Streptomycin tuberculosis therapy

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. 

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. 

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. 

In response to the increasing prevalence of mycobacterial resistance to standard antibiotic chemotherapy, the use of aminoglycosides is increasing in patients at high risk for having resistant infections. Inhaled aminoglycosides may also have a role in patients with persistently positive sputum despite therapy. Streptomycin is useful in the initial therapy of severe or disseminated tuberculosis, which is most common in immunocompromised patients. 

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... 

It (streptomycin) has opened a new field of therapy, it has pointed a way towards the final solution of tuberculosis, whereby this disease as well as syphilis and pneumonia will pass into the limbo of history. 

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-... 

Primary resistance to streptomycin is found in only 2—3% of isolates ofM. tuberculosis. Selection for resistant tubercle bacilli occurs in vivo the longer therapy, the greater the incidence of resistance. 

THERAPEUTIC USES The use of streptomycin for the treatment of pulmonary tuberculosis has declined sharply. Many clinicians still prefer to give 4 drugs, of which streptomycin may be one, for the most serious forms of tuberculosis, (e.g., disseminated disease or meningitis). Adults should be given 15 mg/kg/day in divided doses given by intramuscular injection every 12 hours, not to exceed 1 g/day. Children should receive 20-40 mg/kg/day in divided doses every 12-24 hours, not to exceed 1 g/day. Therapy usually is discontinued after 2-3 months, or sooner if cultures become negative. 

Therapy for drug-sensitive pulmonary tuberculosis consists of isoniazid (5 mg/kg, up to 300 mg/day), rifampin (10 mg/tcg/day, up to 600 mg daily), pyrazinamide (15-30 mg/kg/day or a maximum of 2 g/day), and a fourth agent, typically either ethambutol (usual adult dose cf 15 mg/kg once per day) or streptomycin (1 g daily). The streptomycin dose is reduced to 1 g twice weekly after 2 months. Pyridoxine, 15-50 mg/day, also should be included for most adults to minimize adverse reactions to isoni(K,id. Isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin are given for 2 months isoniazid and rifampin are then continued for 4 more months. Doses in children are isoniazid, 10 mg/kg/day (300 mg maximum) rifampin, 10-20 mg/kg/day (600 mg maximum) pyrazinamide, 15-30 mg/kg/day (2 g maximum). Isoniazid, rifampin, and ethambutol are considered safe during pregnancy. 

Infections caused by Mycobacterium tuberculosis are treated with combination therapy. The primary dmgs used are isoniazid, rifampin, ethambutol, and pyrazinamide. Highly resistant organisms may require the use of additional agents. Backup drugs include streptomycin, fluoroquinolones, capreomycin, and cycloserine. 

Streptomycin, and to a much lesser extent dihydrostreptomycin, have been reported to be sensitizers in humans and also in guinea pigs (John 1960 Smith 1960 Epstein and Wenzel 1962 Chung and Carson 1976). There are a few reports in the literature dealing with anaphylactic shock, urticaria, and serum-sickness-like reactions in patients with tuberculosis who are receiving streptomycin therapy, or in connection with skin tests using streptomycin (Rossen 1948 Grudzinski 1960 ... 

Liver The incidence and susceptibility factors for antituberculosis drug-induced hepa-totoxicity have been assessed in a prospective cohort study in 100 Egyptian patients with active pulmonary and extra-pulmonary tuberculosis [30 ]. Therapy included daily doses of isoniazid, rifampi-cin, ethambutol, and pyrazinamide, or streptomycin. There was drug-induced hep-atotoxicity in 15 patients within 15-60 (median 30) days from the onset of therapy. 

An interesting and unusual adverse effect attributed to pyrazinamide was described in a paper from the United States (54 ). A patient was described who suffered several attacks of acute intermittent porphyria whilst under treatment for tuberculosis. The first attack occurred after 18 months therapy with isoniazid and ethambutol. The second episode occurred after 14 days treatment with rifampicin, 7 days treatment with pyrazinamide and 3 days treatment with streptomycin. The patient was subsequently treated successfully with a combination of rifampicin, ethambutol and capreomycin. The compounds were investigated for their capacity to induce hepatic delta-aminolaev-ulinic acid synthesis in an in vitro preparation of rat Uver. The results showed that pyrazinamide had a greater potential for inducing the enzyme activity than any of the other compounds. It is worthy of note, however, that in this in vitro system para-aminosalicylic acid, rifampicin, cycloserine and ethionamide all induced increased delta-aminolaevulinic acid synthesis. 

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