T F Moriarty

AO Foundation, Давос, Grisons, Switzerland

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Publications (27)84.72 Total impact

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    ABSTRACT: Infectious complications occur in a minor but significant portion of the patients undergoing joint replacement surgery or fracture fixation, particularly those with severe open fractures, those undergoing revision arthroplasty or those at elevated risk because of poor health status. Once established, infections are difficult to eradicate, especially in the case of bacterial biofilm formation on implanted hardware. Local antibiotic carriers offer the prospect of controlled delivery of antibiotics directly in target tissues and implant, without inducing toxicity in non-target organs. Polymeric carriers have been developed to optimize the release and targeting of antibiotics. Passive polymeric carriers release antibiotics by diffusion and/or upon degradation, while active polymeric carriers release their antibiotics upon stimuli provided by bacterial pathogens. Additionally, some polymeric carriers gelate in-situ in response to physiological stimuli to form a depot for antibiotic release. As antibiotic resistance has become a major issue, also other anti-infectives such as silver and antimicrobial peptides have been incorporated in research. Currently, several antibiotic loaded biomaterials for local infection prophylaxis are available for use in the clinic. Here we review their advantages and limitations and provide an overview of new materials emerging that may overcome these limitations.
    Biomaterials 06/2015; 52. DOI:10.1016/j.biomaterials.2015.02.020 · 8.31 Impact Factor
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    ABSTRACT: Infections associated with deep wounds require extensive surgical and medical care. New adjunctive treatments are required to aid in the eradication of the bacterial biofilms found on infected wounds and, in particular, any underlying hardware. Ozone has been used as a safe and efficient disinfectant in water treatment plants for many years. The purpose of this study is to investigate the anti-biofilm potential of ozonated saline against biofilms of Staphylococcus aureus, a microorganism commonly implicated in wound infections. A custom-made bacterial biofilm bioreactor was used to grow S. aureus biofilms on discs of medical grade titanium alloy. An ozone generator was connected in-line and biofilms and planktonic bacteria were exposed to ozone in saline. Cytotoxicity was assessed against primary ovine osteoblasts in the same system. In tests against planktonic S. aureus, a 99% reduction in bacterial numbers was detected within 15 minutes of exposure. S. aureus biofilms were significantly more resistant to ozone, although complete eradication of the biofilm was eventually achieved within 5 hours. Ozonated saline was not found to be cytotoxic to primary ovine osteoblasts. Ozonated saline may be suitable as an adjuvant therapy to treat patients as an instillation fluid for wound irrigation and sterilisation. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.
    International Wound Journal 01/2015; DOI:10.1111/iwj.12412 · 2.02 Impact Factor
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    ABSTRACT: One of the most common pathogens causing musculoskeletal infections remains Staphylococcus aureus. The aim of this multicentre study was to perform a phenotypic and genotypic characterisation of clinical S. aureus isolates recovered from musculoskeletal infections and to investigate differences between isolates cultured from Orthopaedic Implant Related Infections (OIRI) and those from Non-Implant Related Infections (NIRI). OIRI were further differentiated in two groups: Fracture Fixation-Device Infections (FFI) and Prosthetic Joint Infections (PJI). Three-hundred and five S. aureus strains were collected from 4 different Swiss and 2 French hospitals (FFI, n=112; PJI, n=105; NIRI, n=88). NIRI cases were composed of 27 Osteomyelitis (OM), 23 Diabetic Foot Infections (DFI), 27 Soft Tissue Infections (STI) and 11 postoperative Spinal Infections (SI). All isolates were tested for their ability to form biofilm, to produce staphyloxanthin and their haemolytic activity. They were typed by agr (accessory gene regulator) group, spa type and screened by PCR for the presence of genes of the most relevant virulence factors such as MSCRAMMs, Panton Valentine Leukotoxin (PVL), enterotoxins, exotoxins and toxic shock syndrome toxin. Overall, methicillin susceptible S. aureus (MSSA) was more prevalent than methicillin resistant S. aureus (MRSA) in this collection. The OIRI group trended towards a higher incidence of MRSA, gentamicin resistance and haemolysis activity than the NIRI group. Within the OIRI group, PJI isolates were more frequently strong biofilm formers than isolates from the FFI group. A statistically significant difference was observed between OIRI and NIRI isolates for the sdrE gene, the cna gene, the clfA gene and the bbp gene. Certain spa types (t230 and t041) with a specific genetic virulence pattern were only found in isolates cultured from OIRI. In conclusion, our study highlights significant trends regarding the virulence requirements displayed by S. aureus isolates associated with implant related infections in comparison to non-implant related infections. However, future studies including whole genome sequencing will be required to further examine genomic differences among the different infection cases.
