Rifabutin Is Active against Mycobacterium abscessus Complex

Abstract

Lung infections caused by Mycobacterium abscessus are emerging as a global threat to individuals with cystic fibrosis and to other patient groups. Recent evidence for human-to-human transmission worsens the situation. M. abscessus is an intrinsically multidrug-resistant pathogen showing resistance to even standard antituberculosis drugs, such as rifampin. Here, our objective was to identify existing drugs that may be employed for the treatment of M. abscessus lung disease. A collection of more than 2,700 approved drugs was screened at a single-point concentration against an M. abscessus clinical isolate. Hits were confirmed with fresh solids in dose-response experiments. For the most attractive hit, growth inhibition and bactericidal activities against reference strains of the three M. abscessus subspecies and a collection of clinical isolates were determined. Surprisingly, the rifampin derivative rifabutin had MICs of 3 ± 2 μM (3 μg/ml) against the screening strain, the reference strains M. abscessus subsp. abscessus ATCC 19977, M. abscessus subsp. bolletii CCUG 50184-T, and M. abscessus subsp. massiliense CCUG 48898-T, as well as against a collection of clinical isolates. Furthermore, rifabutin was active against clarithromycin-resistant strains. In conclusion, rifabutin, in contrast to rifampin, is active against the Mycobacterium abscessus complex bacteria in vitro and may be considered for treatment of M. abscessus lung disease.

Structural analysis of mycobacterial homoserine transacetylases central to methionine biosynthesis reveals druggable active site

“…38 Cross-species gene transfer has helped to create multidrug-resistant strains, some even showing resistance to TB drugs such as rifampin. 39,40 In summary, by reporting the first medically relevant MtMetA and MaMetA crystal structures, we hope that new avenues of structure-based drug design will be open for developing targeted and effective therapeutics.…”

In vitro and intracellular activity of imipenem combined with tedizolid, rifabutin, and avibactam against Mycobacterium abscessus

“…Since it has recently been shown that rifabutin has a promising activity against M. abscessus (26,29), the second objective of our study was to compare the activity of tedizolid and rifabutin and to evaluate whether combinations comprising these two drugs have a potential therapeutic interest. In the macrophage, tedizolid and rifabutin were similarly active in improving the activity of imipenem alone (Fig.…”

Infections and Outbreaks of Nontuberculous Mycobacteria in Hospital Settings

“…Large studies have estimated that the prevalence of pulmonary NTM among CF patients is between 6–13% [3]. While acquisition of M. abscessus is typically attributed to contaminated water or soil, recent studies have demonstrated human-to-human transmission in patients with cystic fibrosis [4–6]. Two outbreaks of M. abscessus with genetically identical isolates were reported by Bryant et al in the United Kingdom amongst a CF population, raising concern for cross-infection [7].…”

“…M. abscessus pulmonary infection is not considered curable unless surgical resection can be performed. Medical therapy is complex and typically includes parenteral agents such as Amikacin, Imipenem or Cefoxitin and macrolides [4]. Tigecycline, linezolid, and rarely fluoroquinolones may also be administered depending on available susceptibility patterns.…”

“…Tigecycline, linezolid, and rarely fluoroquinolones may also be administered depending on available susceptibility patterns. Additional difficulties in medical management of M. abscessus infection include the widespread occurrence of inducible macrolide resistance mediated by the erm (41) gene [4, 5]. This is particularly of concern amongst M. abscessus subspecies abscessus and M. abscessus subspecies bolletii in which the rates of resistance are high.…”