Timo Weiss

Low minimal inhibitory concentrations of linezolid against multidrug-resistant tuberculosis strains

We are following the debate about the administration and the preferred dosage of linezolid in the treatment of multidrug-resistant (MDR) tuberculosis (TB) and extensively drug-resistant (XDR) TB with great interest. Linezolid is a high potent drug against M. tuberculosis, but its widespread use is limited due to severe side-effects in long-term treatment, which often occurs after the usage of 600 mg twice a day in bacterial disease for >28 days and mainly includes severe haematotoxic effects (i.e. myelosuppression, anaemia, thrombocytopaenia) or polyneuropathy [1]. However, the current standards in MDR- and XDR-TB require several months of treatment. In addition, the administration of 1200 mg linezolid per day leads to high treatment costs, which limits the usage, especially in low-income countries [1, 2]. Lowering the dosage of linezolid could, therefore, be an effective step towards reducing costs and severe side-effects. Reducing linezolid dose in the treatment of MDR-/XDR-TB to a 300 mg OD could reduce severe side-effects and cost http://ow.ly/AtU7F

Value of thyroid transcription factor (TTF)-1 for diagnosis and prognosis of patients with locally advanced or metastatic small cell lung cancer

BackgroundThe aim of this study was to analyze the frequency of Thyroid Transcription Factor (TTF)-1 expression in small cell lung cancer (SCLC) and its value for the diagnosis of SCLC, the response to first line treatment as well as the prognostic impact on overall survival (OS).MethodsWe analyzed a total of 294 patients (m, n = 184; f, n = 110) with SCLC (stage IIIA, n = 32; IIIB, n = 87; IV, n = 175) diagnosed in our institution between January 2005 and December 2008. Patient’s characteristics comprising age, gender, histology and first line treatment were included into the analyses. For the follow-up of patients the governmental death registrar was used. The TTF-1 immunostaining was prospectively performed. CT scans of all patients were reviewed and response to treatment was evaluated using the Response Evaluation Criteria In Solid Tumors 1.0 (RECIST) criteria.ResultsA total of 221 of the 294 patients were eligible for analysis. Patients with TTF-1-positive SCLC had a median OS of 374 (95% CI 306–442) days. The OS of patients with TTF1-negative SCLC was 290 (95% CI 191–389) days, which was not significantly shorter (p = 0.254). Also stratification for tumor stage did not reveal significant difference in OS. Analyzing the disease control rate (DCR) in patients with metastatic disease (stage IV), we observed a significantly (p = 0.006) improved response to treatment in the group of patients with TTF-1-expression (DCR 86% vs. 56%). Regarding the overall response rates (ORR) in the entire population, there was no difference observed between both subgroups. (TTF-1-pos. 75.3% vs. TTF-1-neg. 71.4%; p = 0.642).ConclusionsThe diagnostic information of TTF-1 in SCLC seems to be limited. TTF-1 had no prognostic value concerning OS, but may serve as a predictor for response to first line chemotherapy.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5811254651472285

In vitro susceptibility of Mycobacterium bovis against moxifloxacin.

Introduction: Mycobacterium bovis, the causative agent of bovine tuberculosis is also responsible for diseases in humans. To date there are no data available on the in vitro susceptibility of M. bovis strains to moxifloxacin, an established second line drug in the treatment of disease caused by M. tuberculosis. Methods: From M. bovis-positive cultures from BAL, sputum, pleural effusion or cerebrospinal fluid of 34 pts from the years 1993-2010, we retrospectively evaluated the sensitivity in vitro and the minimum inhibitory concentrations of moxifloxacin. Culturing and resistance testing was performed on solid Middlebrook agar plates. Results: Out of 34 tested M. bovis-positive cultures 33 showed a sensitivity to moxifloxacin at 2 or 4 mcg/ml. Only one strain showed resistance. Conclusion: Our study of a small group of patients shows a high sensitivity rate of moxifloxacin against M. bovis strains. Despite the absence of clinical treatment studies, we see a potential use of moxifloxacin as a second line drug, with regular ineffectiveness of the first-line drug pyrazinamide in M. bovis.