Capreomycin-resistant strain

It is pertinent to add here that the capreomycin-resistant strains are not foimd to be completely resistant to kanamycin, whereas the corresponding kanamycin-resistant strains are invariably resistant to capreomycin. 

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... 

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resistant strains but since agents with lesser toxicity e.g. capreomycin and amikacin are available, its use is obsolete.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. — 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... 

The capreomycins were first isolated in 1960 from Streptomyces capreolus [443]. The structures of capreomycin IA (336) and IB (337) were first proposed in 1971 [444], but were revised in 1976 by Shiba et al. who also achieved the total synthesis [445-449]. The natural mixture, which includes the minor components capreomycins IIA and IIB, is used as an antituberculosis agent. The drug is ineffective orally, but by the subcutaneous route it was a good treatment for mouse and bovine tuberculosis including a streptomycin resistant strain [450]. 

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. 

Capreomycin resembles viomycin both chemically and pharmacologically. It is considered to be second-line antitubercular drug used in combination with other such agents. It is frequently used in place of streptomycin when either the patient is sensitive to it or the strain of M tuberculosis is resistant to it. 

---