Antimicrobial assessment of phage therapy using a porcine model of biofilm infection

Abstract

Antibiotic resistant bacterial communities persist in many types of wounds, chronic wounds in particular, in the form of biofilms. Biofilm formation is a major cause of severe infections and the main reason for a negative treatment outcome and slow healing progression. Chronic wounds are a silent epidemic essentially affecting people with co-morbid conditions such as diabetes and obesity and elderly persons particularly those with movement limitations. The development of complementary and alternative effective strategies to antibiotics for the treatment of chronic wounds is highly desired. Phage therapy constitutes a very promising approach in the control of topical microbial populations. In this work newly isolated phages were tested for their efficacy to control bacterial species that predominate in chronic wounds. Phage effectiveness was studied on 24-h old biofilms formed in polystyrene microplates and in porcine skin explants using two treatment approaches: individual phage and a cocktail of phages against four main pathogens commonly isolated from chronic wounds. The two models produced variations in the surface colonization ability, assessed by viable bacterial counts and microscopy visualization after using peptide nucleic acid (PNA) or locked nucleic acid probes (LNA) and 2′-Omethyl (2′-OMe) in fluorescence in situ hybridization (FISH), and in the phage-host interactions. Phages alone and combined caused greater reductions in the number of viable cells when biofilms had been formed on porcine skins and with greater variations detected at 4 h and 24 h of sampling. These results suggest that porcine skin models should be preferentially used to assess the use of phages and phage cocktails intended for topical use in order to understand the fate, throughout treatment time, of the population when dealing with biofilm-related infections.

Phage-Antibiotic Combination Treatments: Antagonistic Impacts of Antibiotics on the Pharmacodynamics of Phage Therapy?

“…This 'phage therapy' furthermore has been proven to be efficacious in at least one modern efficacy (phase I/II) clinical trial [11], and recently there have been several well publicized phage therapy case-study successes [12][13][14]; see also [4,9,10,[15][16][17]. Phages also can be effective against bacterial biofilms, e.g., [18][19][20][21], as well as against persister cells [22,23], though phages do not necessarily actively kill bacteria while these cells are still in the low-growth persister state [24]. In general terms [25], phages in phage therapy represent an older category of antibacterial agents that just might be able to address current needs for new antibacterial agents.…”

Bacteriophages for Chronic Wound Treatment: From Traditional to Novel Delivery Systems

“…Ex vivo models of wound infection and biofilm formation using porcine skin explants showed the effectiveness of phages against four pathogens commonly isolated from chronic wounds (A. baumannii, P. aeruginosa, E. coli, and P. mirabilis) [121]. In the porcine skin explant model, biofilms formed inside a skin cavity, closely mimicking a contaminated wound.…”

The Principles, Mechanisms, and Benefits of Unconventional Agents in the Treatment of Biofilm Infection

“…They show particular affinity in infections of wounds, lungs, the urinary system, joints, heart valves, teeth, and colonizations on medical implants and catheters are widespread [ 45 , 46 , 47 , 48 ]. Infections with resistant strains are common in cystic fibrosis, urinary tract infections [ 49 ], chronic wounds [ 50 , 51 , 52 , 53 ], prosthetic joint infections, prosthetic endocarditis, diabetic infections [ 51 , 54 ], and periodontal diseases [ 48 ].…”

“…Thus, it is essential to create the conditions to bypass the bacterial biofilm matrix [ 72 , 73 ]. Therefore, bacteriophages are able to penetrate the membrane receptors, but antibiotics cannot due to the biofilm’s defense mechanisms [ 51 , 74 ]. The combination of phage and antibiotics seems to be the optimal combination in the fight against biofilm.…”