title: Polymicrobial Ventilator-Associated Pneumonia: Fighting In Vitro Candida albicans-Pseudomonas aeruginosa Biofilms with Antifungal-Antibacterial Combination Therapy.
abstract: The polymicrobial nature of ventilator-associated pneumonia (VAP) is now evident, with mixed bacterial-fungal biofilms colonizing the VAP endotracheal tube (ETT) surface. The microbial interplay within this infection may contribute for enhanced pathogenesis and exert impact towards antimicrobial therapy. Consequently, the high mortality/morbidity rates associated to VAP and the worldwide increase in antibiotic resistance has promoted the search for novel therapeutic strategies to fight VAP polymicrobial infections. Under this scope, this work aimed to assess the activity of mono- vs combinational antimicrobial therapy using one antibiotic (Polymyxin B; PolyB) and one antifungal (Amphotericin B; AmB) agent against polymicrobial biofilms of Pseudomonas aeruginosa and Candida albicans. The action of isolated antimicrobials was firstly evaluated in single- and polymicrobial cultures, with AmB being more effective against C. albicans and PolyB against P. aeruginosa. Mixed planktonic cultures required equal or higher antimicrobial concentrations. In biofilms, only PolyB at relatively high concentrations could reduce P. aeruginosa in both monospecies and polymicrobial populations, with C. albicans displaying only punctual disturbances. PolyB and AmB exhibited a synergistic effect against P. aeruginosa and C. albicans mixed planktonic cultures, but only high doses (256 mg L-1) of PolyB were able to eradicate polymicrobial biofilms, with P. aeruginosa showing loss of cultivability (but not viability) at 2 h post-treatment, whilst C. albicans only started to be inhibited after 14 h. In conclusion, combination therapy involving an antibiotic and an antifungal agent holds an attractive therapeutic option to treat severe bacterial-fungal polymicrobial infections. Nevertheless, optimization of antimicrobial doses and further clinical pharmacokinetics/pharmacodynamics and toxicodynamics studies underpinning the optimal use of these drugs are urgently required to improve therapy effectiveness and avoid reinfection.
authors.affiliation: Centre of Biological Engineering, LIBRO-Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, Braga, Portugal.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Rodrigues
authors.affiliation: Centre of Biological Engineering, LIBRO-Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, Braga, Portugal.
authors.forename: Susana P
authors.initials: SP
authors.lastname: Lopes
authors.affiliation: Centre of Biological Engineering, LIBRO-Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, Braga, Portugal.
authors.forename: Cláudia R
authors.initials: CR
authors.lastname: Pereira
authors.affiliation: LEPABE-Dep. of Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, Porto, Portugal.
authors.forename: Nuno F
authors.initials: NF
authors.lastname: Azevedo
authors.affiliation: Departamento de Informática-Universidade de Vigo, ESEI-Escuela Superior de Ingeniería Informática, Edificio politécnico, Campus Universitario As Lagoas, Ourense, Spain.|Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga, Portugal.
authors.forename: Anália
authors.initials: A
authors.lastname: Lourenço
authors.affiliation: Centre of Biological Engineering, LIBRO-Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, Braga, Portugal.
authors.forename: Mariana
authors.initials: M
authors.lastname: Henriques
authors.affiliation: Centre of Biological Engineering, LIBRO-Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, Braga, Portugal.
authors.forename: Maria O
authors.initials: MO
authors.lastname: Pereira
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects* / Q000472:pathogenicity; D004359:Drug Therapy, Combination; D006801:Humans; D008826:Microbial Sensitivity Tests; D053717:Pneumonia, Ventilator-Associated / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents