Dataset Information

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

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.

SUBMITTER: Kumaraswamy M

PROVIDER: S-EPMC4830416 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

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

Kumaraswamy Monika M Lin Leo L Olson Joshua J Sun Ching-Fang CF Nonejuie Poochit P Corriden Ross R Döhrmann Simon S Ali Syed Raza SR Amaro Deirdre D Rohde Manfred M Pogliano Joe J Sakoulas George G Nizet Victor V

The Journal of antimicrobial chemotherapy 20160131 5

<h4>Objectives</h4>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.<h4>Methods</h4>MIC testing, chequerboard assays, time-kill assays and fluorescence ...[more]

PMID: 26832758

Similar Datasets

Project description:The polymyxin antibiotic colistin shows in vitro activity against Stenotrophomonas maltophilia. However, an increased incidence of colistin-resistant isolates has been recently observed. In addition, in vitro evaluation of colistin susceptibility for this organism has been problematic. The aims of this study were to investigate the colistin-resistance phenotypes displayed by S. maltophilia and their potential association with the challenging determination of colistin susceptibilities for this organism by even the recommended method. Colistin-resistance phenotypes were inferred by use of the recommended broth microdilution method in different clinical isolates of S. maltophilia. Most of the strains showed non-interpretable minimum inhibitory concentrations (MICs) for colistin due to an incomplete growth inhibition in wells of the microdilution plate. In addition, the subpopulation of bacteria resistant to colistin showed an increased ability to form biofilms on the plastic surface of MIC plates. The observed incomplete growth inhibition in the microdilution plates is compatible with a progressive adaptation to colistin or a heterogeneous susceptibility to this antibiotic. Therefore, to determine the existence of heteroresistance or adaptive resistance, four colistin-resistant clinical isolates were subjected to serial Etest assays, growth rate analyses, and the population analysis profile test. The experiments indicated that these S. maltophilia isolates display a colistin-resistant sub-population that survives and multiplies in the presence of the antibiotic. Interestingly, this phenomenon might not be explainable by the natural background mutation rate alone since the development of a resistant sub-population occurred upon the contact with the antibiotic and it was reversible. This complex colistin-resistance phenotype is exhibited differently by the different isolates and significantly affected colistin susceptibility testing. Furthermore, it can coexist with adaptive resistance to colistin as response to pre-incubation with sub-inhibitory concentrations of the antibiotic. Overall, the combined action of heterogeneous colistin-resistance mechanisms in S. maltophilia isolates, including colistin-induced biofilm formation, may hamper the correct interpretation of colistin susceptibility tests, thus having potentially serious implications on antimicrobial-therapy decision making.

Dataset Information

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

Objectives

Methods

Results

Conclusions

Publications

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

Similar Datasets

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