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1.
Eur Cell Mater ; 42: 264-280, 2021 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-34622431

RESUMEN

Osteomyelitis associated with periprosthetic joint infection (PJI) signals a chronic infection and the need for revision surgery. An osteomyelitic bone exhibits distinct morphological features, including evidence for osteolysis and an accelerated bone remodelling into poorly organised, poor-quality bone. In addition to immune cells, various bone cell-types have been implicated in the pathology. The present study sought to determine the types of bone-cell activities in human PJI bones. Acetabular biopsies from peri-implant bone from patients undergoing revision total hip replacement (THR) for chronic PJI (with several identified pathogens) as well as control bone from the same patients and from patients undergoing primary THR were analysed. Histological analysis confirmed that PJI bone presented increased osteoclastic activity compared to control bone. Analysis of osteocyte parameters showed no differences in osteocyte lacunar area between the acetabular bone taken from PJI patients or primary THR controls. Analysis of bone matrix composition using Masson's trichrome staining and second-harmonic generation microscopy revealed widespread lack of mature collagen, commonly surrounding osteocytes, in PJI bone. Increased expression of known collagenases, such as matrix metallopeptidase (MMP) 13, MMP1 and cathepsin K (CTSK), was measured in infected bone compared to non-infected bone. Human bone and cultured osteocyte-like cells experimentally exposed to Staphylococcus aureus exhibited strongly upregulated expression of MMP1, MMP3 and MMP13 compared to non-exposed controls. In conclusion, the study identified previously unrecognised bone-matrix changes in PJI caused by multiple organisms deriving from osteocytes. Histological examination of bone collagen composition may provide a useful adjunct diagnostic measure of PJI.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Osteólisis , Infecciones Relacionadas con Prótesis , Artroplastia de Reemplazo de Cadera/efectos adversos , Matriz Ósea , Humanos , Osteocitos , Infección Persistente
2.
Public Health ; 195: 142-144, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34111803

RESUMEN

OBJECTIVES: This study examined the prevalence and factors associated with paid sick leave benefits among direct service providers who work with people experiencing homelessness. STUDY DESIGN: Cross-sectional study using an online survey disseminated during the second wave of the COVID-19 pandemic in Canada. METHODS: Survey data from 572 direct service providers working in the homeless, supportive housing, and harm reduction service sectors were analyzed for this study. Univariate and multivariate logistic regression models were used to examine predictors of paid sick leave benefits. RESULTS: One hundred one (17.7%) participants did not have any paid sick leave benefits. In the univariate models, paid sick leave was associated with older age, greater family income, full-time work, specific employment settings (supportive housing and not emergency shelters or harm reduction programs), having a regular medical doctor, and fewer occupational impacts of the COVID-19 pandemic. Older age, full-time work, and non-receipt of emergency financial benefits remained statistically significant predictors in the multivariate model. CONCLUSIONS: Although the majority of service providers working with people experiencing homelessness have some amount of paid sick leave benefits, there is a precariously employed subset of individuals who are younger and working part-time in the sector. Temporary expansion of paid sick leave and removal of waiting periods for new employees to qualify for benefits are recommended.


Asunto(s)
COVID-19 , Servicio de Urgencia en Hospital/estadística & datos numéricos , Empleo/estadística & datos numéricos , Personas con Mala Vivienda , Pandemias , Ausencia por Enfermedad/estadística & datos numéricos , Adulto , Factores de Edad , Anciano , COVID-19/epidemiología , Canadá , Estudios Transversales , Femenino , Reducción del Daño , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , SARS-CoV-2 , Salarios y Beneficios , Ausencia por Enfermedad/economía
3.
BMC Infect Dis ; 20(1): 755, 2020 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-33054720

RESUMEN

BACKGROUND: Saksenaea species (spp.) are uncommon causes of mucormycosis but are emerging pathogens mostly associated with trauma and soil contamination often in immunocompetent hosts. Due to lack of sporulation in the laboratory, diagnosis and susceptibility testing is difficult so optimal treatment regimens are unknown. CASE PRESENTATION: A 67 year-old man from the Northern Territory in Australia, with a history of eosinophilic granulomatosis with polyangiitis, developed disseminated Saksenaea infection after initially presenting with symptoms consistent with bacterial pyelonephritis. Despite a delay in diagnosis; with aggressive surgical management and dual therapy with amphotericin B and posaconazole, he survived. CONCLUSIONS: We describe an unusual case of disseminated infection with a favourable outcome to date.


