Azithromycin possesses biofilm–inhibitory activity and potentiates non-bactericidal colistin methanesulfonate (CMS) and polymyxin B against Klebsiella pneumonia

• Published in: PloS one Vol. 17; no. 7; p. e0270983
• Main Authors: Moshynets, Olena V, Baranovskyi, Taras P, Cameron, Scott, Iungin, Olga S, Pokholenko, Ianina, Jerdan, Robyn, Kamyshnyi, Aleksandr, Krikunov, Alexey A, Potochilova, Viktoria V, Rudnieva, Kateryna L, Spiers, Andrew J
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 01.07.2022; Public Library of Science (PLoS)
• Subjects: Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; Azithromycin; Bacterial infections; Biofilms; Biology and Life Sciences; Care and treatment; Cell culture; Cell surface; Colistin; Colistin methanesulfonate; Complications and side effects; Diffusion plating; Infections; Klebsiella; Klebsiella pneumoniae; Laboratories; Liquid culture; Medicine and Health Sciences; Multidrug resistance; Pathogens; Patient outcomes; Plates; Pneumonia; Polymyxin B; Research and analysis methods; Social Sciences; Swimming; Ukraine; United Kingdom > UK; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0270983

Novel antibiotic combinations may act synergistically to inhibit the growth of multidrug-resistant bacterial pathogens but predicting which combination will be successful is difficult, and standard antimicrobial susceptibility testing may not identify important physiological differences between planktonic free-swimming and biofilm-protected surface-attached sessile cells. Using a nominally macrolide-resistant model Klebsiella pneumoniae strain (ATCC 10031) we demonstrate the effectiveness of several macrolides in inhibiting biofilm growth in multi-well plates, and the ability of azithromycin (AZM) to improve the effectiveness of the antibacterial last-agent-of-choice for K. pneumoniae infections, colistin methanesulfonate (CMS), against biofilms. This synergistic action was also seen in biofilm tests of several K. pneumoniae hospital isolates and could also be identified in polymyxin B disc-diffusion assays on azithromycin plates. Our work highlights the complexity of antimicrobial-resistance in bacterial pathogens and the need to test antibiotics with biofilm models where potential synergies might provide new therapeutic opportunities not seen in liquid culture or colony-based assays.