    International journal of medical microbiology: IJMM 04/2014; DOI:10.1016/j.ijmm.2014.03.003 · 4.54 Impact Factor
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    ABSTRACT: Propionibacterium acnes and coagulase-negative staphylococci (CoNS) are opportunistic pathogens implicated in prosthetic joint and fracture fixation device-related infections. The purpose of this study was to determine whether P. acnes and the CoNS species Staphylococcus lugdunensis, isolated from an “aseptically failed” prosthetic hip joint and a united intramedullary nail-fixed tibial fracture, respectively, could cause osteomyelitis in an established implant-related osteomyelitis model in rabbits in the absence of wear debris from the implant material. The histological features of P. acnes infection in the in vivo rabbit model were consistent with localized pyogenic osteomyelitis, and a biofilm was present on all explanted intramedullary (IM) nails. The animals displayed no outward signs of infection, such as swelling, lameness, weight loss, or elevated white blood cell count. In contrast, infection with S. lugdunensis resulted in histological features consistent with both pyogenic osteomyelitis and septic arthritis, and all S. lugdunensis-infected animals displayed weight loss and an elevated white blood cell count despite biofilm detection in only two out of six rabbits. The differences in the histological and bacteriological profiles of the two species in this rabbit model of infection are reflective of their different clinical presentations: low-grade infection in the case of P. acnes and acute infection for S. lugdunensis. These results are especially important in light of the growing recognition of chronic P. acnes biofilm infections in prosthetic joint failure and nonunion of fracture fixations, which may be currently reported as “aseptic” failure.
    Journal of clinical microbiology 03/2014; 52(5):1595-1606. DOI:10.1128/JCM.03197-13 · 4.23 Impact Factor
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    ABSTRACT: Polyetheretherketone (PEEK) films were oxygen plasma treated to increase surface free energy and characterized by X-ray photoelectron microscopy, atomic force microscopy, and water contact angles. A parallel plate flow chamber was used to measure Staphylococcus epidermidis, Staphylococcus aureus, and U-2 OS osteosarcomal cell-line adhesion to the PEEK films in separate monocultures. In addition, bacteria and U-2 OS cells were cocultured to model competition between osteoblasts and contaminating bacteria for the test surfaces. Plasma treatment of the surfaces increased surface oxygen content and decreased the hydrophobicity of the materials, but did not lead to a significant difference in bacterial or U-2 OS cell adhesion in the monocultures. In the S. epidermidis coculture experiments, the U-2 OS cells adhered in greater numbers on the treated surfaces compared to the untreated PEEK and spread to a similar extent. However, in the presence of S. aureus, cell death of the U-2 OS occurred within 10 h on all surfaces. The results of this study suggest that oxygen plasma treatment of PEEK may maintain the ability of osteoblast-like cells to adhere and spread, even in the presence of S. epidermidis contamination, without increasing the risk of preoperative bacterial adhesion. Therefore, oxygen plasma-treated PEEK remains a promising method to improve implant surface free energy for osseointegration. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2014.
