ST45 is a major global MRSA lineage with huge strain diversity and a high clinical impact. It is one of the most prevalent carrier lineages but also frequently causes severe invasive disease, such as ...bacteremia. Little is known about its evolutionary history. In this study, we used whole-genome sequencing to analyze a large collection of 451 diverse ST45 isolates from 6 continents and 26 countries.
-assembled genomes were used to understand genomic plasticity and to perform coalescent analyses. The ST45 population contained two distinct sublineages, which correlated with the isolates' geographical origins. One sublineage primarily consisted of European/North American isolates, while the second sublineage primarily consisted of African and Australian isolates. Bayesian analysis predicted ST45 originated in northwestern Europe about 500 years ago. Isolation time, host, and clinical symptoms did not correlate with phylogenetic groups. Our phylogenetic analyses suggest multiple acquisitions of the SCC
element and key virulence factors throughout the evolution of the ST45 lineage.
Pigs have been recognised as a reservoir of livestock associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in Europe, Asia and North America. However, little is known about the presence ...and distribution of MRSA in the Australian pig population and pig industry. This study describes the presence, distribution and molecular characteristics of the human adapted Australian CA-MRSA ST93 isolated from pigs, people, and the environment within a piggery. Isolates were subjected to antibiotic susceptibility testing, DNA microarray, whole genome sequencing, multi locus sequence typing, virulence and resistance gene characterization and phylogenetic analysis. MRSA were isolated from 60% (n = 52) of farm workers where 84% of isolates returned ST93 and the rest ST398. Of the thirty-one pig isolates tested further, an equal number of ST398 and ST93 (15 each) and one as ST30-V were identified. Four of six environmental isolates were identified as ST93 and two as ST398. This study has identified for the first time in Australia the occurrence of CA-MRSA ST93 and LA-MRSA ST398 amongst farm workers, pigs, and the farm environment. Comparative genome analysis indicates that ST398 is likely to have been introduced into Australia from Europe or North America. This study also reports the first linezolid resistant MRSA isolated in Australia.
Understanding the mechanism(s) underpinning drug resistance could lead to novel treatments to reverse the increased tolerance of a pathogen. In this study, paromomycin (PMM) resistance (PMM
) was ...induced in three Nepalese clinical strains of
with different inherent susceptibilities to antimony (Sb) drugs by stepwise exposure of promastigotes to PMM. Exposure to PMM resulted in the production of mixed populations of parasites, even though a single cloned population was used at the start of selection. PMM 50% inhibitory concentration (IC
) values for PMM
parasites varied between 104 and 481 μM at the promastigote stage and 32 and 195 μM at the intracellular amastigote stage. PMM resistance was associated with increased resistance to nitric oxide at the amastigote stage but not the promastigote stage (
< 0.05). This effect was most marked in the Sb-resistant (Sb
) PMM
clone, in which PMM resistance was associated with a significant upregulation of glutathione compared to that in its wild type (
< 0.05), although there was no change in the regulation of trypanothione (detected in its oxidized form). Interestingly, PMM
strains showed an increase in either the keto acid derivative of isoleucine (Sb intermediate PMM
) or the 2-hydroxy acids derived from arginine and tyrosine (Sb susceptible PMM
and Sb
PMM
). These results are consistent with the recent finding that the upregulation of the branched-chain amino acid aminotransferase and d-lactate dehydrogenase is linked to PMM
In addition, we found that PMM
is associated with a significant increase in aneuploidy during PMM selection in all the strains, which could allow the rapid selection of genetic changes that confer a survival advantage.
The convergence of socially engaged art and innovative health care was a key focus of Space and Place in End-of-Life Care, a Swedish transdisciplinary research project (2017–2020). For this project, ...researchers created, facilitated, and documented a range of socially engaged art and innovative healthcare practices during their exploration of the end of life in the context of Stockholm elder care residential settings.
