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BACKGROUND: Clinical trials of treatments for serious infections commonly use the primary endpoint of all-cause mortality. However, many trial participants survive their infection and this endpoint may not truly reflect important benefits and risks of therapy. The win ratio uses a hierarchical composite endpoint that can incorporate and prioritize outcome measures by relative clinical importance. METHODS: The win ratio methodology was applied post hoc to outcomes observed in the MERINO trial, which compared piperacillin-tazobactam with meropenem. We quantified the win ratio with a primary hierarchical composite endpoint, including all-cause mortality, microbiological relapse, and secondary infection. A win ratio of 1 would correspond to no difference between the 2 antibiotics, while a ratio <1 favors meropenem. Further analyses were performed to calculate the win odds and to introduce a continuous outcome variable in order to reduce ties. RESULTS: With the hierarchy of all-cause mortality, microbiological relapse, and secondary infection, the win ratio estimate was 0.40 (95% confidence interval [CI], .22-.71]; P = .002), favoring meropenem over piperacillin-tazobactam. However, 73.4% of the pairs were tied due to the small proportion of events. The win odds, a modification of the win ratio accounting for ties, was 0.79 (95% CI, .68-.92). The addition of length of stay to the primary composite greatly minimized the number of ties (4.6%) with a win ratio estimate of 0.77 (95% CI, .60-.99; P = .04). CONCLUSIONS: The application of the win ratio methodology to the MERINO trial data illustrates its utility and feasibility for use in antimicrobial trials.
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Antibacterianos , Infecciones por Klebsiella , Klebsiella pneumoniae , Meropenem , Combinación Piperacilina y Tazobactam , Piperacilina , Humanos , Meropenem/uso terapéutico , Meropenem/farmacología , Combinación Piperacilina y Tazobactam/uso terapéutico , Combinación Piperacilina y Tazobactam/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Klebsiella pneumoniae/efectos de los fármacos , Piperacilina/uso terapéutico , Piperacilina/farmacología , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/mortalidad , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Bacteriemia/mortalidad , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/mortalidad , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/uso terapéutico , Ácido Penicilánico/farmacología , Ceftriaxona/uso terapéutico , Ceftriaxona/farmacología , Masculino , Femenino , Persona de Mediana Edad , Tienamicinas/uso terapéutico , Tienamicinas/farmacología , Anciano , Resultado del TratamientoRESUMEN
BACKGROUND: Evidence about the clinical impact of rapid diagnostic tests (RDTs) for the diagnosis of bloodstream infections is limited, and whether RDT are superior to conventional blood cultures (BCs) embedded within antimicrobial stewardship programs (ASPs) is unknown. METHODS: We performed network meta-analyses using results from studies of patients with bloodstream infection with the aim of comparing the clinical impact of RDT (applied on positive BC broth or whole blood) to conventional BC, both assessed with and without ASP with respect to mortality, length of stay (LOS), and time to optimal therapy. RESULTS: Eighty-eight papers were selected, including 25 682 patient encounters. There was an appreciable amount of statistical heterogeneity within each meta-analysis. The network meta-analyses showed a significant reduction in mortality associated with the use of RDT + ASP versus BC alone (odds ratio [OR], 0.72; 95% confidence interval [CI], .59-.87) and with the use of RDT + ASP versus BC + ASP (OR, 0.78; 95% CI, .63-.96). No benefit in survival was found associated with the use of RDT alone nor with BC + ASP compared to BC alone. A reduction in LOS was associated with RDT + ASP versus BC alone (OR, 0.91; 95% CI, .84-.98) whereas no difference in LOS was shown between any other groups. A reduced time to optimal therapy was shown when RDT + ASP was compared to BC alone (-29 hours; 95% CI, -35 to -23), BC + ASP (-18 hours; 95% CI, -27 to -10), and to RDT alone (-12 hours; 95% CI, -20 to -3). CONCLUSIONS: The use of RDT + ASP may lead to a survival benefit even when introduced in settings already adopting effective ASP in association with conventional BC.