    Journal of Biomedical Materials Research Part A 02/2014; 102(12). DOI:10.1002/jbm.a.35130 · 2.83 Impact Factor
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    T F Moriarty, D W Grainger, R G Richards
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    ABSTRACT: Infections related to implanted medical devices have become a significant health care issue in recent decades. Increasing numbers of medical devices are in use, often in an aging population, and these devices are implanted against a background of increasing antibiotic-resistant bacterial populations. Progressively more antibiotic resistant infections, requiring ever more refined treatment options, are therefore predicted to emerge with greater frequency in the coming decades. Improvements in the prevention, diagnosis and treatment of these device-associated infections will remain priority targets both for clinicians and the translational research community charged with addressing these challenges. Preclinical strategies, predictive of ultimate clinical efficacy, should serve as a control point for effective translation of new technologies to clinical applications. The development of new anti-infective medical devices requires a validated preclinical testing protocol; however, reliable validation of experimental and preclinical antimicrobial methodologies currently suffers from a variety of technical limitations. These include the lack of agreement or standardisation of experimental protocols, a general lack of correlation between in vitro and in vivo preclinicalresults and lack of validation between in vivo preclinical implant infection models and clinical (human) results. Device-associated infections pose additional challenges to practicing clinicians concerning diagnosis and treatment, both of which are complicated by the biofilms formed on the medical device. The critical challenges facing both preclinical research and clinical laboratories in improving both diagnosis and treatment of medical device-associated infections are the focus of this review.
    European cells & materials 01/2014; 28:112-28. · 4.89 Impact Factor
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    ABSTRACT: One of the most common pathogen causing musculoskeletal infections remains Staphylococcus aureus. The aim of this multicentre study was to perform a phenotypic and genotypic characterisation of clinical S. aureus isolates recovered from musculoskeletal infections and to investigate differences between isolates cultured from Orthopaedic Implant Related Infections (OIRI) and those from Non-Implant Related Infections (NIRI). OIRI were further differentiated in two groups: Fracture Fixation-device Infections (FFI) and Prosthetic Joint Infections (PJI). Three-hundred and five S. aureus strains were collected from 4 different Swiss and 2 French hospitals (FFI, n = 112; PJI, n = 105; NIRI, n = 88). NIRI cases were composed of 27 Osteomyelitis (OM), 23 Diabetic Foot Infections (DFI), 27 Soft Tissue Infections (STI) and 11 postoperative Spinal Infections (SI). All isolates were tested for their ability to form biofilm, to produce staphyloxanthin and their haemolytic activity. They were typed by agr (accessory gene regulator) group, spa type and screened by PCR for the presence of genes of the most relevant virulence factors such as MSCRAMMs, Panton Valentine Leukotoxin (PVL), enterotoxins, exotoxins and toxic shock syndrome toxin. Overall, methicillin susceptible S. aureus (MSSA) was more prevalent than methicillin resistant S. aureus (MRSA) in this collection. The OIRI group trended towards a higher incidence of MRSA, gentamicin resistance and haemolysis activity than the NIRI group. Within the OIRI group, PJI isolates were more frequently strong biofilm formers than isolates from the FFI group. A statistically significant difference was observed between OIRI and NIRI isolates for the sdrE gene, the cna gene, the clfA gene and the bbp gene. Certain spa types (t230 and t041) with a specific genetic virulence pattern were only found in isolates cultured from OIRI. In conclusion, our study highlights significant trends regarding the virulence requirements displayed by S. aureus isolates associated with implant related infections in comparison to non-implant related infections. However, future studies including whole genome sequencing will be required to further examine genomic differences among the different infection cases.
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    ABSTRACT: Despite extensive use of polyetheretherketone (PEEK) in biomedical applications, information about bacterial adhesion to this biomaterial is limited. This study investigated Staphylococcus aureus and Staphylococcus epidermidis adhesion to injection moulded and machined PEEK OPTIMA(®) using a custom-built adhesion chamber with medical grade titanium and Thermanox for comparison. Additionally, bacterial adhesion to a novel oxygen plasma modified PEEK was also investigated in both a pre-operative model in physiological saline, and additionally in a post-operative model in human blood plasma. In the pre-operative model, the rougher machined PEEK had a significantly greater number of adherent bacteria compared to injection moulded PEEK. Bacterial adhesion to titanium and Thermanox was similar. Oxygen plasma surface modification of PEEK did not lead to a significant change in bacterial adhesion in the pre-operative contamination model, despite observed changes in surface characteristics. In the post-operative contamination model, S. aureus adhesion was increased from 5×10(5)CFUcm(-2) to approximately 1.3×10(7)CFUcm(-2) on the modified surfaces due to differential protein adhesion during the conditioning period. However, S. epidermidis adhesion to modified PEEK was less than to unmodified PEEK in the post-operative model. These results illustrate the importance of testing bacterial adhesion of several strains in both a pre-operative and post-operative, clinically relevant bacterial contamination model.