Asunto(s)
Mucormicosis/diagnóstico , Mucormicosis/etiología , Anciano , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Granulomatosis con Poliangitis/etiología , Humanos , Huésped Inmunocomprometido , Masculino , Mucormicosis/tratamiento farmacológico , Mucormicosis/cirugía , Northern Territory , Triazoles/uso terapéutico
4.
Artículo en Inglés | MEDLINE | ID: mdl-30323038

RESUMEN

Although the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole, and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method/agent-dependent) 11,171 Candida albicans, 215 C. dubliniensis, 4,418 C. glabrata species complex, 157 C.guilliermondii (Meyerozyma guilliermondii), 676 C. krusei (Pichia kudriavzevii), 298 C.lusitaniae (Clavispora lusitaniae), 911 C.parapsilosissensu stricto, 3,691 C.parapsilosis species complex, 36 C.metapsilosis, 110 C.orthopsilosis, 1,854 C.tropicalis, 244 Saccharomyces cerevisiae, 1,409 Aspergillus fumigatus, 389 A.flavus, 130 A.nidulans, 233 A.niger, and 302 A.terreus complex isolates. SYO/Etest MICs for 282 confirmed non-wild-type (non-WT) isolates were included: ERG11 (C. albicans), ERG11 and MRR1 (C. parapsilosis), cyp51A (A. fumigatus), and CDR2 and CDR1 overexpression (C. albicans and C. glabrata, respectively). Interlaboratory modal agreement was superior by SYO for yeast species and by the Etest for Aspergillus spp. Distributions fulfilling CLSI criteria for epidemiological cutoff value (ECV) definition were pooled, and we proposed SYO ECVs for S. cerevisiae and 9 yeast and 3 Aspergillus species and Etest ECVs for 5 yeast and 4 Aspergillus species. The posaconazole SYO ECV of 0.06 µg/ml for C. albicans and the Etest itraconazole ECV of 2 µg/ml for A. fumigatus were the best predictors of non-WT isolates. These findings support the need for method-dependent ECVs, as, overall, the SYO appears to perform better for susceptibility testing of yeast species and the Etest appears to perform better for susceptibility testing of Aspergillus spp. Further evaluations should be conducted with more Candida mutants.


Asunto(s)
Antifúngicos/farmacología , Aspergillus/efectos de los fármacos , Candida/efectos de los fármacos , Triazoles/farmacología , Aspergilosis/tratamiento farmacológico , Aspergilosis/epidemiología , Aspergilosis/microbiología , Aspergillus/clasificación , Aspergillus/aislamiento & purificación , Candida/clasificación , Candida/aislamiento & purificación , Candidiasis/tratamiento farmacológico , Candidiasis/epidemiología , Candidiasis/microbiología , Pruebas Antimicrobianas de Difusión por Disco , Farmacorresistencia Fúngica , Fluconazol/farmacología , Humanos , Huésped Inmunocomprometido , Itraconazol/farmacología , Voriconazol/farmacología
5.
BMC Infect Dis ; 19(1): 445, 2019 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-31113382

RESUMEN

BACKGROUND: Candidaemia is associated with high mortality. Variables associated with mortality have been published previously, but not developed into a risk predictive model for mortality. We sought to describe the current epidemiology of candidaemia in Australia, analyse predictors of 30-day all-cause mortality, and develop and validate a mortality risk predictive model. METHODS: Adults with candidaemia were studied prospectively over 12 months at eight institutions. Clinical and laboratory variables at time of blood culture-positivity were subject to multivariate analysis for association with 30-day all-cause mortality. A predictive score for mortality was examined by area under receiver operator characteristic curves and a historical data set was used for validation. RESULTS: The median age of 133 patients with candidaemia was 62 years; 76 (57%) were male and 57 (43%) were female. Co-morbidities included underlying haematologic malignancy (n = 20; 15%), and solid organ malignancy in (n = 25; 19%); 55 (41%) were in an intensive care unit (ICU). Non-albicans Candida spp. accounted for 61% of cases (81/133). All-cause 30-day mortality was 31%. A gastrointestinal or unknown source was associated with higher overall mortality than an intravascular or urologic source (p < 0.01). A risk predictive score based on age > 65 years, ICU admission, chronic organ dysfunction, preceding surgery within 30 days, haematological malignancy, source of candidaemia and antibiotic therapy for ≥10 days stratified patients into < 20% or ≥ 20% predicted mortality. The model retained accuracy when validated against a historical dataset (n = 741). CONCLUSIONS: Mortality in patients with candidaemia remains high. A simple mortality risk predictive score stratifying patients with candidaemia into < 20% and ≥ 20% 30-day mortality is presented. This model uses information available at time of candidaemia diagnosis is easy to incorporate into decision support systems. Further validation of this model is warranted.


