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J Antimicrob Chemother. 2016 May;71(5):1264-9. doi: 10.1093/jac/dkv487. Epub 2016 Jan 31.

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

Author information

  • 1Division of Infectious Diseases, University of California, San Diego, La Jolla, CA 92093, USA.
  • 2Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
  • 3Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA School of Medicine, China Medical University, Taichung 40402, Taiwan.
  • 4Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • 5Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA.
  • 6Central Facility for Microscopy, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
  • 7Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA Rady Children's Hospital, San Diego, CA 92123, USA vnizet@ucsd.edu.

Abstract

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

Despite lack of activity in standard MIC testing, azithromycin synergizes with cationic peptide antibiotics to kill SM in medium mimicking tissue fluid conditions. Azithromycin, alone or in combination with colistin, merits further exploration in therapy of drug-resistant SM infections.

PMID:
26832758
PMCID:
PMC4830416
[Available on 2017-05-01]
DOI:
10.1093/jac/dkv487
[PubMed - indexed for MEDLINE]
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