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PubMed1983

Sensitivity to capreomycin and prothionamide in strains of Mycobacterium, Nocardia, Rhodococcus, and related taxa for taxonomical purposes.

Sensitivity to capreomycin and to prothionamide was analysed for 150 strains belonging to the genera Mycobacterium, Nocardia, Rhodococcus, and related taxa. The analyses showed, e.g., that strains of Mycobacterium chelonei and Nocardia brasiliensis were more resistant to capreomycin than the other strains tested and that M. farcinogenes differed from M. senegalense concerning sensitivity to this drug. The analysis showed, furthermore, that strains of Mycobacterium differ from those of Nocardia, Rhodococcus, "Mycobacterium album", and "Gordona aurantiaca" in being more sensitive to prothionamide than these organisms. Strains designated N. amarae were more sensitive to both drugs than were the other tested strains of Nocardia, which indicates that N. amarae diverges from the other species of this genus.

Capreomycin↗
PubMed1995

Analysis of two capreomycin-resistance determinants from Streptomyces capreolus and characterization of the action of their products.

Two genes encoding capreomycin (Cp)-modifying enzymes have been isolated from the producing organism Streptomyces capreolus. Cp acetyltransferase (CAC), encoded by cac, is active against all four components of the Cp complex, whereas Cp phosphotransferase (CPH), the product of cph, is active against Cp components IA and IIA (and also the related antibiotic, Vm) but not against Cp IB or Cp IIB.

Acetylation↗
PubMed2006

Development of liposomal capreomycin sulfate formulations: effects of formulation variables on peptide encapsulation.

PURPOSE: The aim of this work was the investigation of the effects of preparation variables on drug content for the development of capreomycin sulfate (CS) liposomal formulations as potential aerosol antitubercular agents. METHODS: Dipalmitoylphosphatidylcholine (DPPC), hydrogenated phosphatidylcholine (HPC) and distearoylphosphatidylcholine (DSPC) were used for liposome preparation. A freeze-thawing method was chosen for CS encapsulation. Peptide entrapment, size and morphology were evaluated by UV spectrophotometry, photocorrelation spectroscopy (PCS) and transmission electron microscopy (TEM), respectively. A 2(3) full factorial protocol was designed to evaluate the conditions for CS encapsulation improvement. RESULTS: Peptide content ranged between 1 and 8%. Vesicles showed a narrow size distribution, with average diameters around 1 microm and a good morphology. A mathematical model was generated for each liposomal system and check point analyses revealed good agreement between experimental and predicted values. DPPC liposomes were found to provide the highest CS content. CONCLUSIONS: Peptide content was successfully increased by assessing formulation variable effects using a 2(3) factorial design that proved to be a time saving method helpful in developing new CS liposomal formulations for a possible application in aerosol antitubercular therapies.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2006

Preparation of large porous biodegradable microspheres by using a simple double-emulsion method for capreomycin sulfate pulmonary delivery.

The aim of this work was to evaluate if a simple double-emulsion method could be used for developing a new formulation of large porous microspheres (MS) potentially useful for capreomycin sulfate (CS) pulmonary delivery. Poly(DL-lactide-co-glycolide) was used for MS preparation. A simple W/O/W double-emulsion/solvent evaporation preparation method was employed and MS were characterized by UV spectrophotometry, particle size, and scanning electron microscopy. A computer-generated response surface method (RSM) was employed to evaluate % drug content, volume mean diameter (VMD), and span upon variation of two numeric and two categorical factors. MS size distribution was found to be strongly affected by the homogenization method and the type of emulsifier employed. Mean diameters ranged from 1 to 20 microm. The MS presented a proper morphology, with a highly porous interior and a rough surface. Peptide content ranged between 1 and 20%. The region of optimality was referred to as a low VMD and span values, and a high drug content. The best results were found when using a 20% loading, 19.8-3.2 dichloromethane/acetone ratio, ultraturrax mixing, and HPMC as emulsifier. The double-emulsion method allowed the preparation of CS loaded large porous MS having suitable characteristics to match respirability requirements. The use of RSM helped to establish the conditions to obtain formulations potentially useful for a possible CS pulmonary delivery, by using a simple preparation method with a consistent time, cost, and material saving.

Acetone↗
PubMed1998

A reproducible, simple, and sensitive high-performance capillary electrophoresis method for simultaneous determination of capreomycin, ofloxacin and pasiniazide in urine.

Separation and determination of capreomycin (Cp), ofloxacin (Oflx) and pasiniazide (Ipa) in urine by high-performance capillary electrophoresis (HPCE) with 280 nm detection have been studied systematically. The calibration lines were linear in the range of 0.5 approximately 50 mg 1(-1), and the detection limits (S/N = 3) were 0.15, 0.20 and 0.10 mg 1(-1) for Cp, Oflx and Ipa, respectively. The recoveries for these materials from urine were higher than 93.5%. The accuracy and intra- and inter- day reproducibility of Cp, Oflx and Ipa were determined with satisfactory results. This method was successfully used for determining Cp. Oflx and Ipa in human urine.