Asunto(s)
Candidemia/mortalidad , Anciano , Antifúngicos/uso terapéutico , Australia/epidemiología , Candida/clasificación , Candida/genética , Candida/aislamiento & purificación , Candidemia/tratamiento farmacológico , Candidemia/epidemiología , Candidemia/microbiología , Femenino , Neoplasias Hematológicas/complicaciones , Hospitalización/estadística & datos numéricos , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Factores de Riesgo
6.
Public Health ; 176: 163-171, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30143269

RESUMEN

OBJECTIVE: This study was designed to address the need for more detailed information about Indigenous homeless youth, a group overrepresented in the homeless population, using a national-level data set. STUDY DESIGN: The study used a cross-sectional, self-report survey design. METHODS: Surveys were used to gather demographic, mental health, and quality of life data from a sample of 1103 Canadian youth accessing homeless services with data collected in 2015. This article focused on the 332 Indigenous respondents, using both comparisons with non-Indigenous youth and within-group comparisons across key domains. RESULTS: These findings suggested greater mental health and addiction challenges among Indigenous homeless youth compared with non-Indigenous respondents as well as evidence of a more problematic role of child protection. Within-group comparisons suggested that female and sexual and gender minority youth are particularly at risk among Indigenous youth with some added child protection and justice implications for reserve-raised youth. Child protection history and street-victimization were particularly relevant to the current distress levels. CONCLUSION: Overall, such findings reinforce calls for Indigenous-specific interventions for these populations-including policy-driven prevention initiatives to address the legacy of colonization.


Asunto(s)
Jóvenes sin Hogar/etnología , Grupos de Población/estadística & datos numéricos , Adolescente , Adulto , Canadá , Niño , Estudios Transversales , Femenino , Jóvenes sin Hogar/estadística & datos numéricos , Humanos , Masculino , Encuestas y Cuestionarios , Adulto Joven
7.
Artículo en Inglés | MEDLINE | ID: mdl-29437624

RESUMEN

Estimating epidemiological cutoff endpoints (ECVs/ECOFFS) may be hindered by the overlap of MICs for mutant and nonmutant strains (strains harboring or not harboring mutations, respectively). Posaconazole MIC distributions for the Aspergillus fumigatus species complex were collected from 26 laboratories (in Australia, Canada, Europe, India, South and North America, and Taiwan) and published studies. Distributions that fulfilled CLSI criteria were pooled and ECVs were estimated. The sensitivity of three ECV analytical techniques (the ECOFFinder, normalized resistance interpretation [NRI], derivatization methods) to the inclusion of MICs for mutants was examined for three susceptibility testing methods (the CLSI, EUCAST, and Etest methods). The totals of posaconazole MICs for nonmutant isolates (isolates with no known cyp51A mutations) and mutant A. fumigatus isolates were as follows: by the CLSI method, 2,223 and 274, respectively; by the EUCAST method, 556 and 52, respectively; and by Etest, 1,365 and 29, respectively. MICs for 381 isolates with unknown mutational status were also evaluated with the Sensititre YeastOne system (SYO). We observed an overlap in posaconazole MICs among nonmutants and cyp51A mutants. At the commonly chosen percentage of the modeled wild-type population (97.5%), almost all ECVs remained the same when the MICs for nonmutant and mutant distributions were merged: ECOFFinder ECVs, 0.5 µg/ml for the CLSI method and 0.25 µg/ml for the EUCAST method and Etest; NRI ECVs, 0.5 µg/ml for all three methods. However, the ECOFFinder ECV for 95% of the nonmutant population by the CLSI method was 0.25 µg/ml. The tentative ECOFFinder ECV with SYO was 0.06 µg/ml (data from 3/8 laboratories). Derivatization ECVs with or without mutant inclusion were either 0.25 µg/ml (CLSI, EUCAST, Etest) or 0.06 µg/ml (SYO). It appears that ECV analytical techniques may not be vulnerable to overlap between presumptive wild-type isolates and cyp51A mutants when up to 11.6% of the estimated wild-type population includes mutants.


