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      Assessment of Phage-Mediated Inhibition and Removal of Multidrug-Resistant Pseudomonas aeruginosa Biofilm on Medical Implants

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          Abstract

          Purpose

          Despite the growing interest in bacteriophage (phage) usage for the prevention, control, and removal of bacterial biofilms, few scientific data exist on phage applications on medical implant surfaces, while none exists on multiple implants. In this study, we aimed to isolate, biophysically characterize and assess phages as potential antibiofilm agents to inhibit and remove multidrug-resistant (MDR) Pseudomonas aeruginosa biofilm on catheter and endotracheal tube surfaces.

          Methods

          The well-identified stored clinical isolates (n = 7) of MDR P. aeruginosa were obtained from Jimma Medical Center. Specific phages were isolated and characterized based on standard protocols. The phages were tested for their antibiofilm effects in preventing colonization and removing preformed biofilms of MDR P. aeruginosa, following phage coating and treatment of catheter and endotracheal tube segments.

          Results

          Two P. aeruginosa-specific phages (ΦJHS-PA1139 and ΦSMK-PA1139) were isolated from JMC compound sewage sources. The phages were biophysically characterized as being thermally stable up to 40°C and viable between pH 4.0 and 11.0. The two phages tested against clinical MDR strains of P. aeruginosa showed broad host ranges but not on other tested bacterial species. Both phages reduced MDR bacterial biofilms during the screening step. The phage-coated segments showed 1.2 log 10 up to 3.2 log 10 inhibition relative to non-coated segments following 6 h coating of segments prior to microbial load exposure. In both phages, 6 h treatment of the segments with 10 6 PFU/mL yielded 1.0 log 10 up to 1.6 log 10 reductions for ΦJHS and 1.6 log 10 up to 2.4 log 10 reductions for ΦSMK.

          Conclusion

          Our results suggest that phages have great potential to serve the dual purpose as surface coating agents for preventing MDR bacterial colonization in medical implants and as biofilm removal agents in implant-associated infections.

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          Most cited references36

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          Phages in nature.

          Martha Clokie, Andrew D. Millard, Andrey Letarov … (2011)
          Bacteriophages or phages are the most abundant organisms in the biosphere and they are a ubiquitous feature of prokaryotic existence. A bacteriophage is a virus which infects a bacterium. Archaea are also infected by viruses, whether these should be referred to as 'phages' is debatable, but they are included as such in the scope this article. Phages have been of interest to scientists as tools to understand fundamental molecular biology, as vectors of horizontal gene transfer and drivers of bacterial evolution, as sources of diagnostic and genetic tools and as novel therapeutic agents. Unraveling the biology of phages and their relationship with their hosts is key to understanding microbial systems and their exploitation. In this article we describe the roles of phages in different host systems and show how modeling, microscopy, isolation, genomic and metagenomic based approaches have come together to provide unparalleled insights into these small but vital constituents of the microbial world.
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            Mechanisms and consequences of bacterial resistance to antimicrobial peptides.

            D I Andersson, D D Hughes, J Kubicek-Sutherland (2016)
            Cationic antimicrobial peptides (AMPs) are an intrinsic part of the human innate immune system. Over 100 different human AMPs are known to exhibit broad-spectrum antibacterial activity. Because of the increased frequency of resistance to conventional antibiotics there is an interest in developing AMPs as an alternative antibacterial therapy. Several cationic peptides that are derivatives of AMPs from the human innate immune system are currently in clinical development. There are also ongoing clinical studies aimed at modulating the expression of AMPs to boost the human innate immune response. In this review we discuss the potential problems associated with these therapeutic approaches. There is considerable experimental data describing mechanisms by which bacteria can develop resistance to AMPs. As for any type of drug resistance, the rate by which AMP resistance would emerge and spread in a population of bacteria in a natural setting will be determined by a complex interplay of several different factors, including the mutation supply rate, the fitness of the resistant mutant at different AMP concentrations, and the strength of the selective pressure. Several studies have already shown that AMP-resistant bacterial mutants display broad cross-resistance to a variety of AMPs with different structures and modes of action. Therefore, routine clinical administration of AMPs to treat bacterial infections may select for resistant bacterial pathogens capable of better evading the innate immune system. The ramifications of therapeutic levels of exposure on the development of AMP resistance and bacterial pathogenesis are not yet understood. This is something that needs to be carefully studied and monitored if AMPs are used in clinical settings.
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              Antimicrobial-resistant pathogens associated with adult healthcare-associated infections: Summary of data reported to the National Healthcare Safety Network, 2015–2017

