Second-line drug susceptibility breakpoints for Mycobacterium tuberculosis using the MODS assay.

OBJECTIVE: To establish breakpoint concentrations for the fluoroquinolones (moxifloxacin [MFX] and ofloxacin [OFX]) and injectable second-line drugs (amikacin [AMK], kanamycin [KM] and capreomycin [CPM]) using the microscopic observation drug susceptibility (MODS) assay. SETTING: A multinational study conducted between February 2011 and August 2012 in Peru, India, Moldova and South Africa. DESIGN: In the first phase, breakpoints for the fluoroquinolones and injectable second-line drugs (n = 58) were determined. In the second phase, MODS second-line drug susceptibility testing (DST) as an indirect test was compared to MGIT™ DST (n = 89). In the third (n = 30) and fourth (n = 156) phases, we determined the reproducibility and concordance of MODS second-line DST directly from sputum. RESULTS: Breakpoints for MFX (0.5 µg/ml), OFX (1 µg/ml), AMK (2 µg/ml), KM (5 µg/ml) and CPM (2.5 µg/ml) were determined. In all phases, MODS results were highly concordant with MGIT DST. The few discrepancies suggest that the MODS breakpoint concentrations for some drugs may be too low. CONCLUSION: MODS second-line DST yielded comparable results to MGIT second-line DST, and is thus a promising alternative. Further studies are needed to confirm the accuracy of the drug breakpoints and the reliability of MODS second-line DST as a direct test.

Validation of microscopic observation drug susceptibility testing for rapid, direct rifampicin and isoniazid drug susceptibility testing in patients receiving tuberculosis treatment.

Drug susceptibility testing (DST) is often needed in patients clinically failing tuberculosis (TB) therapy. Most studies of phenotypic direct drug susceptibility tests, such as microscopic observation drug susceptibility (MODS) tests, have been performed in patients not receiving TB treatment. The effect of ongoing TB treatment on the performance of MODS direct DST has not been previously explored, but patients failing such therapy constitute an important target group. The aim of this study was to determine the performance of MODS direct rifampicin and isoniazid DST in patients clinically failing first-line TB treatment, and to compare MODS direct DST with indirect proportion method DST. Sputa from 264 TB patients were cultured in parallel in Lowenstein-Jensen (LJ) and MODS assays; strains were tested for rifampicin and isoniazid susceptibility by the proportion method at the national reference laboratory. Ninety-three samples were culture-positive by LJ and MODS (concordance of 96%; kappa 0.92). With conventional MODS plate DST reading (performed on the same day as the sample is classified as culture-positive), the isoniazid DST concordance was 96.8% (kappa 0.89), and the concordance for rifampicin susceptibility testing was 92.6% (kappa 0.80). Reading of MODS DST plates 1 week after cultures had been determined to be culture-positive improved overall performance marginally-the isoniazid DST concordance was 95.7% (kappa 0.85); and the rifampicin DST concordance was 96.8% (kappa 0.91). Sensitivity for detection of multidrug-resistant TB was 95.8%. MODS testing provided reliable rifampicin and isoniazid DST results for samples obtained from patients receiving TB therapy. A modified DST reading schedule for such samples, with a final reading 1 week after a MODS culture turns positive, marginally improves the concordance with reference DST.

Pleurodesis with autologous blood

Objective: Pneumothorax is present as a frequent complication in Acute Respiratory Distress Syndrome (ARDS). Persistent air leak (PAL) prolongs pneumothorax in 2% of cases of ARDS, increasing the rate of mortality by 26%. Pleurodesis using autologous blood (PAB) is an effective method in cases of oncological pulmonary surgery. The goal of this study is to compare PAB with the conventional drain and water seal in the management of PAL in ARDS patients with pneumothorax. Design: Case-control, prospective, non-randomised study, comparing two groups subjected to artificial pairing 1:1. Setting: University of Granada, Department of Medicine and Intensive Care Unit, Almeria. Patients: Two groups of 27 patients, all with ARDS, pneumothorax and PAL. Interventions: One group which had received conventional treatment while the other received PAB. Main results: The server of the conditions of both groups is homogeneous, shown by sex, age, Murray, Marshall and Apache II scores, and aetiology of ARDS The patients in the PAB group had a shorter stay in ICU, shorter weaning time and lower death rate. The average difference between the groups is 11 day less waning time (adjusted odds ratio 0.1), and 9 days less on average spent in the Intensive Care Unit (ICU) (adjusted odds ratio 0,24). The death rates in the PAB group and the control group were 3,7% versus 29,6% respectively (adjusted odds ratio 0.6). Conclusions: The use of PAB makes possible a decrease in the ventilator weaning time and shorter stay in ICU with a resulting increase in functional recuperation and decrease in patient mortality (AU)