1,721,126 research outputs found
Antifungal activity against planktonic and biofilm Candida albicans in an experimental model of foreign-body infection
Objectives: The treatment of Candida implant-associated infections remains challenging. We investigated the antifungal activity against planktonic and biofilm Candida albicans in a foreign-body infection model. Methods: Teflon cages were subcutaneously implanted in guinea pigs, infected with C. albicans (ATCC 90028). Animals were treated intraperitoneally 12 h after infection for 4 days once daily with saline, fluconazole (16 mg/kg), amphotericin B (2.5 mg/kg), caspofungin (2.5 mg/kg) or anidulafungin (20 mg/kg). Planktonic Candida was quantified, the clearance rate and cure rate determined. Results: In untreated animals, planktonic Candida was cleared from cage fluid in 25% (infected with 4.5 × 103 CFU/cage), 8% (infected with 4.8 × 104 CFU/cage) and 0% (infected with 6.2 × 105 CFU/cage). Candida biofilm persisted on all explanted cages. Compared to untreated controls, caspofungin reduced the number of planktonic C. albicans to 0.22 and 0.0 CFU/ml, respectively, and anidulafungin to 0.11 and 0.13 CFU/ml, respectively. Fluconazole cured 2/12 cages (17%), amphotericin B and anidulafungin 1/12 cages (8%) and caspofungin 3/12 cages (25%). Conclusion: Echinocandins showed superior activity against planktonic C. albicans. Caspofungin showed the highest cure rate of C. albicans biofilm. However, no antifungal exceeded 25% cure rate, demonstrating the difficulty of eradicating Candida biofilms from implants
Epidemiology and new developments in the diagnosis of prosthetic joint infection.
Although prosthetic joint infection (PJI) is a rare event after arthroplasty, it represents a significant complication that is associated with high morbidity, need for complex treatment, and substantial healthcare costs. An accurate and rapid diagnosis of PJI is crucial for treatment success. Current
diagnostic methods in PJI are insufficient with 10-30% false-negative cultures. Consequently, there is a need for research and development into new methods aimed at improving diagnostic accuracy and speed of detection.
In this article, we review available conventional diagnostic methods for the diagnosis of PJI (laboratory markers, histopathology, synovial fluid and periprosthetic tissue cultures), new diagnostic methods (sonication of implants, specific and multiplex PCR, mass spectrometry) and innovative techniques under development (new laboratory markers, microcalorimetry, electrical method, reverse transcription [RT]-PCR, fluorescence in situ hybridization [FISH], biofilm microscopy, microarray identification,
and serological tests). The results of highly sensitive diagnostic techniques with unknown specificity should be interpreted with caution. The organism identified by a new method may represent a real pathogen that was unrecognized by conventional diagnostic methods or contamination during specimen sampling, transportation, or processing. For accurate interpretation, additional studies are
needed, which would evaluate the long-term outcome (usually >2 years) with or without antimicrobial treatment. It is expected that new rapid, accurate, and fully automatic diagnostic tests will be developed soon
High activity of fosfomycin and rifampin against methicillin-resistant staphylococcus aureus biofilm in vitro and in an experimental foreign-body infection model
Increasing antimicrobial resistance reduces treatment options for implant-Associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the activity of fosfomycin alone and in combination with vancomycin, daptomycin, rifampin, and tigecycline against MRSA (ATCC 43300) in a foreign-body (implantable cage) infection model. The MICs of the individual agents were as follows: fosfomycin, 1 μg/ml; daptomycin, 0.125 μg/ml; vancomycin, 1 μg/ml; rifampin, 0.04 μg/ ml; and tigecycline, 0.125 μg/ml. Microcalorimetry showed synergistic activity of fosfomycin and rifampin at subinhibitory concentrations against planktonic and biofilm MRSA. In time-kill curves, fosfomycin exhibited time-dependent activity against MRSA with a reduction of 2.5 log10 CFU/ml at 128the MIC. In the animal model, planktonic bacteria in cage fluid were reduced by>1 log10 CFU/ml with fosfomycin and tigecycline, 1.7 log10 with daptomycin, 2.2 log 10 with fosfomycin-tigecycline and fosfomycin-vancomycin, 3.8 log10 with fosfomycin-daptomycin, and>6.0 log10 with daptomycin-rifampin and fosfomycin-rifampin. Daptomycin-rifampin cured 67% of cage-Associated infections and fosfomycin-rifampin cured 83%, whereas all single drugs (fosfomycin, daptomycin, and tigecycline) and rifampin-free fosfomycin combinations showed no cure of MRSA cageassociated infections. No emergence of fosfomycin resistance was observed in animals; however, a 4-fold increase in fosfomycin MIC (from 2 to 16 μg/ml) occurred in the fosfomycin-vancomycin group. In summary, the highest eradication of MRSA cageassociated infections was achieved with fosfomycin in combination with rifampin (83%). Fosfomycin may be used in combination with rifampin against MRSA implant-Associated infections, but it cannot replace rifampin as an antibiofilm agent
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Failure of the surgical treatment in 115 infected hip arthroplasties-analysis of a 12-year prosthetic joint cohort study (1999-2010)