    Colloids and surfaces B: Biointerfaces 09/2013; 113C:213-222. DOI:10.1016/j.colsurfb.2013.09.012 · 4.28 Impact Factor
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    ABSTRACT: Specific bacteria imaging is highly desirable in clinical diagnostics. Probes enabling rapid and specific diagnostics of bacteria are limited. Current clinical infection diagnostics is time consuming and invasive, relays on microbiological cultures. We investigated the potential of Lysostaphin as a specific probe to label staphylococci in a new labeling protocol. We used azido (N(3)) - modified Lysostaphin-N(3) and DIBO-dye in a two-step bacteria-labeling protocol. N(3) and DIBO (di-benzocyclooctyne) are the counterparts of the "click" chemistry. In the first step, Lysostaphin-N(3) binds specifically to Staphylococcus aureus. In the second step, N(3) clicks to DIBO thus achieving the selective for S. aureus labeling. Such a two-step approach effectively distinguishes S. aureus from Escherichia coli; non-toxic and proved to work in vivo. The two-step labeling protocol is a promising approach for diagnostic imaging of staphylococci in clinical settings.
    Journal of microbiological methods 11/2012; 92(1). DOI:10.1016/j.mimet.2012.11.004 · 2.43 Impact Factor
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    ABSTRACT: Tremendous advances in quality, reliability, performance and versatility of surgical instrumentation and devices have been achieved over the past 50 years using biomaterials. The global orthopedic implant industry is expected to grow to $41.8 billion by 2016, driven primarily by advancements in implant designs, including materials that provide improved biocompatibility, durability, and expanded clinical applications. Biomaterials have evolved through three clinical "generations": 1) "bio-inert materials"; 2) materials with intrinsic bioactivity and degradability; and 3) biomaterials that stimulate specific biological host responses. In all cases, surface modifications, including coatings, represent a key strategy for improvements in tissue-contacting properties. Surfaces continue to be a focus for many device improvements and for tissue interfacing, especially for many orthopedic structural implants comprising metal and metal alloys. Progress in implant materials processing, coating technologies, and coating combinations with therapeutic agents provide new properties and functionalities to improve device-tissue integration and reduce foreign body reactions and infections. Performance criteria for these surface modifications success in clinical practice are daunting, and translation of several technologies from in vitro proof-of-concept to in vivo applications has proven challenging.
    Journal of orthopaedic trauma 08/2012; 26(12). DOI:10.1097/BOT.0b013e31826e37a2 · 1.78 Impact Factor
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    E T J Rochford, R G Richards, T F Moriarty
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    ABSTRACT: Clin Microbiol Infect ABSTRACT: The use of implanted devices in modern orthopaedic surgery has greatly improved the quality of life for an increasing number of patients, by facilitating the rapid and effective healing of bone after traumatic fractures, and restoring mobility after joint replacement. However, the presence of an implanted device results in an increased susceptibility to infection for the patient, owing to the creation of an immunologically compromised zone adjacent to the implant. Within this zone, the ability of the host to clear contaminating bacteria may be compromised, and this can lead to biofilm formation on the surface of the biomaterial. Currently, there are only limited data on the mechanisms behind this increased risk of infection and the role of material choice. The impacts of implant material on bacterial adhesion, immune response and infection susceptibility have been investigated individually in numerous preclinical in vitro and in vivo studies. These data provide an indication that material choice does have an impact on infection susceptibility; however, the clinical implications remain to be clearly determined.
    Clinical Microbiology and Infection 07/2012; DOI:10.1111/j.1469-0691.2012.04002.x · 4.58 Impact Factor
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    PEEK Biomaterials Handbook, 1st edited by Steven M Kurtz, 01/2012: chapter 8: pages 93-109; Elsevier.
