RESUMEN
Alphavirus infections are transmitted by mosquitoes, but the mode of transmission for Mycobacterium ulcerans, which causes Buruli ulcer, is contested. Using notification data for Victoria, Australia, during 2017-2022, adjusted for incubation period, we show close alignment between alphavirus and Buruli ulcer seasons, supporting the hypothesis of mosquito transmission of M. ulcerans.
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Infecciones por Alphavirus , Úlcera de Buruli , Mosquitos Vectores , Mycobacterium ulcerans , Úlcera de Buruli/transmisión , Úlcera de Buruli/epidemiología , Úlcera de Buruli/microbiología , Mycobacterium ulcerans/aislamiento & purificación , Infecciones por Alphavirus/transmisión , Infecciones por Alphavirus/epidemiología , Humanos , Animales , Victoria/epidemiología , Mosquitos Vectores/microbiología , Mosquitos Vectores/virología , Alphavirus/aislamiento & purificación , Culicidae/microbiología , Culicidae/virología , Notificación de EnfermedadesRESUMEN
Buruli ulcer (BU) is a destructive soft-tissue infection caused by the environmental pathogen Mycobacterium ulcerans. In response to rising BU notifications in the state of Victoria, Australia, we reviewed all cases that occurred during 2011-2016 to precisely map the time and likely place of M. ulcerans acquisition. We found that 600 cases of BU had been notified; just over half were in residents and the remainder in visitors to defined BU-endemic areas. During the study period, notifications increased almost 3-fold, from 66 in 2013 to 182 in 2016. We identified 4 BU-endemic areas: Bellarine Peninsula, Mornington Peninsula, Frankston region, and the southeastern Bayside suburbs of Melbourne. We observed a decline in cases on the Bellarine Peninsula but a progressive increase elsewhere. Acquisitions peaked in late summer. The appearance of new BU-endemic areas and the decline in established areas probably correlate with changes in the level of local environmental contamination with M. ulcerans.
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Úlcera de Buruli/epidemiología , Enfermedades Endémicas , Mycobacterium ulcerans/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Úlcera de Buruli/tratamiento farmacológico , Úlcera de Buruli/microbiología , Niño , Preescolar , Demografía , Femenino , Geografía , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Mycobacterium ulcerans/genética , Victoria/epidemiología , Adulto JovenRESUMEN
PURPOSE OF REVIEW: To outline key drivers and components of antifungal stewardship (AFS) programmes, the evidence for specific interventions, and methods to assess performance of programmes. RECENT FINDINGS: Recent developments in antifungal resistance and breakthrough invasive fungal diseases have increased the urgency for effective AFS. In practice, however, few hospitals have dedicated AFS programmes. To date, AFS programmes have centred around the provision of expert bedside reviews and have reduced costs and consumption of antifungal agents. Incorporating tools such as fungal diagnostics and therapeutic drug monitoring into AFS programme models is recommended. However, the application and impact of these tools in this context have not been adequately assessed. The effectiveness of AFS programmes has been measured in multiple ways but a standardized method of evaluation remains elusive. Few studies have explored the impact of AFS interventions on patient outcomes. SUMMARY: The uptake of formal AFS programmes has been slow. New initiatives integrating AFS tools in programmes, and measuring the impacts on patient outcomes are required given such data are not readily available. A comprehensive approach to evaluate AFS programmes by correlating the quantity and quality of antifungal prescribing with impacts on patient outcomes is needed. Consensus definitions for core AFS metrics are required to benchmark performance and are essential to the resourcing and sustainability of these programmes.