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Programas de Optimización del Uso de los Antimicrobianos , Prueba de Diagnóstico Rápido , Sepsis , Humanos , Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/métodos , Cultivo de Sangre/métodos , Tiempo de Internación , Metaanálisis en Red , Sepsis/tratamiento farmacológico , Sepsis/diagnóstico , Sepsis/mortalidad , Sepsis/microbiología , Resultado del TratamientoRESUMEN
BACKGROUND: Gram-negative bloodstream infections (GNBSI) more commonly occur in children with comorbidities and are increasingly associated with antimicrobial resistance. There are few large studies of GNBSI in children that relate the clinical presentation, pathogen characteristics and outcomes. METHODS: A 3-year prospective study of GNBSI in children aged <18 years was conducted in five Australian children's hospitals between 2019-2021. The clinical characteristics, disease severity and outcomes were recorded. Causative pathogens underwent antibiotic susceptibility testing and whole genome sequencing. RESULTS: There were 931 GNBSI episodes involving 818 children. Median age was 3 years (IQR 0.6-8.5). 576/931 episodes (62%) were community onset though 661/931 (71%) occurred in children with comorbidities and a central venous catheter (CVC) was present in 558/931 (60%). CVC (145/931) and urinary tract (149/931) were the most common sources (16% each). 100/931 (11%) children required Intensive Care Unit (ICU) admission and a further 11% (105/931) developed GNBSI in ICU. 659/927 (71%) isolates were Enterobacterales of which 22% (138/630) were third generation cephalosporin resistant (3GCR). Extended spectrum beta-lactamase genes (ESBL) were confirmed in 65/138 (47%) 3GCR-Enterobacterales. Most common ESBL genes were blaCTX-M-15 (34/94, 36%) and blaSHV-12 (10/94, 11%). There were 48 deaths overall and 30-day in-hospital mortality was 3% (32/931). Infections with 3GCR Enterobacterales were independently associated with higher mortality (adjusted OR 3.2, 95%CI 1.6-6.4). CONCLUSION: GNBSI in children are frequently healthcare-associated and affect children under 5 years. Infections with 3GCR Enterobacterales were associated with worse outcomes. These findings will inform optimal management guidelines and help prioritise future antimicrobial clinical trials.
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INTRODUCTION: Blood cultures have low sensitivity for candidemia. Sensitivity can be improved by the culture-independent system T2 Magnetic Resonance (T2). SeptiCyte RAPID is a host response assay quantifying the risk of infection-related inflammation through a scoring system (SeptiScore). We investigate the performance of SeptiScore in detecting persistent candidemia as defined by conventional cultures and T2. METHODS: This is a prospective multicentre observational study on patients with candidemia. Blood cultures and blood samples for assessment by T2 and SeptiCyte were collected for 4 consecutive days after the index culture. The performance of SeptiScore was explored to predict persistent candidemia as defined by (1) positive follow-up blood culture (2) either positive follow-up blood culture or T2 sample. RESULTS: 10 patients were enrolled including 34 blood collections assessed with the 3 methods. Overall, 4/34 (12%) follow-up blood cultures and 6/34 (18%) T2 samples were positive. A mixed model showed significantly higher SeptiScores associated with persistent candidemia when this was defined as either a positive follow-up blood culture or T2 sample (0.82, 95%CI 0.06 to 1.58) but not when this was defined as a positive follow-up blood culture only (-0.57, 95%CI -1.28 to 0.14). ROC curve for detection of persistent candidemia by SeptiScore at day 1 follow-up showed an AUC of 0.85 (95%CI 0.52-1.00) when candidemia was defined by positive follow-up blood culture, and an AUC of 1.00 (95%CI 1.00-1.00) when candidemia was defined according to both methods. CONCLUSION: Integrating transcriptome profiling with culture-independent systems and conventional cultures may increase our ability to diagnose persistent candidemia.
