Streptomycin (Mol wt = 1457.41) was the first of the aminoglycoside antibiotics (AGs) developed. It was isolated more than 50 years ago and was initially used to treat pulmonary tuberculosis. Streptomycin is also highly active against gram-negative aerobic pathogens with some activity against gram-positive cocci. Streptomycin use has fallen out of favor due to widespread use of other AGs including gentamicin and tobramycin. Widespread resistance of Enterobacteriaceae has also restricted the use of streptomycin to a few specific clinical situations.1 In general it is now reserved for treatment in combination with other antibiotics for active tuberculosis, streptococcal or enterococcal endocarditis, mycobacterial infections, plague, tularemia and brucellosis. Streptomycin can often be used for multi-drug resistant tuberculosis. Unlike other AGs it is generally ineffective against P. aeruginosa. Streptomycin is almost always used in combination with another antibiotic (eg: a penicillin) but can be used as a single agent in the treatment of tularemia and the plague.
Indications and Dosages
(Mandell's "Principles and Practice of Infectious Diseases", 5th edition, 2000 Churchill Livingstone.) |
Tuberculosis:
- Usual dose ranges from 0.5-1 g q24h to 1 g twice weekly
- Desired peak 25-50 mg/L (MIC for M. Tuberculosis = 4-10 mg/L)
- Rapid resistance develops when used as monotherapy. It is used in combination with INH, rifampin and Pyrazinamide (PZA)
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Endocarditis
- Streptococcal endocarditisRecommended regimen is Streptomycin 0.5-1 g IM/IV q12h in combination with Penicillin-G 10-20 million units /day (divided q6h). The usual duration of therapy is 2 weeks. Penicillin is sometimes given alone for an additional 2 weeks after combination therapy is finished.
- Enterococcal endocarditis
High dose PCN therapy should be combined with streptomycin for duration of 4-6 weeks. Pen-G 20-40 million units /day in 4 divided doses or Ampicillin 2-3 g every 4 hrs have been used in combination with streptomycin 0.5-1 g q12h. Vancomycin can be used in cases of PCN allergy. Streptomycin should not be used in highly resistant strains (MIC > 2000 mg/L).
Streptomycin can sometimes be used to treat life threatening gentamicin resistant enterococci. Up to 30% of these organisms are susceptible to Streptomycin.1 A regimen of 1 gram IM q12h x 2 week has been used for Enterococcal endocarditis that is highly resistant to gentamicin, in combination with penicillin or vancomycin.
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Like all AG's streptomycin is a hydrophilic molecule that penetrates well into extracellular fluid including abscesses, ascites, pericardial, pleural, synovial and peritoneal fluids. However, streptomycin has poor penetration of the blood-brain barrier. It is recommended that streptomycin be administered via the intramuscular route although it has been successfully given intrevenously.2 It is believed that the IV route may be associated with increased peak serum concentrations and a higher incidence of ototoxicity, although this has never been proven. The nephrotoxic potential of streptomycin is very low when compared to other AGs. However, risk of ototoxicity is higher. Hearing loss first begins in the high-tone range and can only be detected with an audiogram. The entire hearing range becomes affected in later stages.3 Other side effects may occur that are not seen with other AG's including neuromuscular blockade and other neurotoxicities. Neuromuscular blockade only occurs at higher than normal doses. Monitoring includes an audiogram to test for hearing loss as well as serum creatinine to assess kidney function. Aminoglycoside-induced nephrotoxicity is usually reversible, but ototoxicity is not.
The recommended dose for adults is 15 mg/kg/day divided in two doses (q12h). For children the dose is usually 20-30 mg/kg/day. Lower doses (10 mg/kg/day) are usually used for elderly patients (³
65 yrs). For treatment of plague the optimal dose for adult patients is ~30 mg/kg/day. Dosing frequency for streptomycin should be adjusted based on estimated creatinine clearance (CLcr):
| Streptomycin Dosage |
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Recommended Adult Dosage (IM/IV):
7.5 mg/kg/dose q12h (usual Dose for an average adult: 0.5 - 1 g q12h)
Pediatric dose:
20 - 40 mg/kg/day (divided q6-12h) |
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Suggested Streptomycin Dosage in Renal Dysfunction |
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Estimated CLcr, mL/min |
Dose (mg/kg/dose) |
Frequency |
|
³
90 |
7.5 |
q12h |
|
50-89 |
7.5 |
q24h |
|
20-49 |
5 |
q24h |
|
10-19 |
5 |
q48h |
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<10 |
5 |
q72h |
The drug is removed by dialysis and should be administered post-dialysis. Serum drug levels for streptomycin should be monitored regularly in high-risk patients. However many institutions are unable to measure it. Target serum levels (mg/L):
The peak should be drawn 1 hr after IM injection or ½ hr after an IV infusion, a trough should be drawn immediately before the next dose.
The drug is in limited supply and is provided free of charge on a per-patient basis from Pfizer Inc. (1-800-254-4454).
References
1 Edson et al. The Aminoglycosides: Streptomycin, Kanamycin, Gentamicin, Tobramycin, Amikacin, Netilmicin, and Sisomicin. Mayo Clin Proc 62:916-920, 1987)
2 Morris JT, Cooper RH. Intravenous Streptomycin: (A Useful Route of Administration. CID 1994; 19 (December) 1150-1151) IM administration may be painful
3 Walter et al. Aminoglycoside Antibiotics in Infectious Diseases. The American Journal of Medicine Vol 80 (suppl 6B) pp2-11 1986)
4 Dodge RA et al. High-Dose Ampicillin Plus Streptomycin for Treatment of a Patient with Severe Infection Due to Multiresistant Enterococci. CID 1997; 25 (November) pp 1269-1268