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Antifúngicos , Programas de Optimización del Uso de los Antimicrobianos , Infecciones Fúngicas Invasoras/tratamiento farmacológico , HumanosRESUMEN
Since 2000, cases of the neglected tropical disease Buruli ulcer, caused by infection with Mycobacterium ulcerans, have increased 100-fold around Melbourne (population 4.4 million), the capital of Victoria, in temperate southeastern Australia. The reasons for this increase are unclear. Here, we used whole-genome sequence comparisons of 178 M. ulcerans isolates obtained primarily from human clinical specimens, spanning 70 years, to model the population dynamics of this pathogen from this region. Using phylogeographic and advanced Bayesian phylogenetic approaches, we found that there has been a migration of the pathogen from the east end of the state, beginning in the 1980s, 300 km west to the major human population center around Melbourne. This move was then followed by a significant increase in M. ulcerans population size. These analyses inform our thinking around Buruli ulcer transmission and control, indicating that M. ulcerans is introduced to a new environment and then expands, rather than it being from the awakening of a quiescent pathogen reservoir.IMPORTANCE Buruli ulcer is a destructive skin and soft tissue infection caused by Mycobacterium ulcerans and is characterized by progressive skin ulceration, which can lead to permanent disfigurement and long-term disability. Despite the majority of disease burden occurring in regions of West and central Africa, Buruli ulcer is also becoming increasingly common in southeastern Australia. Major impediments to controlling disease spread are incomplete understandings of the environmental reservoirs and modes of transmission of M. ulcerans The significance of our research is that we used genomics to assess the population structure of this pathogen at the Australian continental scale. We have then reconstructed a historical bacterial spread and modeled demographic dynamics to reveal bacterial population expansion across southeastern Australia. These findings provide explanations for the observed epidemiological trends with Buruli ulcer and suggest possible management to control disease spread.
Asunto(s)
Úlcera de Buruli/epidemiología , Genoma Bacteriano , Mycobacterium ulcerans/fisiología , Teorema de Bayes , Úlcera de Buruli/microbiología , Genómica , Humanos , Incidencia , Mycobacterium ulcerans/genética , Filogenia , Filogeografía , Victoria/epidemiología , Secuenciación Completa del GenomaRESUMEN
BACKGROUND: Various studies have identified numerous factors associated with poor clinical outcomes in patients with Staphylococcus aureus bacteraemia (SAB). A new study was created to provide deeper insight into in-hospital complications and risk factors for treatment failure. METHODS: Adult patients hospitalised with Staphylococcus aureus bacteraemia (SAB) were recruited prospectively into a multi-centre cohort. The primary outcome was treatment failure at 30 days (composite of all-cause mortality, persistent bacteraemia, or recurrent bacteraemia), and secondary measures included in-hospital complications and mortality at 6- and 12-months. Data were available for 222 patients recruited from February 2011 to December 2012. RESULTS: Treatment failure at 30-days was recorded in 14.4% of patients (30-day mortality 9.5%). Multivariable analysis predictors of treatment failure included age > 70 years, Pitt bacteraemia score ≥ 2, CRP at onset of SAB > 250 mg/L, and persistent fevers after SAB onset; serum albumin at onset of SAB, receipt of appropriate empiric treatment, recent healthcare attendance, and performing echocardiography were protective. 6-month and 12-month mortality were 19.1% and 24.2% respectively. 45% experienced at least one in-hospital complication, including nephrotoxicity in 19.5%. CONCLUSIONS: This study demonstrates significant improvements in 30-day outcomes in SAB in Australia. However, we have identified important areas to improve outcomes from SAB, particularly reducing renal dysfunction and in-hospital treatment-related complications.
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Infecciones Estafilocócicas/epidemiología , Staphylococcus aureus/aislamiento & purificación , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Australia/epidemiología , Proteína C-Reactiva/análisis , Estudios de Cohortes , Ecocardiografía , Femenino , Mortalidad Hospitalaria , Hospitalización , Humanos , Modelos Logísticos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Morbilidad , Factores de Riesgo , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/mortalidad , Staphylococcus aureus/efectos de los fármacos , Insuficiencia del Tratamiento , Vancomicina/farmacologíaRESUMEN
To identify potential reservoirs/vectors of Mycobacterium ulcerans in northern Queensland, Australia, we analyzed environmental samples collected from the Daintree River catchment area, to which Buruli ulcer is endemic, and adjacent coastal lowlands by species-specific PCR. We detected M. ulcerans DNA in soil, mosquitoes, and excreta of bandicoots, which are small terrestrial marsupials.
