Los cambios en los marcadores de composición corporal (peso, masa grasa, masa magra e IMC) a lo largo del tiempo pueden asociarse con el resultado del tratamiento de la TB en pacientes infectados por el VIH. El objetivo de este estudio fue investigar si los cambios en la masa grasa y magra se asociaron con la respuesta al tratamiento entre los pacientes con infección por VIH y tuberculosis pulmonar. Materiales y métodos: Este fue un estudio de cohorte prospectivo. Se analizaron los datos de pacientes infectados por el VIH que comenzaron la terapia contra la tuberculosis. Esto incluyó la medición del peso corporal con equipo de bioimpedancia al inicio del estudio, un mes y dos meses después de comenzar el tratamiento de la TB. Resultados: El estudio se realizó en 125 pacientes, 17 pacientes (13,6%) murieron durante el tratamiento, de los cuales 5 murieron durante el primer mes de t...

Pyrazinamide (PZA) is considered the pivot drug in all tuberculosis treatment regimens due to its particular action on the persistent forms of Mycobacterium tuberculosis. However, no drug susceptibility test (DST) is considered sufficiently reliable for routine application. Although molecular tests are endorsed, their application is limited to known PZA resistance associated mutations. Microbiological DSTs for PZA have been restricted by technical limitations, especially the necessity for an acidic pH. Here, for the first time, MODS culture at neutral pH was evaluated using high PZA concentrations (400 and 800 _g/ml) to determine PZA susceptibility directly from sputum samples. Sputum samples were cultured with PZA for up to 21 days at 37°C. Plate reading was performed at two time points: R1 (mean, 10 days) and R2 (mean, 13 days) for each PZA concentration. A consensus reference test, c...

Although pyrazinamide (PZA) is a key component of first- and second-line tuberculosis treatment regimens, there is no gold standard to determine PZA resistance. Approximately 50% of multidrug-resistant tuberculosis (MDR-TB) and over 90% of extensively drug-resistant tuberculosis (XDR-TB) strains are also PZA resistant. pncA sequencing is the endorsed test to evaluate PZA susceptibility. However, molecular methods have limitations for their wide application. In this study, we standardized and evaluated a new method, MODS-Wayne, to determine PZA resistance. MODS-Wayne is based on the detection of pyrazinoic acid, the hydrolysis product of PZA, directly in the supernatant of sputum cultures by detecting a color change following the addition of 10% ferrous ammonium sulfate. Using a PZA concentration of 800 μg/ml, sensitivity and specificity were evaluated at three different periods of incub...

Mycobacterium tuberculosis nicotinamidase-pyrazinamidase (PZAse) is a metalloenzyme that catalyzes conversion of nicotinamide-pyrazinamide to nicotinic acid-pyrazinoic acid. This study investigated whether a metallochaperone is required for optimal PZAse activity. M. tuberculosis and Escherichia coli PZAses (PZAse-MT and PZAse-EC, respectively) were inactivated by metal depletion (giving PZAse-MT–Apo and PZAse-EC–Apo). Reactivation with the E. coli metallochaperone ZnuA or Rv2059 (the M. tuberculosis analog) was measured. This was repeated following proteolytic and thermal treatment of ZnuA and Rv2059. The CDC1551 M. tuberculosis reference strain had the Rv2059 coding gene knocked out, and PZA susceptibility and the pyrazinoic acid (POA) efflux rate were measured. ZnuA (200 M) achieved 65% PZAse-EC–Apo reactivation. Rv2059 (1 M) and ZnuA (1 M) achieved 69% and 34.3% PZAse-MT–Apo ...