Economic evaluation and catheter-related bloodstream infections

Catheter-related bloodstream infections are a serious problem. Many interventions reduce risk, and some have been evaluated in cost-effectiveness studies. We review the usefulness and quality of these economic studies. Evidence is incomplete, and data required to inform a coherent policy are missing. The cost-effectiveness studies are characterized by a lack of transparency, short time-horizons, and narrow economic perspectives. Data quality is low for some important model parameters. Authors of future economic evaluations should aim to model the complete policy and not just single interventions. They should be rigorous in developing the structure of the economic model, include all relevant economic outcomes, use a systematic approach for selecting data sources for model parameters, and propagate the effect of uncertainty in model parameters on conclusions. This will inform future data collection and improve our understanding of the economics of preventing these infections.

The increased risks of death and extra lengths of hospital and ICU stay from hospital-acquired bloodstream infections : a case-control study

Objectives Hospital-acquired bloodstream infections are known to increase the risk of death and prolong hospital stay, but precise estimates of these two important outcomes from well-designed studies are rare, particularly for non-intensive care unit (ICU) patients. We aimed to calculate accurate estimates, which are vital for estimating the economic costs of hospital-acquired bloodstream infections.

Changes in healthcare-associated Staphylococcus aureus bloodstream infections after the introduction of a national hand hygiene initiative

Background. Interventions that prevent healthcare-associated infection should lead to fewer deaths and shorter hospital stays. Cleaning hands (with soap or alcohol) is an effective way to prevent the transmission of organisms, but rates of compliance with hand hygiene are sometimes disappointingly low. The National Hand Hygiene Initiative in Australia aimed to improve hand hygiene compliance among healthcare workers, with the goal of reducing rates of healthcare-associated infection. Methods. We examined whether the introduction of the National Hand Hygiene Initiative was associated with a change in infection rates. Monthly infection rates for healthcare-associated Staphylococcus aureus bloodstream infections were examined in 38 Australian hospitals across 6 states. We used Poisson regression and examined 12 possible patterns of change, with the best fitting pattern chosen using the Akaike information criterion. Monthly bed-days were included to control for increased hospital use over time. Results. The National Hand Hygiene Initiative was associated with a reduction in infection rates in 4 of the 6 states studied. Two states showed an immediate reduction in rates of 17% and 28%, 2 states showed a linear decrease in rates of 8% and 11% per year, and 2 showed no change in infection rates. Conclusions. The intervention was associated with reduced infection rates in most states. The failure in 2 states may have been because those states already had effective initiatives before the national initiative’s introduction or because infection rates were already low and could not be further reduced.

In Response: "Oral versus IV treatment for catheter-related bloodstream infections - by Burke A. Cunha"

In his letter Cunha suggests that oral antibiotic therapy is safer and less expensive than intravenous therapy via central venous catheters (CVCs) (1). The implication is that costs will fall and increased health benefits will be enjoyed resulting in a gain in efficiency within the healthcare system. CVCs are often used in critically ill patients to deliver antimicrobial therapy, but expose patients to a risk of catheter-related bloodstream infection (CRBSI). Our current knowledge about the efficiency (i.e. costeffectiveness) of allocating resources toward interventions that prevent CRBSI in patients requiring a CVC has already been reviewed (2). If for some patient groups antimicrobial therapy can be delivered orally, instead of through a CVC, then the costs and benefits of this alternate strategy should be evaluated...

Educational interventions for preventing vascular catheter bloodstream infections in critical care: Evidence map, systematic review and economic evaluation