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Úlcera de Buruli/epidemiología , Úlcera de Buruli/veterinaria , Enfermedades Endémicas/veterinaria , Marsupiales/microbiología , Mycobacterium ulcerans/genética , Animales , Úlcera de Buruli/microbiología , Úlcera de Buruli/transmisión , Culicidae/microbiología , ADN Bacteriano/genética , Heces/química , Heces/microbiología , Humanos , Insectos Vectores/microbiología , Mycobacterium ulcerans/clasificación , Mycobacterium ulcerans/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Queensland/epidemiología , Microbiología del SueloRESUMEN
Mycobacterium chimaera is an opportunistic environmental mycobacterium belonging to the Mycobacterium avium-M. intracellulare complex. Although most commonly associated with pulmonary disease, there has been growing awareness of invasive M. chimaera infections following cardiac surgery. Investigations suggest worldwide spread of a specific M. chimaera clone, associated with contaminated hospital heater-cooler units used during the surgery. Given the global dissemination of this clone, its potential to cause invasive disease, and the laboriousness of current culture-based diagnostic methods, there is a pressing need to develop rapid and accurate diagnostic assays specific for M. chimaera Here, we assessed 354 mycobacterial genome sequences and confirmed that M. chimaera is a phylogenetically coherent group. In silico comparisons indicated six DNA regions present only in M. chimaera We targeted one of these regions and developed a TaqMan quantitative PCR (qPCR) assay for M. chimaera with a detection limit of 100 CFU/ml in whole blood spiked with bacteria. In vitro screening against DNA extracted from 40 other mycobacterial species and 22 bacterial species from 21 diverse genera confirmed the in silico-predicted specificity for M. chimaera Screening 33 water samples from heater-cooler units with this assay highlighted the increased sensitivity of PCR compared to culture, with 15 of 23 culture-negative samples positive by M. chimaera qPCR. We have thus developed a robust molecular assay that can be readily and rapidly deployed to screen clinical and environmental specimens for M. chimaera.
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ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Técnicas de Diagnóstico Molecular/métodos , Infecciones por Mycobacterium/diagnóstico , Mycobacterium/genética , Mycobacterium/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Humanos , Infecciones por Mycobacterium/microbiología , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Owing to limited availability of donor organs, previous solid organ transplant (SOT) recipients are increasingly considered as potential organ donors. We report donor-derived transmission of herpes simplex virus type-2 (HSV-2) to two clusters of SOT recipients with transmission from the original donor and an HSV-2-infected recipient who subsequently became a donor. METHODS: We reviewed medical records of the donors and recipients in both clusters. Pre-transplant serology and virological features of HSV-2 were characterized. Genotyping of HSV-2 isolates to determine potential for donor transmission of HSV-2 through transplantation of organs from prior organ recipients was performed. RESULTS: A kidney-pancreas recipient died day 9 post transplant. Following confirmation of brain death, the lungs and recently transplanted kidney were donated to two further recipients. The liver was not retrieved, but biopsy confirmed HSV-2 infection. Testing on the original donor showed negative HSV-2 polymerase chain reaction and HSV immunoglobulin (Ig)M, but positive HSV-2 IgG. The liver recipient from the original donor developed HSV-2 hepatitis and cutaneous infection that responded to treatment with intravenous acyclovir. In the second cluster, lung and kidney recipients both developed HSV-2 viremia that was successfully treated with antiviral therapy. Genotyping of all HSV-2-positive samples showed 100% sequence homology for three recipients. CONCLUSIONS: Donor-derived HSV infection affected two clusters of recipients because of transplantation of organs from a prior organ recipient. HSV should be considered as a possible cause of illness in febrile SOT recipients in the immediate post-transplant period and may cause disseminated disease and re-infection in HSV-2-seropositive recipients. Testing of HSV serology and prophylaxis may be considered in SOT recipients not receiving cytomegalovirus prophylaxis.
Asunto(s)
Herpes Simple/transmisión , Herpesvirus Humano 2 , Trasplante de Órganos/efectos adversos , Donantes de Tejidos , Adulto , Antivirales/uso terapéutico , Femenino , Herpes Simple/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Enterococcus faecium is a major nosocomial pathogen causing significant morbidity and mortality worldwide. Assessment of E. faecium using MLST to understand the spread of this organism is an important component of hospital infection control measures. Recent studies, however, suggest that MLST might be inadequate for E. faecium surveillance. OBJECTIVES: To use WGS to characterize recently identified vancomycin-resistant E. faecium (VREfm) isolates non-typeable by MLST that appear to be causing a multi-jurisdictional outbreak in Australia. METHODS: Illumina NextSeq and Pacific Biosciences SMRT sequencing platforms were used to determine the genome sequences of 66 non-typeable E. faecium (NTEfm) isolates. Phylogenetic and bioinformatics analyses were subsequently performed using a number of in silico tools. RESULTS: Sixty-six E. faecium isolates were identified by WGS from multiple health jurisdictions in Australia that could not be typed by MLST due to a missing pstS allele. SMRT sequencing and complete genome assembly revealed a large chromosomal rearrangement in representative strain DMG1500801, which likely facilitated the deletion of the pstS region. Phylogenomic analysis of this population suggests that deletion of pstS within E. faecium has arisen independently on at least three occasions. Importantly, the majority of these isolates displayed a vancomycin-resistant genotype. CONCLUSIONS: We have identified NTEfm isolates that appear to be causing a multi-jurisdictional outbreak in Australia. Identification of these isolates has important implications for MLST-based typing activities designed to monitor the spread of VREfm and provides further evidence supporting the use of WGS for hospital surveillance of E. faecium.
