Efficacy of ultraviolet C light at sublethal dose in combination with antistaphylococcal antibiotics to disinfect catheter biofilms of methicillin-susceptible and methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis in vitro

Infection and Drug Resistance Dovepress open access to scientific and medical research ORIGINAL RESEARCH Infection and Drug Resistance downloaded from https://www.dovepress.com/ by 37.59.46.207 on 13-Jul-2018 For personal use only. Open Access Full Text Article Efficacy of ultraviolet C light at sublethal dose in combination with antistaphylococcal antibiotics to disinfect catheter biofilms of methicillin-susceptible and methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis in vitro This article was published in the following Dove Press journal: Infection and Drug Resistance 19 August 2016 Number of times this article has been viewed Mohamed El-Azizi 1 Nancy Khardori 2 1 Department of Microbiology, Immunology and Biotechnology, Faculty of Pharmacy and Biotechnology, German University in Cairo, New Cairo City, Egypt; 2 Department of Internal Medicine, Division of Infectious Diseases, Eastern Virginia Medical School, Norfolk, VA, USA Correspondence: Mohamed El-Azizi Department of Microbiology, Immunology and Biotechnology, Faculty of Pharmacy and Biotechnology, German University in Cairo, New Cairo City, Main Entrance El-Tagamoa El-Khames, 11835, Egypt Tel +20 2 2758 9990-8 Fax +20 2 2758 1041 Email 181 submit your manuscript | www.dovepress.com Infection and Drug Resistance 2016:9 181–189 Dovepress © 2016 El-Azizi and Khardori. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/IDR.S109343 Powered by TCPDF (www.tcpdf.org) Background: Biofilm formation inside inserted medical devices leads to their failure and acts as a source of refractory infections. The ultraviolet C (UVC) light is a potential therapy that can be used against the biofilm of bacterial pathogens. Objective: We evaluated the efficacy of sublethal dose of UVC light with anti-staphylococcal antibiotics against biofilms made from 30 isolates of methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus and S. epidermidis on vascular catheters. Materials and methods: A novel biofilm device was used to assess the combined approach. The biofilms on the catheters were irradiated with the UVC light at 254 nm and irradiance of 6.4 mW followed by treatment with vancomycin or quinupristin/dalfopristin at twice their minimum bactericidal concentrations or with linezolid at 64 µg/mL for 24 hours. The catheters were cut into segments and sonicated, and the number of the sessile cells was determined c olorimetrically using XTT viable cells assay. The effect of UVC radiation followed by treatment with an antistaphylococcal antibiotic on the viability of the bacteria in the biofilm was visualized using LIVE/DEAD BacLight bacterial viability stain and confocal laser scanning microscopy. Results: Exposure of the bacterial biofilms to the UVC light or each of the antibiotics alone was ineffective in killing the bacteria. Treatment of the biofilms with the antibiotics following their exposure to UVC light significantly (P<0.001) reduced the number of viable cells within the biofilms but did not completely eradicate them. Conclusion: To our knowledge, this combinatorial approach has not been investigated before. The combined approach can be used as a therapeutic modality for managing biofilm-associated infections by preventing the establishment of biofilms and/or disrupting the formed biofilms on the inserted medical devices with the goal of increasing their usefulness and preventing infectious complications. Further investigations are needed to assess the effectiveness of the combined approach in the clinical settings. Keywords: alternative therapy, biofilm-associated infections, MRSA, MSSA, Staphylococcus epidermidis, indwelling medical devices Dovepress El-Azizi and Khardori Infection and Drug Resistance downloaded from https://www.dovepress.com/ by 37.59.46.207 on 13-Jul-2018 For personal use only. Introduction Biofilms are composed of pure or mixed communities of microorganisms adhering to surfaces. In the medical setting, biofilm-associated infections constitute a steadily increasing problem and can start out from the surface of different indwelling devices.1 Microorganisms upon shedding from the biofilm enter the circulation and result in dissemination and establishment of infection at distant sites. Since the microorganisms in such infections are in aggregates, they remain less susceptible to antimicrobial agents compared to single-cell suspensions tested in the diagnostic laboratories.2 Implant-associated infections lead to considerable morbidity, repeated surgeries, and prolonged antibiotic therapy.3 The mortality associated with cardiovascular device-related, biofilm-associated infections, for example, is estimated to be 12%–25%, with a health care cost of $33,000–$35,000/event.4 The bacteria within the biofilm are protected from the host defense mechanisms and the antimicrobial agents. They can be up to 1,000 times more resistant to antibiotics than their planktonic (free-floating) counterparts.5 Such resistance is demonstrated not only toward antibiotics but also toward preservatives, disinfectants, and antiseptics.6,7 Failure of the antibiotics to manage biofilm-associated infections has led to a significant research effort to find alternative antimicrobial approaches with more efficacy and less resistance developed by the microorganisms. The ultraviolet C (UVC) light could be a potential alternative antimicrobial intervention to which resistance will be difficult to develop. The UVC kills the organisms by damaging the DNA and RNA through dimerization of pyrimidine molecules.8 With appropriate doses, UVC may selectively target microorganisms with a negligible effect on the mammalian cells.9 Several in vitro studies have reported the susceptibility of multidrug-resistant bacteria to inactivation by UVC.9–12 These bacteria include methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative Staphylococcus, Streptococcus pyogenes, Enterococcus faecalis, Pseudomonas aeruginosa, and Mycobacteria.10–12 In clinical studies, the UVC irradiation was used to disinfect surgical wounds and treat infections in cutaneous ulcers.13,14 However, only minimal data are available on the effectiveness of the UVC light against the bacteria in the biofilms. The UVC light was previously studied to control microbial biofilms in water systems and medical devices.15,16 Dis (...truncated)