Streptomycin
Streptomycin (S)
Streptomycin was discovered in 1943. It was the first antibiotic discovered that was effective against TB. Today it is widely used as a first line TB medicine in patients that have previously been treated for TB. Streptomycin is added to first line regimens because patients that have previously been treated for TB are more likely to have developed some drug resistance.
Patients that are resistant to both rifampicin and isoniazid are classified as having MDR TB; these patients should not be retreated with first line medicine but instead initiated onto a second line regimen.
Dosage:
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Adults: |
Adults with liver damage - creatinine clearance < 30 ml/min: |
Children: |
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15 – 20 mg/kg daily (max dose 1000 mg) |
12 – 15 mg/kg 2 or 3 times a week |
20 – 40 mg/kg (max dose 1000 mg) |
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Streptomycin is administered via injection daily or 5 days a week during the intensive phase, in the first two months of treatment. |
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How it works:
Streptomycin is derived from the actinobacteriumStreptomyces griseus. It inhibits protein synthesis and causes the death of microbial cells. It is a useful broad-spectrum antibiotic.
Side effects:
Streptomycin can cause loss of hearing, which can become permanent if treatment levels are continued. The risk of hearing loss is higher in patients with kidney damage. Streptomycin can worsen kidney damage, although this is generally reversible if treatment is stopped. Streptomycin can also cause dizziness, vertigo, impaired coordination, rashes, fevers, yeast infections and oral thrush.
Streptomycin should be avoided during pregnancy as it may cause birth defects including deafness in the foetus. Streptomycin should only be used during pregnancy when benefits outweigh the risks. Streptomycin is secreted in breastmilk but it is not contra-indicated during breast feeding.
Clinical evidence:
Between 1944 and 1948, the United States Veterans Administration carried out extensive clinical trials in thousands of patients treated in Veterans Hospitals. A review of these trials found that streptomycin could temporarily stop the growth of TB but did not offer a permanent cure. It was therefore recommended that streptomycin was used as an additional aid to the other TB medicines in use at the time.1
In 1948, there was also growing awareness that many patients treated with streptomycin developed resistance and that streptomycin-resistant strains of TB could be transmitted between patients.2 In 1951, it was reported that the combination of streptomycin and para-aminosalicyclic acid (PAS) could delay the development of streptomycin resistance.3 TB became curable with the combination of streptomycin and PAS, but treatment took up to 2 years and was difficult to tolerate.
With the development of more effective anti TB medicines such as rifampicin and isoniazid, streptomycin was replaced in the initial treatment of TB, but is still widely used in the retreatment of TB.
However, a systematic review and meta analysis of nearly 2,000 patients retreated for TB with 8 months of rifampicin, isoniazid, ethambul and pyrazinamide in combination with streptomycin demonstrated that this regimen yields poor results, particularly in patient with mono-resistance to isoniazid. In 9 trials of patients with mono-resistance to isoniazid, the combined failure and relapse rates ranged from 0% to over 75%.4
WHO guidelines recommending this regimen for the retreatment of TB state that ‘the evidence for recommending this regimen is of very low quality... [but] when compared with the alternative of providing an MDR regimen to all previously treated patients, the risks outweigh the benefits.’
Pricing (per lowest unit, i.e. single tablet or injection):
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SA Public sector (August 2011 – July 2013 tender) |
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Included in this tender. Prices not yet available. |
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SA Private sector |
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1 g/3 ml for injection |
R8.10 |
* Private sector prices sourced on 26/07/11. Global Drug Facility prices converted to rands on 26/07/11.
* Private and public sector prices may vary between suppliers. The lowest available prices are shown here.
Advocacy issues:
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Too few patients are tested and diagnosed with MDR TB, therefore failure rates of retreatment are high.
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There is little published evidence to support the retreatment of TB using 8 months of first line medicines in combination with streptomycin, particularly in patients with isoniazid resistance. Further research is needed to establish the most effective regimen for treating these patients.
1 E Bogen. Streptomycin Treatment for Tuberculosis. J Natl Med Assoc. 1948 Jan;40(1):32.
2 No authors listed. Streptomycin resistance in tuberculosis. Br Med J. 1948 December 11; 2(4588): 1025–1026.
3 E Dunner et al. Streptomycin para-aminosalicylate in the treatment of pulmonary tuberculosis. Dis Chest. 1951 Apr;19(4):438-43.
4 D Menzies et al.Standardizedtreatment of activetuberculosis in patients with previoustreatment and/or with mono-resistance to isoniazid: a systematic review and meta-analysis.PLoS Med. 2009 Sep;6(9):e1000150.