Asunto(s)
Técnicas de Tipificación Bacteriana/métodos , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Endémicas , Enterococcus faecium/aislamiento & purificación , Genotipo , Infecciones por Bacterias Grampositivas/epidemiología , Enterococos Resistentes a la Vancomicina/aislamiento & purificación , Australia/epidemiología , Enfermedades Transmisibles Emergentes/microbiología , Biología Computacional , Enterococcus faecium/clasificación , Genoma Bacteriano , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Epidemiología Molecular/métodos , Filogenia , Análisis de Secuencia de ADN/métodos , Enterococos Resistentes a la Vancomicina/clasificaciónRESUMEN
Enterococci are a major cause of health care-associated infections and account for approximately 10% of all bacteremias globally. The aim of this study was to determine the proportion of enterococcal bacteremia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterize the molecular epidemiology of the Enterococcus faecalis and Enterococcus faecium isolates. From 1 January to 31 December 2011, 1,079 unique episodes of bacteremia were investigated, of which 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). The majority of bacteremias were health care associated, and approximately one-third were polymicrobial. Ampicillin resistance was detected in 90.4% of E. faecium isolates but was not detected in E. faecalis isolates. Vancomycin nonsusceptibility was reported in 0.6% and 36.5% of E. faecalis and E. faecium isolates, respectively. Unlike Europe and the United States, where vancomycin resistance in E. faecium is predominately due to the acquisition of the vanA operon, 98.4% of E. faecium isolates harboring van genes carried the vanB operon, and 16.1% of the vanB E. faecium isolates had vancomycin MICs at or below the susceptible breakpoint of the CLSI. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis pulsotypes, >50% belonged to two pulsotypes that were isolated across Australia. E. faecium consisted of 73 pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium isolates were identified as CC17 clones, of which approximately half were characterized as ST203, which was isolated Australia-wide. In conclusion, the Australian Enterococcal Sepsis Outcome Programme (AESOP) study has shown that although they are polyclonal, enterococcal bacteremias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.
Asunto(s)
Bacteriemia/epidemiología , Enterococcus faecalis/aislamiento & purificación , Enterococcus faecium/aislamiento & purificación , Infecciones por Bacterias Grampositivas/epidemiología , Antibacterianos/farmacología , Australia/epidemiología , Bacteriemia/microbiología , Coinfección/epidemiología , Coinfección/microbiología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana , Enterococcus faecalis/clasificación , Enterococcus faecalis/genética , Enterococcus faecium/clasificación , Enterococcus faecium/genética , Genes Bacterianos , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Tipificación MolecularRESUMEN
An elevated vancomycin MIC is associated with poor outcomes in Staphylococcus aureus bacteremia (SAB) and is reported in patients with methicillin-susceptible S. aureus (MSSA) bacteremia in the absence of vancomycin treatment. Here, using DNA microarray and phenotype analysis, we investigated the genetic predictors and accessory gene regulator (agr) function and their relationship with elevated vancomycin MIC using blood culture isolates from a multicenter binational cohort of patients with SAB. Specific clonal complexes were associated with elevated (clonal complex 8 [CC8] [P < 0.001]) or low (CC22 [P < 0.001], CC88 [P < 0.001], and CC188 [P = 0.002]) vancomycin MIC. agr dysfunction (P = 0.014) or agr genotype II (P = 0.043) were also associated with an elevated vancomycin MIC. Specific resistance and virulence genes were also linked to an elevated vancomycin MIC, including blaZ (P = 0.002), sea (P < 0.001), clfA (P < 0.001), splA (P = 0.001), and the arginine catabolic mobile element (ACME) locus (P = 0.02). These data suggest that inherent organism characteristics may explain the link between elevated vancomycin MICs and poor outcomes in patients with SAB, regardless of the antibiotic treatment received. A consideration of clonal specificity should be included in future research when attempting to ascertain treatment effects or clinical outcomes.
