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  • Luke-Marshall, Nicole R.  (13)
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  • 1
    Language: English
    In: Gene, 2011, Vol.477(1), pp.19-23
    Description: is a Gram-negative aerobic diplococcus that is a mucosal pathogen of the upper and lower respiratory tracts in humans. In order to colonize the human host and establish an infection, must be able to effectively attach to the respiratory mucosal epithelia. Although little is known about pathogenesis, our laboratory has previously shown that expression of type IV pili (TFP) contributes to mucosal colonization. TFP are filamentous surface appendages primarily composed of a single protein subunit termed pilin, which is encoded by in . These surface structures play a crucial role in the initiation of disease by a wide range of pathogenic bacteria. Our studies also indicate that unlike the pilin of the pathogenic species, which exhibit both phase and antigenic variation, the pilin subunit of appears to be more highly conserved as there are no major pilin variants produced by a single strain and only two major PilA antigenic variants, termed clade 1 and clade 2, have been observed between strains. Moreover, we have determined that these highly conserved bacterial surface structures are expressed by all clinical isolates evaluated. Therapeutic or vaccine-based interventions that prevent or diminish nasopharyngeal colonization will likely decrease acute and recurrent infections in prone populations. Thus, our data indicate that additional studies aimed at elucidating the role of PilA in the pathogenesis and host response to infections are warranted.
    Keywords: Pili ; Pilin ; Antigenic Clades ; Engineering ; Biology ; Anatomy & Physiology
    ISSN: 0378-1119
    E-ISSN: 1879-0038
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  • 2
    In: Clinical Orthopaedics and Related Research, 2015, Vol.473(9), pp.2856-2864
    Description: BACKGROUND: Effective treatments for implant-associated infections are often lacking. Cathodic voltage-controlled electrical stimulation has shown potential as a treatment of implant-associated infections of methicillin-resistant Staphylococcus aureus (MRSA). QUESTIONS/PURPOSES: The primary purpose of this study was to (1) determine if cathodic voltage-controlled electrical stimulation combined with vancomycin therapy is more effective at reducing the MRSA bacterial burden on the implant, bone, and synovial fluid in comparison to either treatment alone or no treatment controls. We also sought to (2) evaluate the histologic effects of the various treatments on the surrounding bone; and to (3) determine if the cathodic voltage-controlled electrical stimulation treatment had an effect on the mechanical properties of the titanium implant as a result of possible hydrogen embrittlement. METHODS: Thirty-two adult male Long-Evans rats (Harlan Laboratories, Indianapolis, IN, USA) with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, eight animals received a treatment of cathodic voltage-controlled electrical stimulation at −1.8 V versus Ag/AgCl for 1 hour (STIM), eight received vancomycin twice daily for 1 week (VANCO), eight received the cathodic voltage-controlled electrical stimulation and vancomycin therapy combined (STIM + VANCO), and eight served as controls with no treatment (CONT). Two weeks after initial infection, the implant, bone, and synovial fluid were collected for colony-forming unit (CFU) enumeration, qualitative histological analysis by a pathologist blinded to the treatments each animal received, and implant three-point bend testing. RESULTS: The implant-associated CFU enumerated from the STIM + VANCO (mean, 3.7 × 10; SD, 6.3 × 10) group were less than those from the CONT (mean, 1.3 × 10; SD, 2.8 × 10; 95% confidence interval [CI] of difference, −4.3 × 10 to −9.9 × 10; p 〈 0.001), STIM (mean, 1.4 × 10; SD, 2.0 × 10; 95% CI of difference, −2.1 × 10 to −1.8 × 10; p = 0.002), and VANCO (mean, 5.8 × 10; SD, 5.7 × 10; 95% CI of difference, −6.4 × 10 to −1.7 × 10; p 〈 0.001) group. The bone-associated CFU enumerated from the STIM + VANCO group (6.3 × 10; SD, 1.1 × 10) were less than those from the CONT (mean, 2.8 × 10; SD, 4.8 × 10; 95% CI of difference, −9.4 × 10 to −5.0 × 10; p 〈 0.001) and STIM (mean, 2.6 × 10; SD, 2.5 × 10; 95% CI of difference, −4.1 × 10 to −1.6 × 10; p 〈 0.001) groups. The VANCO group (4.3 × 10; SD, 6.3 × 10) also had lower bone-associated CFU as compared with the CONT (mean 95% CI