Impregnated central venous catheters for prevention of bloodstream infection in children (the CATCH trial): a randomised controlled trial.

BACKGROUND: Impregnated central venous catheters are recommended for adults to reduce bloodstream infections but not for children because there is not enough evidence to prove they are effective. We aimed to assess the effectiveness of any type of impregnation (antibiotic or heparin) compared with standard central venous catheters to prevent bloodstream infections in children needing intensive care. METHODS: We did a randomised controlled trial of children admitted to 14 English paediatric intensive care units. Children younger than 16 years were eligible if they were admitted or being prepared for admission to a participating paediatric intensive care unit and were expected to need a central venous catheter for 3 or more days. Children were randomly assigned (1:1:1) to receive a central venous catheter impregnated with antibiotics, a central venous catheter impregnated with heparin, or a standard central venous catheter with computer generated randomisation in blocks of three and six, stratified by method of consent, site, and envelope storage location within the site. The clinician responsible for inserting the central venous catheter was not masked to allocation, but allocation was concealed from patients, their parents, and the paediatric intensive care unit personnel responsible for their care. The primary outcome was time to first bloodstream infection between 48 h after randomisation and 48 h after central venous catheter removal with impregnated (antibiotic or heparin) versus standard central venous catheters, assessed in the intention-to-treat population. Safety analyses compared central venous catheter-related adverse events in the subset of children for whom central venous catheter insertion was attempted (per-protocol population). This trial is registered with ISRCTN number, ISRCTN34884569. FINDINGS: Between Nov 25, 2010, and Nov 30, 2012, 1485 children were recruited to this study. We randomly assigned 502 children to receive standard central venous catheters, 486 to receive antibiotic-impregnated catheters, and 497 to receive heparin-impregnated catheters. Bloodstream infection occurred in 18 (4%) of those in the standard catheters group, 7 (1%) in the antibiotic-impregnated group, and 17 (3%) assigned to heparin-impregnated catheters. Primary analyses showed no effect of impregnated (antibiotic or heparin) catheters compared with standard central venous catheters (hazard ratio [HR] for time to first bloodstream infection 0.71, 95% CI 0.37-1.34). Secondary analyses showed that antibiotic central venous catheters were better than standard central venous catheters (HR 0.43, 0.20-0.96) and heparin central venous catheters (HR 0.42, 0.19-0.93), but heparin did not differ from standard central venous catheters (HR 1.04, 0.53-2.03). Clinically important and statistically significant absolute risk differences were identified only for antibiotic-impregnated catheters versus standard catheters (-2.15%, 95% CI -4.09 to -0.20; number needed to treat [NNT] 47, 95% CI 25-500) and antibiotic-impregnated catheters versus heparin-impregnated catheters (-1.98%, -3.90 to -0.06, NNT 51, 26-1667). Nine children (2%) in the standard central venous catheter group, 14 (3%) in the antibiotic-impregnated group, and 8 (2%) in the heparin-impregnated group had catheter-related adverse events. 45 (8%) in the standard group, 35 (8%) antibiotic-impregnated group, and 29 (6%) in the heparin-impregnated group died during the study. INTERPRETATION: Antibiotic-impregnated central venous catheters significantly reduced the risk of bloodstream infections compared with standard and heparin central venous catheters. Widespread use of antibiotic-impregnated central venous catheters could help prevent bloodstream infections in paediatric intensive care units. FUNDING: National Institute for Health Research, UK

Nerve conduction studies are safe in patients with central venous catheters

IntroductionIt is unknown if central venous catheters bypass the skin’s electrical resistance and engender a risk of nerve conduction study‐induced cardiac arrhythmia. The objective of this study is to determine if nerve conduction studies affect cardiac conduction and rhythm in patients with central venous catheters.MethodsUnder continuous 12‐lead electrocardiogram monitoring, subjects with and without central venous catheters underwent a series of upper extremity nerve conduction studies. A cardiologist reviewed the electrocardiogram tracings for evidence of cardiac conduction abnormality or arrhythmia.ResultsTen control subjects and 10 subjects with central venous catheters underwent the nerve conduction study protocol. No malignant arrhythmias or conduction abnormalities were noted in either group.ConclusionsNerve conduction studies of the upper extremities, including both proximal stimulation and repetitive stimulation, do not appear to confer increased risk of cardiac conduction abnormality in those patients with central venous catheters who are not critically ill or have a prior history of arrhythmia. Muscle Nerve 56: 321–323, 2017Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137740/1/mus25497.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137740/2/mus25497_am.pd

