Tuberculosis capreomycin

Antituberculin Agents. Rifampin [13292-46-17, a semisynthetic derivative of rifamycin SV, is a most valuable dmg for treatment of tuberculosis, an infection caused by mycobacteria, leprosy, and an expanding range of other infections (23). Cycloserine [64-41-7] has been used to a limited extent for treatment of tuberculosis as a reserve dmg. Although cycloserine inhibits bacteria by interfering with their cell wall biosynthesis, it has toxic side effects in humans in the form of neurotoxicity. Capreomycin [11003-38-6] and to a much lesser extent viomycin [32988-50-4] both of which are peptides, have also been used for treatment of this disease. 

Gapreomycin, Viomycin, and Enviomycin. Capreomycin (Capastat, Lilly), a bacteriostatic, antimycobacterial peptide mixture isolated from Streptomjces capreolus was first reported in 1961 (106—108). This tuberactinomycin family member, shown in Table 4, was introduced into the U.S. market in 1971 where it has remained a usehil but nephrotoxic and ototoxic second-line alternative to first-line tuberculosis therapies. Because capreomycin is somewhat less toxic than viomycin (tuberoactinomycin B [32988-50-4]) C25H42N23O2Q (109,110), capreomycin has now displaced viomycin in the United States and most other markets. The stmcture of viomycin is shown in Figure 2. The related enviomycin (tuberactinomycin N [33103-22-9]), C23H43N23O2Q,... 

Capreomycin and viomycin show activity against M. tuberculosis and may be regarded as being second-line antituberculosis drugs. 

Capreomycin has a pronounced suppressive effect against Mycobacterium tuberculosis and Mycobacterium bovis. Most strains of Mycobacterium kansasii are also sensitive to kanamycin, while other, nontuberculous strains are not sensitive to it. It is often used upon necessity of using parentemal therapy through deep intramuscular injections. Capreomycin is less toxic than kanamycin and has somewhat more of a bacteriostatic effect. Synonyms of this drug are capromycin, capastat, ogostal, and others. 

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. 

Intended for use concomitantly with other antituberculosis agents in pulmonary infections caused by capreomycin-susceptible strains of Mycobacterium tuberculosis, when the primary agents (eg, isoniazid, rifampin) have been ineffective or cannot be used because of toxicity or the presence of resistant tubercle bacilli. Administration and Dosage... 

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... 

Viomycin is a complex polypeptide antibiotic that is active against MDR strains of tuberculosis. Cross-resistance between viomycin and kanamycin is less frequent than between viomycin and capreomycin. 

It is used in the treatment of tuberculosis caused by streptomycin resistant strains but since agents with lesser toxicity e.g. capreomycin and amikacin are available, its use is obsolete. 

Capreomycin is a peptide protein synthesis inhibitor antibiotic obtained from Streptomyces capreolus. Daily injection of 1 g intramuscularly results in blood levels of 10 mcg/mL or more. Such concentrations in vitro are inhibitory for many mycobacteria, including multidrug-resistant strains of M 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. 

The aminoglycoside antibiotics are discussed in Chapter 45. Kanamycin has been used for treatment of tuberculosis caused by streptomycin-resistant strains, but the availability of less toxic alternatives (eg, capreomycin and amikacin) has rendered it obsolete. 

Capreomycin (Capastat) is used as an adjunct or alternative drug for the treatment of tuberculosis. The drug s mechanism of action is unknown. The primary problems associated with this drug include ototoxicity and nephrotoxicity. 

Capreomycin is a mixture of cyclic polypeptides obtained from cultures of Streptomyces capreolus, and contains about 90% of capreomycins I, principally capreomycin IB (Figure 7.21). The capreomycin structures incorporate an L-capreomycidine moiety derived by cyclization of L-arginine, and three molecules of 2,3-diaminopropionic acid (Dap), which originate from serine via dehydroalanine. This antibiotic is given intramuscularly to treat tuberculosis patients who do not respond to first-line drugs, or where patients are sensitive to... 

Capreomycin has been abandoned for the treatment of tuberculosis and replaced by first-choice drugs. In rare cases, it has been administered in infections with non-tuberculous mycobacteria when there is multiple drug resistance to the first-line antituberculosis drugs (1). 

A Bartter-hke syndrome has been reported in a 25-year-old man taking prolonged capreomycin for drug-resistant pulmonary tuberculosis (2). 

Capreomycin. — Because of low toxicity and remarkable activity against drug-resistant strains of M. tuberculosis, capreomycin, a polypeptide antibiotic, was recommended for use in multiple-drug therapy... 

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

M. tuberculosis Isoniazid -1- rifampin - -pyrazinamide -1- ethambutol or streptomycin Moxifloxacin or gatifloxacin cycloserine capreomycin kanamycin amikacin ethionamide clofazimine aminosalicylic acid... 

Capreomycin (capasiat) is an antimycobacterial cyclic peptide elaborated by Streptococcus capreolus. Bacterial resistance to capreomycin develops when it is given alone such microorganisms show cross-resistance with kanamycin and neomycin. Capreomycin is used only in conjunction with other appropriate drugs in treatment of pulmonary tuberculosis when bactericidal agents cannot be tolerated or when causative organisms have become resistant. 

Aminoglycosides such as capreomycin, viomycin, kana-mycin and amikacin and the newer quinolones (e.g. pefloxacin, ofloxacin and ciprofloxacin) were only used in drug resistance situations. Tuberculosis in particular experienced a resurgence. In the mid-1980s, the worldwide decline in tuberculosis cases levelled off and then began to rise. 

The second-line drugs for tuberculosis are found to be more toxic but may be required with certain resistance problems. These drugs essentially include fluroquinolones (e.g., ofloxacin, ciprofloxacin), cycloserine, ethionosamide, aminosalicylic acid, aminoglycosides (viz., amikacin, kanamycin), clofazimine, and capreomycin. 

Capreomycin is a cyclic polypeptide complex antibiotic having a structure very much similar to viomycin, and produced by Streptomyces capreolus as a mixture of about four different components. It exerts its bacteriostatie aetion against certain mycobacterial strains, such as M. tuberculosis M. bovis M. kansasii, andM. avium by an unknown mechanism of action. However, its pharmacological and antibacterial activities are quite akin to the aminoglycosides. 

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