Disease relevance of Capastat

• The cyclic peptide antibiotics capreomycin and viomycin are generally effective against the bacterial pathogen Mycobacterium tuberculosis [1].
• Many bacterial genera including enterobacteria lack a tlyA gene and the ensuing methylations and are less susceptible than mycobacteria to capreomycin and viomycin [1].
• Capreomycin, an important drug for the treatment of multidrug-resistant tuberculosis, is a macrocyclic peptide antibiotic produced by Saccharothrix mutabolis subspecies capreolus [2].
• Seven days later, treatment with either liposomal or free capreomycin at 60 or 120 mg/kg of body weight was administered daily for 5 days [3].
• Pharmacokinetics, toxicity, and efficacy of liposomal capreomycin in disseminated Mycobacterium avium beige mouse model [3].

High impact information on Capastat

• Loss of these previously unidentified rRNA methylations confers resistance to capreomycin and viomycin [1].
• The location of these methylations indicates the binding site and inhibitory mechanism of capreomycin and viomycin at the ribosome subunit interface [1].
• We investigated the role of rrs mutations in capreomycin resistance and examined the molecular basis of cross-resistance to the four drugs in M. tuberculosis laboratory-generated mutants and clinical isolates [4].
• A recent study revealed that mutation of the tlyA gene, encoding a putative rRNA methyltransferase, confers capreomycin and viomycin resistance in Mycobacterium tuberculosis bacteria [4].
• We have tested 150 Mycobacterium tuberculosis isolates against the second-line drugs ethionamide, kanamycin, capreomycin, ofloxacin, and para-aminosalicylic acid by the colorimetric resazurin microtiter assay and the proportion method [5].

Chemical compound and disease context of Capastat

• Aminoglycoside-aminocyclitols including streptomycin, kanamycin, capreomycin and amikacin showed considerable activity against Mycobacterium tuberculosis, with MICs well below their Cmax and relatively low MBC/MIC ratios [6].
• Sensitivity to capreomycin and prothionamide in strains of Mycobacterium, Nocardia, Rhodococcus, and related taxa for taxonomical purposes [7].

Biological context of Capastat

• The pharmacokinetics and nephrotoxicity of capreomycin in the free and liposomal forms were studied in normal mice [3].
• Treatment was initiated with IV capreomycin, levofloxacin, para-aminosalicylic acid, pyrazinamide, cycloserine, and high-dose vitamin B(6) at 26 weeks' gestation [8].
• High rates of drug resistance were also found for capreomycin (42.9%) and kanamycin (41.6%), while nearly all strains (98.7%) were susceptible to ofloxacin [9].
• The single-dose kinetics of capreomycin are described for 12 renal patients and seven healthy control subjects [10].
• Capreomycin IA and IB were concluded to possess the similar amino acid sequences in their cyclic peptide moieties to those of tuberactinomycins [11].

Associations of Capastat with other chemical compounds

• After 5 days of treatment with dosages of 60 or 120 mg/kg/day, the level of blood urea nitrogen increased in the group treated with free capreomycin but not in the group treated with liposomal capreomycin [3].
• Fifty-one of the isolates were susceptible in vitro to all of the antituberculosis drugs tested, 11 were monoresistant to capreomycin, rifampin, isoniazid (INH), pyrazinamide, or streptomycin (STR), 4 were resistant to STR and INH, and 1 was resistant to STR, INH, and ethambutol [12].
• A reproducible, simple, and sensitive high-performance capillary electrophoresis method for simultaneous determination of capreomycin, ofloxacin and pasiniazide in urine [13].

Gene context of Capastat

• Marked renal potassium and magnesium wasting, alkalosis, and a progressive increase in plasma renin and eventual hyperaldosteronemia developed during a 15-month course of in-hospital capreomycin therapy that was necessary for drug-resistant pulmonary tuberculosis [14].

Analytical, diagnostic and therapeutic context of Capastat

• Such regimens are usually based on a quinolone and an injectable agent (i.e. an aminoglycoside or capreomycin) supplemented by other 'second-line' drugs [15].
• After intravenous injection of 120 mg/kg, liposomes enhanced the diffusion of capreomycin in the spleen, lungs, and kidneys and increased the half-life in serum [3].
• UV spectroscopy and reverse-phase HPLC as novel methods to determine Capreomycin of liposomal fomulations [16].
• Hemodialysis cleared clinically significant amounts of capreomycin [10].
• This phenomenon requires further studies on the mechanism of action of capreomycin, and evaluation of its activity in appropriate animal models [17].

References