Background Bloodstream infections resulting from intravascular catheters (catheter-BSI) in critical care increase patients' length of stay, morbidity and mortality, and the management of these infections and their complications has been estimated to cost the NHS annually £19.1–36.2M. Catheter-BSI are thought to be largely preventable using educational interventions, but guidance as to which types of intervention might be most clinically effective is lacking. Objective To assess the effectiveness and cost-effectiveness of educational interventions for preventing catheter-BSI in critical care units in England. Data sources Sixteen electronic bibliographic databases – including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Cumulative Index to Nursing and Allied Health Literature (CINAHL), NHS Economic Evaluation Database (NHS EED), EMBASE and The Cochrane Library databases – were searched from database inception to February 2011, with searches updated in March 2012. Bibliographies of systematic reviews and related papers were screened and experts contacted to identify any additional references. Review methods References were screened independently by two reviewers using a priori selection criteria. A descriptive map was created to summarise the characteristics of relevant studies. Further selection criteria developed in consultation with the project Advisory Group were used to prioritise a subset of studies relevant to NHS practice and policy for systematic review. A decision-analytic economic model was developed to investigate the cost-effectiveness of educational interventions for preventing catheter-BSI. Results Seventy-four studies were included in the descriptive map, of which 24 were prioritised for systematic review. Studies have predominantly been conducted in the USA, using single-cohort before-and-after study designs. Diverse types of educational intervention appear effective at reducing the incidence density of catheter-BSI (risk ratios statistically significantly < 1.0), but single lectures were not effective. The economic model showed that implementing an educational intervention in critical care units in England would be cost-effective and potentially cost-saving, with incremental cost-effectiveness ratios under worst-case sensitivity analyses of < £5000/quality-adjusted life-year. Limitations Low-quality primary studies cannot definitively prove that the planned interventions were responsible for observed changes in catheter-BSI incidence. Poor reporting gave unclear estimates of risk of bias. Some model parameters were sourced from other locations owing to a lack of UK data. Conclusions Our results suggest that it would be cost-effective and may be cost-saving for the NHS to implement educational interventions in critical care units. However, more robust primary studies are needed to exclude the possible influence of secular trends on observed reductions in catheter-BSI.

Changes in healthcare-associated infections after the introduction of a national hand hygiene initiative

Introduction: Interventions that prevent healthcare-associated infections should lead to fewer deaths and shorter hospital stays. Cleaning hands with soap and water or alcohol rub is an effectiveway to prevent the transmission of organisms, but compliance is sometimes low. The National Hand Hygiene Initiative in Australia aimed to improve hand hygiene compliance among healthcare workers, with the goal of reducing rates of healthcare-associated infections. Methods: We examined if the introduction of the National Hand Hygiene Initiative was associated with a change in infection rates. Monthly infection rates for six types of healthcare-associated infections were examined in 38 Australian hospitals across six states. Infection categories were: bloodstream infections, centralline associated bloodstream infections, methicillin-resistant and methicillin-sensitive Staphylococcus aureus, Staphylococcus aureus bacteraemia and surgical site infections. Results: The National Hand Hygiene Initiative was associated with a statistically significant reduction in infection rates in 11 out of 23 state and infection combinations studied. There was no change in infection rates for nine combinations, and there was an increase in three infection rates in South Australia. Conclusions: The intervention was associated with reduced infection rates in many cases. The lack of improvement in nine cases may have been because they already had effective initiatives before the national initiative’s introduction.

Using the collaborative evidence based practice model : a systematic review and uptake of chlorhexidine-impregnated sponge dressings on central venous access devices in a tertiary cancer centre

Background: Greater research utilisation in cancer nursing practice is needed, in order to provide well-informed and effective nursing care to people affected by cancer. This paper aims to report on the implementation of evidence-based practice in a tertiary cancer centre. Methods: Using a case report design, this paper reports on the use of the Collaborative Model for Evidence Based Practice (CMEBP) in an Australian tertiary cancer centre. The clinical case is the uptake of routine application of chlorhexidine-impregnated sponge dressings for preventing centrally inserted catheter-related bloodstream infections. In this case report, a number of processes that resulted in a service-wide practice change are described. Results: This model was considered a feasible method for successful research utilisation. In this case report, chlorhexidine-impregnated sponge dressings were proposed and implemented in the tertiary cancer centre with an aim of reducing the incidence of centrally inserted catheter-related bloodstream infections and potentially improving patient health outcomes. Conclusion: The CMEBP is feasible and effective for implementing clinical evidence into cancer nursing practice. Cancer nurses and health administrators need to ensure a supportive infrastructure and environment for clinical inquiry and research utilisation exists, in order to enable successful implementation of evidence-based practice in their cancer centres.

