Jahan Saeed Mallick1, Parvati Nair1, Elizabeth Tabitha Abbew1,2, Armand Van Deun3, Tom Decroo1. 1. Institute of Tropical Medicine Antwerp, Department of Clinical Sciences, Kronenburgstraat 43, 2000 Antwerpen, Belgium. 2. Cape Coast Teaching Hospital, Interberton Road, Cape Coast, Ghana. 3. Independent consultant, Leuven, Belgium.
Abstract
Background: Drug-resistant tuberculosis (DR-TB) is considered to be a public health threat and is difficult to cure, requiring a lengthy treatment with potent, potentially toxic drugs. The novel antimicrobial agent bedaquiline has shown promising results for patients with DR-TB, improving the rate of culture conversion and reducing TB-related mortality. However, increasing numbers of cases with acquired bedaquiline resistance (ABR) have been reported in recent years. Methods: This systematic review aimed to assess the frequency of ABR and characteristics of patients acquiring it. Studies showing data on sequential bedaquiline drug-susceptibility testing in patients treated with a bedaquiline-containing regimen were included. The databases CENTRAL, PubMed and Embase were manually searched, and 866 unique records identified, eventually leading to the inclusion of 13 studies. Phenotypic ABR was assessed based on predefined MIC thresholds and genotypic ABR based on the emergence of resistance-associated variants. Results: The median (IQR) frequency of phenotypic ABR was 2.2% (1.1%-4.6%) and 4.4% (1.8%-5.8%) for genotypic ABR. Among the studies reporting individual data of patients with ABR, the median number of likely effective drugs in a treatment regimen was five, in accordance with WHO recommendations. In regard to the utilization of important companion drugs with high and early bactericidal activity, linezolid was included in the regimen of most ABR patients, whereas the usage of other group A (fluoroquinolones) and former group B drugs (second-line injectable drugs) was rare. Conclusions: Our findings suggest a relevant frequency of ABR, urging for a better protection against it. Therefore, treatment regimens should include drugs with high resistance-preventing capacity through high and early bactericidal activity.
Background: Drug-resistant tuberculosis (DR-TB) is considered to be a public health threat and is difficult to cure, requiring a lengthy treatment with potent, potentially toxic drugs. The novel antimicrobial agent bedaquiline has shown promising results for patients with DR-TB, improving the rate of culture conversion and reducing TB-related mortality. However, increasing numbers of cases with acquired bedaquiline resistance (ABR) have been reported in recent years. Methods: This systematic review aimed to assess the frequency of ABR and characteristics of patients acquiring it. Studies showing data on sequential bedaquiline drug-susceptibility testing in patients treated with a bedaquiline-containing regimen were included. The databases CENTRAL, PubMed and Embase were manually searched, and 866 unique records identified, eventually leading to the inclusion of 13 studies. Phenotypic ABR was assessed based on predefined MIC thresholds and genotypic ABR based on the emergence of resistance-associated variants. Results: The median (IQR) frequency of phenotypic ABR was 2.2% (1.1%-4.6%) and 4.4% (1.8%-5.8%) for genotypic ABR. Among the studies reporting individual data of patients with ABR, the median number of likely effective drugs in a treatment regimen was five, in accordance with WHO recommendations. In regard to the utilization of important companion drugs with high and early bactericidal activity, linezolid was included in the regimen of most ABR patients, whereas the usage of other group A (fluoroquinolones) and former group B drugs (second-line injectable drugs) was rare. Conclusions: Our findings suggest a relevant frequency of ABR, urging for a better protection against it. Therefore, treatment regimens should include drugs with high resistance-preventing capacity through high and early bactericidal activity.
Authors: Andreas H Diacon; Alexander Pym; Martin Grobusch; Ramonde Patientia; Roxana Rustomjee; Liesl Page-Shipp; Christoffel Pistorius; Rene Krause; Mampedi Bogoshi; Gavin Churchyard; Amour Venter; Jenny Allen; Juan Carlos Palomino; Tine De Marez; Rolf P G van Heeswijk; Nacer Lounis; Paul Meyvisch; Johan Verbeeck; Wim Parys; Karel de Beule; Koen Andries; David F Mc Neeley Journal: N Engl J Med Date: 2009-06-04 Impact factor: 91.245
Authors: Payam Nahid; Sundari R Mase; Giovanni Battista Migliori; Giovanni Sotgiu; Graham H Bothamley; Jan L Brozek; Adithya Cattamanchi; J Peter Cegielski; Lisa Chen; Charles L Daley; Tracy L Dalton; Raquel Duarte; Federica Fregonese; C Robert Horsburgh; Faiz Ahmad Khan; Fayez Kheir; Zhiyi Lan; Alfred Lardizabal; Michael Lauzardo; Joan M Mangan; Suzanne M Marks; Lindsay McKenna; Dick Menzies; Carole D Mitnick; Diana M Nilsen; Farah Parvez; Charles A Peloquin; Ann Raftery; H Simon Schaaf; Neha S Shah; Jeffrey R Starke; John W Wilson; Jonathan M Wortham; Terence Chorba; Barbara Seaworth Journal: Am J Respir Crit Care Med Date: 2019-11-15 Impact factor: 21.405
Authors: R R Kempker; L Mikiashvili; Y Zhao; D Benkeser; K Barbakadze; N Bablishvili; Z Avaliani; C A Peloquin; H M Blumberg; M Kipiani Journal: Clin Infect Dis Date: 2020-12-03 Impact factor: 9.079
Authors: E Huitric; P Verhasselt; A Koul; K Andries; S Hoffner; D I Andersson Journal: Antimicrob Agents Chemother Date: 2009-12-28 Impact factor: 5.191
Authors: Patrick Beckert; Elisabeth Sanchez-Padilla; Matthias Merker; Viola Dreyer; Thomas A Kohl; Christian Utpatel; Claudio U Köser; Ivan Barilar; Nazir Ismail; Shaheed Vally Omar; Marisa Klopper; Robin M Warren; Harald Hoffmann; Gugu Maphalala; Elisa Ardizzoni; Bouke C de Jong; Bernhard Kerschberger; Birgit Schramm; Sönke Andres; Katharina Kranzer; Florian P Maurer; Maryline Bonnet; Stefan Niemann Journal: Genome Med Date: 2020-11-25 Impact factor: 11.117