Sepsis: the LightCycler SeptiFast Test MGRADE®, SepsiTest™ and IRIDICA BAC BSI assay for rapidly identifying bloodstream bacteria and fungi – a systematic review and economic evaluation

Background: Sepsis can lead to multiple organ failure and death. Timely and appropriate treatment can reduce in-hospital mortality and morbidity. Objectives: To determine the clinical effectiveness and cost-effectiveness of three tests [LightCycler SeptiFast Test MGRADE® (Roche Diagnostics, Risch-Rotkreuz, Switzerland); SepsiTest™ (Molzym Molecular Diagnostics, Bremen, Germany); and the IRIDICA BAC BSI assay (Abbott Diagnostics, Lake Forest, IL, USA)] for the rapid identification of bloodstream bacteria and fungi in patients with suspected sepsis compared with standard practice (blood culture with or without matrix-absorbed laser desorption/ionisation time-offlight mass spectrometry). Data sources: Thirteen electronic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched from January 2006 to May 2015 and supplemented by hand-searching relevant articles. Review methods: A systematic review and meta-analysis of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. A decision tree was used to estimate the costs and quality-adjusted life-years (QALYs) associated with each test; all other parameters were estimated from published sources. The model was populated with evidence from the systematic review or individual studies, if this was considered more appropriate (base case 1). In a secondary analysis, estimates (based on experience and opinion) from seven clinicians regarding the benefits of earlier test results were sought (base case 2). A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Scenario analyses were used to assess uncertainty. Results: For the review of diagnostic test accuracy, 62 studies of varying methodological quality were included. A meta-analysis of 54 studies comparing SeptiFast with blood culture found that SeptiFast had an estimated summary specificity of 0.86 [95% credible interval (CrI) 0.84 to 0.89] and sensitivity of 0.65 (95% CrI 0.60 to 0.71). Four studies comparing SepsiTest with blood culture found that SepsiTest had an estimated summary specificity of 0.86 (95% CrI 0.78 to 0.92) and sensitivity of 0.48 (95% CrI 0.21 to 0.74), and four studies comparing IRIDICA with blood culture found that IRIDICA had an estimated summary specificity of 0.84 (95% CrI 0.71 to 0.92) and sensitivity of 0.81 (95% CrI 0.69 to 0.90). Owing to the deficiencies in study quality for all interventions, diagnostic accuracy data should be treated with caution. No randomised clinical trial evidence was identified that indicated that any of the tests significantly improved key patient outcomes, such as mortality or duration in an intensive care unit or hospital. Base case 1 estimated that none of the three tests provided a benefit to patients compared with standard practice and thus all tests were dominated. In contrast, in base case 2 it was estimated that all cost per QALY-gained values were below £20,000; the IRIDICA BAC BSI assay had the highest estimated incremental net benefit, but results from base case 2 should be treated with caution as these are not evidence based. Limitations: Robust data to accurately assess the clinical effectiveness and cost-effectiveness of the interventions are currently unavailable. Conclusions: The clinical effectiveness and cost-effectiveness of the interventions cannot be reliably determined with the current evidence base. Appropriate studies, which allow information from the tests to be implemented in clinical practice, are required.

Clinical and technical factors associated with skin intrinsic fluorescence in subjects with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications(EDIC) studies have established multiyear mean hemoglobin A1c (HbA1c) as predictive of microvascular complications in persons with type 1 diabetes. However, multiyear mean HbA1c is not always available in the clinical setting. Skin advanced glycation end products (AGEs) are thought to partially reflect effects of hyperglycemia over time, and measurement of skin AGEs might be a surrogate for multiyear mean HbA1c. As certain AGEs fluoresce and skin fluorescence has been demonstrated to correlate with the concentration of skin AGEs, noninvasive measurement by skin intrinsic fluorescence(SIF) facilitates the exploration of the association of mean HbA1c and other clinical/technical factors with SIF using the detailed phenotypic database available in DCCT/EDIC.

Cost-effectiveness analysis of screening for lung cancer with low dose spiral CT (computed tomography) in the Australian setting

