminoglycosides currently used in the United States include streptomycin, gentamicin, tobramycin, amikacin and neomycin.  Streptomycin is currently used largely as adjunctive therapy of tuberculosis and its hepatotoxicity is discussed in sections dealing with antitubercular therapy.  Aminoglycosides are poorly absorbed orally and effective serum concentrations can only be achieved with parenteral administration.  Indeed, based upon its poor absorption, neomycin is used orally to decrease colonic bacteria and as therapy of hepatic encephalopathy.  Although aminoglycosides are widely used and important agents, they have serious toxicities which limit their applicability.  The common serious adverse effects of the aminoglycosides are ototoxicity and nephrotoxicity.  Liver injury from the aminoglycosides is rare.  Isolated case reports of idiosyncratic hepatotoxicity have been published for most but not all of the aminoglycosides.

Each aminoglycoside is discussed separately while the references for all aminoglycosides are provided below.  The following are links to each drug record.

 

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REFERENCES
Aminoglycosides

 

References last updated: 7 July 2011

  1. Zimmerman HJ.  Aminoglycosides.  Hepatic injury from the treatment of infectious and parasitic diseases.  In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999. p 589.  (Expert review of hepatotoxicity of aminoglycosides published in 1999; “few instances of significant hepatic injury have been attributed to agents in this group”).

  2. Moseley RH. Antibacterial and Antifungal Agents. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 2nd Edition. New York:  Informa Healthcare USA, Inc, 2007. p. 527-46. (Review of hepatotoxicity of antibiotics published in 2007; the aminoglycosides are not discussed).

  3. Chambers HF. Aminoglycosides. In, Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill, 2006, pp. 1155-71.  (Textbook of pharmacology and therapeutics).

  4. Gentry LO. Efficacy and safety of cefamandole plus either gentamicin or tobramycin in therapy of severe gram-negative bacterial infections. J Infect Dis 1978; 137 Suppl: S144-9. PubMed Citation  (Prospective study in 31 patients given cephalosporin and standard [n=20] or high doses [n=11] of either gentamicin [12] or tobramycin [19]; higher doses were associated with more increases in Alk P [27% vs 5%] and ALT [27% vs 0%], one patient with jaundice had acute tobramycin hepatitis B).

  5. Mor F, Leibovici L, Cohen O, Wysenbeek AJ. Prospective evaluation of liver function tests in patients treated with aminoglycosides. DICP 1990; 24: 135-7. PubMed Citation  (Prospective study in 104 patients given gentamicin and 10 given amikacin found no change in ALT, LDH or bilirubin levels, but mild increases in Alk P in 23% of patients; no symptomatic hepatitis).

  6. Lucena MI, Andrade RJ. [Aminoglycoside nephrotoxicity and obstructive jaundice] Med Clin (Barc) 1995; 105: 457-60. Spanish. PubMed Citation  (Review of the increased risk of nephrotoxicity in patients with obstructive jaundice).

  7. Nisly SA, Ray SM, Moye RA. Tobramycin-induced hepatotoxicity. Ann Pharmacother 2007; 41: 2061-5. PubMed Citation  (Patient with pseudomonas bacteremia treated with multiple antibiotics, developed elevations in AST [970 U/L], ALT [315 U/L] and Alk P [432 U/L] and mild jaundice within days of starting tobramycin; changing antibiotics did not affect enzyme elevations until tobramycin was stopped with resolution in 1-2 weeks; apparently no symptoms or allergic signs).

  8. Lindblad A, Hultcrantz R, Strandvik B. High doses of aminoglycosides did not produce liver toxicity in patients with cystic fibrosis. J Hepatol 1994; 20: 201-5. PubMed Citation  (Five patients with cystic fibrosis underwent yearly liver biopsies; those on intermittent aminoglycoside therapy showed no hepatic abnormalities and liver tests were normal in all).

  9. Nassberger L, DePierre J. High doses of aminoglycoside antibiotics do not induce liver toxicity because uptake is limited. J Hepatol 1994; 21: 1156. PubMed Citation  (Letter in response to Lindblad et al. postulating that lack of hepatic injury is due to limited uptake of aminoglycosides in the liver compared to kidney and inner ear).

  10. Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135: 1924-34. PubMed Citation  (Among 300 cases of drug induced liver disease in the US collected from 2004 to 2008, 1 case was attributed to gentamicin and none to other aminoglycosides; no details of case provided).

  11. Wang YP, Shi B, Chen YX, Xu J, Jiang CF, Xie WF. Drug-induced liver disease: an 8-year study of patients from one gastroenterological department. J Dig Dis 2009; 10: 195-200. PubMed Citation  (30 cases of drug induced liver disease were seen at a single large hospital in Bejing between 2000 and 2007, including one case of cholestatic hepatitis attributed to gentamicin arising 1 day after starting therapy with ALT 2.6 times ULN, Alk P 2.3 times ULN, bilirubin 6.8 mg/dL, with few other details that might separate it from jaundice of sepsis).

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OTHER REFERENCE LINKS
Aminoglycosides

 

  1. PubMed logoRecent References on Aminoglycosides

  2. Clinical Trials logoTrials on Aminoglycosides

  3. TOXLINE logoTOXLINE Citations on Aminoglycosides

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