News & Updates

Pneumonia – prevention and correct treatment made easy

Jul 2, 2015

Lower Respiratory Tract Infections (LTRI) including Community-acquired Pneumonia (CAP) was the 4th leading cause of death in the world in 2012 according to the World Health organization (WHO). This is particularly relevant in lower income countries where LRTI are the number 1 cause of death with 91 deaths per 100 000 population. This is of particular importance in South Africa with a high HIV prevalence rate. LRTI are 25 times more common in the HIV population than the general population.

Furthermore, Medscheme has identified CAP as an emerging risk. Pneumonia also ranked as one of the top two conditions for GP-driven hospital-admissions for Bonitas Medical Scheme in all nine provinces.

There is a clear need to better understand CAP & LRTI, its aetiology, management and prevention

Read the full article here:
http://www.thegooddoctors.co.za/article/pneumonia-%E2%80%93-prevention-and-correct-treatment-made-easy

Randomized Dose-Ranging Study of the 14-Day Early Bactericidal Activity of Bedaquiline (TMC207) in Patients with Sputum Microscopy Smear-Positive Pulmonary Tuberculosis

May 10, 2015

ABSTRACT

Bedaquiline is a new antituberculosis agent targeting ATP synthase. This randomized, double-blinded study enrolling 68 sputum smear-positive pulmonary tuberculosis patients evaluated the 14-day early bactericidal activity of daily doses of 100 mg, 200 mg, 300 mg, and 400 mg bedaquiline, preceded by loading doses of 200 mg, 400 mg, 500 mg, and 700 mg, respectively, on the first treatment day and 100 mg, 300 mg, 400 mg, and 500 mg on the second treatment day. All groups showed activity with a mean (standard deviation) daily fall in log10 CFU over 14 days of 0.040 (0.068), 0.056 (0.051), 0.077 (0.064), and 0.104 (0.077) in the 100-mg, 200-mg, 300-mg, and 400-mg groups, respectively. The linear trend for dose was significant (P = 0.001), and activity in the 400-mg dose group was greater than that in the 100-mg group (P = 0.014). All of the bedaquiline groups showed significant bactericidal activity that was continued to the end of the 14-day evaluation period. The finding of a linear trend for dose suggests that the highest dose compatible with safety considerations should be taken forward to longer-term clinical studies.
SOURCE
Andreas H. Diacon, Rodney Dawson, Florian Von Groote-Bidlingmaier, Gregory Symons, Amour Venter, Peter R. Donald, Almari Conradie, Ngozi Erondu, Ann M. Ginsberg, Erica Egizi, Helen Winter, Piet Becker and Carl M. Mendel

New antimycobacterial compound PA 824 show promise in early Phase 2 study in the treatment of tuberculosis

May 23, 2013

Background

New drugs, but also shorter, better-tolerated regimens are needed to tackle the high global burden of tuberculosis complicated by drug resistance and retroviral disease. We investigated new multiple-agent combinations over the first 14 days of treatment to assess their suitability for future development.

Methods

In this prospective, randomised, early bactericidal activity (EBA) study, treatment-naive, drug-susceptible patients with uncomplicated pulmonary tuberculosis were admitted to hospitals in Cape Town, South Africa, between Oct 7, 2010, and Aug 19, 2011. Patients were randomised centrally by computer-generated randomisation sequence to receive bedaquiline, bedaquiline-pyrazinamide, PA-824-pyrazinamide, bedaquiline-PA-824, PA-824-moxifloxacin-pyrazinamide, or unmasked standard antituberculosis treatment as positive control. The primary outcome was the 14-day EBA assessed in a central laboratory from the daily fall in colony forming units (CFU) of M tuberculosis per mL of sputum in daily overnight sputum collections. Bilinear regression curves were fitted for each group separately and groups compared with ANOVA for ranks, followed by pair-wise comparisons adjusted for multiplicity. Clinical staff were partially masked but laboratory personnel were fully masked. This study is registered, NCT01215851.

Findings

The mean 14-day EBA of PA-824-moxifloxacin-pyrazinamide (n=13; 0·233 [SD 0·128]) was significantly higher than that of bedaquiline (14; 0·061 [0·068]), bedaquiline-pyrazinamide (15; 0·131 [0·102]), bedaquiline-PA-824 (14; 0·114 [0·050]), but not PA-824-pyrazinamide (14; 0·154 [0·040]), and comparable with that of standard treatment (ten; 0·140 [0·094]). Treatments were well tolerated and appeared safe. One patient on PA-824-moxifloxacin-pyrazinamide was withdrawn because of corrected QT interval changes exceeding criteria prespecified in the protocol.

Interpretation

PA-824-moxifloxacin-pyrazinamide is potentially suitable for treating drug-sensitive and multidrug-resistant tuberculosis. Multiagent EBA studies can contribute to reducing the time needed to develop new antituberculosis regimens.

Funding

The Global Alliance for TB Drug Development (TB Alliance).

SOURCE

Prof Andreas H Diacon MD [Corresponding Author] , Rodney Dawson MD, Florian von Groote-Bidlingmaier MD, Gregory Symons MBChB, Amour Venter NatDipTech, Prof Peter R Donald MD, Christo van Niekerk MD, Daniel Everitt MD, Helen Winter PhD, Piet Becker PhD, Carl M Mendel MD, Melvin K Spigelman MD

Published Online: 23 July 2012, Viewed May 2013,  http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2961080-0/abstract