Introduction:
Low dose spiral computed tomography (CT) is a sensitive screening tool for lung cancer that is currently being evaluated in both non-randomised studies and randomised controlled trials.
Methods:
We conducted a quantitative decision analysis using a Markov model to determine whether, in the Australian setting, offering spiral CT screening for lung cancer to high risk individuals would be cost-effective compared with current practice. This exploratory analysis was undertaken predominantly from the perspective of the government as third-party funder. In the base-case analysis, the costs and health outcomes (life-years saved and quality-adjusted life years) were calculated in a hypothetical cohort of 10,000 male current smokers for two alternatives: (1) screen for lung cancer with annual CT for 5 years starting at age 60 year and treat those diagnosed with cancer or (2) no screening and treat only those who present with symptomatic cancer.
Results:
For male smokers aged 60–64 years, with an annual incidence of lung cancer of 552 per 100,000, the incremental cost-effectiveness ratio was $57,325 per life-year saved and $105,090 per QALY saved. For females aged 60–64 years with the same annual incidence of lung cancer, the cost-effectiveness ratio was $51,001 per life-year saved and $88,583 per QALY saved. The model was used to examine the relationship between efficacy in terms of the expected reduction in lung cancer mortality at 7 years and cost-effectiveness. In the base-case analysis lung cancer mortality was reduced by 27% and all cause mortality by 2.1%. Changes in the estimated proportion of stage I cancers detected by screening had the greatest impact on the efficacy of the intervention and the cost-effectiveness. The results were also sensitive to assumptions about the test performance characteristics of CT scanning, the proportion of lung cancer cases overdiagnosed by screening, intervention rates for benign disease, the discount rate, the cost of CT, the quality of life in individuals with early stage screen-detected cancer and disutility associated with false positive diagnoses. Given current knowledge and practice, even under favourable assumptions, reductions in lung cancer mortality of less than 20% are unlikely to be cost-effective, using a value of $50,000 per life-year saved as the threshold to define a “cost-effective” intervention.
Conclusion:
The most feasible scenario under which CT screening for lung cancer could be cost-effective would be if very high-risk individuals are targeted and screening is either highly effective or CT screening costs fall substantially.

Subclavian vein catheter -related infection and hospital costs associated with exchange via a guidewire

An observational study was conducted in a SICU to determine the frequency of subclavian vein catheter-related infection at 72 hours, to identify the hospital cost of exchange via a guidewire and the estimated hospital cost-savings of a 72 hour vs 144 hour exchange policy.^ An overall catheter-related infection ($\geq$15 col. by Maki's technique (1977)) occurred in 3% (3/100) of the catheter tips cultured. Specific infections rates were: 9.7% (3/31) for triple lumen catheters, 0% (0/30) for Swan-Ganz catheters, 0% (0/30) for Cordes catheters, and 0% (0/9) for single lumen catheters.^ An estimated annual hospital cost-savings of $35,699.00 was identified if exchange of 72 hour policy were changed to every 144 hours.^ It was recommended that a randomized clinical trial be conducted to determine the effect of changing a subclavian vein catheter via a guidewire every 72 hours vs 144 hours. ^

Implementation Guide for Surveillance of Central Line Associated Bloodstream Infection -- [Consultation Edition]

The implementation guide for the surveillance of CLABSI in intensive care units (ICU) was produced by the Healthcare Associated Infection (HAI) Technical Working Group of the Australian Commission on Safety and Quality in Health Care(ACSQHC), and endorsed by the ACSQHC HAI Advisory Committee. State surveillance units, the ACSQHC and the Australian and New Zealand Intensive Care Society (ANZICS) have representatives on the Technical Working Group, and have provided input into this document.

Idle central venous catheter-days pose infection risk for patients after discharge from intensive care

This prospective observational study measured idle central venous catheter (CVC)-days (no medical indication), and ward clinicians' adherence to evidence-based practices for preventing short-term central line-associated bloodstream infections (CLABSIs). In 340 patients discharged from ICU over a 1-year period, 208 of 794 CVC-days (26.2%) were idle. Interventions to prevent CLABSIs were poorly implemented. Ward clinicians need education regarding risk management strategies to prevent CLABSIs, and clear accountability processes for prompt catheter removal are recommended.

Comparison between qualitative and semiquantitative catheter-tip cultures: laboratory diagnosis of catheter-related infection in newborns

Este estudo prospectivo avaliou os métodos semiquantitativo e qualitativo de cultura de cateter para o diagnóstico de infecção relacionada a cateter (IRC) em recém-nascidos (RN). Foram incluídas pontas de cateteres provenientes de recém-nascidos internados na Unidade Neonatal do Hospital das Clínicas da Faculdade de Medicina de Botucatu, UNESP. Foram utilizadas as técnicas semiquantitativa e qualitativa de cultura de cateter. Para o diagnóstico de IRC, os microrganismos isolados das culturas de cateteres e de hemoculturas periféricas foram identificados e submetidos ao teste de sensibilidade a antimicrobianos. O padrão ouro correspondeu ao diagnóstico de certeza de IRC, com o isolamento do mesmo microrganismo (espécie e perfil de sensibilidade a antimicrobianos) isolado em hemocultura periférica. Foram estudados 85 cateteres provenientes de 63 RN. A cultura semiquantitativa, embora tenha apresentado menor sensibilidade (90%), apresentou uma maior especificidade (71%) em comparação à sensibilidade de 100% e especificidade de 60% encontradas na cultura qualitativa. Através da identificação dos microrganismos obtidos nas culturas de cateteres, observou-se uma predominância de espécies de Estafilococos coagulase-negativa (ECN). A espécie Staphylococcus epidermidis foi a prevalente (77,5%) nos cateteres com culturas semiquantitativas positivas. Dos 11 episódios de IRC diagnosticados, 8 (72,7%) foram associados a espécies de ECN, dos quais 6 eram da espécie S. epidermidis. Também foram detectados dois casos de IRC por S. aureus e um caso por Candida parapsilosis. O método de cultura semiquantitativo cateter apresentou vantagens para o diagnóstico de IRC em RN quando comparado com o método qualitativo tradicional.

