[Assessment of Renal Function and Simulation Using Serum Cystatin-C in an Elderly Patient with Uncontrollable Plasma Vancomycin Levels Due to Muscular Dystrophy: A Case Report].

Herein, we describe a case of an elderly patient with muscular dystrophy for whom control of the plasma vancomycin (VCM) concentration proved difficult when he developed a catheter-related bloodstream infection. The pharmacist initially carried out therapeutic drug monitoring using an estimate of the creatinine clearance (CLcr) level, which was based on the serum creatinine (SCr) and serum cystatin-C (CysC) levels, but was ultimately unable to control the plasma VCM concentration. Therefore, the plasma VCM concentration was predicted ex post facto using population pharmacokinetic parameters as a covariate; that is, directly including the glomerular filtration rate (GFRCysC) estimated from the CysC level, which is not affected by the muscle mass. As a result, the estimated VCM concentration was closer to the actual concentration than that predicted using CLcr. Furthermore, the results of examining the predictive accuracy according to the assessment of renal function at the time of initial VCM administration suggested that estimation of the trough concentration using GFRCysC might be useful in elderly patients with muscular dystrophy.

Optimizing Duration of Empiric Management of Suspected Central Line-Associated Bloodstream Infections in Pediatric Patients with Intestinal Failure.

OBJECTIVES: To assess whether a 24-hour length of hospitalization and empiric antibiotic therapy to exclude central line-associated bloodstream infection (CLABSI) in children with intestinal failure is potentially as safe as 48 hours, which is the duration most commonly used but not evidence based. STUDY DESIGN: A prospective single-institution observational cohort study was conducted among pediatric patients with intestinal failure from July 1, 2015, through June 30, 2018, to identify episodes of suspected CLABSI. The primary end point was time from blood sampling to positive blood culture. Secondary end points included presenting symptoms, laboratory test results, responses to a parent/legal guardian-completed symptom survey, length of inpatient stay, costs, and charges. RESULTS: Seventy-three patients with intestinal failure receiving nutritional support via central venous catheters enrolled; 35 were hospitalized with suspected CLABSI at least once during the study. There were 49 positive blood cultures confirming CLABSI in 128 episodes (38%). The median time from blood sampling to positive culture was 11.1 hours. The probability of a blood culture becoming positive after 24 hours was 2.3%. Elevated C-reactive protein and neutrophil predominance in white blood cell count were associated with positive blood cultures. Estimated cost savings by transitioning from a 48-hour to a 24-hour admission to rule-out CLABSI was $4639 per admission. CONCLUSIONS: A 24-hour duration of empiric management to exclude CLABSI may be appropriate for patients with negative blood cultures and no clinically concerning signs. A multi-institutional study would more robustly differentiate patients safe for discharge after 24 hours from those who warrant longer empiric treatment.

The hidden cost of catheter related blood stream infections in patients on parenteral nutrition.

BACKGROUND & AIMS: Parenteral nutrition (PN) is a valuable and life-saving treatment for patients with intestinal failure. While its use is increasing, it has been demonstrated to be a risk factor for intravenous catheter-related blood stream infection (CRBSI) - a significant, serious and potentially fatal complication of PN use. CRBSI can have serious secondary consequences for patients, though, there is a paucity of literature describing these. The aim of this study is to audit the incidence of, and evaluate the consequences of, complications associated with CRBSI. METHODS: Medical records were examined for all parenterally fed patients diagnosed with a CRBSI from 01/01/16 to 31/12/17 in a UK tertiary referral centre for patients requiring intravenous nutritional support. Patients were identified prospectively; data relating to the infection and complications was collected retrospectively. RESULTS: 114 episodes of CRBSI were recorded in 80 patients. 57 occurred during an inpatient admission, 57 occurred in the community and resulted in admission. 21 different adverse events occurred as a result of the CRBSI. The complications identified were varied with the most common being acute kidney injury, deranged electrolytes and urinary tract infections. Other significant complications included DVT, pulmonary abscess and infective endocarditis. 35% of episodes resulted in delayed discharge and 12% required escalation to a critical care bed. The financial impact is estimated at over £800,000 per annum. CONCLUSIONS: The findings demonstrate a plethora of complications which can arise following CRBSI, which pose a significant health risk to parenterally fed patients who already have reduced physiological reserve. Moreover, these findings represent additional financial and resource burden to the health service. The adverse events resulting from CRBSIs should, therefore, be audited to improve outcomes: well-resourced specialist centres are best placed to provide this service.