Formulated as a year-long transdisciplinary research residency, two or more art, design, and/or innovative healthcare researchers met in a Stockholm residential elder care home on a weekly basis to observe and encounter people and place and interact, converse, produce, and exchange knowledge in collaboration with the residents, carers, management, friends, family members, and other researchers.
Researchers engaged in a weekly transdisciplinary research residency in a Stockholm elder care residence to encounter and interact with the people, space and place of the study setting, and learn from and contribute to the residential home. The scientific researchers engaged in a community-based participatory action research project that utilized interviews, photo-elicitation processes, and community round table discussions. This happened in dialogue with the artistic residency process, wherein the artists collaborated with the inhabitants, staff, and visitors of the residential elder care home to produce a series of socially engaged events, experiences, and artifacts, one of which was the participatory art event, the Handfestival that is the case study of this article.
The weekly artistic residency for the Space and Place in End-of-Life Care project resulted in the Handfestival, a participatory art event exploring hands, touch and conversation generated by researchers from the fields of art, design, innovative health and elder care in collaboration with residents, staff and family of a Swedish elder care residence. The Handfestival is a model on the intersection between socially engaged art practices and innovative health care approaches and demonstrates how elder care residences and public health agencies could engage in regular, creative, and relational activities for the participation of inhabitants in healthcare settings.
Socially engaged and participatory art practices increase levels of social engagement and promote a greater sense of interconnectivity within health care settings. As such, the Handfestival participatory event reveals the potential for the convergence of art and health via social practice, modeling a way to develop, orchestrate and disseminate events, experiences, and/or artifacts as health services that public health agencies can and should deliver, but might find challenging to imagine and manifest.
The clinical and molecular epidemiology of Staphylococcus aureus disease has changed considerably over the past two decades, particularly with the emergence and spread of community-associated ...methicillin-resistant S. aureus (CA-MRSA) clones. Indeed, some of the first global descriptions of CA-MRSA were from remote indigenous communities in Western Australia, and from Pacific Peoples in New Zealand. The epidemiology of S. aureus infections in the South West Pacific has several unique features, largely because of the relative geographical isolation and unique indigenous communities residing in this region. In particular, a number of distinct CA-MRSA clones circulate in Australia and New Zealand, such as sequence type (ST) 93 methicillin-resistant S. aureus (MRSA) (Queensland clone) and clonal complex 75 S. aureus (Staphylococcus argenteus) in Australia, and ST30 MRSA (Southwest Pacific clone) in New Zealand. In addition, there is a disproportionate burden of S. aureus disease in indigenous paediatric populations, particularly in remote Aboriginal communities in Australia, and in Pacific Peoples and Maori in New Zealand. In this review, we provide a contemporary overview of the clinical and molecular epidemiology of S. aureus disease in the South West Pacific region, with a particular focus on features distinct to this region.
To determine the impact of infectious diseases consultation (IDC) in
Staphylococcus aureus
bacteraemia. All MRSA bacteraemia and a random subset of MSSA bacteraemia were retrospectively analysed. Out ...of 599 SAB episodes, 162 (27%) were followed by an IDC. Patients with IDC were younger and more frequently intravenous drug users, but fewer resided in a long-term care facility or were indigenous. Hospital length of stay was longer (29.5 vs 17 days,
p
< 0.001), and endocarditis (19.1% vs 7.3%,
p
< 0.001) and metastatic seeding (22.2% vs 10.1%,
p
< 0.001) were more frequent in the IDC group; however, SAPS II scores were lower in the IDC group (27 vs 37,
p
< 0.001). ICU admission rates in the two groups were similar. The isolate tested susceptible to empirical therapy more frequently in the IDC group (88.9% vs 78.0%,
p
= 0.003). Seven-day (3.1 vs 16.5%), 30-day (8.0% vs 27.0%) and 1-year mortality (22.2% vs 44.9%) were all lower in the IDC group (all
p
< 0.001). Multivariate analysis showed that effective initial therapy was the only variable associated with the protective effect of IDC. In patients with SAB, all-cause mortality was significantly lower in patients who had an IDC, because of the higher proportion of patients receiving effective initial antibiotics.