The Bacterial Amyloid Curli Is Associated with Urinary Source Bloodstream Infection

Urinary tract infections are the most common cause of E. coli bloodstream infections (BSI) but the mechanism of bloodstream invasion is poorly understood. Some clinical isolates have been observed to shield themselves with extracellular amyloid fibers called curli at physiologic temperature. We hypothesize that curli fiber assembly at 37 °C promotes bacteremic progression by urinary E. coli strains. Curli expression by cultured E. coli isolates from bacteriuric patients in the presence and absence of bacteremia were compared using Western blotting following amyloid fiber disruption with hexafluoroisopropanol. At 37 °C, urinary isolates from bacteremic patients were more likely to express curli than those from non-bacteremic patients [16/22 (73%) vs. 7/21 (33%); p = 0.01]. No significant difference in curli expression was observed at 30 °C [86% (19/22) vs. 76% (16/21); p = 0.5]. Isolates were clonally diverse between patients, indicating that this phenotype is distributed across multiple lineages. Most same-patient urine and blood isolates were highly related, consistent with direct invasion of urinary bacteria into the bloodstream. 37 °C curli expression was associated with bacteremic progression of urinary E. coli isolates in this population. These findings suggest new future diagnostic and virulence-targeting therapeutic approaches

Bloodstream infection in paediatric cancer centres--leukaemia and relapsed malignancies are independent risk factors.

UNLABELLED In a prospective multicentre study of bloodstream infection (BSI) from November 01, 2007 to July 31, 2010, seven paediatric cancer centres (PCC) from Germany and one from Switzerland included 770 paediatric cancer patients (58% males; median age 8.3 years, interquartile range (IQR) 3.8-14.8 years) comprising 153,193 individual days of surveillance (in- and outpatient days during intensive treatment). Broviac catheters were used in 63% of all patients and Ports in 20%. One hundred forty-two patients (18%; 95% CI 16 to 21%) experienced at least one BSI (179 BSIs in total; bacteraemia 70%, bacterial sepsis 27%, candidaemia 2%). In 57%, the BSI occurred in inpatients, in 79% after conventional chemotherapy. Only 56 % of the patients showed neutropenia at BSI onset. Eventually, patients with acute lymphoblastic leukaemia (ALL) or acute myeloblastic leukaemia (AML), relapsed malignancy and patients with a Broviac faced an increased risk of BSI in the multivariate analysis. Relapsed malignancy (16%) was an independent risk factor for all BSI and for Gram-positive BSI. CONCLUSION This study confirms relapsed malignancy as an independent risk factor for BSIs in paediatric cancer patients. On a unit level, data on BSIs in this high-risk population derived from prospective surveillance are not only mandatory to decide on empiric antimicrobial treatment but also beneficial in planning and evaluating preventive bundles. WHAT IS KNOWN • Paediatric cancer patients face an increased risk of nosocomial bloodstream infections (BSIs). • In most cases, these BSIs are associated with the use of a long-term central venous catheter (Broviac, Port), severe and prolonged immunosuppression (e.g. neutropenia) and other chemotherapy-induced alterations of host defence mechanisms (e.g. mucositis). What is New: • This study is the first multicentre study confirming relapsed malignancy as an independent risk factor for BSIs in paediatric cancer patients. • It describes the epidemiology of nosocomial BSI in paediatric cancer patients mainly outside the stem cell transplantation setting during conventional intensive therapy and argues for prospective surveillance programmes to target and evaluate preventive bundle interventions.

