Jodie A Schildkraut1, Lian J Pennings1, Mike M Ruth1, Arjan Pm de Brouwer2, Heiman Fl Wertheim1, Wouter Hoefsloot3, Arjan de Jong1, Jakko van Ingen1. 1. Department of Medical Microbiology & Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Gelderland, The Netherlands. 2. Department of Human Genetics, Donders Institute for Brain, Cognition & Behaviour, Radboud University Medical Center, Gelderland, The Netherlands. 3. Department of Pulmonary Diseases & Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Gelderland, The Netherlands.
Abstract
Aim: Antibiotic resistance in Mycobacterium abscessus renders treatment poorly effective. Despite erm(41)-gene-mediated macrolide resistance, treatment with azithromycin or clarithromycin is recommended. It is contested whether macrolides differ in erm(41) induction. We determine whether this is the case. Methods: M. abscessus CIP104536 was used. Minimum inhibitory concentrations of clarithromycin and azithromycin were determined. Time-kill kinetics of M. abscessus exposed to azithromycin or clarithromycin were performed and RNA was isolated at predetermined intervals for erm(41) quantification. Results: Minimum inhibitory concentrations increased >30-fold. Time-kill kinetics showed a temporary bacteriostatic effect, abrogated by induced resistance. Erm(41) expression was increased following exposure to either macrolide for 7 days. Conclusion: Both macrolides induce resistance similarly, and this should not be an argument in choosing either macrolide for therapy.
Aim: Antibiotic resistance in Mycobacterium abscessus renders treatment poorly effective. Despite erm(41)-gene-mediated macrolide resistance, treatment with azithromycin or clarithromycin is recommended. It is contested whether macrolides differ in erm(41) induction. We determine whether this is the case. Methods:M. abscessusCIP104536 was used. Minimum inhibitory concentrations of clarithromycin and azithromycin were determined. Time-kill kinetics of M. abscessus exposed to azithromycin or clarithromycin were performed and RNA was isolated at predetermined intervals for erm(41) quantification. Results: Minimum inhibitory concentrations increased >30-fold. Time-kill kinetics showed a temporary bacteriostatic effect, abrogated by induced resistance. Erm(41) expression was increased following exposure to either macrolide for 7 days. Conclusion: Both macrolides induce resistance similarly, and this should not be an argument in choosing either macrolide for therapy.