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Cultivo de Sangre , Candidemia , Humanos , Candidemia/diagnóstico , Candidemia/microbiología , Candidemia/sangre , Estudios Prospectivos , Masculino , Femenino , Cultivo de Sangre/métodos , Anciano , Persona de Mediana Edad , Candida/genética , Candida/aislamiento & purificación , Sensibilidad y Especificidad , Anciano de 80 o más Años , Curva ROCRESUMEN
BACKGROUND: Although Proteus species are occasional causes of serious infections, their epidemiology has not been well defined. The objective was to describe the overall and species-specific occurrence and determinants of Proteus species bloodstream infection (BSI) in a large Australian population. METHODS: All Queensland residents with Proteus species BSI identified within the publicly funded healthcare system between 2000 and 2019 were included. RESULTS: A total of 2,143 incident episodes of Proteus species BSI were identified among 2,079 Queensland residents. The prevalence of comorbid illness differed with higher Charlson comorbidity scores observed with P. penneri and P. vulgaris, and higher prevalence of liver disease with P. penneri, higher comorbid cancer with P. vulgaris, and lower diabetes and renal disease prevalence with P. mirabilis BSIs. CONCLUSION: This study provides novel information on the epidemiology of Proteus species BSI.
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Bacteriemia , Infecciones por Proteus , Proteus , Humanos , Bacteriemia/epidemiología , Bacteriemia/microbiología , Masculino , Persona de Mediana Edad , Femenino , Infecciones por Proteus/epidemiología , Infecciones por Proteus/microbiología , Anciano , Queensland/epidemiología , Proteus/clasificación , Proteus/aislamiento & purificación , Prevalencia , Adulto , Comorbilidad , Anciano de 80 o más Años , Adulto Joven , Proteus mirabilis/aislamiento & purificación , Proteus mirabilis/clasificaciónRESUMEN
Background: Bloodstream infections (BSIs) caused by carbapenem-resistant Enterobacterales (CRE) are a global health concern. Rapid identification of CRE may improve patient outcomes and reduce inappropriate antibiotic prescription. The use of risk-scoring tools (RSTs) can be valuable for optimizing the decision-making process for empirical antibiotic therapy of suspected CRE bacteraemia. These tools can also be used to triage use of expensive rapid diagnostic methods. Methods: We systematically reviewed the relevant literature in PubMed/MEDLINE, CINAHL, Cochrane, Web of Science, Embase and Scopus up to 1 November 2022 to identify RSTs that predict CRE BSIs. The literature review and analysis of the articles were performed by two researchers; any inconsistencies were resolved through discussion. Results: We identified 9 RSTs developed for early prediction of CRE BSIs and only logistic regression was used for most studies. These RSTs were quite different from each other in terms of their performance and the variables they included. They also had notable limitations and very few of them were externally validated. Conclusions: RSTs for early prediction of CRE BSIs have limitations and lack of external validity outside the local setting in which they were developed. Future studies to identify optimal RSTs in high and low CRE-endemic settings are warranted. Approaches based on rapid diagnostics and RSTs should be compared with a treatment approach using both methods in a randomized controlled trial.
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OBJECTIVES: Studies examining time to positivity (TTP) of blood cultures as a risk factor for death have shown conflicting results. The study objective was to examine the effect of TTP on all-cause-30-day case-fatality among a population-based cohort of patients with bloodstream infections (BSI). METHODS: A retrospective cohort study including all residents of Queensland, Australia with incident monomicrobial BSI managed in the publicly funded healthcare system from 2000 to 2019 was performed. Clinical, TTP and all-cause 30-day case-fatality information was obtained from state-wide sources. RESULTS: A cohort of 88 314 patients was assembled. The median TTP was 14 hours, with 5th, 25th, 75th, and 95th percentiles of 4, 10, 20, and 53 hours, respectively. The TTP varied significantly by BSI aetiology. The 30-day all-cause case-fatality rate was 2606/17 879 (14.6%), 2834/24 272 (11.7%), 2378/20 359 (11.7%), and 2752/22 431 (12.3%) within the first, second, third, and fourth TTP quartiles, respectively (p < 0.0001). After adjustment for age, sex, onset, comorbidity, and focus of infection, TTP within 10 hours (first quartile) was associated with a significantly increased risk for death (odds ratio 1.43; 95% CI, 1.35-1.50; p < 0.001). After adjustment for confounding variables (odds ratio; 95% CI), TTP within the first quartile for Staphylococcus aureus (1.56; 1.41-1.73), Streptococcus pneumoniae (1.91; 1.49-2.46), ß-hemolytic streptococci (1.23; 1.00-1.50), Pseudomonas species (2.23; 1.85-2.69), Escherichia coli (1.37; 1.23-1.53), Enterobacterales (1.38; 1.16-1.63), other Gram-negatives (1.68; 1.36-2.06), and anaerobes (1.58; 1.28-1.94) increased the risk for case-fatality. DISCUSSION: This population-based analysis provides evidence that TTP is an important determinant of mortality among patients with BSI.
