Inhaled tigecycline is effective against Mycobacterium abscessus in vitro and in vivo
C Pearce, MM Ruth, LJ Pennings… - Journal of …, 2020 - academic.oup.com
C Pearce, MM Ruth, LJ Pennings, HFL Wertheim, A Walz, W Hoefsloot, C Ruesen…
Journal of Antimicrobial Chemotherapy, 2020•academic.oup.comBackground Mycobacterium abscessus causes chronic pulmonary infections. Owing to its
resistance to most classes of antibiotics, treatment is complex and cure rates are only 45%.
Tigecycline is active against M. abscessus, but severe toxicity and the need for IV
administration limit its use. Objectives To assess the potential of inhaled tigecycline as a
treatment for M. abscessus pulmonary disease, by measuring its efficacy in a mouse model
of chronic M. abscessus pulmonary disease, establishing the intracellular activity of …
resistance to most classes of antibiotics, treatment is complex and cure rates are only 45%.
Tigecycline is active against M. abscessus, but severe toxicity and the need for IV
administration limit its use. Objectives To assess the potential of inhaled tigecycline as a
treatment for M. abscessus pulmonary disease, by measuring its efficacy in a mouse model
of chronic M. abscessus pulmonary disease, establishing the intracellular activity of …
Background
Mycobacterium abscessus causes chronic pulmonary infections. Owing to its resistance to most classes of antibiotics, treatment is complex and cure rates are only 45%. Tigecycline is active against M. abscessus, but severe toxicity and the need for IV administration limit its use.
Objectives
To assess the potential of inhaled tigecycline as a treatment for M. abscessus pulmonary disease, by measuring its efficacy in a mouse model of chronic M. abscessus pulmonary disease, establishing the intracellular activity of tigecycline against M. abscessus in human macrophages and measuring the activity of tigecycline in the sputum of cystic fibrosis patients.
Methods
We infected GM-CSF knockout mice with M. abscessus by intrapulmonary aerosol. Infected mice were treated with tigecycline in 0.25, 1.25 and 2.5 mg doses, by inhalation, or untreated, for 28 days. Tigecycline was added to human peripheral blood-derived macrophages infected with M. abscessus to assess its intracellular activity. We performed a time–kill kinetics experiment of tigecycline against M. abscessus with and without sputum of cystic fibrosis patients.
Results
Inhaled tigecycline proved highly effective against M. abscessus in GM-CSF knockout mice. The effect was dose dependent. Tigecycline showed potent activity against M. abscessus in macrophages and retained most of its activity in the presence of sputum of cystic fibrosis patients.
Conclusions
Inhaled tigecycline may represent a viable treatment option for M. abscessus pulmonary disease, where treatment outcomes are currently very poor. A stable and safe formulation is required to proceed to further pharmacodynamic studies and ultimately clinical trials.
Oxford University Press以上显示的是最相近的搜索结果。 查看全部搜索结果