Tuberculosis streptomycin activity

Before the discovery of streptomycin, pyrazinamide (126) was one of the front runners in the treatment of tuberculosis. A broad spectrum of biological activity has been associated with pyrazine derivatives, ranging from the herbicidal activity of (127) to antibiotic activity... 

Substitution of an amino group into the molecule affords an iigent with antibacterial activity. Although seldom used alone, l, ira- aminosalicylic acid (PAS, 7) has been employed as an adjunct Id streptomycin and isoniazid in treatment of tuberculosis. 

Most aiititubercular drag s are bacteriostatic (slow or retard the growth of bacteria) against the M. tuberculosis bacillus. These dm usually act to inhibit bacterial cell wall synthesis, which slows the multiplication rate of the bacteria. Only isoniazid is bactericidal, with rifampin and streptomycin having some bactericidal activity. 

Discovery of Kanamycin, and Establishment oflMC. Chloramphenicol, chlor- and oxy-tetracyclines, and pyridomycin (H. Umezawa, 1967) were active, in in vitro experiments, against strains of tuberculosis, but these drugs, in contrast to streptomycin, were clinically inactive. H. Umezawa... 

Stiepton dn was isolated by Waksman in 1944, and its activity against M tuberculosis ensured its use as a primaiy ding in the treatment of tuberculosis. Unfortunately, its ototoxicity and the rapid development of resistance have tended to modify its usefulness, and although it still remains a front-hne dmg against tuberculosis it is usually used in combination with isoniazid and p(4)-aminosalicyhc acid (section 11.5). Streptomycin also shows activity against other types of bacteria,... 

Streptomycin possesses a broad spectrum of antibacterial activity. It is the first clinically effective drug used for treating tuberculosis. Synonyms of this drug are streptan, strepto-col, and others. 

Amikacin and kanamycin (see Chapter 46) have been used in the treatment of tuberculosis. Amikacin is very active against several mycobacterium species however, it is expensive and has significant toxicity. It is considered in the treatment of MDR tuberculosis after streptomycin and capreomycin. An additional use of amikacin is in the treatment of disseminated MAC in AIDS patients. There is no cross-resistance between streptomycin and other aminoglycosides most M. tuberculosis strains that are resistant to streptomycin are... 

Thiacetazone is active against many strains of M. tuberculosis. It is not marketed in the United States. However, because of its low cost, it is used as a first-line agent in East Africa, especially in combination with compounds such as isoniazid. The most common side effects of thiacetazone include GI intolerance and development of rashes. It causes significant ototoxicity, especially when coadministered with streptomycin. Life-threatening hypersensitivity reactions, such as hepatitis, transient marrow aplastic syndromes, neutropenia, and thrombocytopenia, have been reported. 

It is chemically related to nicotinamide and thiosemicarbazone. It is bactericidal. It is effective against Mycobacterium tuberculosis resistant to INH and streptomycin. It is converted to pyrazinoic acid (active... 

Streptomycin Prevents bacterial protein synthesis by binding to the S12 ribosomal subunit (see also Chapter 45) Bactericidal activity against susceptible mycobacteria Used in tuberculosis when an injectable drug is needed or desirable and in treatment of drug-resistant strains IM, IV renal clearance (half-life 2.5 h) administered daily initially, then 2 x week Toxicity Nephrotoxicity, ototoxicity... 

Acler Actiluatics. Other antibiotics were quickly discovered after the introduction of penicillin. A different type of antibiotic, streptomycin, which is active against a widei lange of pathogens than penicillin and is a potent inhibitor of Mycobacterium tuberculosis, was isolated from a strain of actinomycete from the throat of a chicken by Waksman at Rutgers in 1944 (Aiba and Evans). Actinomycetes are commonly found in soil and are intermediate between fungi and bacteria. Since 1944. numerous other metabolic products of actinomycetes have been isolated and have made a transition from the bench scale to wide therapeutic use. 

Streptomycin (Figure 8.25) is produced by cultures of a strain of Streptomyces griseus, and is mainly active against Gram-negative organisms. Because of its toxic properties it is rarely used in modern medicine except against resistant strains of Mycobacterium tuberculosis in the treatment of tuberculosis. 

Isoniazid (INH), rifampin, pyrazinamide, ethambutol, and streptomycin are the five first-line agents for treatment of tuberculosis (Table 47-1). Isoniazid and rifampin are the two most active drugs. An isoniazid-rifampin combination administered for 9 months will cure 95-98% of cases of tuberculosis caused by susceptible strains. The addition of pyrazinamide to an isoniazid-rifampin combination for the first 2 months allows the total duration of therapy to be reduced to 6 months without loss of efficacy (Table 47-2). In practice, therapy is initiated with a four-drug regimen of isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin until susceptibility of the clinical isolate has been determined. Neither ethambutol nor streptomycin adds substantially to the overall activity of the regimen (ie, the duration of treatment cannot be further reduced if either drug is used), but they do provide additional coverage should the isolate prove to be resistant to isoniazid, rifampin, or both. Unfortunately, such resistance occurs in up to 10% of cases in the United States. Most patients with tuberculosis can be treated entirely as outpatients, with... 

Dickinson JM, Aber VR, Mitchison DA. Bactericidal activity of streptomycin, isoniazid, rifampin, ethambutol, and pyrazinamide alone and in combination against Mycobacterium tuberculosis. Am Rev Respir Dis 1977 116(4) 627-35. 

Streptomycin [7], the first aminoglycoside to find clinical use, was second only to penicillin as an antibiotic in so doing. It was the very first antibiotic with activity against Mycobacterium tuberculosis, the microorganism that causes tuberculosis. In-... 

Another alkylamino derivative tested was a conjugate of streptomycin and isoniazid, another prominent anti-tuberculosis drug. This compound termed streptohydrazid, was synthesized and found to be at least as active as combined therapy using both streptomycin and isoniazid (51).Streptohydrazid was tested long before the mechanism of action of streptomycin was known (the mechanism of isoni-... 

---