RESUMEN
BACKGROUND: Patients at elevated risk of drug-resistant tuberculosis (TB) are prioritized for Xpert(®) MTB/RIF testing; however, the clinical usefulness of the test in this population is understudied. DESIGN: From November 2011 to June 2014, consecutive out-patients with a history of previous TB in high-density suburbs of Harare, Zimbabwe, were tested using Xpert, solid and liquid culture, and the microscopic observation drug susceptibility assay. Diagnostic accuracy for rifampin (RMP) resistance and time to initiation of second-line regimens were ascertained. The rpoB gene was sequenced in cases with culture-confirmed RMP resistance and genotypic susceptibility. RESULTS: Among 352 retreatment patients, 71 (20%) were RMP-resistant, 98 (28%) RMP-susceptible, 64 (18%) culture-negative/Xpert-positive, and 119 (34%) culture-negative/Xpert-negative. Xpert had a sensitivity of 86% (95%CI 75-93) and a specificity of 98% (95%CI 92-100) for RMP-resistant TB. The positive predictive value of Xpert-determined RMP resistance for multidrug-resistant TB (MDR-TB) was 82% (95%CI 70-91). Of 71 (83%) participants, 59 initiated treatment with second-line drugs, with a median time to treatment initiation of 18 days (IQR 10-44). CONCLUSION: The diagnostic accuracy of Xpert for RMP resistance is high, although the predictive value for MDR-TB was lower than anticipated. Xpert allows for faster initiation of second-line treatment than culture-based drug susceptibility testing under programmatic conditions.
Asunto(s)
Antituberculosos/uso terapéutico , Proteínas Bacterianas/genética , Análisis Mutacional de ADN , ARN Polimerasas Dirigidas por ADN/genética , Farmacorresistencia Bacteriana/genética , Técnicas de Diagnóstico Molecular , Mutación , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Rifampin/uso terapéutico , Tiempo de Tratamiento , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Retratamiento , Factores de Tiempo , Resultado del Tratamiento , Tuberculosis/microbiología , ZimbabweRESUMEN
Despite intensive searches for therapeutic agents, few substances have been convincingly shown to enhance nerve regeneration in patients with peripheral neuropathies. Recent biochemical evidence suggests that an ultra-high dose of methylcobalamin (methyl-B12) may up-regulate gene transcription and thereby protein synthesis. We examined the effects of ultra-high dose of methyl-B12 on the rate of nerve regeneration in rats with acrylamide neuropathy, using the amplitudes of compound muscle action potentials (CMAPs) after tibial nerve stimulation as an index of the number of regenerating motor fibers. After intoxication with acrylamide, all the rats showed equally decreased CMAP amplitudes. The animals were then divided into 3 groups; rats treated with ultra-high (500 micrograms/kg body weight, intraperitoneally) and low (50 micrograms/kg) doses of methyl-B12, and saline-treated control rats. Those treated with ultra-high dose showed significantly faster CMAP recovery than saline-treated control rats, whereas the low-dose group showed no difference from the control. Morphometric analysis revealed a similar difference in fiber density between these groups. Ultra-high doses of methyl-B12 may be of clinical use for patients with peripheral neuropathies.