Antimicrobial-impregnated central venous catheters for preventing neonatal bloodstream infection: the PREVAIL RCT

BACKGROUND: Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies. OBJECTIVES: The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS. DESIGN: Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England. SETTING: The randomised controlled trial was conducted in 18 neonatal intensive care units in England. PARTICIPANTS: Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size). INTERVENTIONS: The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation. MAIN OUTCOME MEASURE: Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data. RESULTS: Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, n = 430; standard peripherally inserted central venous catheter, n = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; p = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; p = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation - the mean cost of babies' hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23-27 and 28-32 weeks' gestation, respectively. Study 3, generalisability analysis - risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days. LIMITATIONS: The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance. CONCLUSIONS: No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN81931394. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 57. See the NIHR Journals Library website for further project information

DNA fingerprinting analysis of coagulase negative staphylococci implicated in catheter related bloodstream infections

AIMS: The epidemiological assessment of cases of coagulase negative staphylococcal catheter related bloodstream infection. METHODS: Two hundred and thirty patients with suspected catheter related bloodstream infection were evaluated over a two year period. Central venous catheters were cultured both endoluminally and extraluminally. Peripheral blood, catheter hubs, skin entry, and skin control sites were also cultured. Pulsed field gel electrophoresis (PFGE) was used to DNA fingerprint coagulase negative staphylococci isolated from patients with presumptive catheter related bloodstream infection. RESULTS: Sixty cases of catheter related bloodstream infection were identified, 21 of which were attributed to coagulase negative staphylococci. Two hundred and ninety four separate isolates of coagulase negative staphylococci from the 21 cases of catheter related bloodstream infection were subjected to PFGE (mean of 14 for each case). Catheter related bloodstream infection was only confirmed by PFGE analysis in 16 of the 21 cases because in the remaining five cases peripheral blood and central venous catheter coagulase negative staphylococci isolates were different. Skin entry, control skin, and central venous catheter hub isolates matched peripheral blood isolates in six, four, and seven cases, respectively. Coagulase negative staphylococci isolates could not be cultured from the patients’ own skin in seven cases of catheter related bloodstream infection. Central venous catheter lumens were colonised in all cases of catheter related bloodstream infection compared with 44–81% of cases that had positive external surface catheter tip cultures, depending on the threshold used to define significant growth. CONCLUSIONS: Catheter related bloodstream infection as a result of coagulase negative staphylococci may be over stated in about a quarter of cases, unless a discriminatory technique is used to fingerprint isolates. No single, simplistic route of bacterial contamination of central venous catheters was identified, but endoluminal catheter colonisation is invariably present in cases of catheter related bloodstream infection. The use of central venous catheters as a means of access for monitoring and as a route of administration of drugs has become almost mandatory in patients with serious illnesses. Infections of central venous catheters are common and coagulase negative staphylococci remain the most frequent pathogens—for example, 37% of 1267 isolates in one meta-analysis.Controversy remains over the source of, and route of access by, these bacteria to the central venous catheters. Recent developments, such as catheters with antimicrobial properties, are an important advance, but until such issues are resolved it remains unclear how best to reduce the risk of catheter related bloodstream infection. “Pulsed field gel electrophoresis is well recognised as the gold standard for fingerprinting coagulase negative staphylococci” Because there are at least 33 distinct coagulase negative staphylococci species that have been identified, and because methods that use phenotyping alone cannot accurately distinguish between strains of coagulase negative staphylococci, DNA fingerprinting is required to clarify the epidemiology of coagulase negative staphylococci catheter related bacterial bloodstream infection. Despite the accepted difficulties in determining the relatedness of coagulase negative staphylococci, diagnostic laboratories routinely rely on limited information from phenotypic tests to compare isolates fro

Cost effectiveness of antimicrobial catheters in the intensive care unit: addressing uncertainty in the decision