of difference, −9.3 × 10 to −4.5 × 10; p 〈 0.001) and STIM (95% CI of difference, −4.0 × 10 to −1.5 × 10; p 〈 0.001) groups. In comparison to the synovial fluid CFU enumerated from the CONT group (mean, 3.3 × 10; SD, 6.0 × 10), lower synovial CFU were reported for both the STIM + VANCO group (mean, 4.6 × 10; SD, 1.2 × 10; 95% CI of difference, −4.9 × 10 to −3.0 × 10; p 〈 0.001) and the VANCO group (mean, 6.8 × 10; SD, 9.2 × 10; 95% CI of difference, −4.9 × 10 to −2.8 × 10; p = 0.007). The histological analysis showed no discernable deleterious effects on the surrounding tissue as a result of the treatments. No brittle fracture occurred during mechanical testing and with the numbers available, no differences in implant flexural yield strength were detected between the groups. CONCLUSIONS: In this rodent model, cathodic voltage-controlled electrical stimulation combined with vancomycin is an effective treatment for titanium implant-associated infections showing greater than 99.8% reduction in bacterial burden on the implant, surrounding bone, and synovial fluid as compared with the controls and the stimulation alone groups. CLINICAL RELEVANCE: Cathodic voltage-controlled electrical stimulation combined with vancomycin may enable successful treatment of titanium orthopaedic implant-associated infections with implant retention. Future studies will focus on optimization of the stimulation parameters for complete eradication of infection and the ability to promote beneficial host tissue responses.
    Keywords: Staphylococcus Aureus Infections – Care and Treatment ; Staphylococcus Aureus Infections – Analysis ; Staphylococcus Aureus Infections – Health Aspects ; Vancomycin – Analysis ; Vancomycin – Health Aspects ; Staphylococcus Aureus – Analysis ; Staphylococcus Aureus – Health Aspects ; Microbial Drug Resistance – Care and Treatment ; Microbial Drug Resistance – Analysis ; Microbial Drug Resistance – Health Aspects;
    ISSN: 0009-921X
    E-ISSN: 15281132
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  • 3
    Language: English
    In: Clinical Orthopaedics and Related Research®, 2016, Vol.474(7), pp.1668-1675
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s11999-016-4705-7 Byline: Scott R. Nodzo (1), Menachem Tobias (1), Richard Ahn (1), Lisa Hansen (2), Nicole R. Luke-Marshall (2), Craig Howard (1), Linda Wild (3), Anthony A. Campagnari (2), Mark T. Ehrensberger (4) Abstract: Background Cathodic voltage-controlled electrical stimulation (CVCES) of titanium implants, either alone or combined with a short course of vancomycin, has previously been shown to reduce the bone and implant bacterial burden in a rodent model of methicillin-resistant Staphylococcus aureus (MRSA) implant-associated infection (IAI). Clinically, the goal is to achieve complete eradication of the IAI therefore, the rationale for the present study was to evaluate the antimicrobial effects of combining CVCES with prolonged antibiotic therapy with the goal of decreasing the colony-forming units (CFUs) to undetectable levels. Questions/purposes (1) In an animal MRSA IAI model, does combining CVCES with prolonged vancomycin therapy decrease bacteria burden on the implant and surrounding bone to undetectable levels? (2) When used with prolonged vancomycin therapy, are two CVCES treatments more effective than one? (3) What are the longer term histologic effects (inflammation and granulation tissue) of CVCES on the surrounding tissue? Methods Twenty adult male Long-Evans rats with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, the rats were randomly divided into four groups of five: (1) VANCO: only vancomycin treatment (150 mg/kg, subcutaneous, twice daily for 5 weeks) (2) VANCO + 1STIM: vancomycin treatment (same as the VANCO group) coupled with one CVCES treatment (-1.8 V for 1 hour on postoperative day [POD] 7) (3) VANCO + 2STIM: vancomycin treatment (same as the VANCO group) coupled with two CVCES treatments (-1.8 V for 1 hour on POD 7 and POD 21) or (4) CONT: no treatment. On POD 42, the implant, bone, and peripheral blood were collected for CFU enumeration and histological analysis, where we compared CFU/mL on the implants and bone among the groups. A pathologist, blinded to the experimental conditions, performed a semiquantitative analysis of inflammation and granulation tissue present in serial sections of the humeral head for animals in each experimental group. Results The VANCO + 1STIM decreased the implant bacterial burden (median = 0, range = 0--10 CFU/mL) when compared