Streptomycin tuberculosis

D. Treatment of bacterial infections Antibiotics that selectively affect bacterial function and have minimal side effects in humans are usually selected to treat bacterial infections. Rifampicin, which inhibits the initiation of prokaryotic RNA synthesis, is used to treat tuberculosis. Streptomycin, tetracycline, chloramphenicol, and erythromycin inhibit protein synthesis on prokaiyotic ribosomes and are used for many infections. Chloramphenicol affects mitochondrial ribosomes and must be used with caution. 

Tuberculosis In the treatment of tuberculosis, streptomycin always should be used in combination with at least one or two other drugs to which the causative strain is susceptible (see Chapter 47). 

Streptomycin was the first of the class of aminoglycoside antibiotics to be discovered in 1943. Isolated from Streptomyces griseus, it was the first antibiotic remedy for tuberculosis. Streptomycin, also known as streptomycin A, is an oligosaccharide with basic properties. Like other representatives of the aminoglycoside family, it consists of a monosaccharide, an amino sugar, and a guanidino-substituted cyclohexane with at least three hydroxide groups. 

Cuanidino groups are also present in streptomycin, which was the first aminoglycoside antibiotic used in treating tuberculosis. Streptomycin and related antibiotics interfere in the translation of RNA into protein and this is probably due to their polycationic nature and ability to mimic both Mg and polyamines that are involved in phosphate group stabilisation. 

R = R = H) are intermediate, and gentamicin and tobramycin are most susceptible (66). Resistance to streptomycin is widespread, and its use is currently confined primarily to infections caused by Mycobacterium tuberculosis Yersiniapestis and Francisella tularensis. 

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. 

Control of tuberculosis, long one of the scourges of mankind, began with the introduction of effective antibacterial agents. Thus, this disease was treated initially with some small measure of success with various sulfa drugs the advent of the antibiotic, streptomycin, provided a major advance in antitubercular therapy, as did the subsequent discovery of isoniazid and its analogs. 

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. 

The initial phase must contain three or more of the following drugp isoniazid, rifampin, and pyrazin-amide, along with either ethambutol or streptomycin. The CDC recommends treatment to begin as soon as possible after the diagnosis of tuberculosis. The treatment recommendation regimen is for the administration of rifampin, isoniazid, and pyrazinamide for a minimum of 2 months (8 weeks), followed by rifampin and isoniazid for 4 months (16 weeks) in areas with a low incidence of tuberculosis. In areas of high incidence of tuberculosis, the CDC recommends the addition of streptomycin or ethambutol for the first 2 months. 

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,... 

The three standard drugs used in the treatment of tuberculosis were streptomycin (considered above), -aminosalicylic acid (PAS) and isoniazid (isonicotinylhydrazide, INH synonym, isonicotinic acid hydrazine, INAH). The tubercle bacillus rapidly becomes resistant to streptomycin, and the role of PAS was mainly that of preventing this development of resistance. The current approach is to treat tuberculosis in two phases an initial phase where a combination of three dmgs is used to reduce the bacterial level as rapidly as possible, and a continuation phase in which a combination of... 

The advent of multidrug resistant strains of Mycobacterium tuberculosis (MDR-TB) has led to increased fears of untreatable infections by serious pathogens. Rifampicin, streptomycin and, occasionally, the quinolones are drugs used in the treatment of mycobacterial infections and resistance to those agents is as described previously. There... 

Karl MyrbAck, Products of the Enzymic Degradation of Starch and Glycogen 252 M. Stacey and P. W. Kent, The Polysaccharides of Mycobacterium tuberculosis 311 R. U. Lemieux and M. L. Wolfrom, The Chemistry of Streptomycin. 337... 

In experimental typhoid disease in mice treated with colimycin, the addition of pentoxyl prevents immunological disorders and stimulates an immunological reaction [294]. This compound potentiates the action of sulphonamides in mice infected with type II pneumococcus [295]. In combination with streptomycin, pentoxyl is beneficial in the treatment of experimental tuberculosis in guinea-pigs [296]. However, a single pharmacological report, relative to effects on the central nervous system, was unfavourable [297]. 

Although streptomycin was not the first antibiotic (penicillin, a fungal product, had been isolated some years earlier), its discovery was a landmark in antibiotic history. It was the first effective therapeutic for tuberculosis, a disease that had terrorized humans for cenmries and a cause of human morbidity and mortality unmatched by wars or any other pestilence. Streptomycin was the first aminoglycoside to be identified and characterized and is noteworthy in being the first useful antibiotic isolated from a bacterial source. At the present time, the use... 

The introduction of streptomycin as an antibiotic in 1944 was welcomed as the long-sought solution to combat tuberculosis and other intractable gram-negative infections. The first clinical trial, however, already highlighted the side effects... 

Medical Research Council Streptomycin in Tuberculosis Trials Committee. Streptomycin treatment for pulmonary tuberculosis. Br Med J 1948 ii 769-82. 

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. 

Previous reactions to these agents. With the exception of the use of streptomycin in tuberculosis, these agents generally are not indicated in long-term therapy because of the ototoxic and nephrotoxic hazards of extended administration. 

Do not use tuberculosis regimens consisting of isoniazid, ethambutol, and pyrazinamide (ie, 3-drug regimens that do not contain a rifamycin, an aminoglycoside [eg, streptomycin, amikacin, kanamycin], or capreomycin) for the treatment of patients with HIV-related tuberculosis. The minimum duration of therapy is 18 months (or 12 months after documented culture conversion) if these regimens are used for the treatment of tuberculosis. 

Pharmacology Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis. It inhibits the onset of bacterial resistance to streptomycin and isoniazid. The mechanism of action has been postulated to be inhibition of folic acid synthesis (but without potentiation with antifolic compounds) or inhibition of synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis. 

Mycobacterium tuberculosis Add streptomycin or ethambutol as a fourth drug in a regimen containing isoniazid (INH), rifampin, and pyrazinamide for initial treatment of tuberculosis unless the likelihood of INH or rifampin resistance is very low. Streptomycin also is indicated for therapy of tuberculosis when one or more of the above drugs is contraindicated because of toxicity or intolerance. 

Tuberculosis The standard regimen for the treatment of drug-susceptible tuberculosis has been 2 months of INH, rifampin, and pyrazinamide followed by 4 months of INH and rifampin (patients with concomitant infection with tuberculosis and HIV may require treatment for a longer period). When streptomycin is added to this regimen because of suspected or proven drug resistance, the recommended dosing for streptomycin is as follows ... 

UK from 1840 until near the end of the 20th Century. Horton Hinshaw and William Feldman s paper on Streptomycin in treatment of clinical tuberculosis A preliminary report appeared in the Proceedings of the Mayo Clinic in 1945. For his work on... 

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