Abstract
Nosocomial diseases represent a huge health and economic burden. A significant portion is associated with the use of medical devices, with 80% of these infections being caused by a bacterial biofilm. The insertion of a foreign material usually elicits inflammation, which can result in hampered antimicrobial capacity of the host immunity due to the effort of immune cells being directed to degrade the material. The ineffective clearance by immune cells is a perfect opportunity for bacteria to attach and form a biofilm. In this study, we analyzed the antibiofilm capacity of three naturally derived biofilm inhibitors when combined with immune cells in order to assess their applicability in implantable titanium devices and low-density polyethylene (LDPE) endotracheal tubes. To this end, we used a system based on the coculture of HL-60 cells differentiated into polymorphonuclear leukocytes (PMNs) and Staphylococcus aureus (laboratory and clinical strains) on titanium, as well as LDPE surfaces. Out of the three inhibitors, the one coded DHA1 showed the highest potential to be incorporated into implantable devices, as it displayed a combined activity with the immune cells, preventing bacterial attachment on the titanium and LDPE. The other two inhibitors seemed to also be good candidates for incorporation into LDPE endotracheal tubes.
Highlights
Over 2.6 million new cases of healthcare-associated infections are annually reported just in the European Union [1], and over 33,000 result in death [2] due to the increasing number of antimicrobial-resistance cases [3]
Before performing the experiments with the titanium coupons and the antimicrobial compounds, the initial concentration of S. aureus ATCC 25923 was determined where the bacteria were able to form a biofilm in absence of the HL-60 cells, but were prevented from forming a biofilm when cocultured with 105 HL-60 cells
A reduction on the adhered S. aureus ATCC 25923 viable cell counts was observed at an S. aureus ATCC 25923 concentration of 107 CFU/mL and below (p < 0.001 in all cases when comparing the bacterial control with bacteria cocultured with HL-60 cells, and p = 0.001 for cells activated with phorbol 12-myristate 13-acetate (PMA) and a starting inoculum of 103 CFU/Ml), with the exception of the lowest bacterial concentration tested, i.e., 102 CFU/mL, where no difference was found
Summary
Over 2.6 million new cases of healthcare-associated infections are annually reported just in the European Union [1], and over 33,000 result in death [2] due to the increasing number of antimicrobial-resistance cases [3]. Biofilms are defined as a community of microorganisms encased within a self-produced matrix that adheres to biological or nonbiological surfaces [6,7]. They are currently regarded as the most important nonspecific mechanism of antimicrobial resistance [8,9]. Infection of orthopedic implants is problematic, as these devices remain in the body, often causing chronic and/or recurring infections mediated by biofilms. These infections frequently require removal of the infected implant, thereby causing implant failure [14,15,16]. Given the rising number of implantations, the absolute number of complications is inevitably increasing at the same pace, causing distress for the patients and an increasing economic burden [15,16]
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