Antibiotic or silver versus standard ventriculoperitoneal shunts (BASICS): a multicentre, single-blinded, randomised trial and economic evaluation.

BACKGROUND: Insertion of a ventriculoperitoneal shunt for hydrocephalus is one of the commonest neurosurgical procedures worldwide. Infection of the implanted shunt affects up to 15% of these patients, resulting in prolonged hospital treatment, multiple surgeries, and reduced cognition and quality of life. Our aim was to determine the clinical and cost-effectiveness of antibiotic (rifampicin and clindamycin) or silver shunts compared with standard shunts at reducing infection. METHODS: In this parallel, multicentre, single-blind, randomised controlled trial, we included patients with hydrocephalus of any aetiology undergoing insertion of their first ventriculoperitoneal shunt irrespective of age at 21 regional adult and paediatric neurosurgery centres in the UK and Ireland. Patients were randomly assigned (1:1:1 in random permuted blocks of three or six) to receive standard shunts (standard shunt group), antibiotic-impregnated (0·15% clindamycin and 0·054% rifampicin; antibiotic shunt group), or silver-impregnated shunts (silver shunt group) through a randomisation sequence generated by an independent statistician. All patients and investigators who recorded and analysed the data were masked for group assignment, which was only disclosed to the neurosurgical staff at the time of operation. Participants receiving a shunt without evidence of infection at the time of insertion were followed up for at least 6 months and a maximum of 2 years. The primary outcome was time to shunt failure due the infection and was analysed with Fine and Gray survival regression models for competing risk by intention to treat. This trial is registered with ISRCTN 49474281. FINDINGS: Between June 26, 2013, and Oct 9, 2017, we assessed 3505 patients, of whom 1605 aged up to 91 years were randomly assigned to receive either a standard shunt (n=536), an antibiotic-impregnated shunt (n=538), or a silver shunt (n=531). 1594 had a shunt inserted without evidence of infection at the time of insertion (533 in the standard shunt group, 535 in the antibiotic shunt group, and 526 in the silver shunt group) and were followed up for a median of 22 months (IQR 10-24; 53 withdrew from follow-up). 32 (6%) of 533 evaluable patients in the standard shunt group had a shunt revision for infection, compared with 12 (2%) of 535 evaluable patients in the antibiotic shunt group (cause-specific hazard ratio [csHR] 0·38, 97·5% CI 0·18-0·80, p=0·0038) and 31 (6%) of 526 patients in the silver shunt group (0·99, 0·56-1·74, p=0·96). 135 (25%) patients in the standard shunt group, 127 (23%) in the antibiotic shunt group, and 134 (36%) in the silver shunt group had adverse events, which were not life-threatening and were mostly related to valve or catheter function. INTERPRETATION: The BASICS trial provides evidence to support the adoption of antibiotic shunts in UK patients who are having their first ventriculoperitoneal shunt insertion. This practice will benefit patients of all ages by reducing the risk and harm of shunt infection. FUNDING: UK National Institute for Health Research Health Technology Assessment programme.

CATheter Infections in CHildren (CATCH): a randomised controlled trial and economic evaluation comparing impregnated and standard central venous catheters in children.

