Streptomycin Drug resistance

The answer is c. (Hardman, pp 1161-1162.) An important problem in the chemotherapy of TB is bacterial drug resistance For this reason, concurrent administration of two or more drugs should be employed to delay the development of drug resistance. Isoniazid is often combined with ethambutol for this purpose. Streptomycin or rifampin may also be added to the regimen to delay even further the development of drug resistance. 

Genes encoding phosphotransferases confer resistance to streptomycin Genes encoding a drug-resistant dihydropteroate synthase enzyme required for folate biosynthesis confer resistance to sulfonamide Tetracycline... 

INH and rifampin. When streptomycin is added to this regimen because of suspected or proven drug resistance, the recommended dosing for streptomycin is as follows ... 

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 ... 

Streptomycin is indicated as a fourth drug in combination with isoniazid, rifampin, and pyrazinamide in patients at high risk for drug resistance. It is also used in the treatment of streptomycin-susceptible MDR tuberculosis. 

Capreomycin (15 mg/kg/d) is an important injectable agent for treatment of drug-resistant tuberculosis. Strains of M tuberculosis that are resistant to streptomycin or amikacin (eg, the multidrug-resistant W strain) usually are susceptible to capreomycin. Resistance to capreomycin, when it occurs, may be due to an rrs mutation. 

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... 

Numerous episodes have occurred in which humans have developed drug-resistant nontyphoid Salmonella infections that have been traced to animal sources (23). These bacteria can be transmitted to humans in food or through direct contact with animals. Antimicrobial resistance limits the tlierapeutic options available to veterinarians and physicians for the subset of clinical cases of nontyphoid Salmonella that require treatment. A recent example is a clone of Salmonella typhimurium DT 104 with chromosomally encoded resistance to ampicillin, tetracycline, streptomycin, chloramphenicol and sulfonamides, which has become increasingly common in humans in England and Wales since 1990 (24). Since 1992, only Salmonella enteritidis has accounted for more cases of human salmonellosis than Salmonella typhimurium DT 104 (25, 26). Multiresistant DT 104 has currently emerged in several European countries (27-29) outbreaks have been also reported in the United States in both cattle (30) and humans (31). 

With both the above regimens, ethambutol by mouth or streptomycin i.m. should be added for the first 2 months if there is a likelihood of drug-resistant organisms, or if the patient is severely ill with extensive active lesions. 

These mutations occur naturally and randomly and do not require the presence of the drug. Indeed, it is likely that a drug-resistant cell is present in a bacterial population even before the drug is encountered. This was demonstrated with the identification of streptomycin-resistant cells from old cultures of a bacterium called E. coli which had been freeze-dried to prevent multiplication before the introduction of streptomycin into medicine. 

This enzyme was first found by Umezawa and coworkers in Escherichia coli K12 ML1629, which was obtained by transmission of R factor from a naturally isolated, drug-resistant strain to E. coli K12 ML1410 resistant to nalidixic acid. The inhibitory concentrations of kanamydn A, paromomycin, and neomydn toward E. coli ML1629 were higher than 320 u.g/ml, that of paromamine was 320 /ig/ml, and that of streptomycin was 20 yiig/ml. The inhibitory concentrations for . coU K12 were as follows kanamycin A, 1.25 tig/ml paromamine, 40 /ig/ml paromomycin, 1.25 ju,g/ml neomydn, 1.25 jug/ml and streptomycin, 2.5 jug/ml. 

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