Streptomycin

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Chapter: Essential pharmacology : Aminoglycoside Antibiotics

It is the oldest aminoglycoside antibiotic obtained from Streptomyces griseus; used extensively in the past, but now practically restricted to treatment of tuberculosis.


STREPTOMYCIN

 

It is the oldest aminoglycoside antibiotic obtained from Streptomyces griseus; used extensively in the past, but now practically restricted to treatment of tuberculosis. It is less potent (MICs are higher) than other aminoglycosides. The antimicrobial spectrum of streptomycin is relatively narrow: active primarily against aerobic gram-negative bacilli, but potency is low. Sensitive organisms are—H. ducreyi, Brucella, Yersinia pestis, Francisella tularensis, Nocardia, Calym. granulomatis, M. tuberculosis. Only few strains of E. coli, H. influenzae, V. cholerae, Shigella, Klebsiella, enterococci and some gram-positive cocci are now inhibited, that too at higher concentrations. All other organisms including Pseudomonas are unaffected.

 

Resistance

 

Many organisms develop rapid resistance to streptomycin, either by onestep mutation or by acquisition of plasmid which codes for inactivating enzymes. In the intestinal and urinary tracts, resistant organisms may emerge within 2 days of therapy. E. coli., H. influenzae, Str. pneumoniae, Str. pyogenes, Staph. aureus have become largely resistant. If it is used alone, M. tuberculosis also become resistant.

 

Streptomycin Dependence

 

Certain mutants grown in the presence of streptomycin become dependent on it. Their growth is promoted rather than inhibited by the antibiotic. This occurs when the antibiotic induced misreading of the genetic code becomes a normal feature for the organism. This phenomenon is probably significant only for use of streptomycin in tuberculosis.

 

Cross Resistance

 

Only partial and often unidirectional cross resistance occurs between streptomycin and other aminoglycosides.

 

Pharmacokinetics

 

Streptomycin is highly ionized. It is neither absorbed nor destroyed in the g.i.t. However, absorption from injection site in muscles is rapid. It is distributed only extracellularly: volume of distribution (0.3 L/kg) is nearly equal to the extracellular fluid volume. Low concentrations are attained in serous fluids like synovial, pleural, peritoneal. Concentrations in CSF and aqueous humour are often nontherapeutic, even in the presence of inflammation. Plasma protein binding is clinically insignificant.

 

Streptomycin is not metabolized—excreted unchanged in urine. Glomerular filtration is the main channel: tubular secretion and reabsorption are negligible. The plasma t½ is 2–4 hours, but the drug persists longer in tissues. Renal clearance of streptomycin parallels creatinine clearance and is approximately 2/3 of it. Halflife is prolonged and accumulation occurs in patients with renal insufficiency, in the elderly and neonates who have low g.f.r. Reduction in dose or increase in dose-interval is essential in these situations.

 

These pharmacokinetic features apply to all systemically administered aminoglycosides.

 

Adverse Effects

 

About 1/5 patients given streptomycin 1 g BD i.m. experience vestibular disturbances. Auditory disturbances are less common.

 

Streptomycin has the lowest nephrotoxicity among aminoglycosides; probably because it is not concentrated in the renal cortex. Hypersensitivity reactions are rare; rashes, eosinophilia, fever and exfoliative dermatitis have been noted. Anaphylaxis is very rare. Topical use is contraindicated for fear of contact sensitization.

 

Superinfections are not significant. Pain at injection site is common. Paraesthesias and scotoma are occasional.

 

AMBISTRYNS 0.75, 1 g dry powder per vial for inj.

 

Acute infections: 1 g (0.75 g in those above 50 yr age) i.m. BD for 7–10 days.

 

Tuberculosis: 1 g or 0.75 g i.m. OD or twice weekly for 30–60 days.

 

Uses

 

1.  Tuberculosis: see Ch. No. 55.

 

2. Subacute bacterial endocarditis (SABE): Streptomycin (now mostly gentamicin) is given in conjunction with penicillin. A 4–6 weeks treatment is needed.

 

3. Plague: It effects rapid cure (in 7–12 days), may be employed in confirmed cases, but tetracyclines have been more commonly used for mass treatment of suspected cases during an epidemic.

 

4. Tularemia: Streptomycin is the drug of choice for this rare disease: effects cure in 7–10 days. Tetracyclines are the alternative drugs, especially in milder cases.

 

In most other situations, e.g. urinary tract infection, peritonitis, septicaemias, etc. where streptomycin was used earlier, gentamicin or one of the newer aminoglycosides is now preferred due to low potency and widespread resistance to streptomycin.

 

Oral use of streptomycin for diarrhoea is banned in India.

 

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