Introduction: Some types of antimicrobial-coated central venous catheters (A-CVC) have been shown to be cost-effective in preventing catheter-related bloodstream infection (CR-BSI). However, not all types have been evaluated, and there are concerns over the quality and usefulness of these earlier studies. There is uncertainty amongst clinicians over which, if any, antimicrobial-coated central venous catheters to use. We re-evaluated the cost-effectiveness of all commercially available antimicrobialcoated central venous catheters for prevention of catheter-related bloodstream infection in adult intensive care unit (ICU) patients. Methods: We used a Markov decision model to compare the cost-effectiveness of antimicrobial-coated central venous catheters relative to uncoated catheters. Four catheter types were evaluated; minocycline and rifampicin (MR)-coated catheters; silver, platinum and carbon (SPC)-impregnated catheters; and two chlorhexidine and silver sulfadiazine-coated catheters, one coated on the external surface (CH/SSD (ext)) and the other coated on both surfaces (CH/SSD (int/ext)). The incremental cost per qualityadjusted life-year gained and the expected net monetary benefits were estimated for each. Uncertainty arising from data estimates, data quality and heterogeneity was explored in sensitivity analyses. Results: The baseline analysis, with no consideration of uncertainty, indicated all four types of antimicrobial-coated central venous catheters were cost-saving relative to uncoated catheters. Minocycline and rifampicin-coated catheters prevented 15 infections per 1,000 catheters and generated the greatest health benefits, 1.6 quality-adjusted life-years, and cost-savings, AUD $130,289. After considering uncertainty in the current evidence, the minocycline and rifampicin-coated catheters returned the highest incremental monetary net benefits of$948 per catheter; but there was a 62% probability of error in this conclusion. Although the minocycline and rifampicin-coated catheters had the highest monetary net benefits across multiple scenarios, the decision was always associated with high uncertainty. Conclusions: Current evidence suggests that the cost-effectiveness of using antimicrobial-coated central venous catheters within the ICU is highly uncertain. Policies to prevent catheter-related bloodstream infection amongst ICU patients should consider the cost-effectiveness of competing interventions in the light of this uncertainty. Decision makers would do well to consider the current gaps in knowledge and the complexity of producing good quality evidence in this area

Alcaligenes xylosoxidans Bloodstream Infections in Outpatient Oncology Office

Gaps in infection control led to biofilm production in central venous catheters and resultant bloodstream infection

Early removal versus expectant management of central venous catheters in neonates with bloodstream infection

BACKGROUND: Uncertainty exists regarding the management of newborn infants with a bloodstream infection and a central venous catheter in place. The central venous catheter may act as a nidus for infecting organisms and observational studies have suggested that early removal of the catheter is associated with a lower incidence of persistent or complicated infection. However, since central venous catheters provide secure vascular access to deliver nutrition and medications, the possible harms of early removal versus expectant management also need to be considered. OBJECTIVES: To determine the effect of early removal versus expectant management of central venous catheters on morbidity and mortality in newborn infants with bloodstream infections. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 11), MEDLINE (1966 to October 2015), EMBASE (1980 to October 2015), CINAHL (1982 to October 2015), conference proceedings and previous reviews. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared early removal versus expectant management of central venous catheters in neonates with bloodstream infections. DATA COLLECTION AND ANALYSIS: We used the standard methods of the Cochrane Neonatal Review Group. MAIN RESULTS: We did not identify any eligible randomised controlled trials. AUTHORS' CONCLUSIONS: There are no trial data to guide practice regarding early removal versus expectant management of central venous catheters in newborn infants with bloodstream infections. A simple and pragmatic randomised controlled trial is needed to resolve the uncertainty about optimal management in this common and important clinical scenario

Making co-enrolment feasible for randomised controlled trials in paediatric intensive care.

Enrolling children into several trials could increase recruitment and lead to quicker delivery of optimal care in paediatric intensive care units (PICU). We evaluated decisions taken by clinicians and parents in PICU on co-enrolment for two large pragmatic trials: the CATCH trial (CATheters in CHildren) comparing impregnated with standard central venous catheters (CVCs) for reducing bloodstream infection in PICU and the CHIP trial comparing tight versus standard control of hyperglycaemia

Access via the femoral vein

Central venous access via the femoral vein (FV) is safe, relatively easy and very usual in infants and children undergoing cardiac surgery for congenital heart disease. It has a low insertion-related complication rate. It is therefore a good choice for short-term central venous lines and a preferred insertion site for less experienced staff. The maintenance-related complications of thrombus formation and infections are higher compared to the internal jugular and the subclavian venous access. Some of these complications are reduced by the use of heparin bonded catheters, routine use of antibiotics, and timely removal of these lines in patients with persistent signs of infection but without another focus being defined.peer-reviewe

Access via the internal jugular vein

Central venous access via the internal jugular vein (IJV) is safe, relatively easy and very commonly used in infants and children undergoing cardiac surgery for congenital heart disease. Because of the wide range of anatomical variations an ultrasound-guided technique is advantageous in many cases, in particular in patients who have had previous punctures or those in whom difficulties are anticipated for various reasons. The right internal jugular vein is the preferred vein for central venous access as it offers straight access to the superior vena cava. The rate of complications - insertion-related as well as long term - are lower compared to the femoral and the subclavian access.peer-reviewe