•The traditional epidemiology of MRSA is blurring.•Genomic studies have helped in understanding the evolving epidemiology.•Genomic tools are useful in relation to epidemiology and outbreaks.
The ...evolution of meticillin-resistant Staphylococcus aureus (MRSA) from meticillin-susceptible S. aureus has been a result of the accumulation of genetic elements under selection pressure from antibiotics. The traditional classification of MRSA into healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) is no longer relevant as there is significant overlap of identical clones between these groups, with an increasing recognition of human infection caused by livestock-associated MRSA (LA-MRSA). Genomic studies have enabled us to model the epidemiology of MRSA along these lines. In this review, we discuss the clinical relevance of genomic studies, particularly whole-genome sequencing, in the investigation of outbreaks. We also discuss the blurring of each of the three epidemiological groups (HA-MRSA, CA-MRSA and LA-MRSA), demonstrating the limited relevance of this classification.
Abstract
Objectives
Implementation of EUCAST susceptibility testing in an Australian hospital laboratory demonstrated higher rates of aminopenicillin and amoxicillin/clavulanate resistance in ...Haemophilus influenzae than previously recognized. This study aimed to better define the variability in the detection of β-lactam resistance based on EUCAST and CLSI disc diffusion (DD) methodology, by comparison with the recommended reference method, broth microdilution (BMD), and by concordance with genomic analysis.
Methods
A total of 100 random H. influenzae isolates were assessed for ampicillin and amoxicillin/clavulanate susceptibility by EUCAST and CLSI DD and BMD. WGS was used to analyse the ftsI gene of a subset of isolates with β-lactam resistance, other than that due to isolated β-lactamase production.
Results
Of the 100 isolates, 32 were categorized as either β-lactamase negative, ampicillin resistant (BLNAR) (n = 18) or β-lactamase positive, amoxicillin/clavulanate resistant (BLPACR) (n = 14) by EUCAST DD. All 18 EUCAST BLNAR isolates were genotypically confirmed by WGS. Five of 18 BLNAR isolates were concordant by CLSI DD, 12 by EUCAST BMD and 4 by CLSI BMD. Nine of 14 EUCAST BLPACR isolates were confirmed by WGS; the remaining 5 were 1 mm below the EUCAST DD breakpoint. Only one isolate was detected as BLPACR by CLSI DD. Group III mutations associated with high-level ampicillin resistance were identified in 10/32 isolates.
Conclusions
The EUCAST DD susceptibility method is more reliable than either CLSI or BMD for the detection of genotypically defined BLNAR resistance. However, accurate categorization of amoxicillin/clavulanate resistance remains problematic. Continuous and reproducible surveillance of resistance is needed; for this to be possible, robust susceptibility methods are required.
The chemotherapy currently available for leishmaniasis is far from satisfactory. Resistance to the pentavalent antimonials, which have been the recommended drugs for the treatment of both visceral ...(VL) and cutaneous leishmaniasis (CL) for >50 years, is now widespread in India. Although new drugs have become available in recent years for the treatment of VL, including AmBisome®, the excellent but highly expensive liposomal formulation of amphotericin B, and the oral drug miltefosine, which has now been registered in India, treatment problems remain. Parenteral and topical formulations of the aminoglycoside paromomycin offer potential treatments for VL and CL, respectively. The search for new drugs continues, with bisphosphonates, for example, risedronate and pamidronate, and plant derivatives such as licochalcone A and quinoline alkaloids being reported to have activity against experimental animal infections. The immunomodulator imiquimod has proved to be an adjunct for CL therapy. Many potential drug targets have been identified in biochemical and molecular studies, and some have been validated. Attempts to exploit these targets are in progress.
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