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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: September 15, 2021.



Streptomycin is a broad spectrum aminoglycoside antibiotic typically used for treatment of active tuberculosis, always in combination with other antituberculosis agents. Streptomycin is usually used in combination with agents that are known to be hepatotoxic and the role of streptomycin in liver injury has been difficult to assess, but most information suggests that streptomycin is not hepatotoxic.


Streptomycin (strep" toe mye' sin), an aminoglycoside antibiotic, must be given by parenteral injection and is now considered a second line antituberculosis agent, used largely when toxicity has limited use of first line agents. Like other aminoglycosides, streptomycin is thought to act by binding to bacterial ribosomes and inhibiting protein synthesis. Nevertheless, streptomycin is considered bacteriocidal as well as bacteriostatic. Streptomycin was approved for use in the United States in 1956, but its use for most indications has been replaced by more modern aminoglycoside antibiotics. Streptomycin is available in vials and as lyophilized powder for injection in multiple generic formulations. The typical adult dose is 15 mg/kg per day (1 gram daily) intramuscularly or intravenously, usually for the first 2 to 4 months of antituberculosis therapy only. The dose must be modified based upon renal function. Streptomycin is also effective against several other bacterial infections but its use is generally limited to cases in which conventional, less toxic antibiotics have been ineffective. Common side effects are auditory and renal dysfunction, and routine monitoring with of kidney function and hearing is recommended. Less common but potentially severe adverse reactions include rash, fever, neurologic toxicity, C. difficile associated diarrhea, and acute hypersensitivity reactions.


Intravenous and intramuscular therapy with streptomycin has been linked to mild and asymptomatic elevations in serum alkaline phosphatase, but therapy rarely affects aminotransferase levels or bilirubin and changes typically resolve rapidly once streptomycin is stopped. Only isolated case reports of acute liver injury with jaundice have been associated with streptomycin therapy and always in combination with other antituberculosis medications which are more clearly hepatotoxic, such as isoniazid, pyrazinamide and rifampin. Streptomycin and the aminoglycosides are not mentioned in large case series of drug induced liver disease and acute liver failure; thus, hepatic injury from streptomycin must be exceedingly rare, if it occurs at all.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Injury

Uptake of aminoglycosides into hepatocytes is limited and they are rapidly excreted in the urine; high concentrations are found in mainly in renal tubular cells and hair cells of the inner ear, perhaps explaining why they are more likely to cause nephro- or oto- rather than hepatotoxicity.

[First line medications used in the therapy of tuberculosis in the US include ethambutol, isoniazid, pyrazinamide, rifabutin, rifampin, and rifapentine. Second line medications include streptomycin, capreomycin, cycloserine, ethionamide, fluoroquinolones such as levofloxacin and moxifloxacin, aminoglycosides such as amikacin, and para-aminosalicylic acid (PAS).]

Drug Class: Antituberculosis Agents, Aminoglycosides

Other Drugs in the Class: Bedaquiline, Capreomycin, Cycloserine, Ethambutol, Ethionamide, Isoniazid, Pyrazinamide, Rifabutin, Rifampin, Rifapentine



Streptomycin – Generic


Antituberculosis Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Streptomycin 57-92-1 C21-H39-N7-O12 image 134971352 in the ncbi pubchem database


References updated: 15 September 2021

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    (Extensive review of hepatotoxicity of antituberculosis medications published in 1999: “Nevertheless, use of streptomycin alone provided data that seem to exonerate it from a hepatotoxic role”).
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    (Among 313 cases of drug induced liver injury seen between 1997 and 2008 at a large hospital in Bangalore, India, 181 [58%] were attributed to antituberculosis agents, which accounted for 39 of 54 [72%] fatal cases; streptomycin and aminoglycosides were not specifically mentioned).
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    (Analysis of adverse effects of second line drugs for tuberculosis; the aminoglycosides [streptomycin, amikacin and kanamycin] are second line agents for tuberculosis and side effects include ototoxicity, neurotoxicity, nephrotoxicity, neuormuscular blockade and hypersensitivity reactions; hepatotoxicity not mentioned).
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  • Nataprawira HM, Aliyannissa A, Febrianti SA. Unusual recurrence of antituberculosis drug-induced hepatotoxicity in children: a case series. Am J Case Rep. 2021;22:e930828. [PMC free article: PMC8295927] [PubMed: 34267172]
    (Among 6 children with recurred liver injury on therapy for tuberculosis, in 4 instances the children tolerated streptomycin and ethambutol after having an initial bout, and redeveloped acute injury with reintroduction of isoniazid).
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    (Review of the second line injectable drugs for tuberculosis including streptomycin, discusses ototoxicity, nephrotoxicity, electrolyte disturbances, local injection site reactions, but not hepatotoxicity).


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