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Bacteriemia , Cultivo de Sangre , Humanos , Masculino , Femenino , Estudios Retrospectivos , Factores de Riesgo , Persona de Mediana Edad , Anciano , Bacteriemia/mortalidad , Bacteriemia/epidemiología , Bacteriemia/microbiología , Queensland/epidemiología , Factores de Tiempo , Adulto , Anciano de 80 o más Años , Adulto JovenRESUMEN
BACKGROUND: Local governments are the closest level of government to the communities they serve. Traditionally providing roads, rates and garbage services, they are also responsible for policy and regulation, particularly land use planning and community facilities and services that have direct and indirect impacts on (equitable) health and well-being. Partnerships between health agencies and local government are therefore an attractive proposition to progress actions that positively impact community health and well-being. Yet, the factors underpinning these partnerships across different contexts are underdeveloped, as mechanisms to improve population health and well-being. METHODS: A scoping review was conducted to gain insight into the concepts, theories, sources, and knowledge gaps that shape partnerships between health and local governments. The search strategy followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines and was informed by a critical realist approach that identifies necessary, contingent and contextual factors in the literature. MEDLINE, Scopus, Web of Science, and ProQuest Central databases were searched for studies published between January 2005 and July 2021. RESULTS: The search yielded 3472 studies, after deleting duplicates and initial title and abstract screening, 188 papers underwent full text review. Twenty-nine papers were included in the review. Key themes shaping partnerships included funding and resources; partnership qualities; governance and policy; and evaluation and measures of success. The functional, organisational and individual aspects of these themes are explored and presented in a framework. CONCLUSION: Given that local government are the closest level of government to community, this paper provides a sophisticated roadmap that can underpin partnerships between local government and health agencies aiming to influence population health outcomes. By identifying key themes across contexts, we provide a framework that may assist in designing and evaluating evidence-informed health and local government partnerships.
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Gobierno Local , Humanos , Colaboración Intersectorial , Política de Salud , Atención a la Salud/organización & administraciónRESUMEN
BACKGROUND: The recognition of Pseudomonas stutzeri as a cause of infections in humans has been increasing. However, only case reports and small series of P. stutzeri bloodstream infections have been published. Epidemiological data on these infections are extremely scarce. Our objective was to describe the incidence, epidemiology, antimicrobial resistance rates, and outcomes of P. stutzeri bloodstream infections in a large population-based cohort in Australia. METHODS: Retrospective, laboratory-based surveillance study conducted in Queensland, Australia (population ≈ 5 million) during 2000-2019. Clinical information was obtained from public hospital admissions and vital statistics databases. RESULTS: In total, 228 episodes of P. stutzeri bloodstream infections were identified. Increased incidence was observed in the later years, especially in older men, and was higher during the rainy months of the year and in the warmest and more humid regions of the state. The majority of bloodstream infections were community-onset with 120 (52.6%) community-associated and 59 (25.9%) ambulatory healthcare-associated episodes. Only 49 cases (21.5%) were nosocomial. The most common foci of infection were skin and soft tissue, lower respiratory tract, and intra-abdominal. No isolate showed antimicrobial resistance. Thirty-one patients (13.6%) died. The mortality rate in patients with a respiratory infectious source was higher (21%). CONCLUSIONS: P. stutzeri bloodstream infection was predominantly a community-onset condition including ambulatory healthcare related cases, with increasing incidence, especially in older males. No antimicrobial resistance was observed. Mortality was high in patients with respiratory infectious source. This new observational data have implications when considering the epidemiology of these infections and for patient management.