with CONT (median = 5.7 x 10.sup.4, range = 4.0 x 10.sup.3-8.0 x 10.sup.5 CFU/mL difference of medians = -5.6 x 10.sup.4 p 〈 0.001) and VANCO (median = 4.9 x 10.sup.3, range = 9.0 x 10.sup.2-2.1 x 10.sup.4 CFU/mL difference of medians = -4.9 x 10.sup.3 p 〈 0.001). The VANCO + 1STIM decreased the bone bacterial burden (median = 0, range = 0--0 CFU/mL) when compared with CONT (median = 1.3 x 10.sup.2, range = 0--9.4 x 10.sup.2 CFU/mL difference of medians = -1.3 x 10.sup.2 p 〈 0.001) but was not different from VANCO (median = 0, range = 0--1.3 x 10.sup.2 CFU/mL difference of medians = 0 p = 0.210). The VANCO + 2STIM group had implant CFU (median = 0, range = 0--8.0 x 10.sup.1 CFU/mL) and bone CFU (median = 0, range = 0--2.0 x 10.sup.1 CFU/mL) that were not different from the VANCO + 1STIM treatment group implant CFU (median = 0, range = 0--10 CFU/mL difference of medians = 0 p = 0.334) and bone CFU (median = 0, range = 0--0 CFU/mL difference of medians = 0 p = 0.473). The histological analysis showed no deleterious effects on the surrounding tissue as a result of the treatments. Conclusions Using CVCES in combination with prolonged vancomycin resulted in decreased MRSA bacterial burden, and it may be beneficial in treating biofilm-related implant infections. Clinical Relevance CVCES combined with clinically relevant lengths of vancomycin therapy may be a treatment option for IAI and allow for component retention in certain clinical scenarios. However, more animal research and human trials confirming the efficacy of this approach are needed before such a clinical recommendation could be made. Author Affiliation: (1) Department of Orthopedics, State University of New York at Buffalo, Buffalo, NY, USA (2) Department of Microbiology and Immunology, State University of New York at Buffalo, Buffalo, NY, USA (3) Department of Pathology and Anatomical Sciences, State University of New York at Buffalo, Buffalo, NY, USA (4) Department of Biomedical Engineering, State University of New York at Buffalo, 162 Farber Hall, 3435 Main Street, Buffalo, NY, 14214, USA Article History: Registration Date: 08/01/2016 Online Date: 22/01/2016 Article note: The institution of one or more of the authors (MTE) has received, during the study period, funding from the Congressionally Directed Medical Research Program, Peer Reviewed Orthopedic Research Program, and the Bruce Holm Memorial Catalyst Fund. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research [R] editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research [R] neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA-approval status, of any drug or device prior to clinical use. Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research. A comment to this article is available at http://dx.doi.org/10.1007/s11999-016-4744-0.
    Keywords: Vancomycin – Health Aspects ; Vancomycin – Analysis;
    ISSN: 0009-921X
    E-ISSN: 1528-1132
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  • 4
    Language: English
    In: Biomaterials, February 2015, Vol.41, pp.97-105
    Description: Effective treatment options are often limited for implant-associated orthopedic infections. In this study we evaluated the antimicrobial effects of applying cathodic voltage-controlled electrical stimulation (CVCES) of -1.8 V (vs. Ag/AgCl) to commercially pure titanium (cpTi) substrates with preformed biofilm-like structures of methicillin-resistant Staphylococcus aureus (MRSA). The in vitro studies showed that as compared to the open circuit potential (OCP) conditions, CVCES of -1.8 V for 1 h significantly reduced the colony-forming units (CFU) of MRSA enumerated from the cpTi by 97% (1.89 × 106 vs 6.45 × 104 CFU/ml) and from the surrounding solution by 92% (6.63 × 105 vs. 5.15 × 104 CFU/ml). The in vivo studies, utilizing a rodent periprosthetic infection model, showed that as compared to the OCP conditions, CVCES at -1.8 V for 1 h significantly reduced MRSA CFUs in the bone tissue by 87% (1.15 × 105 vs. 1.48 × 104 CFU/ml) and reduced CFU on the cpTi implant by 98% (5.48 × 104 vs 1.16 × 103 CFU/ml). The stimulation was not associated with histological changes in the host tissue surrounding the implant. As compared to the OCP conditions, the −1.8 V stimulation significantly increased the interfacial capacitance (18.93 vs. 98.25 μF/cm ) and decreased polarization resistance (868,250 vs. 108 Ω-cm ) of the cpTi. The antimicrobial effects are thought to be associated with these voltage-dependent electrochemical surface properties of the cpTi.