The complete genome sequence of Escherichia coli EC958: a high quality reference sequence for the globally disseminated multidrug resistant E. coli O25b:H4-ST131 clone

Escherichia coli ST131 is now recognised as a leading contributor to urinary tract and bloodstream infections in both community and clinical settings. Here we present the complete, annotated genome of E. coli EC958, which was isolated from the urine of a patient presenting with a urinary tract infection in the Northwest region of England and represents the most well characterised ST131 strain. Sequencing was carried out using the Pacific Biosciences platform, which provided sufficient depth and read-length to produce a complete genome without the need for other technologies. The discovery of spurious contigs within the assembly that correspond to site-specific inversions in the tail fibre regions of prophages demonstrates the potential for this technology to reveal dynamic evolutionary mechanisms. E. coli EC958 belongs to the major subgroup of ST131 strains that produce the CTX-M-15 extended spectrum β-lactamase, are fluoroquinolone resistant and encode the fimH30 type 1 fimbrial adhesin. This subgroup includes the Indian strain NA114 and the North American strain JJ1886. A comparison of the genomes of EC958, JJ1886 and NA114 revealed that differences in the arrangement of genomic islands, prophages and other repetitive elements in the NA114 genome are not biologically relevant and are due to misassembly. The availability of a high quality uropathogenic E. coli ST131 genome provides a reference for understanding this multidrug resistant pathogen and will facilitate novel functional, comparative and clinical studies of the E. coli ST131 clonal lineage.

Global dissemination of a multidrug resistant Escherichia coli clone

Escherichia coli sequence type 131 (ST131) is a globally disseminated, multidrug resistant (MDR) clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with several factors, including resistance to fluoroquinolones, high virulence gene content, the possession of the type 1 fimbriae FimH30 allele, and the production of the CTX-M-15 extended spectrum β-lactamase (ESBL). Here, we used genome sequencing to examine the molecular epidemiology of a collection of E. coli ST131 strains isolated from six distinct geographical locations across the world spanning 2000–2011. The global phylogeny of E. coli ST131, determined from whole-genome sequence data, revealed a single lineage of E. coli ST131 distinct from other extraintestinal E. coli strains within the B2 phylogroup. Three closely related E. coli ST131 sublineages were identified, with little association to geographic origin. The majority of single-nucleotide variants associated with each of the sublineages were due to recombination in regions adjacent to mobile genetic elements (MGEs). The most prevalent sublineage of ST131 strains was characterized by fluoroquinolone resistance, and a distinct virulence factor and MGE profile. Four different variants of the CTX-M ESBL–resistance gene were identified in our ST131 strains, with acquisition of CTX-M-15 representing a defining feature of a discrete but geographically dispersed ST131 sublineage. This study confirms the global dispersal of a single E. coli ST131 clone and demonstrates the role of MGEs and recombination in the evolution of this important MDR pathogen.

The serum resistome of a globally disseminated multidrug resistant uropathogenic Escherichia coli Clone

Escherichia coli ST131 is a globally disseminated, multidrug resistant clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with antibiotic resistance; however, this phenotype alone is unlikely to explain its dominance amongst multidrug resistant uropathogens circulating worldwide in hospitals and the community. Thus, a greater understanding of the molecular mechanisms that underpin the fitness of E. coli ST131 is required. In this study, we employed hyper-saturated transposon mutagenesis in combination with multiplexed transposon directed insertion-site sequencing to define the essential genes required for in vitro growth and the serum resistome (i.e. genes required for resistance to human serum) of E. coli EC958, a representative of the predominant E. coli ST131 clonal lineage. We identified 315 essential genes in E. coli EC958, 231 (73%) of which were also essential in E. coli K-12. The serum resistome comprised 56 genes, the majority of which encode membrane proteins or factors involved in lipopolysaccharide (LPS) biosynthesis. Targeted mutagenesis confirmed a role in serum resistance for 46 (82%) of these genes. The murein lipoprotein Lpp, along with two lipid A-core biosynthesis enzymes WaaP and WaaG, were most strongly associated with serum resistance. While LPS was the main resistance mechanism defined for E. coli EC958 in serum, the enterobacterial common antigen and colanic acid also impacted on this phenotype. Our analysis also identified a novel function for two genes, hyxA and hyxR, as minor regulators of O-antigen chain length. This study offers novel insight into the genetic make-up of E. coli ST131, and provides a framework for future research on E. coli and other Gram-negative pathogens to define their essential gene repertoire and to dissect the molecular mechanisms that enable them to survive in the bloodstream and cause disease.

