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Azithromycin Synergizes with Cationic Antimicrobial Peptides to Exert Bactericidal and Therapeutic Activity Against Highly Multidrug-Resistant Gram-Negative Bacterial Pathogens

التفاصيل البيبلوغرافية
العنوان: Azithromycin Synergizes with Cationic Antimicrobial Peptides to Exert Bactericidal and Therapeutic Activity Against Highly Multidrug-Resistant Gram-Negative Bacterial Pathogens
المؤلفون: Leo Lin, Poochit Nonejuie, Jason Munguia, Andrew Hollands, Joshua Olson, Quang Dam, Monika Kumaraswamy, Heriberto Rivera Jr., Ross Corriden, Manfred Rohde, Mary E. Hensler, Michael D. Burkart, Joe Pogliano, George Sakoulas, Victor Nizet
المصدر: EBioMedicine, Vol 2, Iss 7, Pp 690-698 (2015)
بيانات النشر: Elsevier, 2015.
سنة النشر: 2015
المجموعة: LCC:Medicine
LCC:Medicine (General)
مصطلحات موضوعية: Azithromycin, Macrolides, Antimicrobial peptides, Cathelicidin, LL-37, Antibiotic resistance, Colistin, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Medicine, Medicine (General), R5-920
الوصف: Antibiotic resistance poses an increasingly grave threat to the public health. Of pressing concern, rapid spread of carbapenem-resistance among multidrug-resistant (MDR) Gram-negative rods (GNR) is associated with few treatment options and high mortality rates. Current antibiotic susceptibility testing guiding patient management is performed in a standardized manner, identifying minimum inhibitory concentrations (MIC) in bacteriologic media, but ignoring host immune factors. Lacking activity in standard MIC testing, azithromycin (AZM), the most commonly prescribed antibiotic in the U.S., is never recommended for MDR GNR infection. Here we report a potent bactericidal action of AZM against MDR carbapenem-resistant isolates of Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. This pharmaceutical activity is associated with enhanced AZM cell penetration in eukaryotic tissue culture media and striking multi-log-fold synergies with host cathelicidin antimicrobial peptide LL-37 or the last line antibiotic colistin. Finally, AZM monotherapy exerts clear therapeutic effects in murine models of MDR GNR infection. Our results suggest that AZM, currently ignored as a treatment option, could benefit patients with MDR GNR infections, especially in combination with colistin.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2352-3964
Relation: http://www.sciencedirect.com/science/article/pii/S2352396415300244; https://doaj.org/toc/2352-3964
DOI: 10.1016/j.ebiom.2015.05.021
URL الوصول: https://doaj.org/article/e18293e0ce8842e89a217c56927c7952
رقم الأكسشن: edsdoj.18293e0ce8842e89a217c56927c7952
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:23523964
DOI:10.1016/j.ebiom.2015.05.021