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Bacteriemia , Infecciones Comunitarias Adquiridas , Infecciones por Pseudomonas , Pseudomonas stutzeri , Humanos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/mortalidad , Infecciones Comunitarias Adquiridas/epidemiología , Anciano , Incidencia , Infecciones por Pseudomonas/mortalidad , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/microbiología , Bacteriemia/mortalidad , Bacteriemia/microbiología , Bacteriemia/epidemiología , Adulto , Queensland/epidemiología , Anciano de 80 o más Años , Infección Hospitalaria/mortalidad , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Adulto Joven , Adolescente , Antibacterianos/uso terapéuticoRESUMEN
Joint infections cause significant morbidity and mortality. Rapid diagnosis enables prompt initiation of appropriate antimicrobial therapy and surgical treatment. We conducted a systematic review and meta-analysis to evaluate the accuracy of genus- or species-specific polymerase chain reaction (PCR) in diagnosing joint infections. The literature databases were searched for articles from January 2010 to December 2022. The meta-analysis using the split component synthesis (SCS) method, included 20 studies with 2,457 adult participants. The pooled sensitivity, specificity, diagnostic odds ratio, and AUC of PCR were 49 % (95 % CI [37.9-60.2]), 95.7 % (95 % CI [91.6-97.8]), 21.32, and 0.82 respectively. Sensitivity was highest for sonicate fluid and lowest for periprosthetic tissue. The mean turnaround time to results was 4.7 hours (SD 1.1). PCR is a favourable option for diagnosing joint infections due to its rapid results, but it has low sensitivity. To enhance diagnostic yield, the test should be used in conjunction with other methods.
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Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad , Humanos , Reacción en Cadena de la Polimerasa/métodos , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/clasificación , Artritis Infecciosa/diagnóstico , Artritis Infecciosa/microbiología , Técnicas de Diagnóstico Molecular/métodosRESUMEN
Existing tools for phylogeographic and epidemiological visualisation primarily provide a macro-geographic view of epidemic and pandemic transmission events but offer little support for detailed investigation of outbreaks in healthcare settings. Here, we present HAIviz, an interactive web-based application designed for integrating and visualising genomic epidemiological information to improve the tracking of healthcare-associated infections (HAIs). HAIviz displays and links the outbreak timeline, building map, phylogenetic tree, patient bed movements, and transmission network on a single interactive dashboard. HAIviz has been developed for bacterial outbreak investigations but can be utilised for general epidemiological investigations focused on built environments for which visualisation to customised maps is required. This paper describes and demonstrates the application of HAIviz for HAI outbreak investigations.
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Infección Hospitalaria , Genómica , Humanos , Filogenia , Brotes de Enfermedades , Infección Hospitalaria/epidemiología , PandemiasRESUMEN
Background: This targeted and comprehensive policy scan examined how different levels of governments in Australia and Canada responded to the financial crisis brought on by the COVID-19 pandemic. We mapped the types of early policy responses addressing financial strain and promoting financial wellbeing. We also examined their equity considerations. Methods: Through a systematic search, snowballing, and manual search, we identified Canadian and Australian policies at all government levels related to financial strain or financial wellbeing enacted or amended in 2019-2020. Using a deductive-inductive approach, policies were categorized by jurisdiction level, focal areas, and target population groups. Results: In total, 213 and 97 policies in Canada and Australia, respectively, were included. Comparisons between Canadian and Australian policies indicated a more diversified and equity-targeted policy landscape in Canada. In both countries, most policies focused on individual and family finances, followed by housing and employment areas. Conclusions: The policy scan identified gaps and missed opportunities in the early policies related to financial strain and financial wellbeing. While fast, temporary actions addressed individuals' immediate needs, we recommend governments develop a longer-term action plan to tackle the root causes of financial strain and poor financial wellbeing for better health and non-health crisis preparedness. Statement on Ethics and Informed Consent: This research reported in this paper did not require ethical clearance or patient informed consent as the data sources were published policy documents. This study did not involve data collection with humans (or animals), nor any secondary datasets involving data provided by humans (or from animal studies).