Aminosalicylic Acid↗
PubMed2003

Asymmetric synthesis of (2S,3R)-capreomycidine and the total synthesis of capreomycin IB.

A 27 step total synthesis of the tuberculostatic macrocyclic peptide antibiotic capreomycin IB has been accomplished. The synthesis features the use of an enolate-aldimine condensation between a chiral glycine aluminum enolate and the benzyl imine of 3-tert-butyldimethylsiloxy-propanal as a means of preparing the cyclic guanidine amino acid (2S,3R)-capreomycidine. Additionally, a Hofmann rearrangement was exacted on a late-stage pentapeptide in order to transform an asparagine residue into a diaminopropanoic acid residue.

Anti-Bacterial Agents↗
PubMed2004

Unilamellar vesicles as potential capreomycin sulfate carriers: preparation and physicochemical characterization.

The aim of this work was to evaluate unilamellar liposomes as new potential capreomycin sulfate (CS) delivery systems for future pulmonary targeting by aerosol administration. Dipalmitoylphosphatidylcholine, hydrogenated phosphatidylcholine, and distearoylphosphatidylcholine were used for liposome preparation. Peptide-membrane interaction was investigated by differential scanning calorimetry (DSC) and attenuated total internal reflection Fourier-transform infrared spectroscopy (ATIR-FTIR). Peptide entrapment, size, and morphology were evaluated by UV spectrophotometry, photocorrelation spectroscopy, and transmission electron microscopy, respectively. Interaction between CS and the outer region of the bilayer was revealed by DSC and ATIR-FTIR. DSPC liposomes showed enhanced interdigitation when the CS molar fraction was increased. Formation of a second phase on the bilayer surface was observed. From kinetic and permeability studies, CS loaded DSPC liposomes resulted more stable if compared to DPPC and HPC over the period of time investigated. The amount of entrapped peptide oscillated between 10% and 13%. Vesicles showed a narrow size distribution, from 138 to 166 nm, and a good morphology. These systems, in particular DSPC liposomes, could represent promising carriers for this peptide.

Anti-Bacterial Agents↗
PubMed1982

The ototoxic interaction of viomycin, capreomycin and polymyxin B with ethacrynic acid.

The ototoxic interaction between the aminoglycoside antibiotics (streptomycin, kanamycin, etc.) and the loop-inhibiting diuretics (ethacrynic acid, furosemide and bumetanide) has been well documented. This interaction causes extensive destruction of the hair cells of the cochlea. Brummett et al. (1974) demonstrated that this interaction did not occur with the non-loop-inhibiting diuretics and kanamycin. The present study was undertaken to determine if antibiotics other than the aminoglycosides could produce the ototoxic interaction when combined with a loop-inhibiting diuretic. Three antibiotics-viomycin, capreomycin, and polymyxin B- when given with ethacrynic acid were found to produce cochlear hair cell damage that was similar to that produced by aminoglycoside antibiotics administered with ethacrynic acid. Therefore, the interaction appears to be specific to the loop-inhibiting diuretics but not specific for the aminoglycoside antibiotics.

Aminoglycosides↗
PubMed2003

[A study on the clinical efficacy of a combination regimen with levofloxacin and capreomycin in the treatment of multi-drug resistant pulmonary tuberculosis].

OBJECTIVE: To study the clinical efficacy of a combination therapy with levofloxacin (LVFX), capreomycin (CPM) and other second-line antituberculosis drugs in the treatment of multi-drug resistant pulmonary tuberculosis (MDR-TB). METHODS: 177 patients with MDR-TB were assigned to a study group (88 cases), treated with LVFX, CPM, pyrazinamide (PZA), rifapentine (RFT) and pasiniazid (PSZ); or a control group, treated with streptomycin (SM), ethambutol (EMB), PZA, RFT and PSZ. The course of treatment was 21 months. RESULTS: 82 cases in the study group and 79 cases in the control group completed the treatment. The sputum negative conversion rate in the study group (83%) was significantly higher than that in the control group (58%) (P < 0.01). The radiographic improvement rate was 50% in the study group, significantly higher than that in the control group (28%) (P < 0.01). The closure rate of the lung cavities in the study group (63%) was higher than that in the control group (42%) (P < 0.05). No significant difference was found in side-effects between the two groups (31% in the study group, and 35% in the control group respectively) (P > 0.05). CONCLUSION: The regimen including LEVX, CPM and other second-line anti-TB drugs was effective and safe for patients with MDR-TB.

Adolescent↗