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Use of Calgary and Microfluidic BioFlux Systems To Test the Activity of Fosfomycin and Tobramycin Alone and in Combination against Cystic Fibrosis Pseudomonas aeruginosa Biofilms.
Antimicrob Agents Chemother. 2018 01; 62(1)AA

Abstract

Pseudomonas aeruginosa is a major cause of morbidity and mortality in chronically infected cystic fibrosis patients. Novel in vitro biofilm models which reliably predict the therapeutic success of antimicrobial therapies against biofilm bacteria should be implemented. The activity of fosfomycin, tobramycin, and the fosfomycin-tobramycin combination against 6 susceptible P. aeruginosa strains isolated from respiratory samples from cystic fibrosis patients was tested by using two in vitro biofilm models: a closed system (Calgary device) and an open model based on microfluidics (BioFlux). All but one of the isolates formed biofilms. The fosfomycin and tobramycin minimal biofilm inhibitory concentrations (MBIC) were 1,024 to >1,024 μg/ml and 8 to 32 μg/ml, respectively. According to fractional inhibitory concentration analysis, the combination behaved synergistically against all the isolates except the P. aeruginosa ATCC 27853 strain. The dynamic formation of the biofilm was also studied with the BioFlux system, and the MIC and MBIC of each antibiotic were tested. For the combination, the lowest tobramycin concentration that was synergistic with fosfomycin was used. The captured images were analyzed by measuring the intensity of the colored pixels, which was proportional to the biofilm biomass. A statistically significant difference was found when the intensity of the inoculum was compared with the intensity of the microchannel in which the MBIC of tobramycin, fosfomycin, or their combination was used (P < 0.01) but not when the MIC was applied (P > 0.01). Fosfomycin-tobramycin was demonstrated to be synergistic against cystic fibrosis P. aeruginosa strains in the biofilm models when both the Calgary and the microfluidic BioFlux systems were tested. These results support the clinical use of this combination.

Authors+Show Affiliations

Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal (IRYCIS), Madrid, Spain. Red Española de Investigación en Patología Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain.Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal (IRYCIS), Madrid, Spain mariaisabel.morosini@salud.madrid.org. Red Española de Investigación en Patología Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain.Koç University, Faculty of Engineering, Electrical and Electronics Engineering, Istanbul, Turkey.Red Española de Investigación en Patología Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain. Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain.Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal (IRYCIS), Madrid, Spain. Red Española de Investigación en Patología Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29084746

Citation

Díez-Aguilar, María, et al. "Use of Calgary and Microfluidic BioFlux Systems to Test the Activity of Fosfomycin and Tobramycin Alone and in Combination Against Cystic Fibrosis Pseudomonas Aeruginosa Biofilms." Antimicrobial Agents and Chemotherapy, vol. 62, no. 1, 2018.
Díez-Aguilar M, Morosini MI, Köksal E, et al. Use of Calgary and Microfluidic BioFlux Systems To Test the Activity of Fosfomycin and Tobramycin Alone and in Combination against Cystic Fibrosis Pseudomonas aeruginosa Biofilms. Antimicrob Agents Chemother. 2018;62(1).
Díez-Aguilar, M., Morosini, M. I., Köksal, E., Oliver, A., Ekkelenkamp, M., & Cantón, R. (2018). Use of Calgary and Microfluidic BioFlux Systems To Test the Activity of Fosfomycin and Tobramycin Alone and in Combination against Cystic Fibrosis Pseudomonas aeruginosa Biofilms. Antimicrobial Agents and Chemotherapy, 62(1). https://doi.org/10.1128/AAC.01650-17
Díez-Aguilar M, et al. Use of Calgary and Microfluidic BioFlux Systems to Test the Activity of Fosfomycin and Tobramycin Alone and in Combination Against Cystic Fibrosis Pseudomonas Aeruginosa Biofilms. Antimicrob Agents Chemother. 2018;62(1) PubMed PMID: 29084746.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Use of Calgary and Microfluidic BioFlux Systems To Test the Activity of Fosfomycin and Tobramycin Alone and in Combination against Cystic Fibrosis Pseudomonas aeruginosa Biofilms. AU - Díez-Aguilar,María, AU - Morosini,María Isabel, AU - Köksal,Emin, AU - Oliver,Antonio, AU - Ekkelenkamp,Miquel, AU - Cantón,Rafael, Y1 - 2017/12/21/ PY - 2017/08/09/received PY - 2017/10/21/accepted PY - 2017/11/1/pubmed PY - 2019/4/20/medline PY - 2017/11/1/entrez KW - BioFlux system KW - Calgary device KW - P. aeruginosa biofilms KW - cystic fibrosis KW - fosfomycin-tobramycin JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 62 IS - 1 N2 - Pseudomonas aeruginosa is a major cause of morbidity and mortality in chronically infected cystic fibrosis patients. Novel in vitro biofilm models which reliably predict the therapeutic success of antimicrobial therapies against biofilm bacteria should be implemented. The activity of fosfomycin, tobramycin, and the fosfomycin-tobramycin combination against 6 susceptible P. aeruginosa strains isolated from respiratory samples from cystic fibrosis patients was tested by using two in vitro biofilm models: a closed system (Calgary device) and an open model based on microfluidics (BioFlux). All but one of the isolates formed biofilms. The fosfomycin and tobramycin minimal biofilm inhibitory concentrations (MBIC) were 1,024 to >1,024 μg/ml and 8 to 32 μg/ml, respectively. According to fractional inhibitory concentration analysis, the combination behaved synergistically against all the isolates except the P. aeruginosa ATCC 27853 strain. The dynamic formation of the biofilm was also studied with the BioFlux system, and the MIC and MBIC of each antibiotic were tested. For the combination, the lowest tobramycin concentration that was synergistic with fosfomycin was used. The captured images were analyzed by measuring the intensity of the colored pixels, which was proportional to the biofilm biomass. A statistically significant difference was found when the intensity of the inoculum was compared with the intensity of the microchannel in which the MBIC of tobramycin, fosfomycin, or their combination was used (P < 0.01) but not when the MIC was applied (P > 0.01). Fosfomycin-tobramycin was demonstrated to be synergistic against cystic fibrosis P. aeruginosa strains in the biofilm models when both the Calgary and the microfluidic BioFlux systems were tested. These results support the clinical use of this combination. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/29084746/Use_of_Calgary_and_Microfluidic_BioFlux_Systems_To_Test_the_Activity_of_Fosfomycin_and_Tobramycin_Alone_and_in_Combination_against_Cystic_Fibrosis_Pseudomonas_aeruginosa_Biofilms_ DB - PRIME DP - Unbound Medicine ER -