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    ABSTRACT: Preclinical modeling of human disease with animals has not been standardized for many common pathologic processes. Assorted animal models are being used to investigate the pathogenesis, prevention, and treatment of disease processes. Certainly it is difficult to interpret the current literature because there are diverse and often irrelevant models being implemented. Some models are used for reasons of size or ease rather than the true modeling of a physiological process. Application to granting agencies and design of animal studies is difficult without standardization of the ideal preclinical model for disease states. The current article addresses the preclinical animal modeling of osteoporosis, infection, bone defects, and cartilage injury. This article is a discussion of the current literature, commonly used models, and suggests preferred preclinical models for future research design.
    Journal of orthopaedic trauma 08/2011; 25(8):488-93. DOI:10.1097/BOT.0b013e3182251421 · 1.78 Impact Factor
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    ABSTRACT: Anaerobic bacteria are increasingly regarded as important in cystic fibrosis (CF) pulmonary infection. The aim of this study was to determine the effect of antibiotic treatment on aerobic and anaerobic microbial community diversity and abundance during exacerbations in patients with CF. Sputum was collected at the start and completion of antibiotic treatment of exacerbations and when clinically stable. Bacteria were quantified and identified following culture, and community composition was also examined using culture-independent methods. Pseudomonas aeruginosa or Burkholderia cepacia complex were detected by culture in 24/26 samples at the start of treatment, 22/26 samples at completion of treatment and 11/13 stable samples. Anaerobic bacteria were detected in all start of treatment and stable samples and in 23/26 completion of treatment samples. Molecular analysis showed greater bacterial diversity within sputum samples than was detected by culture; there was reasonably good agreement between the methods for the presence or absence of aerobic bacteria such as P aeruginosa (κ=0.74) and B cepacia complex (κ=0.92), but agreement was poorer for anaerobes. Both methods showed that the composition of the bacterial community varied between patients but remained relatively stable in most individuals despite treatment. Bacterial abundance decreased transiently following treatment, with this effect more evident for aerobes (median decrease in total viable count 2.3×10(7) cfu/g, p=0.005) than for anaerobes (median decrease in total viable count 3×10(6) cfu/g, p=0.046). Antibiotic treatment targeted against aerobes had a minimal effect on abundance of anaerobes and community composition, with both culture and molecular detection methods required for comprehensive characterisation of the microbial community in the CF lung. Further studies are required to determine the clinical significance of and optimal treatment for these newly identified bacteria.
    Thorax 06/2011; 66(7):579-84. DOI:10.1136/thx.2010.137281 · 8.56 Impact Factor
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    Comprehensive Biomaterials, Edited by P. Ducheyne, 01/2011: chapter 4.407: pages 75–100; Elsevier., ISBN: 978-0-08-055294-1
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    ABSTRACT: Fractures of the tibia and femoral diaphysis are commonly repaired by intramedullary (IM) nails, which are currently composed of either electropolished stainless steel (EPSS) or standard, non-polished titanium-aluminum-niobium (TAN). Once the fracture has fully healed, removal of IM nails is common, but the strong adhesion of bone to standard TAN complicates removal. Polishing the surface of TAN IM nails has been shown to reduce bony adhesion and ease implant removal without compromising fixation. Polished TAN nails are, therefore, expected to have significant clinical benefit in situations where the device is to be removed. The aim of the present study was to determine the effect of polishing TAN IM nails on susceptibility to infection in an animal model. Solid IM nails (Synthes, Betlach, Switzerland) composed of standard TAN were compared with polished equivalents and also to clinically available EPSS nails. The surface chemical and topographical properties of the materials were assessed by X-ray photon spectroscopy (XPS), white light profilometry, and scanning electron microscopy (SEM). An in vivo infection study was performed using a clinical isolate of Staphylococcus aureus that was characterized with respect to various virulence factors. Polishing TAN IM nails caused no significant change to the chemistry of the nails, but the topography of the polished TAN nails was significantly smoother than standard TAN nails. In the infection study, the rank order based on descending infectious dose 50 (ID(50)) was: standard TAN, polished TAN, and finally EPSS. The ID(50) values did not differ greatly between any of the groups. Polishing the surface TAN IM nails was not found to influence the susceptibility to infection in our animal model.