Background:¦Infection after total or partial hip arthroplasty (HA) leads to significant long-term morbidity and high healthcare cost. We evaluated reasons for treatment failure of different surgical modalities in a 12-year prosthetic hip joint infection cohort study.¦Method:¦All patients hospitalized at our institution with infected HA were included either retrospectively (1999-‐2007) or prospectively¦(2008-‐2010). HA infection was defined as growth of the same microorganism in ≥2 tissues or synovialfluid culture, visible purulence, sinus tract or acute inflammation on tissue histopathology. Outcome analysis was performed at outpatient visits, followed by contacting patients, their relatives and/or treating physicians afterwards.¦Results:¦During the study period, 117 patients with infected HA were identified. We excluded 2 patients due to missing data. The average age was 69 years (range, 33-‐102 years); 42% were female. HA was mainly performed for osteoarthritis (n=84), followed by trauma (n=22), necrosis (n=4), dysplasia(n=2), rheumatoid arthritis (n=1), osteosarcoma (n=1) and tuberculosis (n=1). 28 infections occurred early(≤3 months), 25 delayed (3-‐24 months) and 63 late (≥24 months after surgery). Infected HA were¦treated with (i) two-‐stage exchange in 59 patients (51%, cure rate: 93%), (ii) one-‐stage exchange in 5 (4.3%, cure rate: 100%), (iii) debridement with change of mobile parts in 18 (17%, cure rate: 83%), (iv) debridement without change of mobile¦parts in 17 (14%, cure rate : 53% ), (v) Girdlestone in 13 (11%, cure rate: 100%), and (vi) two-‐stage exchange followed by¦removal in 3 (2.6%). Patients were followed for an average of 3.9 years (range, 0.1 to 9 years), 7 patients died unrelated to the infected HA. 15 patients (13%) needed additional operations, 1 for mechanical reasons(dislocation of spacer) and 14 for persistent infection: 11 treated with debridement and retention (8 without change; and 3 with change of mobile parts) and 3 with two-‐stage exchange. The average number of surgery was 2.2 (range, 1 to 5). The infection was finally eradicated in all patients, but the functional outcome remained unsatisfactory in 20% (persistent pain or impaired mobility due to spacer or Girdlestone situation).¦Conclusions:¦Non-‐respect of current treatment concept leads to treatment failure with subsequent operations. Precise analysis of each treatment failure can be used for improving the treatment algorithm leading to better results
Activité d'un ciment chargé avec daptomycine seule et/ou combiné avec gentamicin ou PEG600 contre le biofilm de staphylococcus epidermidis
Les ciments osseux chargés d'antibiotiques sont utilisés en orthopédie à titre prophylactique dans le cimentage de prothèses et à titre thérapeutique dans le traitement des infections de prothèses et des infections osseuses. L'avantage de l'utilisation d'antibiotiques localement est sa haute concentration au site infectieux avec peu de toxicité générale qu'on trouve lors d'une utilisation systémique. Pas tous les antibiotiques peuvent être ajoutés au ciment. L'antibiotique choisit ne doit pas modifier les propriétés mechaniques du ciment et en même temps l'antibiotique doit être hydophil pour une bonne élution et thermostable. Cette condition limite le nombre d'antibiotiques disponibles sur le marché. Les germes les plus fréquemment responsables d'infection de prothèses sont le Staphylococcus epidermidis et Staphylococcus aureus. L'apparition de souches résistantes aux antibiotiques classiquement utilisés comme la gentamicine ou l'augmentation de la prévalence de S. aureus ou S. epidermidis methicillin résistant et vancomycine résistant (MRSA, VRSA/MRSE, VRSE) nous amènent à tester de nouveaux antibiotiques dans le ciment. Nous avons proposé l'utilisation de la daptomycine comme alternative car il s'agit d'une molécule efficace, in vitro, contre les germes Gram positifs comme MRSA/E, VRSA/E, Streptococcus pneumonia résistent à la pénicilline et contre les enterococci résistants à l'ampicilline et à la vancomycine. Cette lipopeptide, d'activité dépendant de sa concentration dans le site d'infection (concentration-dependent killing), remplie toutes les conditions nécessaires pour être utilisée en combinaison avec du ciment.
Pour notre expérience, nous avons utilisés de cylindres de ciment sans antibiotique, avec daptomycine seule, daptomycine en combinaison avec gentamicine ou PEG600 (polyéthylène glycol utilisé, dans notre cas, pour augmenter l'élution des antibiotiques du ciment), vancomycine et gentamicine qu'ont été incubés avec du S. epidermidis RP62A. Nous avons mesuré, par microcalorimétrie, l'émission de chaleur produite par le "biofilm" du Staphylococcus epidermidis sur les cylindres de ciment.
Le résultat de notre étude montre que la vancomycine est supérieure à la daptomycine et gentamicine utilisées seules, en inhibant l'adhérence du S. epidermidis in vitro. Mais, nous avons constaté que la daptomycine utilisée avec la gentamicine ou PEG600 inhibe complètement la formation du biofilm par le S. epidermidis.
Nous avons conclu que l'utilisation de cette dernière combinaison dans le ciment peut représenter une stratégie efficace pour le traitement local des infections à staplylococci multirésistants
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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