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We describe the demographics, clinical and molecular epidemiology of extended-spectrum ß-lactamase (ESBL) Escherichia coli bloodstream infections (BSI) in Central Australia. All ESBL-producing E. coli bloodstream isolates from January 2018 to December 2020 were retrospectively identified. Demographic and clinical information was extracted by chart review. Whole-genome sequencing was performed for multi-locus sequence typing, antibiotic-resistance genes, and phylogenetic relationships. We identified 41 non-duplicate episodes of ESBL E. coli BSI. Median age was 55 years (IQR 47-63), 78% were female, 93% were Aboriginal, and half came from a remote community. Infections were predominantly urinary (68%, 28/41). In the 12 months prior, 70% (26/37) of identified patients had been hospitalised and 81% (30/37) prescribed antibiotics. Meropenem and piperacillin-tazobactam susceptibility was maintained in 100% and 95% of isolates, respectively. Co-resistance to non-ß-lactam antibiotics was 32% to gentamicin, 61% to trimethoprim/sulfamethoxazole, and 68% to ciprofloxacin. For sequenced isolates, 41% (16/35) were sequence type 131 (ST131). Mean acquired antibiotic-resistance genes for each isolate was 12.3 (SD 3.1). Four isolates carried an OXA-1 gene. Only non-ST131 isolates carried AmpC and acquired quinolone-resistance genes. There was some evidence of clustering of closely related strains, but no evidence of community or healthcare admission overlap. ESBL rates are rapidly rising in Central Australia, which is a conducive environment for antibiotic resistance development (e.g., overcrowding, socioeconomic disadvantages, high healthcare exposure and high antibiotic use). Future research is required to explore resistance-transmission dynamics in this unique setting.
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Background:Burkholderia pseudomallei, the causative agent of melioidosis, is highly genetically recombinant, resulting in significant genomic diversity. Multiple virulence factors have been associated with specific disease presentations. To date, there are limited data relating to genomic diversity and virulence factors associated with melioidosis cases in North Queensland, Australia. Aim: To describe the genetic diversity of B. pseudomallei and identify virulence factors associated with clinical risk factors and patient outcomes. Methods: Whole genome sequencing of clinical isolates was performed and analysed with clinical data obtained from a retrospective melioidosis cohort study. Results: Fifty-nine distinct sequence types (STs) were identified from the 128 clinical isolates. Six STs comprised 64/128 (50%) isolates. Novel STs accounted for 38/59 (64%) STs, with ST TSV-13 as the most prevalent (n = 7), and were less likely to possess an LPS A genotype or YLF gene cluster (p < 0.001). These isolates were most likely to be found outside the inner city (aOR: 4.0, 95% CI: 1.7-9.0, p = 0.001). ST TSV-13 was associated with increased mortality (aOR: 6.1, 95% CI: 1.2-30.9, p = 0.03). Patients with a history of alcohol excess were less likely to be infected by fhaB3 (aOR 0.2, 95% CI: 0.1-0.7, p = 0.01) or YLF (aOR: 0.4, 95% CI: 0.2-0.9, p = 0.04) positive isolates. Conclusions: There are a significant number of novel sequence types in Townsville, Australia. An emerging novel ST appears to have an association with geographic location and mortality. Ongoing investigation is required to further understand the impact of this ST on the Townsville region.
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The past decade has seen an increase in the prevalence of sequence type (ST) 45 methicillin-resistant Staphylococcus aureus (MRSA), yet the underlying drivers for its emergence and spread remain unclear. To better understand the worldwide dissemination of ST45 S. aureus, we performed phylogenetic analyses of Australian isolates, supplemented with a global population of ST45 S. aureus genomes. Our analyses revealed a distinct lineage of multidrug-resistant ST45 MRSA harbouring qacA, predominantly found in Australia and Singapore. Bayesian inference predicted that the acquisition of qacA occurred in the late 1990s. qacA was integrated into a structurally variable region of the chromosome containing Tn552 (carrying blaZ) and Tn4001 (carrying aac(6')-aph(2")) transposable elements. Using mutagenesis and in vitro assays, we provide phenotypic evidence that qacA confers tolerance to chlorhexidine. These findings collectively suggest both antimicrobial resistance and the carriage of qacA may play a role in the successful establishment of ST45 MRSA.
