Elina Eleftheria Pliakos

Colonization With Toxinogenic C. difficile Upon Hospital Admission, and Risk of Infection: A Systematic Review and Meta-Analysis

Objectives:It has been suggested that colonization with C. difficile protects from infection. Nevertheless, the association between carriage of toxinogenic strains and ensuing C. difficile infections (CDIs) has not been studied.Methods:We searched PubMed and EMBASE databases up to 20 June 2014, using the term “difficile”. Our primary outcomes of interest included the prevalence of isolation of toxinogenic C. difficile or its toxins from asymptomatic patients on hospital admission through stool or rectal swab testing and the risk of ensuing infection among colonized and noncolonized patients. Data on previous hospitalization, antibiotic, and proton pump inhibitor (PPI) use and prior CDIs among colonized and noncolonized patients were also extracted.Results:Nineteen out of 26,081 studies on 8,725 patients were included. The pooled prevalence of toxinogenic C. difficile colonization was 8.1% (95% confidence interval (CI) 5.7–11.1%), with an increasing trend over time (P=0.003), and 10.0% (95% CI 7.1–13.4%) among North American studies. Patients colonized upon hospital admission had a 5.9 times higher risk of subsequent CDIs compared with noncolonized patients (relative risk (RR) 5.86; 95% CI 4.21–8.16). The risk of CDI for colonized patients was 21.8% (95% CI 7.9–40.1%), which was significantly higher than that of noncolonized patients (3.4%; 95% CI 1.5–6.0%; P=0.03), with an attributable risk of 18.4%. History of hospitalization during the previous 3 months was associated with a higher risk of colonization (RR 1.63; 95% CI 1.13–2.34), as opposed to previous antibiotic (RR 1.07; 95% CI 0.75–1.53) and PPI use (RR 1.44; 95% CI 0.94–2.23), as well as history of CDI (RR 1.45; 95% CI 0.66–3.18) that had no impact.Conclusions:Over 8% of admitted patients are carriers of toxinogenic C. difficile with an almost 6 times higher risk of infection. These findings update current knowledge regarding the contribution of colonization in CDI epidemiology and stress the importance of preventive measures toward colonized patients.

MRSA and VRE colonization in solid organ transplantation: a meta-analysis of published studies.

The burden of methicillin‐resistant Staphylococcus aureus (MRSA) and vancomycin‐resistant enterococcus (VRE) colonization among the increasing number of solid organ transplant patients has not been systematically explored. We searched PubMed and EMBASE for pertinent articles, performed a meta‐analysis of prevalence across eligible studies and estimated the risk of ensuing MRSA or VRE infections relative to colonization status. We stratified effects in the pretransplant and posttransplant period. Twenty‐three studies were considered eligible. Seventeen out of 23 (74%) referred to liver transplants. Before transplantation, the pooled prevalence estimate for MRSA and VRE was 8.5% (95% confidence interval [CI] 3.2–15.8) and 11.9% (95% CI 6.8–18.2), respectively. MRSA estimate was influenced by small studies and was lower (4.0%; 95% CI 0.4–10.2) across large studies (>200 patients). After transplantation, the prevalence estimates were 9.4% (95% CI 3.0–18.5) for MRSA and 16.2% (95% CI 10.7–22.6) for VRE. Pretransplant as well as posttransplant MRSA colonization significantly increased the risk for MRSA infections (pooled risk ratio [RR] 5.51; 95% CI 2.36–12.90 and RR 10.56; 95% CI 5.58–19.95, respectively). Pretransplant and posttransplant VRE colonization were also associated with significant risk of VRE infection (RR 6.65; 95% CI 2.54–17.41 and RR 7.93; 95% CI 2.36–26.67, respectively). Solid organ transplantation is a high‐risk setting for MRSA and VRE colonization, and carrier state is associated with infection. Upgraded focus in prevention and eradication strategies is warranted.

Asymptomatic Carriers of Toxigenic C. difficile in Long-Term Care Facilities: A Meta-Analysis of Prevalence and Risk Factors

Background The impact of Clostridium difficile colonization in C. difficile infection (CDI) is inadequately explored. As a result, asymptomatic carriage is not considered in the development of infection control policies and the burden of carrier state in long-term care facilities (LTCFs) is unknown. Purpose To explore the epidemiology of C. difficile colonization in LTCFs, identify predisposing factors and describe its impact on healthcare management. Data Sources PubMed, Embase and Web of Science (up to June 2014) without language restriction, complemented by reference lists of eligible studies. Study Selection All studies providing extractable data on the prevalence of toxigenic C. difficile colonization among asymptomatic residents in LTCFs. Data Extraction Two authors extracted data independently. Statistical Methods The pooled colonization estimates were calculated using the double arcsine methodology and reported along with their 95% random-effects confidence intervals (CIs), using DerSimonian-Laird weights. We assessed the impact of patient-level covariates on the risk of colonization and effects were reported as odds ratios (OR, 95% CI). We used the colonization estimates to simulate the effective reproduction number R through a Monte Carlo technique. Results Based on data from 9 eligible studies that met the specified criteria and included 1,371 subjects, we found that 14.8% (95%CI 7.6%-24.0%) of LTCF residents are asymptomatic carriers of toxigenic C. difficile. Colonization estimates were significantly higher in facilities with prior CDI outbreak (30.1% vs. 6.5%, p = 0.01). Patient history of CDI (OR 6.07; 95% CI 2.06–17.88; effect derived from 3 studies), prior hospitalization (OR 2.11; 95% CI 1.08–4.13; derived from 3 studies) and antimicrobial use within previous 3 months (OR 3.68; 95% CI 2.04–6.62; derived from 4 studies) were associated with colonization. The predicted colonization rate at admission was 8.9%. Conclusion Asymptomatic carriage of toxigenic C. difficile represents a significant burden in LTCFs and is associated with prior CDI outbreaks in the facility, a history of CDI, prior hospitalization and antimicrobial use. These findings can impact infection control measures at LTCFs.