    Keywords: Titanium ; Infection ; Electrical Stimulation ; Antimicrobial ; Bacteria ; Biofilm ; Medicine ; Engineering
    ISSN: 0142-9612
    E-ISSN: 1878-5905
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  • 5
    Language: English
    In: Infection and immunity, March 2013, Vol.81(3), pp.915-22
    Description: The emergence of extremely resistant and panresistant Gram-negative bacilli, such as Acinetobacter baumannii, requires consideration of nonantimicrobial therapeutic approaches. The goal of this report was to evaluate the K1 capsular polysaccharide from A. baumannii as a passive immunization target. Its structure was determined by a combination of mass spectrometric and nuclear magnetic resonance (NMR) techniques. Molecular mimics that might raise the concern for autoimmune disease were not identified. Immunization of CD1 mice demonstrated that the K1 capsule is immunogenic. The monoclonal antibody (MAb) 13D6, which is directed against the K1 capsule from A. baumannii, was used to determine the seroprevalence of the K1 capsule in a collection of 100 A. baumannii strains. Thirteen percent of the A. baumannii isolates from this collection were seroreactive to MAb 13D6. Opsonization of K1-positive strains, but not K1-negative strains, with MAb 13D6 significantly increased neutrophil-mediated bactericidal activity in vitro (P 〈 0.05). Lastly, treatment with MAb 13D6 3 and 24 h after bacterial challenge in a rat soft tissue infection model resulted in a significant decrease in the growth/survival of a K1-positive strain compared to that of a K1-negative strain or to treatment with a vehicle control (P 〈 0.0001). These data support the proof of principle that the K1 capsule is a potential therapeutic target via passive immunization. Other serotypes require assessment, and pragmatic challenges exist, such as the need to serotype infecting strains and utilize serotype-specific therapy. Nonetheless, this approach may become an important therapeutic option with increasing antimicrobial resistance and a diminishing number of active antimicrobials.
    Keywords: Acinetobacter Infections -- Prevention & Control ; Acinetobacter Baumannii -- Metabolism ; Antibodies, Monoclonal -- Immunology ; Bacterial Capsules -- Metabolism ; Bacterial Vaccines -- Immunology
    ISSN: 00199567
    E-ISSN: 1098-5522
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  • 6
    In: Lasers in Surgery and Medicine, November 2014, Vol.46(9), pp.712-717
    Keywords: Antimicrobial Photodynamic Therapy ; Biofilm ; Gram‐Negative Bacteria ; Otitis Media ; Photofrin
    ISSN: 0196-8092
    E-ISSN: 1096-9101
    Source: John Wiley & Sons, Inc.
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  • 7
    Language: English
    In: mBio, 2016-08-16, Vol.7(4)
    Description: UNLABELLED: Staphylococcus aureus is a ubiquitous opportunistic human pathogen and a major health concern worldwide, causing a wide variety of diseases from mild skin infections to systemic disease. S. aureus is a major source of severe secondary bacterial pneumonia after influenza A virus infection,...
    Keywords: Journal Article ; Medicin Och Hälsovetenskap ; Klinisk Medicin ; Infektionsmedicin ; Medical And Health Sciences ; Clinical Medicine ; Infectious Medicine
    ISSN: 2161-2129
    ISSN: 21507511
    E-ISSN: 21507511
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  • 8
    Language: English
    In: mBio, 2018-01-09, Vol.9(1)
    Description: Streptococcus pneumoniae and Staphylococcus aureus are ubiquitous upper respiratory opportunistic pathogens. Individually, these Gram-positive microbes are two of the most common causative agents of secondary bacterial pneumonia following influenza A virus infection, and they constitute a significant...