BACKGROUND: Impregnated central venous catheters (CVCs) are recommended for adults to reduce bloodstream infection (BSI) but not for children. OBJECTIVE: To determine the effectiveness of impregnated compared with standard CVCs for reducing BSI in children admitted for intensive care. DESIGN: Multicentre randomised controlled trial, cost-effectiveness analysis from a NHS perspective and a generalisability analysis and cost impact analysis. SETTING: 14 English paediatric intensive care units (PICUs) in England. PARTICIPANTS: Children aged < 16 years admitted to a PICU and expected to require a CVC for ≥ 3 days. INTERVENTIONS: Heparin-bonded, antibiotic-impregnated (rifampicin and minocycline) or standard polyurethane CVCs, allocated randomly (1 : 1 : 1). The intervention was blinded to all but inserting clinicians. MAIN OUTCOME MEASURE: Time to first BSI sampled between 48 hours after randomisation and 48 hours after CVC removal. The following data were used in the trial: trial case report forms; hospital administrative data for 6 months pre and post randomisation; and national-linked PICU audit and laboratory data. RESULTS: In total, 1859 children were randomised, of whom 501 were randomised prospectively and 1358 were randomised as an emergency; of these, 984 subsequently provided deferred consent for follow-up. Clinical effectiveness - BSIs occurred in 3.59% (18/502) of children randomised to standard CVCs, 1.44% (7/486) of children randomised to antibiotic CVCs and 3.42% (17/497) of children randomised to heparin CVCs. Primary analyses comparing impregnated (antibiotic and heparin CVCs) with standard CVCs showed no effect of impregnated CVCs [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.37 to 1.34]. Secondary analyses showed that antibiotic CVCs were superior to standard CVCs (HR 0.43, 95% CI 0.20 to 0.96) but heparin CVCs were not (HR 1.04, 95% CI 0.53 to 2.03). Time to thrombosis, mortality by 30 days and minocycline/rifampicin resistance did not differ by CVC. Cost-effectiveness - heparin CVCs were not clinically effective and therefore were not cost-effective. The incremental cost of antibiotic CVCs compared with standard CVCs over a 6-month time horizon was £1160 (95% CI -£4743 to £6962), with an incremental cost-effectiveness ratio of £54,057 per BSI avoided. There was considerable uncertainty in costs: antibiotic CVCs had a probability of 0.35 of being dominant. Based on index hospital stay costs only, antibiotic CVCs were associated with a saving of £97,543 per BSI averted. The estimated value of health-care resources associated with each BSI was £10,975 (95% CI -£2801 to £24,751). Generalisability and cost-impact - the baseline risk of BSI in 2012 for PICUs in England was 4.58 (95% CI 4.42 to 4.74) per 1000 bed-days. An estimated 232 BSIs could have been averted in 2012 using antibiotic CVCs. The additional cost of purchasing antibiotic CVCs for all children who require them (£36 per CVC) would be less than the value of resources associated with managing BSIs in PICUs with standard BSI rates of > 1.2 per 1000 CVC-days. CONCLUSIONS: The primary outcome did not differ between impregnated and standard CVCs. However, antibiotic-impregnated CVCs significantly reduced the risk of BSI compared with standard and heparin CVCs. Adoption of antibiotic-impregnated CVCs could be beneficial even for PICUs with low BSI rates, although uncertainty remains whether or not they represent value for money to the NHS. Limitations - inserting clinicians were not blinded to allocation and a lower than expected event rate meant that there was limited power for head-to-head comparisons of each type of impregnation. Future work - adoption of impregnated CVCs in PICUs should be considered and could be monitored through linkage of electronic health-care data and clinical data on CVC use with laboratory surveillance data on BSI. TRIAL REGISTRATION: ClinicalTrials.gov NCT01029717. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 18. See the NIHR Journals Library website for further project information.

The harder you look, the more you find: Catheter-associated bloodstream infection surveillance variability.