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Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus/genética , Teorema de Bayes , Filogenia , Infecciones Estafilocócicas/epidemiología , Proteínas de Transporte de Membrana/genética , Proteínas Bacterianas/genética , AustraliaRESUMEN
Neonatal meningitis is a devastating disease associated with high mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis in full-term infants (herein NMEC) and the most common cause of meningitis in preterm neonates. Here, we investigated the genomic relatedness of a collection of 58 NMEC isolates spanning 1974-2020 and isolated from seven different geographic regions. We show NMEC are comprised of diverse sequence types (STs), with ST95 (34.5%) and ST1193 (15.5%) the most common. No single virulence gene profile was conserved in all isolates; however, genes encoding fimbrial adhesins, iron acquisition systems, the K1 capsule, and O antigen types O18, O75, and O2 were most prevalent. Antibiotic resistance genes occurred infrequently in our collection. We also monitored the infection dynamics in three patients that suffered recrudescent invasive infection caused by the original infecting isolate despite appropriate antibiotic treatment based on antibiogram profile and resistance genotype. These patients exhibited severe gut dysbiosis. In one patient, the causative NMEC isolate was also detected in the fecal flora at the time of the second infection episode and after treatment. Thus, although antibiotics are the standard of care for NMEC treatment, our data suggest that failure to eliminate the causative NMEC that resides intestinally can lead to the existence of a refractory reservoir that may seed recrudescent infection.
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Infecciones por Escherichia coli , Meningitis , Recién Nacido , Humanos , Escherichia coli/genética , Virulencia/genética , Células ClonalesRESUMEN
We aimed to evaluate the performance of Oxford Nanopore Technologies (ONT) sequencing from positive blood culture (BC) broths for bacterial identification and antimicrobial susceptibility prediction. Patients with suspected sepsis in four intensive care units were prospectively enrolled. Human-depleted DNA was extracted from positive BC broths and sequenced using ONT (MinION). Species abundance was estimated using Kraken2, and a cloud-based system (AREScloud) provided in silico predictive antimicrobial susceptibility testing (AST) from assembled contigs. Results were compared to conventional identification and phenotypic AST. Species-level agreement between conventional methods and AST predicted from sequencing was 94.2% (49/52), increasing to 100% in monomicrobial infections. In 262 high-quality AREScloud AST predictions across 24 samples, categorical agreement (CA) was 89.3%, with major error (ME) and very major error (VME) rates of 10.5% and 12.1%, respectively. Over 90% CA was achieved for some taxa (e.g., Staphylococcus aureus) but was suboptimal for Pseudomonas aeruginosa. In 470 AST predictions across 42 samples, with both high quality and exploratory-only predictions, overall CA, ME, and VME rates were 87.7%, 8.3%, and 28.4%. VME rates were inflated by false susceptibility calls in a small number of species/antibiotic combinations with few representative resistant isolates. Time to reporting from sequencing could be achieved within 8-16 h from BC positivity. Direct sequencing from positive BC broths is feasible and can provide accurate predictive AST for some species. ONT-based approaches may be faster but significant improvements in accuracy are required before it can be considered for clinical use.IMPORTANCESepsis and bloodstream infections carry a high risk of morbidity and mortality. Rapid identification and susceptibility prediction of causative pathogens, using Nanopore sequencing direct from blood cultures, may offer clinical benefit. We assessed this approach in comparison to conventional phenotypic methods and determined the accuracy of species identification and susceptibility prediction from genomic data. While this workflow holds promise, and performed well for some common bacterial species, improvements in sequencing accuracy and more robust predictive algorithms across a diverse range of organisms are required before this can be considered for clinical use. However, results could be achieved in timeframes that are faster than conventional phenotypic methods.