    The International journal of artificial organs 09/2010; 33(9):667-75. · 1.45 Impact Factor
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    T Fintan Moriarty, U Schlegel, S Perren, R Geoff Richards
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    ABSTRACT: Musculoskeletal infection is one of the most common complications associated with surgical fixation of bones fractured during trauma. These infections usually involve bacterial colonisation and biofilm formation on the fracture fixation device itself, as well as infection of the surrounding tissues. Antibiotic prophylaxis, wound debridement and postsurgical care can reduce the incidence of, but do not prevent, these infections. Much research and development has been focussed on ways to further reduce the incidence of infection and in the following short review we describe our experiences investigating the contribution of the basic design of fracture fixation devices on the susceptibility to infection. It has been shown in animal studies that device size, shape, mode of action and material and topography play an interrelated role in the susceptibility to infection. Although direct extrapolation from animal studies to the clinical setting is difficult, close consideration of the design factors that can reduce the incidence of infection in animal models is expected to help minimise the incidence of infection associated with any clinically implemented fracture fixation device.
    Journal of Materials Science Materials in Medicine 10/2009; 21(3):1031-5. DOI:10.1007/s10856-009-3907-x · 2.14 Impact Factor
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    ABSTRACT: Polishing the surface of internal fracture fixation (IFF) implant materials can ease implant removal and reduce irritation to gliding tissues by reducing soft tissue adhesion and bony overgrowth. Thus, polishing the surface of these implants is expected to have significant clinical benefit in certain situations. The aim of the present study was to determine if polishing the surface of an IFF device influences susceptibility to infection. The local infection rate associated with 4-hole 2.0 mm Synthes locking compression plates (LCPs) composed of clinically available commercially pure titanium (cpTi) and titanium aluminium niobium (TAN) in their standard microrough form was compared with that of their test polished equivalents and also to clinically available electropolished stainless steel (EPSS). The LCPs were fixed in locking mode onto the tibia of mature, female New Zealand White rabbits and a clinical strain of Staphylococcus aureus was added to the implantation site. Twenty eight days after surgery the rabbits were euthanized and assessed for infection. The rank order based on descending ID50 was; polished TAN, standard TAN, standard cpTi, EPSS and finally polished cpTi, however, the ID50 values did not differ greatly between the groups with the same material. Using the LCP model in locking mode, polishing the surface of both cpTi and TAN was not found to influence the susceptibility to infection in our animal model.
    The International journal of artificial organs 10/2009; 32(9):663-70. · 1.45 Impact Factor
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    ABSTRACT: Implant-related infections are broadly recognized as one of the most serious and devastating complications associated with the use of biomaterials in medical practice. The growing interest and need for the development of implant materials with reduced susceptibility to microbial colonization and biofilm formation has necessitated the development of a series of in vitro and in vivo models for evaluation and preclinical testing. Current technologies provide these investigations with an ample choice of qualitative and quantitative techniques for an accurate assessment of the bioactivity and anti-infective efficacy of any new compound or device. These tests are typically performed using a reference bacterial strain designated as the test or reference strain. Recent molecular epidemiological studies have identified the complex clonal nature of most prevalent etiological agents implicated in implant-associated infections. New information which is continually emerging on the identity and the characteristics of both sporadic and epidemic clones must be considered when selecting a reference. A new emerging requirement is that the strain should be representative of the clones causing clinically relevant infections; they should, therefore, belong to the most prevalent epidemic clones rather than to sporadic ones, which may occur in only 1 out of 200 infections or even fewer. The correct choice of reference strain for preclinical tests is of crucial importance for the clinical significance of the achieved results. In this paper we report our experience and recommendations regarding this issue.
    The International journal of artificial organs 10/2008; 31(9):841-7. · 1.45 Impact Factor
  • Journal of Cystic Fibrosis 06/2008; 7. DOI:10.1016/S1569-1993(08)60156-3 · 3.82 Impact Factor