Asunto(s)
Antifúngicos/farmacología , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/genética , Mutación/genética , Triazoles/farmacología , Farmacorresistencia Fúngica/genética , Pruebas de Sensibilidad Microbiana , Voriconazol/farmacología
8.
Epidemiol Infect ; 146(4): 409-422, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29415790

RESUMEN

In this retrospective study, we describe and analyse Salmonella data from four livestock species in Great Britain between 1983 and 2014, focusing on Salmonella Typhimurium. A total of 96 044 Salmonella isolates were obtained during the study period. S. Typhimurium was the predominant serovar isolated from cattle and pigs and represented 40.7% (18 455/45 336) and 58.3% (4495/7709) of isolates from these species respectively, while it only accounted for 6.7% (2114/31 492) of chicken isolates and 8.1% (926/11 507) of turkey isolates. Over the study period, DT104 was the most common phage type in all four species; however, DT104 peaked in occurrence between 1995 and 1999, but is currently rare. Monophasic strains of S. Typhimurium represented less than 3% of all Salmonella isolates in cattle and chickens in 2014, but accounted for 10.4% of all turkey isolates and 39.0% of all pig isolates in the same year. Salmonella isolates were tested for their in vitro susceptibility to 16 antimicrobials. Antimicrobial resistance of S. Typhimurium isolates is largely influenced by the dominance of specific phage types at a certain time, which are commonly associated with particular resistance patterns. Changes in resistance patterns over time were analysed and compared between species.


Asunto(s)
Antibacterianos/farmacología , Ganado/microbiología , Salmonelosis Animal/tratamiento farmacológico , Salmonelosis Animal/epidemiología , Salmonelosis Animal/microbiología , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/aislamiento & purificación , Animales , Tipificación de Bacteriófagos , Bovinos/microbiología , Pollos/microbiología , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Estudios Retrospectivos , Serotipificación , Porcinos/microbiología , Pavos/microbiología , Reino Unido/epidemiología
9.
Artículo en Inglés | MEDLINE | ID: mdl-28739796

RESUMEN

Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrixschenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 µg/ml; itraconazole, 2 and 2 µg/ml; posaconazole, 2 and 2 µg/ml; and voriconazole, 64 and 32 µg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 µg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii, as well as ECVs for S. globosa and S. mexicana These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.


Asunto(s)
Anfotericina B/farmacología , Antifúngicos/farmacología , Equinocandinas/farmacología , Flucitosina/farmacología , Lipopéptidos/farmacología , Naftalenos/farmacología , Sporothrix/efectos de los fármacos , Esporotricosis/tratamiento farmacológico , Triazoles/farmacología , Caspofungina , Humanos , Pruebas de Sensibilidad Microbiana , Sporothrix/clasificación , Sporothrix/aislamiento & purificación , Terbinafina
10.
BMC Health Serv Res ; 17(1): 234, 2017 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-28340614

RESUMEN

BACKGROUND: Family-focused practice (FFP) is an effective approach to supporting individuals with mental illness. 'Recovery' is also central to contemporary mental health care. However, there is a dearth of evidence about how the two concepts are related and subsequently implemented in practice. The aim of this study was to explore practitioners' understandings and practices of FFP within a recovery framework. METHODS: Purposive/snowball sampling was used to recruit and conduct qualitative interviews with 11 mental health practitioners in rural Australia. Concurrent sampling and data collection were informed by thematic analysis and continued until data saturation was reached. RESULTS: Participants found it difficult to articulate their understandings of FFP within a recovery framework. Nonetheless they were able to describe practices that embodied family-focused recovery. Barriers to such practices included medical models of care, where there are often a shortage of skilled staff and high demands for care. Stigma (self and from others) and confidentiality were also identified as barriers to involving family members in recovery focused care. CONCLUSIONS: Family-focused recovery care is a priority in many high-income countries. A family-focused recovery framework is needed to assist service planners, practitioners, family members and those with mental health needs and ensure such care is embedded within practice guidelines.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Trastornos Mentales/rehabilitación , Adulto , Actitud del Personal de Salud , Salud de la Familia , Medicina Familiar y Comunitaria , Femenino , Accesibilidad a los Servicios de Salud , Humanos , Masculino , Persona de Mediana Edad , Nueva Gales del Sur , Investigación Cualitativa , Salud Rural , Estigma Social , Apoyo Social , Victoria , Adulto Joven
11.
Antimicrob Agents Chemother ; 60(2): 1079-84, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26643334

