Azithromycin Possesses Biofilm-inhibitory Activity and Potentiates Non-bactericidal Colistin Methanesulfonate (CMS) and Polymyxin B Against Klebsiella Pneumonia

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2022 Jul 1

PMID 35776759

Authors

Olena V Moshynets

Taras P Baranovskyi

Scott Cameron

Olga S Iungin

Ianina Pokholenko

Robyn Jerdan

Aleksandr Kamyshnyi

Alexey A Krikunov

Viktoria V Potochilova

Kateryna L Rudnieva

Andrew J Spiers

Affiliations

Soon will be listed here.

Abstract

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.

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References

Moshynets O, Chernii S, Chernii V, Losytskyy M, Karakhim S, Czerwieniec R . Fluorescent β-ketoenole AmyGreen dye for visualization of amyloid components of bacterial biofilms. Methods Appl Fluoresc. 2020; 8(3):035006. DOI: 10.1088/2050-6120/ab90e0. View

Karvanen M, Plachouras D, Friberg L, Paramythiotou E, Papadomichelakis E, Karaiskos I . Colistin methanesulfonate and colistin pharmacokinetics in critically ill patients receiving continuous venovenous hemodiafiltration. Antimicrob Agents Chemother. 2012; 57(1):668-71. PMC: 3535942. DOI: 10.1128/AAC.00985-12. View

Imberti R, Cusato M, Villani P, Carnevale L, Iotti G, Langer M . Steady-state pharmacokinetics and BAL concentration of colistin in critically Ill patients after IV colistin methanesulfonate administration. Chest. 2010; 138(6):1333-9. DOI: 10.1378/chest.10-0463. View

Saiman L, Marshall B, Mayer-Hamblett N, Burns J, Quittner A, Cibene D . Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2003; 290(13):1749-56. DOI: 10.1001/jama.290.13.1749. View

Yang D, Zhang Z . Biofilm-forming Klebsiella pneumoniae strains have greater likelihood of producing extended-spectrum beta-lactamases. J Hosp Infect. 2008; 68(4):369-71. DOI: 10.1016/j.jhin.2008.02.001. View

Paul M, Daikos G, Durante-Mangoni E, Yahav D, Carmeli Y, Dishon Benattar Y . Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial. Lancet Infect Dis. 2018; 18(4):391-400. DOI: 10.1016/S1473-3099(18)30099-9. View

Swatton J, Davenport P, Maunders E, Griffin J, Lilley K, Welch M . Impact of Azithromycin on the Quorum Sensing-Controlled Proteome of Pseudomonas aeruginosa. PLoS One. 2016; 11(1):e0147698. PMC: 4726577. DOI: 10.1371/journal.pone.0147698. View

Albiger B, Glasner C, Struelens M, Grundmann H, Monnet D . Carbapenemase-producing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015. Euro Surveill. 2015; 20(45). DOI: 10.2807/1560-7917.ES.2015.20.45.30062. View

Cai Y, Lee W, Kwa A . Polymyxin B versus colistin: an update. Expert Rev Anti Infect Ther. 2015; 13(12):1481-97. DOI: 10.1586/14787210.2015.1093933. View

10.

Imperi F, Leoni L, Visca P . Antivirulence activity of azithromycin in Pseudomonas aeruginosa. Front Microbiol. 2014; 5:178. PMC: 4001013. DOI: 10.3389/fmicb.2014.00178. View

11.

Gillis R, Iglewski B . Azithromycin retards Pseudomonas aeruginosa biofilm formation. J Clin Microbiol. 2004; 42(12):5842-5. PMC: 535287. DOI: 10.1128/JCM.42.12.5842-5845.2004. View

12.

Seifi K, Kazemian H, Heidari H, Rezagholizadeh F, Saee Y, Shirvani F . Evaluation of Biofilm Formation Among Klebsiella pneumoniae Isolates and Molecular Characterization by ERIC-PCR. Jundishapur J Microbiol. 2016; 9(1):e30682. PMC: 4834130. DOI: 10.5812/jjm.30682. View

13.

Ceri H, Olson M, Stremick C, Read R, Morck D, Buret A . The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol. 1999; 37(6):1771-6. PMC: 84946. DOI: 10.1128/JCM.37.6.1771-1776.1999. View

14.

Galani I, Orlandou K, Moraitou H, Petrikkos G, Souli M . Colistin/daptomycin: an unconventional antimicrobial combination synergistic in vitro against multidrug-resistant Acinetobacter baumannii. Int J Antimicrob Agents. 2014; 43(4):370-4. DOI: 10.1016/j.ijantimicag.2013.12.010. View

15.

Flemming H, Baveye P, Neu T, Stoodley P, Szewzyk U, Wingender J . Who put the film in biofilm? The migration of a term from wastewater engineering to medicine and beyond. NPJ Biofilms Microbiomes. 2021; 7(1):10. PMC: 7840925. DOI: 10.1038/s41522-020-00183-3. View

16.

Daikos G, Tsaousi S, Tzouvelekis L, Anyfantis I, Psichogiou M, Argyropoulou A . Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother. 2014; 58(4):2322-8. PMC: 4023796. DOI: 10.1128/AAC.02166-13. View

17.

Plachouras D, Karvanen M, Friberg L, Papadomichelakis E, Antoniadou A, Tsangaris I . Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by gram-negative bacteria. Antimicrob Agents Chemother. 2009; 53(8):3430-6. PMC: 2715599. DOI: 10.1128/AAC.01361-08. View

18.

BAUER A, KIRBY W, SHERRIS J, Turck M . Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 1966; 45(4):493-6. View

19.

Orhan G, Bayram A, Zer Y, Balci I . Synergy tests by E test and checkerboard methods of antimicrobial combinations against Brucella melitensis. J Clin Microbiol. 2005; 43(1):140-3. PMC: 540140. DOI: 10.1128/JCM.43.1.140-143.2005. View

20.

Musken M, Klimmek K, Sauer-Heilborn A, Donnert M, Sedlacek L, Suerbaum S . Towards individualized diagnostics of biofilm-associated infections: a case study. NPJ Biofilms Microbiomes. 2017; 3:22. PMC: 5620081. DOI: 10.1038/s41522-017-0030-5. View