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Secuenciación de Nanoporos , Sepsis , Humanos , Cultivo de Sangre/métodos , Pruebas de Sensibilidad Microbiana , Sepsis/microbiología , Antibacterianos , Cuidados CríticosRESUMEN
INTRODUCTION: Improving sustainable transportation options will help cities tackle growing challenges related to population health, congestion, climate change and inequity. Interventions supporting active transportation face many practical and political hurdles. Implementation science aims to understand how interventions or policies arise, how they can be translated to new contexts or scales and who benefits. Sustainable transportation interventions are complex, and existing implementation science frameworks may not be suitable. To apply and adapt implementation science for healthy cities, we have launched our mixed-methods research programme, CapaCITY/É. We aim to understand how, why and for whom sustainable transportation interventions are successful and when they are not. METHODS AND ANALYSIS: Across nine Canadian municipalities and the State of Victoria (Australia), our research will focus on two types of sustainable transportation interventions: all ages and abilities bicycle networks and motor vehicle speed management interventions. We will (1) document the implementation process and outcomes of both types of sustainable transportation interventions; (2) examine equity, health and mobility impacts of these interventions; (3) advance implementation science by developing a novel sustainable transportation implementation science framework and (4) develop tools for scaling up and scaling out sustainable transportation interventions. Training activities will develop interdisciplinary scholars and practitioners able to work at the nexus of academia and sustainable cities. ETHICS AND DISSEMINATION: This study received approval from the Simon Fraser University Office of Ethics Research (H22-03469). A Knowledge Mobilization Hub will coordinate dissemination of findings via a website; presentations to academic, community organisations and practitioner audiences; and through peer-reviewed articles.
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Creación de Capacidad , Ciencia de la Implementación , Humanos , Ciudades , Canadá , VictoriaRESUMEN
PURPOSE: Early recognition and effective treatment of sepsis improves outcomes in critically ill patients. However, antibiotic exposures are frequently suboptimal in the intensive care unit (ICU) setting. We describe the feasibility of the Bayesian dosing software Individually Designed Optimum Dosing Strategies (ID-ODS™), to reduce time to effective antibiotic exposure in children and adults with sepsis in ICU. METHODS: A multi-centre prospective, non-randomised interventional trial in three adult ICUs and one paediatric ICU. In a pre-intervention Phase 1, we measured the time to target antibiotic exposure in participants. In Phase 2, antibiotic dosing recommendations were made using ID-ODS™, and time to target antibiotic concentrations were compared to patients in Phase 1 (a pre-post-design). RESULTS: 175 antibiotic courses (Phase 1 = 123, Phase 2 = 52) were analysed from 156 participants. Across all patients, there was no difference in the time to achieve target exposures (8.7 h vs 14.3 h in Phase 1 and Phase 2, respectively, p = 0.45). Sixty-one courses in 54 participants failed to achieve target exposures within 24 h of antibiotic commencement (n = 36 in Phase 1, n = 18 in Phase 2). In these participants, ID-ODS™ was associated with a reduction in time to target antibiotic exposure (96 vs 36.4 h in Phase 1 and Phase 2, respectively, p < 0.01). These patients were less likely to exhibit subtherapeutic antibiotic exposures at 96 h (hazard ratio (HR) 0.02, 95% confidence interval (CI) 0.01-0.05, p < 0.01). There was no difference observed in in-hospital mortality. CONCLUSIONS: Dosing software may reduce the time to achieve target antibiotic exposures. It should be evaluated further in trials to establish its impact on clinical outcomes.
Asunto(s)
Antibacterianos , Sepsis , Adulto , Niño , Humanos , Antibacterianos/uso terapéutico , Teorema de Bayes , Enfermedad Crítica/terapia , Unidades de Cuidado Intensivo Pediátrico , Estudios Prospectivos , Sepsis/tratamiento farmacológico , Programas InformáticosRESUMEN
Powell and Manion present an important review of reviews about health and policy research. They zero in on theories of the policy process as the most likely to unearth what is really going on in health policy. Here I contend that their analysis insufficiently attends to institutions. Powell and Manion situate 'institutions' (with 'Ideas' and 'Interests') as a 'health policy process models' that 'tend to' list factors rather than connect them. Rather, I show how there is a rich history of considering institutions in the political science literature that is under considered by Powell and Manion. By necessity for a Public Health audience I quickly pull back the covers on 'rigour' and 'causation' to demonstrate what is 'fit for purpose' in rigorous institution focussed policy analysis. I conclude by arguing how institutionally focussed public health policy analysis is vital for understanding and addressing heath inequities. That focus necessitates research that provides better, explicit, conceptualisations of power in health policy: especially drawing out the roles played by structure and agency. I offer some recent examples.