              Lindsey M. Weiner-Lastinger, Sheila Abner, Jonathan Edwards … (2019)
              Describe common pathogens and antimicrobial resistance patterns for healthcare-associated infections (HAIs) that occurred during 2015–2017 and were reported to the Centers for Disease Control and Prevention’s (CDC’s) National Healthcare Safety Network (NHSN). Data from central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events (VAEs), and surgical site infections (SSIs) were reported from acute-care hospitals, long-term acute-care hospitals, and inpatient rehabilitation facilities. This analysis included device-associated HAIs reported from adult location types, and SSIs among patients ≥18 years old. Percentages of pathogens with nonsusceptibility (%NS) to selected antimicrobials were calculated for each HAI type, location type, surgical category, and surgical wound closure technique. Overall, 5,626 facilities performed adult HAI surveillance during this period, most of which were general acute-care hospitals with <200 beds. Escherichia coli (18%), Staphylococcus aureus (12%), and Klebsiella spp (9%) were the 3 most frequently reported pathogens. Pathogens varied by HAI and location type, with oncology units having a distinct pathogen distribution compared to other settings. The %NS for most pathogens was significantly higher among device-associated HAIs than SSIs. In addition, pathogens from long-term acute-care hospitals had a significantly higher %NS than those from general hospital wards. This report provides an updated national summary of pathogen distributions and antimicrobial resistance among select HAIs and pathogens, stratified by several factors. These data underscore the importance of tracking antimicrobial resistance, particularly in vulnerable populations such as long-term acute-care hospitals and intensive care units.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Infect Drug Resist
                Journal ID (iso-abbrev): Infect Drug Resist
                Journal ID (publisher-id): idr
                Title: Infection and Drug Resistance
                Publisher: Dove
                ISSN (Electronic): 1178-6973
                Publication date (Electronic): 31 May 2022
                Publication date Collection: 2022
                Volume: 15
                Pages: 2797-2811
                Affiliations
                [1 ]School of Medical Laboratory Sciences, Jimma University , Jimma, Ethiopia
                [2 ]Accra Medical Centre , Accra, Ghana
                [3 ]Department of Medical Laboratory Sciences, Wollega University , Nekemte, Ethiopia
                [4 ]Microbiology Laboratory of Jimma Medical Center , Jimma, Ethiopia
                [5 ]St Paul’s Hospital Millennium Medical College , Addis Ababa, Ethiopia
                Author notes
                Correspondence: Tesfaye Kassa, School of Medical Laboratory Sciences, Jimma University , P.O. Box 788, Jimma, Ethiopia, Tel +251 931057195, Email ktes36@gmail.com; tesfaye.kassa@ju.edu.et
                Author information
                http://orcid.org/0000-0002-0397-5810
                http://orcid.org/0000-0001-5259-2245
                Article
                Publisher ID: 367460
                DOI: 10.2147/IDR.S367460
                PMC ID: 9166914
                PubMed ID: 35668859
                SO-VID: f254c98d-f84d-41f0-ae2f-dff17b0a5a29
                Copyright © © 2022 Amankwah et al.
                License:

                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).

                History
                Date received : 23 March 2022
                Date accepted : 27 May 2022
                Page count
                Figures: 6, Tables: 6, References: 41, Pages: 15
                Funding
                Funded by: Jimma University, Ethiopia;
                This study was supported by Jimma University, Ethiopia.
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: bacteriophage,biofilm,multidrug-resistant p. aeruginosa,catheter,endotracheal tube
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: bacteriophage, biofilm, multidrug-resistant p. aeruginosa, catheter, endotracheal tube

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