TY - JOUR
T1 - Synergistic efficacy of β-lactam combinations against mycobacterium abscessus pulmonary infection in mice
AU - Story-Roller, Elizabeth
AU - Maggioncalda, Emily C.
AU - Lamichhane, Gyanu
N1 - Funding Information:
This study was supported by the Cystic Fibrosis Foundation award LAMICH17GO and National Institutes of Health award R21 AI137720 to G.L. E.S.-R. was supported by NIH T32 AI007291.
Publisher Copyright:
© 2019 American Society for Microbiology.
PY - 2019
Y1 - 2019
N2 - Mycobacterium abscessus is an emerging pathogen capable of causing invasive pulmonary infections in patients with chronic lung diseases. These infections are difficult to treat, necessitating prolonged multidrug therapy, which is further complicated by extensive intrinsic and acquired resistance exhibited by clinical M. abscessus isolates. Therefore, development of novel treatment regimens effective against drug-resistant strains is crucial. Prior studies have demonstrated synergistic efficacy of several β-lactams against M. abscessus in vitro; however, these combinations have never been tested in an animal model of M. abscessus pulmonary disease. We utilized a recently developed murine system of sustained M. abscessus lung infection delivered via an aerosol route to test the bactericidal efficacy of four novel dual β-lactam combinations and one β-lactam/β-lactamase inhibitor combination. All five of the novel combinations exhibited synergy and resulted in at least 6-log10 reductions in bacterial burden in the lungs of mice at 4 weeks compared to untreated controls (P=0.038).
AB - Mycobacterium abscessus is an emerging pathogen capable of causing invasive pulmonary infections in patients with chronic lung diseases. These infections are difficult to treat, necessitating prolonged multidrug therapy, which is further complicated by extensive intrinsic and acquired resistance exhibited by clinical M. abscessus isolates. Therefore, development of novel treatment regimens effective against drug-resistant strains is crucial. Prior studies have demonstrated synergistic efficacy of several β-lactams against M. abscessus in vitro; however, these combinations have never been tested in an animal model of M. abscessus pulmonary disease. We utilized a recently developed murine system of sustained M. abscessus lung infection delivered via an aerosol route to test the bactericidal efficacy of four novel dual β-lactam combinations and one β-lactam/β-lactamase inhibitor combination. All five of the novel combinations exhibited synergy and resulted in at least 6-log10 reductions in bacterial burden in the lungs of mice at 4 weeks compared to untreated controls (P=0.038).
KW - Mycobacterium abscessus
KW - Synergy
KW - β-lactams
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U2 - 10.1128/AAC.00614-19
DO - 10.1128/AAC.00614-19
M3 - Article
C2 - 31109979
AN - SCOPUS:85070658712
SN - 0066-4804
VL - 63
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 8
M1 - e00614-19
ER -