Combined effect of oxacillin and photodynamic inactivation on Meticillin-Resistant Staphylococcus aureus

Introduction: Antimicrobial resistance is a high healthiness problem due to constant limitation of their treatment. Methicillin resistance in Staphylococcus aureus strains is alarming, due to their unresponsiveness to other β-lactams. With the rise of antimicrobial resistance, Photodynamic Inactivation emerges as alternative in concomitant treatment of infections. Photodynamic inactivation technique uses light to activate photosensitizers, which, when irradiated, generate reactive oxygen species, leading to cell death and cytoskeletal disruption.

Methodology: Zincoporphyrin, ZnP, (ZnTE-2-PyP⁴⁺) was used as a photosensitizer (final concentration 4 μmol∙L^-1), and oxacillin at concentrations of 8 mg∙L^-1, 4 mg∙L^-1, 2 mg∙L^-1, 1 mg∙L^-1, and 0.5 mg∙L^-1 in Mueller-Hinton Broth. Strain of Staphylococcus aureus MRSA was grown on Mueller-Hinton Agar at 35 ± 1 °C for 24 h, with preparation of suspensions in Saline solution (0.9% w/w) adjusted to optical density (OD) of 0.1 at 625 nm, corresponding to 1.0∙10⁸ cells∙mL^-1 with final working solution of 106 cells∙mL^-1. Equals aliquots of ZnP and previous solution were mixed and irradiated for 3 min (6.26 J∙cm^-2) under blue light, with subsequent exposure of MRSA+ZnP to oxacillin concentrations and incubated at same conditions, with subsequent visual reading to determine the Minimum Inhibitory Concentration. Control conditions in absence of light were performed to ensure the reliability of the tests.

Results and discussion: The light-treated systems showed a reduction in minimum inhibitory concentration on oxacillin from 8 mg∙L^-1 to 0.5 mg∙L^-1. The systems not exposed to light continued to show oxacillin resistance. The momentary susceptibility to oxacillin in the light-treated group may be due to damage to the bacterial cell wall caused by the photodynamic treatment.

Conclusion: It was observed that concomitant treatment of IFD and oxacillin presents a positive in vitro perspective for infections caused by Staphylococcus MRSA, playing an important role in antimicrobial resistance.