RESUMEN

The CLSI epidemiological cutoff values (ECVs) of antifungal agents are available for various Candida spp., Aspergillus spp., and the Mucorales. However, those categorical endpoints have not been established for Fusarium spp., mostly due to the difficulties associated with collecting sufficient CLSI MICs for clinical isolates identified according to the currently recommended molecular DNA-PCR-based identification methodologies. CLSI MIC distributions were established for 53 Fusarium dimerum species complex (SC), 10 F. fujikuroi, 82 F. proliferatum, 20 F. incarnatum-F. equiseti SC, 226 F. oxysporum SC, 608 F. solani SC, and 151 F. verticillioides isolates originating in 17 laboratories (in Argentina, Australia, Brazil, Canada, Europe, Mexico, and the United States). According to the CLSI guidelines for ECV setting, ECVs encompassing ≥97.5% of pooled statistically modeled MIC distributions were as follows: for amphotericin B, 4 µg/ml (F. verticillioides) and 8 µg/ml (F. oxysporum SC and F. solani SC); for posaconazole, 2 µg/ml (F. verticillioides), 8 µg/ml (F. oxysporum SC), and 32 µg/ml (F. solani SC); for voriconazole, 4 µg/ml (F. verticillioides), 16 µg/ml (F. oxysporum SC), and 32 µg/ml (F. solani SC); and for itraconazole, 32 µg/ml (F. oxysporum SC and F. solani SC). Insufficient data precluded ECV definition for the other species. Although these ECVs could aid in detecting non-wild-type isolates with reduced susceptibility to the agents evaluated, the relationship between molecular mechanisms of resistance (gene mutations) and MICs still needs to be investigated for Fusarium spp.


Asunto(s)
Antifúngicos/farmacología , Fusarium/efectos de los fármacos , Pruebas de Sensibilidad Microbiana/métodos , Américas , Farmacorresistencia Fúngica Múltiple , Europa (Continente) , Fusarium/genética , Fusarium/aislamiento & purificación , Humanos , Reacción en Cadena de la Polimerasa/métodos
12.
Emerg Infect Dis ; 21(6): 1041-4, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25988348

RESUMEN

To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.


Asunto(s)
Antifúngicos/farmacología , Aspergilosis/epidemiología , Aspergilosis/microbiología , Aspergillus fumigatus/efectos de los fármacos , Azoles/farmacología , Farmacorresistencia Fúngica , Vigilancia de la Población , Aspergillus fumigatus/genética , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Prevalencia , Estudios Prospectivos
13.
Antimicrob Agents Chemother ; 59(3): 1745-50, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25583714

RESUMEN

Clinical breakpoints (CBPs) have not been established for the Mucorales and any antifungal agent. In lieu of CBPs, epidemiologic cutoff values (ECVs) are proposed for amphotericin B, posaconazole, and itraconazole and four Mucorales species. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) were defined with available pooled CLSI MICs from 14 laboratories (Argentina, Australia, Canada, Europe, India, Mexico, and the United States) as follows: 10 Apophysomyces variabilis, 32 Cunninghamella bertholletiae, 136 Lichtheimia corymbifera, 10 Mucor indicus, 123 M. circinelloides, 19 M. ramosissimus, 349 Rhizopus arrhizus, 146 R. microsporus, 33 Rhizomucor pusillus, and 36 Syncephalastrum racemosum isolates. CLSI broth microdilution MICs were aggregated for the analyses. ECVs comprising ≥95% and ≥97.5% of the modeled populations were as follows: amphotericin B ECVs for L. corymbifera were 1 and 2 µg/ml, those for M. circinelloides were 1 and 2 µg/ml, those for R. arrhizus were 2 and 4 µg/ml, and those for R. microsporus were 2 and 2 µg/ml, respectively; posaconazole ECVs for L. corymbifera were 1 and 2, those for M. circinelloides were 4 and 4, those for R. arrhizus were 1 and 2, and those for R. microsporus were 1 and 2, respectively; both itraconazole ECVs for R. arrhizus were 2 µg/ml. ECVs may aid in detecting emerging resistance or isolates with reduced susceptibility (non-WT MICs) to the agents evaluated.


