Standard susceptibility testing overlooks potent azithromycin activity and cationic peptide synergy against MDR Stenotrophomonas maltophilia

The Journal of Antimicrobial Chemotherapy
Monika KumaraswamyVictor Nizet

Abstract

The Gram-negative bacillus Stenotrophomonas maltophilia (SM) is an emerging MDR opportunistic pathogen. Recent studies identify a potentially relevant activity of azithromycin against Gram-negative bacteria overlooked in standard bacteriological testing. We investigated azithromycin activity against SM in testing conditions incorporating mammalian tissue culture medium and host defence factors. MIC testing, chequerboard assays, time-kill assays and fluorescence microscopy were performed for azithromycin, the cationic peptide antibiotic colistin and the human defence peptide cathelicidin LL-37 alone or in combination in cation-adjusted Mueller-Hinton broth or mammalian tissue culture media. Azithromycin sensitization of SM to host immune clearance was tested in a human neutrophil killing assay and a murine pneumonia model. We observed potent bactericidal activity of azithromycin against SM in mammalian tissue culture medium absent in bacteriological medium. Colistin and LL-37 strongly potentiated azithromycin killing of SM by increasing drug entry. Additionally, azithromycin sensitized SM to neutrophil killing and increased SM clearance in the murine pneumonia model. Despite lack of activity in standard MIC testing, azithromycin...Continue Reading

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Citations

Apr 24, 2019·Antimicrobial Agents and Chemotherapy·Selvi C ErsoyArnold S Bayer
Jul 21, 2020·PloS One·Rebecca BrouwersRosalind J Allen
Nov 28, 2019·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Erlinda R UlloaGeorge Sakoulas
Feb 29, 2020·Nature Reviews. Drug Discovery·Neeloffer MookherjeeDonald J Davidson
Aug 23, 2020·Pharmaceutics·Alina Nussbaumer-Pröll, Markus Zeitlinger
Aug 1, 2020·Frontiers in Cellular and Infection Microbiology·Derry K MercerAlfredo M Angeles-Boza
Jul 1, 2020·Frontiers in Immunology·Peter BergmanGudmundur H Gudmundsson
Jan 24, 2021·Brazilian Journal of Microbiology : [publication of the Brazilian Society for Microbiology]·Hoda Mohamed OwaisMarwa Ahmed Meheissen
Jun 3, 2021·Antibiotics·Kylen E Ridyard, Joerg Overhage
May 28, 2021·Clinical Microbiology Reviews·Joanna S Brooke
May 10, 2021·The Journal of Infectious Diseases·Erlinda R UlloaGeorge Sakoulas
Dec 5, 2019·Journal of Natural Products·Lei ZhaoHelge B Bode

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