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In vitro activity of ceragenins against Burkholderia cepacia complex
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.ORCID iD: 0000-0002-2851-9651
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2022 (English)In: Journal of Antibiotics, ISSN 0021-8820, E-ISSN 1881-1469, Vol. 75, no 7, p. 403-409Article in journal (Refereed) Published
Abstract [en]

Burkholderia cepacia complex (Bcc) species are aerobic, Gram-negative and non-fermantative bacilli. Bcc can cause clinical symptoms in patients with cystic fibrosis, ranging from asymptomatic carriage to fatal pneumonia. A pressing need exists for new antimicrobial agents that target Bcc. Ceragenins, CSA-13, CSA-131 and CSA-131 with 5% Pluronic® F127 (CSA-131P), were evaluated against Bcc clinical isolates (n = 42). MICs of ceragenins and conventional antibiotics were determined. Time-kill curve experiments were performed with 1x, 4x MICs of ceragenins and sulfamethoxazole-trimethoprim (SXT), levofloxacin. MIC50/ MIC90 results (mg l−1) of CSA-13, CSA-131 and CSA-131P were determined as 16/64, 16/128 and 16/128, respectively. CSA-13 and CSA-131 showed bactericidal activity. CSA-13 - levofloxacin combination displayed synergistic activity against Bcc. First-generation (CSA-13) and second-generation (CSA-131 and CSA-131P) ceragenins have significant antimicrobial effects on Bcc. The findings of this study demonstrate that combinations of ceragenins with currently marketed antibiotics could be synergistic in vitro against Bcc isolates. These results suggest that combination therapy with conventional antibiotics could be an alternative approach for treating Bcc infections in the future. 

Place, publisher, year, edition, pages
Springer Nature , 2022. Vol. 75, no 7, p. 403-409
Keywords [en]
antibiotic agent, ceftazidime, ceragenin derivative, cotrimoxazole, levofloxacin, meropenem, unclassified drug, antiinfective agent, ceragenins, steroid, antibacterial activity, antibiotic sensitivity, Article, bactericidal activity, bacterium isolate, Burkholderia, Burkholderia cenocepacia, Burkholderia cepacia complex, Burkholderia contaminans, Burkholderia glaidoli, Burkholderia infection, Burkholderia multivorans, clinical article, comparative study, controlled study, cystic fibrosis, cytotoxicity, drug potentiation, drug screening, encapsulation, human, in vitro study, matrix assisted laser desorption ionization time of flight mass spectrometry, minimum bactericidal concentration, minimum inhibitory concentration, multilocus sequence typing, Pseudomonas aeruginosa, Turkey (republic), viable cell count, microbial sensitivity test, Anti-Bacterial Agents, Humans, Microbial Sensitivity Tests, Steroids
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Microbiology in the medical area
Identifiers
URN: urn:nbn:se:kth:diva-324572DOI: 10.1038/s41429-022-00530-wISI: 000795190600001PubMedID: 35562592Scopus ID: 2-s2.0-85131607875OAI: oai:DiVA.org:kth-324572DiVA, id: diva2:1742037
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QC 20230308

Available from: 2023-03-08 Created: 2023-03-08 Last updated: 2023-03-08Bibliographically approved

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Altay, Özlem

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