Asunto(s)
Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Farmacorresistencia Fúngica Múltiple/efectos de los fármacos , Itraconazol/uso terapéutico , Mucorales/efectos de los fármacos , Mucormicosis/tratamiento farmacológico , Triazoles/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana
14.
Antimicrob Agents Chemother ; 59(11): 6725-32, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26282428

RESUMEN

Neither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established for Candida spp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable. Candida species wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007 Candida albicans, 186 C. dubliniensis, 3,188 C. glabrata complex, 119 C. guilliermondii, 493 C. krusei, 205 C. lusitaniae, 3,136 C. parapsilosis complex, and 1,016 C. tropicalis isolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing ≥97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 µg/ml for C. albicans, 0.12, 0.25, and 0.03 µg/ml for C. glabrata complex, 4, 2, and 4 µg/ml for C. parapsilosis complex, 0.5, 0.25, and 0.06 µg/ml for C. tropicalis, 0.25, 1, and 0.25 µg/ml for C. krusei, 0.25, 1, and 0.12 µg/ml for C. lusitaniae, 4, 2, and 2 µg/ml for C. guilliermondii, and 0.25, 0.25, and 0.12 µg/ml for C. dubliniensis. Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81 Candida isolates with identified fks mutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities of Candida spp. to caspofungin by reference methodologies is not recommended.


Asunto(s)
Antifúngicos/farmacología , Candida/efectos de los fármacos , Equinocandinas/farmacología , Lipopéptidos/farmacología , Anidulafungina , Candida/genética , Caspofungina , Micafungina , Pruebas de Sensibilidad Microbiana , Mutación/genética
15.
Transpl Infect Dis ; 16(3): 490-5, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24797402

RESUMEN

Prototheca species are achlorophyllus algae. Prototheca wickerhamii and Prototheca zopfii cause human disease. In immunocompetent individuals, they cause soft tissue infections and olecranon bursitis, but in transplant recipients, these organisms can cause disseminated disease. We report a fatal case of disseminated P. zopfii infection in an hematopoietic stem cell transplant (HSCT) recipient with bloodstream infection and involvement of multiple soft tissue sites. We review all previous cases of protothecosis in HSCT reported in the literature. Protothecosis is uncommon after HSCT, but has a disseminated presentation that is frequently fatal. It is commonly misidentified as a yeast. Tumor necrosis factor-alpha inhibitors and contamination of central venous catheters may contribute to development of protothecosis. Optimal treatment approaches are yet to be defined. New agents such as miltefosine may be possible future therapies.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones/etiología , Prototheca/clasificación , Resultado Fatal , Humanos
16.
Med Sci Law ; 54(3): 167-73, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24003083

RESUMEN

A recent English study demonstrated high rates of kitchen knife use in homicides by mentally disordered offenders subject to independent inquiries. Everyone accused of homicide in Scotland undergoes psychiatric examination; all such evaluations in a Scottish region between 2006 and 2011 were systematically analysed to identify homicide characteristics. It was hypothesised that kitchen knives would be the commonest sharp instruments used, and would be associated with unplanned domestic homicide against known victims, with no independent association with mental disorder. Kitchen knives were used in 32 of 55 homicides: 94% of 34 sharp object homicides (p < 0.05). No independent association was found between kitchen knife use and planning, location, relationship, intoxication or mental disorder. Kitchen knife use in homicide appears to be a significant public health issue, and not only in the mentally disordered population. Research is recommended into kitchen knife use in non-fatal violence, and weapon control in populations at increased risk of knife violence.


Asunto(s)
Utensilios de Comida y Culinaria/estadística & datos numéricos , Homicidio/estadística & datos numéricos , Heridas Punzantes/mortalidad , Adolescente , Adulto , Distribución por Edad , Anciano , Niño , Preescolar , Víctimas de Crimen/estadística & datos numéricos , Criminales/estadística & datos numéricos , Femenino , Humanos , Masculino , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Escocia/epidemiología , Distribución por Sexo , Adulto Joven
17.
ESMO Open ; 9(7): 103622, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39002179