Adaptation of Cost Analysis Studies in Practice Guidelines.

AbstractClinical guidelines play a central role in day-to-day practice. We assessed the degree of incorporation of cost analyses to guidelines and identified modifiable characteristics that could affect the level of incorporation.We selected the 100 most cited guidelines listed on the National Guideline Clearinghouse (http://www.guideline.gov) and determined the number of guidelines that used cost analyses in their reasoning and the overall percentage of incorporation of relevant cost analyses available in PubMed. Differences between medical specialties were also studied. Then, we performed a case–control study using incorporated and not incorporated cost analyses after 1:1 matching by study subject and compared them by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement requirements and other criteria.We found that 57% of guidelines do not use any cost justification. Guidelines incorporate a weighted average of 6.0% (95% confidence interval [CI] 4.3–7.9) among 3396 available cost analyses, with cardiology and infectious diseases guidelines incorporating 10.8% (95% CI 5.3–18.1) and 9.9% (95% CI 3.9– 18.2), respectively, and hematology/oncology and urology guidelines incorporating 4.5% (95% CI 1.6–8.6) and 1.6% (95% CI 0.4–3.5), respectively. Based on the CHEERS requirements, the mean number of items reported by the 148 incorporated cost analyses was 18.6 (SD = 3.7), a small but significant difference over controls (17.8 items; P = 0.02). Included analyses were also more likely to directly relate cost reductions to healthcare outcomes (92.6% vs 81.1%, P = 0.004) and declare the funding source (72.3% vs 53.4%, P < 0.001), while similar number of cases and controls reported a noncommercial funding source (71% vs 72.7%; P = 0.8).Guidelines remain an underused mechanism for the cost-effective allocation of available resources and a minority of practice guidelines incorporates cost analyses utilizing only 6% of the available cost analyses. Fulfilling the CHEERS requirements, directly relating costs with healthcare outcomes and transparently declaring the funding source seem to be valued by guideline-writing committees.

The Cost-Effectiveness of Rapid Diagnostic Testing for the Diagnosis of Bloodstream Infections with or without Antimicrobial Stewardship

SUMMARY Bloodstream infections are associated with considerable morbidity and health care costs. Molecular rapid diagnostic tests (mRDTs) are a promising complement to conventional laboratory methods for the diagnosis of bloodstream infections and may reduce the time to effective therapy among patients with bloodstream infections. The concurrent implementation of antimicrobial stewardship programs (ASPs) may reinforce these benefits. The aim of this study was to evaluate the cost-effectivenesses of competing strategies for the diagnosis of bloodstream infection alone or combined with an ASP. To this effect, we constructed a decision-analytic model comparing 12 strategies for the diagnosis of bloodstream infection. The main arms compared the use of mRDT and conventional laboratory methods with or without an ASP. The baseline strategy used as the standard was the use of conventional laboratory methods without an ASP, and our decision-analytic model assessed the cost-effectivenesses of 5 principal strategies: mRDT (with and without an ASP), mRDT with an ASP, mRDT without an ASP, conventional laboratory methods with an ASP, and conventional laboratory methods without an ASP. Furthermore, based on the availability of data in the literature, we assessed the cost-effectivenesses of 7 mRDT subcategories, as follows: PCR with an ASP, matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) analysis with an ASP, peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) with an ASP, a blood culture nanotechnology microarray system for Gram-negative bacteria (BC-GP) with an ASP, a blood culture nanotechnology microarray system for Gram-positive bacteria (BC-GN) with an ASP, PCR without an ASP, and PNA-FISH without an ASP. Our patient population consisted of adult inpatients in U.S. hospitals with suspected bloodstream infection. The time horizon of the model was the projected life expectancy of the patients. In a base-case analysis, cost-effectiveness was determined by calculating the numbers of bloodstream infection deaths averted, the numbers of quality-adjusted life years gained, and incremental cost-effectiveness ratios (ICERs). In a probabilistic analysis, uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. In the base-case analysis, MALDI-TOF analysis with an ASP was the most cost-effective strategy, resulting in savings of

The impact of HIV infection and socioeconomic factors on the incidence of gonorrhea: A county-level, US-wide analysis

29,205 per quality-adjusted life year and preventing 1 death per 14 patients with suspected bloodstream infection tested compared to conventional laboratory methods without an ASP (ICER, −

The impact of antibiotic prescription rates on the incidence of MRSA bloodstream infections: a county-level, U.S.-wide analysis

29,205/quality-adjusted life year). BC-GN with an ASP (ICER, −

The Cost-effectiveness of Antimicrobial Lock Solutions for the Prevention of Central Line–Associated Bloodstream Infections

23,587/quality-adjusted life year), PCR with an ASP (ICER, −

Erratum: response to McDonald et al.

19,833/quality-adjusted life year), and PCR without an ASP (ICER, −

Response to Matuchansky

21,039/quality-adjusted life year) were other cost-effective options. In the probabilistic analysis, mRDT was dominant and cost-effective in 85.1% of simulations. Importantly, mRDT with an ASP had an 80.0% chance of being cost-effective, while mRDT without an ASP had only a 41.1% chance. In conclusion, our findings suggest that mRDTs are cost-effective for the diagnosis of patients with suspected bloodstream infection and can reduce health care expenditures. Notably, the combination of mRDT and an ASP can result in substantial health care savings.