Insights into a multidrug resistant Escherichia coli pathogen of the globally disseminated ST131 lineage : genome analysis and virulence mechanisms

Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum β-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI.

The role of H4 flagella in Escherichia coli ST131 virulence

Escherichia coli sequence type 131 (ST131) is a globally dominant multidrug resistant clone associated with urinary tract and bloodstream infections. Most ST131 strains exhibit resistance to multiple antibiotics and cause infections associated with limited treatment options. The largest sub-clonal ST131 lineage is resistant to fluoroquinolones, contains the type 1 fimbriae fimH30 allele and expresses an H4 flagella antigen. Flagella are motility organelles that contribute to UPEC colonisation of the upper urinary tract. In this study, we examined the specific role of H4 flagella in ST131 motility and interaction with host epithelial and immune cells. We show that the majority of H4-positive ST131 strains are motile and are enriched for flagella expression during static pellicle growth. We also tested the role of H4 flagella in ST131 through the construction of specific mutants, over-expression strains and isogenic mutants that expressed alternative H1 and H7 flagellar subtypes. Overall, our results revealed that H4, H1 and H7 flagella possess conserved phenotypes with regards to motility, epithelial cell adhesion, invasion and uptake by macrophages. In contrast, H4 flagella trigger enhanced induction of the anti-inflammatory cytokine IL-10 compared to H1 and H7 flagella, a property that may contribute to ST131 fitness in the urinary tract.

Staphylococcus epidermidis as a cause of bacteremia

Staphylococcus epidermidis is a biofilm-producing commensal organism found ubiquitously on human skin and mucous membranes, as well as on animals and in the environment. Biofilm formation enables this organism to evade the host immune system. Colonization of percutaneous devices or implanted medical devices allows bacteria access to the bloodstream. Isolation of this organism from blood cultures may represent either contamination during the blood collection procedure or true bacteremia. S. epidermidis bloodstream infections may be indolent compared with other bacteria. Isolation of S. epidermidis from a blood culture may present a management quandary for clinicians. Over-treatment may lead to patient harm and increases in healthcare costs. There are numerous reports indicating the difficulty of predicting clinical infection in patients with positive blood cultures with this organism. No reliable phenotypic or genotypic algorithms currently exist to predict the pathogenicity of a S. epidermidis bloodstream infection. This review will discuss the latest advances in identification methods, global population structure, pathogenicity, biofilm formation, antimicrobial resistance and clinical significance of the detection of S. epidermidis in blood cultures. Previous studies that have attempted to discriminate between invasive and contaminating strains of S. epidermidis in blood cultures will be analyzed.

The need for cost-effectiveness analyses of antimicrobial stewardship programmes: A structured review

The cost effectiveness of antimicrobial stewardship (AMS) programmes was reviewed in hospital settings of Organisation for Economic Co-operation and Development (OECD) countries, and limited to adult patient populations. In each of the 36 studies, the type of AMS strategy and the clinical and cost outcomes were evaluated. The main AMS strategy implemented was prospective audit with intervention and feedback (PAIF), followed by the use of rapid technology, including rapid polymerase chain reaction (PCR)-based methods and matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) technology, for the treatment of bloodstream infections. All but one of the 36 studies reported that AMS resulted in a reduction in pharmacy expenditure. Among 27 studies measuring changes to health outcomes, either no change was reported post-AMS, or the additional benefits achieved from these outcomes were not quantified. Only two studies performed a full economic evaluation: one on a PAIF-based AMS intervention; and the other on use of rapid technology for the selection of appropriate treatment for serious Staphylococcus aureus infections. Both studies found the interventions to be cost effective. AMS programmes achieved a reduction in pharmacy expenditure, but there was a lack of consistency in the reported cost outcomes making it difficult to compare between interventions. A failure to capture complete costs in terms of resource use makes it difficult to determine the true cost of these interventions. There is an urgent need for full economic evaluations that compare relative changes both in clinical and cost outcomes to enable identification of the most cost-effective AMS strategies in hospitals.