RESUMEN

BACKGROUND: PLAnning Treatment For Oesophago-gastric Cancer: a Randomised Maintenance Therapy Trial (PLATFORM) is an adaptive phase II study assessing the role of maintenance therapies in advanced oesophago-gastric (OG) adenocarcinoma. We evaluated the role of the anti-programmed death-ligand 1 (PD-L1) inhibitor durvalumab in these patients. PATIENTS AND METHODS: Patients with human epidermal growth factor receptor 2-negative locally advanced or metastatic OG adenocarcinoma with disease control or response to 18 weeks of platinum-based first-line chemotherapy were randomised to active surveillance or maintenance durvalumab. The primary endpoint was progression-free survival (PFS). Safety was assessed in all patients who had commenced surveillance visits or received at least one dose of durvalumab. Exploratory survival analyses according to PD-L1 Combined Positive Score (CPS) and immune (biomarker-positive) or angiogenesis dominant (biomarker-negative) tumour microenvironment (TME) phenotypes were conducted. RESULTS: Between March 2015 and April 2020, 205 patients were randomised to surveillance (n = 100) and durvalumab (n = 105). No significant differences were seen in PFS [hazard ratio (HR) 0.84, P = 0.13] and overall survival (OS; HR 0.98, P = 0.45) between surveillance and durvalumab. Five patients randomised to durvalumab demonstrated incremental radiological responses compared with none with surveillance. Treatment-related adverse events occurred in 77 (76.2%) durvalumab-assigned patients. A favourable effect in OS with durvalumab over surveillance in CPS ≥5 and immune biomarker-positive patients was observed compared with CPS <5 and biomarker-negative subgroups, respectively: CPS ≥5 versus <5: HR 0.63, 95% confidence interval (CI) 0.32-1.22 versus HR 0.93, 95% CI 0.44-1.96; biomarker-positive versus negative: HR 0.60, 95% CI 0.29-1.23 versus HR 0.84, 95% CI 0.42-1.65. CONCLUSION: Maintenance durvalumab does not improve PFS in patients with OG adenocarcinoma who respond to first-line chemotherapy but induced incremental radiological responses in a subset of patients. TME characterisation could refine patient selection for anti-PD-L1 therapy above PD-L1 CPS alone.


Asunto(s)
Adenocarcinoma , Anticuerpos Monoclonales , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Gástricas/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/farmacología , Adenocarcinoma/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Adulto , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Receptor ErbB-2/metabolismo , Anciano de 80 o más Años , Supervivencia sin Progresión
18.
J Fish Dis ; 36(4): 411-8, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23134104

RESUMEN

Francisella noatunensis subsp. orientalis (Fno) (syn. F. asiatica) is an emergent Gram-negative facultative intracellular bacterium. Although it is considered one of the most pathogenic bacteria in fish, there are no commercially available treatments or vaccines. The objective of this project was to determine the most efficacious concentration of florfenicol (FFC) [10, 15 or 20 mg FFC kg(-1) body weight (bw) per days for 10 days] administered in feed to control experimentally induced infections of Fno in Nile tilapia, Oreochromis niloticus (L.), reared in a recirculating aquaculture system. The cumulative mortality of fish that received 0, 10, 15 or 20 mg FFC kg(-1)  bw per day was 60, 37, 14 and 16%, respectively. Francisella noatunensis subsp. orientalis genome equivalents were detected in water from all challenged groups with slight reduction in the concentration in the florfenicol-treated groups 4 days after treatment. The mean LOG of CFU Fno mg(-1) spleen was 3-5 and was present in all challenged groups at necropsy 11 days after treatment (21 days after challenge). Results show that florfenicol administered at doses of 15 and 20 mg FFC kg(-1)  bw per days for 10 days significantly reduced mortality associated with francisellosis in Nile tilapia.


Asunto(s)
Antibacterianos/uso terapéutico , Cíclidos , Enfermedades de los Peces/tratamiento farmacológico , Francisella/clasificación , Infecciones por Bacterias Gramnegativas/veterinaria , Tianfenicol/análogos & derivados , Alimentación Animal , Animales , Esquema de Medicación , Ingestión de Alimentos , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/mortalidad , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Tianfenicol/uso terapéutico
19.
Antimicrob Agents Chemother ; 56(6): 3107-13, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22391546

RESUMEN

Clinical breakpoints (CBPs) are not available for the Cryptococcus neoformans-Cryptococcus gattii species complex. MIC distributions were constructed for the wild type (WT) to establish epidemiologic cutoff values (ECVs) for C. neoformans and C. gattii versus amphotericin B and flucytosine. A total of 3,590 amphotericin B and 3,045 flucytosine CLSI MICs for C. neoformans (including 1,002 VNI isolates and 8 to 39 VNII, VNIII, and VNIV isolates) and 985 and 853 MICs for C. gattii, respectively (including 42 to 259 VGI, VGII, VGIII, and VGIV isolates), were gathered in 9 to 16 (amphotericin B) and 8 to 13 (flucytosine) laboratories (Europe, United States, Australia, Brazil, Canada, India, and South Africa) and aggregated for the analyses. Additionally, 442 amphotericin B and 313 flucytosine MICs measured by using CLSI-YNB medium instead of CLSI-RPMI medium and 237 Etest amphotericin B MICs for C. neoformans were evaluated. CLSI-RPMI ECVs for distributions originating in ≥3 laboratories (with the percentages of isolates for which MICs were less than or equal to ECVs given in parentheses) were as follows: for amphotericin B, 0.5 µg/ml for C. neoformans VNI (97.2%) and C. gattii VGI and VGIIa (99.2 and 97.5%, respectively) and 1 µg/ml for C. neoformans (98.5%) and C. gattii nontyped (100%) and VGII (99.2%) isolates; for flucytosine, 4 µg/ml for C. gattii nontyped (96.4%) and VGI (95.7%) isolates, 8 µg/ml for VNI (96.6%) isolates, and 16 µg/ml for C. neoformans nontyped (98.6%) and C. gattii VGII (97.1%) isolates. Other molecular types had apparent variations in MIC distributions, but the number of laboratories contributing data was too low to allow us to ascertain that the differences were due to factors other than assay variation. ECVs may aid in the detection of isolates with acquired resistance mechanisms.