BACKGROUND: Catheter-related bloodstream infections are an important quality performance measure and remain a significant source of added morbidity, mortality, and medical costs. OBJECTIVE: Our objectives were to assess variability in catheter-associated bloodstream infections (CA-BSI) surveillance practices, management, and attitudes/beliefs in pediatric intensive care units (PICUs) and to determine whether any correlation exists between surveillance variation and CA-BSI rates. METHODS: We used a survey of 5 health care professions at multiple institutions. RESULTS: One hundred forty-six respondents from 5 professions in 16 PICUs completed surveys with a response rate of 40%. All 10 (100%) infection control departments reported inclusion or exclusion of central line types inconsistent with the Centers for Disease Control and Prevention CA-BSI definition, 5 (50%) calculated line-days inconsistently, and only 5 (50%) used a strict, written policy for classifying BSIs. Infection control departments report substantial variation in methods, timing, and resources used to screen and adjudicate BSI cases. Greater than 80% of centers report having a formal, written policy about obtaining blood cultures, although less than 80% of these address obtaining samples from patients with central venous lines, and any such policies are reportedly followed less than half of the time. Substantial variation exists in blood culturing practices, such as temperature thresholds, preemptive antipyretics, and blood sampling (volumes, number, sites, frequencies). A surveillance aggressiveness score was devised to quantify practices likely to increase identification of bloodstream infections, and there was a significant correlation between the surveillance aggressiveness score and CA-BSI rates (r = 0.60, P = .034). In assessing attitudes and beliefs, there was much greater confidence in the validity of CA-BSI as an internal/historical benchmark than as an external/peer benchmark, and the factor most commonly believed to contribute to CA-BSI occurrences was patient risk factors, not central line maintenance or insertion practices. CONCLUSION: There is substantial variation in reported CA-BSI surveillance practices among PICUs, and more aggressive surveillance correlates to higher CA-BSI rates, which has important implications in pay-for-performance and benchmarking applications. There is a compelling opportunity to improve standardized CA-BSI surveillance to enhance the validity of this metric for interinstitutional comparisons. Health care professionals' attitudes and beliefs about CA-BSI being driven by patient risk factors would benefit from recalibration that emphasized more important drivers-such as the quality of central line insertion and maintenance.

Procalcitonin and other biomarkers to improve assessment and antibiotic stewardship in infections--hope for hype?

This review aims to provide physicians with an overview of the potential of procalcitonin to guide antibiotic therapy in respiratory tract infections and in sepsis. Knowledge of the strengths and weaknesses of procalcitonin are prerequisites for a rational and safe use in clinical routine. In most infections a true gold standard for diagnosis does not exist, therefore physicians must remain sceptical towards observational studies evaluating procalcitonin. Interpretation of procalcitonin levels must always include the clinical setting and knowledge of assay characteristics, particularly the setting of specific cut-off ranges and functional assay sensitivities. Highly sensitive procalcitonin measurements, embedded in a clearly defined setting and prospectively validated with clinical algorithms were repeatedly effective in markedly reducing the (over)-utilisation of antimicrobial therapy. Today, this concept has been proven for lower respiratory tract infections and in pilot studies for meningitis and critically ill patients with sepsis. The higher the absolute risk for adverse outcome of a patient, the more cautious physicians must remain and empirical antibiotic therapies must be considered despite initial low procalcitonin levels at the initial presentation. In these patients a procalcitonin-guided shortening of antibiotic courses seems appropriate. The prognostic utility of initial procalcitonin measurement in respiratory tract infections is suboptimal. Other biomarkers including cortisol, human growth hormone and prohormones from adrenomedullin and vasopressin ("copeptin") have a superior predictive potential to estimate the risk for short and long term mortality and other adverse outcomes in different diseases. An accurate prognostic assessment has the potential to optimise the management of patients and the allocation of our limited health care resources by lowering unnecessary hospitalisations and associated cost. Future intervention studies must prove if these biomarkers indeed improve clinical decision making and thus the overall medical management of patients.