    Keywords: Streptococcus Pneumoniae ; Staphylococcus Aureus ; Biofilm ; Colonization ; Medicin Och Hälsovetenskap ; Medicinska Och Farmaceutiska Grundvetenskaper ; Mikrobiologi Inom Det Medicinska Området ; Medical And Health Sciences ; Basic Medicine ; Microbiology In The Medical Area
    ISSN: 2161-2129
    ISSN: 21507511
    E-ISSN: 21507511
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  • 9
    Language: English
    In: Lasers in surgery and medicine, November 2014, Vol.46(9), pp.712-7
    Description: Moraxella catarrhalis is a significant cause of pediatric otitis media (OM), which is the most prevalent bacterial infection in children and primary reason for antibiotic administration in this population. Moreover, biofilm formation has been implicated as a primary mechanism of chronic or recurrent OM disease. As bacterial biofilms are inherently resistant to most antibiotics and these complex structures also present a significant challenge to the immune system, there is a clear need to identify novel antimicrobial approaches to treat OM infections. In this study, we evaluated the potential efficacy of antibacterial photodynamic therapy (aPDT) with porfimer sodium (Photofrin (PF)) against planktonic as well as biofilm-associated M. catarrhalis. The bactericidal activity of aPDT with PF was assessed against multiple recent clinical isolates of M. catarrhalis grown planktonically as well as in biofilms. The bactericidal activity of PF-aPDT was quantified by enumeration of colony forming units post-treatment. The effect of aPDT on M. catarrhalis biofilms was further investigated with scanning electron microscopy (SEM) imaging. aPDT with PF significantly reduced M. catarrhalis viability. Although PF-aPDT caused higher killing in planktonic grown organisms (5-6 log kill), biofilm grown bacteria also demonstrated a statistically significant reduction in viable organisms (3-4 log decrease in recoverable bacteria) following treatment as compared to saline only controls (P 〈 0.01). SEM studies indicated the PF-aPDT treated bacteria exhibited prominent morphological changes with visibly distorted cell membranes. aPDT with PF elicits significant bactericidal activity against both planktonic and biofilm-associated M. catarrhalis, suggesting this technology warrants further analysis as a potential novel antimicrobial treatment for acute or recurrent OM.
    Keywords: Antimicrobial Photodynamic Therapy ; Biofilm ; Gram-Negative Bacteria ; Otitis Media ; Photofrin ; Photochemotherapy ; Biofilms -- Drug Effects ; Dihematoporphyrin Ether -- Pharmacology ; Moraxella (Branhamella) Catarrhalis -- Drug Effects ; Photosensitizing Agents -- Pharmacology
    ISSN: 01968092
    E-ISSN: 1096-9101
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  • 10
    Language: English
    In: Journal of biomedical materials research. Part B, Applied biomaterials, January 2018, Vol.106(1), pp.221-227
    Description: Magnesium alloys hold great promise for developing orthopedic implants that are biocompatible, biodegradable, and mechanically similar to bone tissue. This study evaluated the in vitro and in vivo antimicrobial properties of magnesium-9%aluminum-1%zinc (AZ91) and commercially pure titanium (cpTi) against Acinetobacter baumannii (Ab307). The in vitro results showed that as compared to cpTi, incubation with AZ91 significantly reduced both the planktonic (cpTi = 3.45e8, AZ91 = 8.97e7, p 〈 0.001) colony forming units (CFU) and biofilm-associated (cpTi = 3.89e8, AZ91 = 1.78e7, p = 0.01) CFU of Ab307. However, in vivo results showed no significant differences in the CFU enumerated from the cpTi and AZ91 implants following a 1-week implantation in an established rodent model of Ab307 implant associated infection (cpTi = 5.23e3, AZ91 = 2.46e3, p = 0.29). It is proposed that the in vitro results were associated with an increased pH in the bacterial culture as a result of the AZ91 corrosion process. The robust in vivo buffering capacity likely diminished this corrosion associated pH antimicrobial effect. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 221-227, 2018.
    Keywords: Antimicrobial ; Biodegradable ; in Vivo ; Infection ; Magnesium ; Acinetobacter Baumannii -- Growth & Development ; Alloys -- Pharmacology ; Anti-Infective Agents -- Pharmacology ; Implants, Experimental -- Microbiology ; Magnesium -- Pharmacology
    ISSN: 15524973
    E-ISSN: 1552-4981
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