The source, cost and prevention of central venous catheter-related infection

Central venous catheters have become an integral part of patient management however they are associated with many complications including infection. Despite efforts being made to reduce the incidence of such infect ions the problem continues to increase and has resource implications for the Health Service. Studies relating to the source of microorganisms causing CVC-associated infection, the cost of such infections and the efficacy of an antimicrobial catheter have been undertaken. Thirty patients who required a CVC as part of their medical management and underwent cardiac surgery had the distal tips of their catheters sampled whilst in situ. Sampling took place within 1 h of catheter placement. Bacteria were isolated from 16% of the catheter distal tips sampled in situ. The guidewires used to insert the devices were also contaminated (50%). When CVC were inserted via a protective sheath, avoiding contact with the skin. the incidence of microbial contamination was reduced. These findings suggest that despite rigorous skin disinfection and strict aseptic technique, viable microorganisms are impacted onto the distal tip of CVC during the insertion procedure. Needleless intravascular access devices have been introduced in order to reduce the incidence of need1estick injury. However, it was unclear whether such connectors would act as a portal of entry for microorganisms to CVC. The efficacy of these devices was investigated. Within the controlled laboratory environment it was demonstrated that needleless devices, when challenged with microorganisms, did not allow the passage of microbes when flu id was injected. This therefore suggested that the devices should not increase the risk of catheter colonisation. When used in clinical practice however microbial contamination of the needleless connectors was 55 % in comparison to the routinely used luer connectors (23%). The cost of infections associated with CVC was determined. Twenty patients catheterised with a CVC designed for long term use who were admitted to hospital with a presumptive diagnosis of catheter-related infection were studied. The treatment given specifically for this infection was costed. The mean cost of such an infection was £ 1781.81. Throughout the UK this may amount to £1.565.906 per annum. The cost of infections associated with CVC designed for short term use was estimated to be between 5 and 7 million pounds per annum in the UK. In an attempt to reduce both the incidence and cost of catheter- related infection antimicrobial CVC have been developed. The efficacy of a novel polyurethane CVC impregnated on both the internal and external catheter surface with the quaternary ammonium compound benzalkonium chloride was investigated. Eighty eight patients received an antimicrobial catheter and 78 patients a conventional polyurethane CVC. The anti-microbial CVC resulted in a reduction in microbial colonisation of the external and internal polymer surfaces as compared to the control device. The observed reduction in microbial colonisation with the anti-microbial CVC may decrease the likelihood of subsequent infection offering a useful approach to the prevention of catheter-related infections.

Diagnosis of central venous catheter related infection in adult patients

Intravascular catheters are one of the main causes of bacteraemia and septicaemia in hospitalised patients and continue to be associated with a significant morbidity and mortality. Two main types of infections occur, they can be either localised at the catheter insertion site of systemic with a septicaemia. The clinical parameters related to these infections are presented. The laboratory diagnosis of these infections is also extensively reviewed and recommendations are made as to the most appropriate diagnostic method to be used. © 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

Key priorities for Australian infection control : summary of findings from the launch of the Centre for Research Excellence in Reducing Healthcare Associated Infections

The launch of the Centre of Research Excellence in Reducing Healthcare Associated Infection (CRE-RHAI) took place in Sydney on Friday 12 October 2012. The mission of the CRE-RHAI is to generate new knowledge about strategies to reduce healthcare associated infections and to provide data on the cost-effectiveness of infection control programs. As well as launching the CRE-RHAI, an important part of this event was a stakeholder Consultation Workshop, which brought together several experts in the Australian infection control community. The aims of this workshop were to establish the research and clinical priorities in Australian infection control, assess the importance of various multi-resistant organisms, and to gather information about decision making in infection control. We present here a summary and discussion of the responses we received.

Bacteriemia asociada a catéter epicutáneo en la unidad de cuidado intensivo neonatal de la Fundación Cardioinfantil

La bacteriemia asociada a catéter afecta a pacientes en las unidades de cuidado intensivo con una alta morbilidad, mortalidad y aumento de los costos al sistema de salud. Los recién nacidos son la población de más alto riesgo por el mayor uso de catéteres centrales. Objetivo: Caracterizar factores de riesgo para bacteriemia asociada a catéter en la Unidad de Cuidado Intensivo Neonatal de la Fundación Cardioinfantil entre 2005 - 2010 Materiales y método: Estudio descriptivo de corte transversal, incluyó todos los recién nacidos con diagnostico de bacteriemia asociada a catéter. Se analizó la información utilizando frecuencias y medidas de tendencia central. Resultados: Se encontraron 50 pacientes con diagnostico de bacteriemia asociada a catéter. 50% de género masculino, 52% con edad gestacional al nacimiento menor a 36 semanas y 24% con peso menor a 1500 gramos al momento de la inserción del catéter. La edad fue de 24.2 días al momento de la inserción del catéter. En el 66% de los pacientes el sitio de inserción fue el miembro superior, siendo el Sthaphylococcus Epidermidis el germen con el 50% de las bacteriemias. Conclusión: La bacteriemia asociada a catéter afecta paciente prematuros, de bajo peso sin diferencias en genero. La manipulación de dichos dispositivos, el sitio de inserción, el uso previo de antibióticos, la duración del catéter y el uso de nutrición parenteral son factores que están asociados al mayor riesgo de infección. Siendo el Staphylococcus Epidermidis el germen mas frecuente.