Streptomycin, development

Hiscox has shown that when dihydrostreptomycin is heated in dilute sulphuric acid solution a maximum appears in the absorption spectrum at 265 mfx. Under identical conditions, streptomycin develops maxima at 245 and 315 m// and a minimum at 285 m//. Provided the conditions described below are strictly followed dihydrostreptomycin may be determined in the presence of small amounts of streptomycin, but larger amounts of the latter material, as well as other antibiotics, will interfere. 

Sreptomycin. Streptomycin is usually administered daily as a single IM injection. The preferred site is the upper outer quadrant of the buttock or die midlateral thigh. The deltoid area is used only if die area is well developed. In patients 60 years of age or older, the dosage is reduced because of die risk of increased toxicity. 

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... 

Method. Figure 3 shows the equipment used by us for loading a culture medium with radon and decay products. Air was circulated in a closed system, driven by a membran pump (MP). The system consisted of a Ra-226 solution (Ra), a security bubble flask with water (H20), a membran bacteria filter (MF) and a second bubble flask containing 100 ml RPMI 1640 culture medium (CM). This medium contains 100 IE/ml penicilin and streptomycin and 0.75% L-glutamin. Foetal calf serum, an essential part of blood cultures, must not be added, else the airstream would develop foam. Furthermore we added a small amount of Pb(N03)2 and Bi(N03)2, about 10 ng of each, as "carriers" for the radon decay products to avoid a "wall effect". 

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. 

The answer is a. (Hardman, pp 1105-1108.) The activity of streptomycin is bactericidal for the tubercle bacillus organism. Other aminoglycosides (e.g., gentamicin, tobramycin, neomycin, amikacin, and kanamycin) have activity against this organism but are seldom used clinically because of toxicity or development of resistance. 

The conventional bioassays based on methodology developed by FDA and expanded by FSIS use four extractant buffers, five test organisms, five growth media, two incubation temperatures, and penicillinase to detect, identify, and/or quantify antibiotics such as the penicillins, streptomycins, tetracyclines, neomycins, erythromycin, tylosin, etc. Bioassay laboratory results are used by FSIS to take regulatory action and by FDA to prosecute farmers with histories of improperly withdrawing antibiotics before marketing their herds or flocks. 

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. 

They are active against many gram-negative bacteria but resistance develops rapidly and limits their use. Streptomycin and dihydrostreptomycin are less nephrotoxic than other aminoglycosides. They may cause neurological distur-... 

R-plasmid-mediated resistance is almost invariably associated with crossresistance to a number of related and unrelated antibiotics. The reasons for the association lie in the resistance mechanism to related compounds that have been coded, the usual presence of more than one R determinant in the same plasmid, and the frequent coexistence of several different plasmids in the same bacterial cell. As a result, use of any antibiotic can lead to development of resistance to itself and to other related and unrelated antibiotics. If, for example, a plasmid is encoded for resistance to ampicillin, tetracycline, sulfonamide, and streptomycin, exposure to any of these antibiotics results in resistance to all the others, whereas the use of a -lactamase-containing strain results in resistance to other members of this group. 

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). 

Fru thermore, 156,078 samples from cattle, sheep/lambs, goats, swine, and other animals were screened for antibiotics and sulfonamide drug residues using the fast antimicrobial screen test (FAST) developed in 1991 to replace CAST and STOP. There were 1022 violations for cattle and 2 for swine samples. In cattle, violative cases included 335 for penicillin, 142 for streptomycin, 128 for tetracycline, 28 for erythromycin, 48 for neomycin, 174 for oxytetracycline, 17 for chlortetracycline, 109 for gentamicin, 87 for sulfamethazine, 22 for sulfamethoxazole, 141 for sulfadimethoxine, 7 for sulfachlorpyridazine, 2 for tylosin, and 19 for sulfathiazole. In swine, violative samples were limited to one for oxytetracycline and one for penicillin. Analogous surveys conducted in 1995 showed 804 violative specimens of the 68,139 samples tested. 

An indirect competitive ELISA has been also developed for the determination of streptomycin and dihydrosticptomyciri in milk (24). Prior to the analysis, the milk sample was skimmed and treated with oxalic acid. The antiserum was raised in rabbits using streptomycin linked to a bacterial protein as the antigen. To perform the test, microtiter plates were coated with streptomycin, and antiserum and milk samples were mixed to be added in the wells where they were incubated for 1 h. Depending on the amount of residues in the sample, more or less antibody remained available for binding to the streptomycin coat. A pig antirabbit antibody-enzyme conjugate was subsequently added and incubated for 90 min. Using a suitable substrate, streptomycin and dihydrostreptomycin could be detected down to 1.6 ppb, whereas quantification could be made possible up to 100 ppb when samples were used undiluted. 

Streptomycin (Boxes 20-B, 20-H) was introduced into clinical use against tuberculosis in about 1943. However, resistant mutants always survived until newer drugs were developed. Isonicotinylhydrazide (isoniazid) is especially effective in combinations with suitable antibiotics and other drugs.8 The four-drug combination isoniazid, rifampicin (Box 28-A), pyrazinamide, and ethambutol is often used. Nevertheless, bacteria resistant to all of these have developed. 

Dr. Tishler published more than 100 scientific papers and is cited as an inventor on more than 100 United States patents. A partial list of research contributions include development of processes for the commercial production of vitamin B6, vitamin K, vitamin E, penicillin, streptomycin, and cortisone. 

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