Asunto(s)
Anfotericina B/farmacología , Antibacterianos/farmacología , Cryptococcus gattii/efectos de los fármacos , Cryptococcus neoformans/efectos de los fármacos , Flucitosina/farmacología , Pruebas de Sensibilidad Microbiana
20.
Antimicrob Agents Chemother ; 56(11): 5898-906, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22948877

RESUMEN

Epidemiological cutoff values (ECVs) for the Cryptococcus neoformans-Cryptococcus gattii species complex versus fluconazole, itraconazole, posaconazole, and voriconazole are not available. We established ECVs for these species and agents based on wild-type (WT) MIC distributions. A total of 2,985 to 5,733 CLSI MICs for C. neoformans (including isolates of molecular type VNI [MICs for 759 to 1,137 isolates] and VNII, VNIII, and VNIV [MICs for 24 to 57 isolates]) and 705 to 975 MICs for C. gattii (including 42 to 260 for VGI, VGII, VGIII, and VGIV isolates) were gathered in 15 to 24 laboratories (Europe, United States, Argentina, Australia, Brazil, Canada, Cuba, India, Mexico, and South Africa) and were aggregated for analysis. Additionally, 220 to 359 MICs measured using CLSI yeast nitrogen base (YNB) medium instead of CLSI RPMI medium for C. neoformans were evaluated. CLSI RPMI medium ECVs for distributions originating from at least three laboratories, which included ≥95% of the modeled WT population, were as follows: fluconazole, 8 µg/ml (VNI, C. gattii nontyped, VGI, VGIIa, and VGIII), 16 µg/ml (C. neoformans nontyped, VNIII, and VGIV), and 32 µg/ml (VGII); itraconazole, 0.25 µg/ml (VNI), 0.5 µg/ml (C. neoformans and C. gattii nontyped and VGI to VGIII), and 1 µg/ml (VGIV); posaconazole, 0.25 µg/ml (C. neoformans nontyped and VNI) and 0.5 µg/ml (C. gattii nontyped and VGI); and voriconazole, 0.12 µg/ml (VNIV), 0.25 µg/ml (C. neoformans and C. gattii nontyped, VNI, VNIII, VGII, and VGIIa,), and 0.5 µg/ml (VGI). The number of laboratories contributing data for other molecular types was too low to ascertain that the differences were due to factors other than assay variation. In the absence of clinical breakpoints, our ECVs may aid in the detection of isolates with acquired resistance mechanisms and should be listed in the revised CLSI M27-A3 and CLSI M27-S3 documents.


Asunto(s)
Antifúngicos/uso terapéutico , Criptococosis/tratamiento farmacológico , Criptococosis/epidemiología , Cryptococcus gattii/efectos de los fármacos , Fluconazol/uso terapéutico , Itraconazol/uso terapéutico , Pirimidinas/uso terapéutico , Triazoles/uso terapéutico , Antifúngicos/farmacología , Australia/epidemiología , Criptococosis/microbiología , Cryptococcus gattii/crecimiento & desarrollo , Cryptococcus gattii/aislamiento & purificación , Farmacorresistencia Fúngica/efectos de los fármacos , Europa (Continente)/epidemiología , Fluconazol/farmacología , Humanos , India/epidemiología , Itraconazol/farmacología , Pruebas de Sensibilidad Microbiana , América del Norte/epidemiología , Pirimidinas/farmacología , Sudáfrica/epidemiología , América del Sur/epidemiología , Triazoles/farmacología , Voriconazol
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