RESUMEN
Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection.We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12â months of treatment; hazard of failure using monthly culture was the reference.Data were obtained for 5410 patients across 12 observational studies. During the last 12â months of treatment, failure detection occurred in a median of 3â months by monthly culture; failure detection was delayed by 2, 7, and 9â months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34-0.42) for all patients and 0.33 (0.25-0.42) for HIV-co-infected patients.Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.
Asunto(s)
Antituberculosos/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/terapia , Adulto , Estudios de Cohortes , Coinfección , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Modelos de Riesgos Proporcionales , Riesgo , Esputo/microbiología , Insuficiencia del Tratamiento , Tuberculosis Pulmonar/diagnósticoRESUMEN
The bioassay-guided fractionation of the EtOH extract of the leaves of Galenia africana led to the isolation of three known flavonoids, (2S)-5,7,2'-trihydroxyflavanone (1), (E)-3,2',4'-trihydroxychalcone (2), and (E)-2',4'-dihydroxychalcone (3), and the new (E)-3,2',4'-trihydroxy-3'-methoxychalcone (4). Compounds 1 and 3 exhibited moderate antituberculosis activity. During synergistic studies, a combination of compound 4 and an existing antituberculosis drug, isoniazid, reduced their original MICs 4-fold, resulting in a fractional inhibitory concentration of 0.50. The most pronounced effect was demonstrated by compound 1 and isoniazid reducing their MICs 16-fold and resulting in an FIC of 0.12. Both EtOH extract and isolated compounds failed to exhibit any NADPH oxidase activity at 800.0 muM concentrations, indicating that mycothiol disulfide reductase is not the target for their antituberculosis activity.