Asunto(s)
Antibacterianos/farmacología , Bacteriemia/microbiología , Tolerancia a Medicamentos , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/efectos de los fármacos , Vancomicina/farmacología , Adolescente , Adulto , Anciano , Proteínas Bacterianas/genética , Niño , Preescolar , Estudios de Cohortes , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Análisis por Micromatrices , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Prospectivos , Staphylococcus aureus/genética , Staphylococcus aureus/aislamiento & purificación , Transactivadores/genética , Factores de Virulencia/genética , Adulto JovenRESUMEN
⢠Guidelines reflecting contemporary clinical practice in the management of Buruli ulcer (Mycobacterium ulcerans infection) in Australia were published in 2007. ⢠Management has continued to evolve, as new evidence has become available from randomised trials, case series and increasing clinical experience with oral antibiotic therapy. ⢠Therefore, guidelines on the diagnosis, treatment and prevention of Buruli ulcer in Australia have been updated. They include guidance on the new role of antibiotics as first-line therapy; the shortened duration of antibiotic treatment and the use of all-oral antibiotic regimens; the continued importance, timing and role of surgery; the recognition and management of paradoxical reactions during antibiotic treatment; and updates on the prevention of disease.
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Úlcera de Buruli/tratamiento farmacológico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Australia , Úlcera de Buruli/prevención & control , Úlcera de Buruli/cirugía , Desbridamiento , Quimioterapia Combinada , Calor/uso terapéutico , Humanos , Mycobacterium ulcerans , Guías de Práctica Clínica como Asunto , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Estreptomicina/administración & dosificación , Estreptomicina/uso terapéuticoAsunto(s)
Amidohidrolasas/genética , Antituberculosos/uso terapéutico , Mutación/genética , Pirazinamida/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/genética , Adulto , Femenino , Humanos , Análisis de Secuencia de ADN/métodosRESUMEN
An 82-year-old woman on long-term prednisolone for chronic obstructive airways disease presented with a 2-month history of nodules on her left forearm. This occurred 10 years after nodules on her right forearm caused by a culture-proven Mycobacterium marinum infection. Histopathological examination, polymerase chain reaction and culture of biopsy specimens were positive for M. chelonae. To our knowledge this is the first case of metachronous nontuberculous mycobacterial skin infection reported, and it highlights the diagnostic and therapeutic challenges of such infections.
Asunto(s)
Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium chelonae , Mycobacterium marinum , Enfermedades Cutáneas Bacterianas/microbiología , Anciano de 80 o más Años , Animales , Femenino , Peces , Antebrazo , Pasatiempos , Humanos , Huésped Inmunocomprometido , RecurrenciaRESUMEN
From 1 January to 31 December 2013, 26 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2013 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, and to characterise the molecular epidemiology of the Enterococcus faecium isolates. Of the 826 unique episodes of bacteraemia investigated, 94.6% were caused by either E. faecalis (56.1%) or E. faecium (38.5%). Ampicillin resistance was not detected in E. faecalis but was detected in over 90% of E. faecium. Vancomycin non-susceptibility was reported in 0.2% and 40.9% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Overall, 41.6% of E. faecium harboured vanA or vanB genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is significantly higher than that seen in most European countries. E. faecium isolates consisted of 81 pulsed-field gel electrophoresis pulsotypes of which 72.3% were classified into 14 major pulsotypes containing five or more isolates. Multilocus sequence typing grouped the 14 major pulsotypes into clonal cluster 17, a major hospital-adapted polyclonal E. faecium cluster. Of the 2 predominant sequence types, ST203 (80 isolates) was identified across Australia and ST555 (40 isolates) was isolated primarily in the western and central regions (Northern Territory, South Australia and Western Australia) respectively. In conclusion, the AESOP 2013 has shown enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanB E. faecium, which have limited treatment options.
Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Infección Hospitalaria/tratamiento farmacológico , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecium/efectos de los fármacos , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Sepsis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Informes Anuales como Asunto , Australia/epidemiología , Bacteriemia/epidemiología , Bacteriemia/microbiología , Bacteriemia/mortalidad , Niño , Preescolar , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Infección Hospitalaria/mortalidad , Enterococcus faecalis/clasificación , Enterococcus faecalis/genética , Enterococcus faecalis/crecimiento & desarrollo , Enterococcus faecium/clasificación , Enterococcus faecium/genética , Enterococcus faecium/crecimiento & desarrollo , Monitoreo Epidemiológico , Femenino , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/mortalidad , Humanos , Lactante , Recién Nacido , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Sepsis/epidemiología , Sepsis/microbiología , Sepsis/mortalidad , Serotipificación , Análisis de Supervivencia , Resultado del Tratamiento , Resistencia a la VancomicinaRESUMEN
From 1 January to 31 December 2011, 29 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2011 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterise the molecular epidemiology of the Enterococcus faecalis and E. faecium isolates. Of the 1,079 unique episodes of bacteraemia investigated, 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). Ampicillin resistance was detected in 90.4% of E. faecium but not detected in E. faecalis. Using Clinical and Laboratory Standards Institute breakpoints (CLSI), vancomycin non-susceptibility was reported in 0.6% and 31.4% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Approximately 1 in 6 vanB E. faecium isolates however, had an minimum inhibitory concentration at or below the CLSI vancomycin susceptible breakpoint of ≤ 4 mg/L. Overall, 37% of E. faecium harboured vanA or vanB genes. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis (PFGE) pulsotypes, more than 50% belonged to 2 pulsotypes that were isolated across Australia. E. faecium consisted of 73 PFGE pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium were identified as clonal complex 17 clones, of which approximately half were characterised as sequence type 203, which was isolated Australia-wide. In conclusion, the AESOP 2011 has shown that although polyclonal, enterococcal bacteraemias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.
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Enterococcus , Vigilancia de la Población , Sepsis/epidemiología , Sepsis/microbiología , Antibacterianos/farmacología , Australia/epidemiología , Enterococcus/clasificación , Enterococcus/efectos de los fármacos , Enterococcus/genética , Genotipo , Historia del Siglo XXI , Humanos , Pruebas de Sensibilidad Microbiana , Sepsis/diagnóstico , Sepsis/historiaRESUMEN
Critical scientific questions remain regarding infection with Mycobacterium ulcerans, the organism responsible for the neglected tropical disease, Buruli ulcer (BU). A controlled human infection model has the potential to accelerate our knowledge of the immunological correlates of disease, to test prophylactic interventions and novel therapeutics. Here we present microbiological evidence supporting M. ulcerans JKD8049 as a suitable human challenge strain. This non-genetically modified Australian isolate is susceptible to clinically relevant antibiotics, can be cultured in animal-free and surfactant-free media, can be enumerated for precise dosing, and has stable viability following cryopreservation. Infectious challenge of humans with JKD8049 is anticipated to imitate natural infection, as M. ulcerans JKD8049 is genetically stable following in vitro passage and produces the key virulence factor, mycolactone. Also reported are considerations for the manufacture, storage, and administration of M. ulcerans JKD8049 for controlled human infection.
Asunto(s)
Úlcera de Buruli , Mycobacterium ulcerans , Mycobacterium ulcerans/genética , Úlcera de Buruli/microbiología , Úlcera de Buruli/inmunología , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , AustraliaRESUMEN
Buruli ulcer, a chronic subcutaneous infection caused by Mycobacterium ulcerans, is increasing in prevalence in southeastern Australia. Possums are a local wildlife reservoir for M. ulcerans and, although mosquitoes have been implicated in transmission, it remains unclear how humans acquire infection. We conducted extensive field survey analyses of M. ulcerans prevalence among mosquitoes in the Mornington Peninsula region of southeastern Australia. PCR screening of trapped mosquitoes revealed a significant association between M. ulcerans and Aedes notoscriptus. Spatial scanning statistics revealed overlap between clusters of M. ulcerans-positive Ae. notoscriptus, M. ulcerans-positive possum excreta and Buruli ulcer cases, and metabarcoding analyses showed individual mosquitoes had fed on humans and possums. Bacterial genomic analysis confirmed shared single-nucleotide-polymorphism profiles for M. ulcerans detected in mosquitoes, possum excreta and humans. These findings indicate Ae. notoscriptus probably transmit M. ulcerans in southeastern Australia and highlight mosquito control as a Buruli ulcer prevention measure.