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Region Hovedstaden - en del af Københavns Universitetshospital
E-pub ahead of print

Biofilms of Mycobacterium abscessus complex can be sensitized to antibiotics by disaggregation and oxygenation

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Background: Pulmonary infection with the multidrug-resistant Mycobacterium abscessus complex (MABSC) is difficult to treat in individuals with cystic fibrosis (CF). MABSC grows as biofilm aggregates in CF lungs, which is known to have anaerobic niches. How aggregation and anoxic conditions affect antibiotic tolerance is not well understood.Objectives: We sought to determine whether disaggregation and oxygen availability sensitizes MABSC isolates to recommended antibiotics.Methods: We tested susceptibility of the following antibiotics amikacin, azithromycin, cefoxitin, ciprofloxacin, clarithromycin, imipenem, kanamycin, linezolid, moxifloxacin, rifampicin, tigecycline and sulfamethizole + trimethoprim for 33 isolates from 22 CF patients with MABSC infection and a reference strain. Isolates were grown in Müeller-Hinton broth with and without the disaggregating detergent Tween®80 (5%). Time-kill curves at day 1 and 3 were generated for oxic and anoxic amikacin treatment in four-fold dilutions from 2 to 512 mg L-1 Scanning electron microscopy were used to visualize aggregation patterns while confocal laser scanning microscopy and micro-respirometry were used to visualize biofilm growth patterns.Measurements and main results: Disruption of MABSC aggregates increased susceptibility to amikacin, tigecycline, kanamycin, azithromycin, imipenem, cefoxitin and clarithromycin (P<0.05, n=29-31). Oxygenation enhanced bacterial killing by amikacin in disaggregated MABSC isolates (P<0.05) by 1-6 log using 2-512 mg L-1 of amikacin.Conclusions: This study explains why current drug susceptibility testing correlates poorly to treatment outcomes. Oxic culturing of planktonic isolates in vitro does not resemble the hypoxic conditions in CF lungs. Biofilm disruption and increasing O2 availability during antibiotic therapy may be new therapeutic strategies for chronic MABSC infection.

OriginalsprogEngelsk
TidsskriftAntimicrobial Agents and Chemotherapy
Sider (fra-til)epub
ISSN0066-4804
DOI
StatusE-pub ahead of print - 2020

Bibliografisk note

Copyright © 2019 American Society for Microbiology.

ID: 58993453