OBJECTIVES: Our main objective was to assess the effectiveness of antimicrobial impregnation, coating or bonding on CVCs in reducing clinically-diagnosed sepsis, catheter-related blood stream infection (CRBSI), all-cause mortality, catheter colonization and other catheter-related infections in adult participants who required central venous catheterization, along with their safety and cost effectiveness where data were available. We undertook the following comparisons: 1) catheters with antimicrobial modifications in the form of antimicrobial impregnation, coating or bonding, against catheters without antimicrobial modifications and 2) catheters with one type of antimicrobial impregnation against catheters with another type of antimicrobial impregnation. We planned to analyse the comparison of catheters with any type of antimicrobial impregnation against catheters with other antimicrobial modifications, e.g. antiseptic dressings, hubs, tunnelling, needleless connectors or antiseptic lock solutions, but did not find any relevant studies. Additionally, we planned to conduct subgroup analyses based on the length of catheter use, settings or levels of care (e.g. intensive care unit, standard ward and oncology unit), baseline risks, definition of sepsis, presence or absence of co-interventions and cost-effectiveness in different currencies.
SEARCH METHODS: We used the standard search strategy of the Cochrane Anaesthesia, Critical and Emergency Care Review Group (ACE). In the updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), MEDLINE (OVID SP; 1950 to March 2015), EMBASE (1980 to March 2015), CINAHL (1982 to March 2015), and other Internet resources using a combination of keywords and MeSH headings. The original search was run in March 2012.
SELECTION CRITERIA: We included randomized controlled trials (RCTs) that assessed any type of impregnated catheter against either non-impregnated catheters or catheters with another type of impregnation in adult patients cared for in the hospital setting who required CVCs. We planned to include quasi-RCT and cluster-RCTs, but we identified none. We excluded cross-over studies.
DATA COLLECTION AND ANALYSIS: We extracted data using the standard methodological procedures expected by Cochrane. Two authors independently assessed the relevance and risk of bias of the retrieved records. We expressed our results using risk ratio (RR), absolute risk reduction (ARR) and number need to treat to benefit (NNTB) for categorical data and mean difference (MD) for continuous data, where appropriate, with their 95% confidence intervals (CIs).
MAIN RESULTS: We included one new study (338 participants/catheters) in this update, which brought the total included to 57 studies with 16,784 catheters and 11 types of impregnations. The total number of participants enrolled was unclear, as some studies did not provide this information. Most studies enrolled participants from the age of 18, including patients in intensive care units (ICU), oncology units and patients receiving long-term total parenteral nutrition. There were low or unclear risks of bias in the included studies, except for blinding, which was impossible in most studies due to the catheters that were being assessed having different appearances. Overall, catheter impregnation significantly reduced catheter-related blood stream infection (CRBSI), with an ARR of 2% (95% CI 3% to 1%), RR of 0.62 (95% CI 0.52 to 0.74) and NNTB of 50 (high-quality evidence). Catheter impregnation also reduced catheter colonization, with an ARR of 9% (95% CI 12% to 7%), RR of 0.67 (95% CI 0.59 to 0.76) and NNTB of 11 (moderate-quality evidence, downgraded due to substantial heterogeneity). However, catheter impregnation made no significant difference to the rates of clinically diagnosed sepsis (RR 1.0, 95% CI 0.88 to 1.13; moderate-quality evidence, downgraded due to a suspicion of publication bias), all-cause mortality (RR 0.92, 95% CI 0.80 to 1.07; high-quality evidence) and catheter-related local infections (RR 0.84, 95% CI 0.66 to 1.07; 2688 catheters, moderate quality evidence, downgraded due to wide 95% CI).In our subgroup analyses, we found that the magnitudes of benefits for impregnated CVCs varied between studies that enrolled different types of participants. For the outcome of catheter colonization, catheter impregnation conferred significant benefit in studies conducted in ICUs (RR 0.70;95% CI 0.61 to 0.80) but not in studies conducted in haematological and oncological units (RR 0.75; 95% CI 0.51 to 1.11) or studies that assessed predominantly patients who required CVCs for long-term total parenteral nutrition (RR 0.99; 95% CI 0.74 to 1.34). However, there was no such variation for the outcome of CRBSI. The magnitude of the effects was also not affected by the participants' baseline risks.There were no significant differences between the impregnated and non-impregnated groups in the rates of adverse effects, including thrombosis/thrombophlebitis, bleeding, erythema and/or tenderness at the insertion site.
AUTHORS' CONCLUSIONS: This review confirms the effectiveness of antimicrobial CVCs in reducing rates of CRBSI and catheter colonization. However, the magnitude of benefits regarding catheter colonization varied according to setting, with significant benefits only in studies conducted in ICUs. A comparatively smaller body of evidence suggests that antimicrobial CVCs do not appear to reduce clinically diagnosed sepsis or mortality significantly. Our findings call for caution in routinely recommending the use of antimicrobial-impregnated CVCs across all settings. Further randomized controlled trials assessing antimicrobial CVCs should include important clinical outcomes like the overall rates of sepsis and mortality.
OBJECTIVES: To assess the effects of skin antisepsis as part of CVC care for reducing catheter-related BSIs, catheter colonisation, and patient mortality and morbidities.
SEARCH METHODS: In May 2016 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations and Epub Ahead of Print); Ovid EMBASE and EBSCO CINAHL Plus. We also searched clinical trial registries for ongoing and unpublished studies. There were no restrictions with respect to language, date of publication or study setting.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed any type of skin antiseptic agent used either alone or in combination, compared with one or more other skin antiseptic agent(s), placebo or no skin antisepsis in patients with a CVC in place.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed the studies for their eligibility, extracted data and assessed risk of bias. We expressed our results in terms of risk ratio (RR), absolute risk reduction (ARR) and number need to treat for an additional beneficial outcome (NNTB) for dichotomous data, and mean difference (MD) for continuous data, with 95% confidence intervals (CIs).
MAIN RESULTS: Thirteen studies were eligible for inclusion, but only 12 studies contributed data, with a total of 3446 CVCs assessed. The total number of participants enrolled was unclear as some studies did not provide such information. The participants were mainly adults admitted to intensive care units, haematology oncology units or general wards. Most studies assessed skin antisepsis prior to insertion and regularly thereafter during the in-dwelling period of the CVC, ranging from every 24 h to every 72 h. The methodological quality of the included studies was mixed due to wide variation in their risk of bias. Most trials did not adequately blind the participants or personnel, and four of the 12 studies had a high risk of bias for incomplete outcome data.Three studies compared different antisepsis regimens with no antisepsis. There was no clear evidence of a difference in all outcomes examined, including catheter-related BSI, septicaemia, catheter colonisation and number of patients who required systemic antibiotics for any of the three comparisons involving three different antisepsis regimens (aqueous povidone-iodine, aqueous chlorhexidine and alcohol compared with no skin antisepsis). However, there were great uncertainties in all estimates due to underpowered analyses and the overall very low quality of evidence presented.There were multiple head-to-head comparisons between different skin antiseptic agents, with different combinations of active substance and base solutions. The most frequent comparison was chlorhexidine solution versus povidone-iodine solution (any base). There was very low quality evidence (downgraded for risk of bias and imprecision) that chlorhexidine may reduce catheter-related BSI compared with povidone-iodine (RR of 0.64, 95% CI 0.41 to 0.99; ARR 2.30%, 95% CI 0.06 to 3.70%). This evidence came from four studies involving 1436 catheters. None of the individual subgroup comparisons of aqueous chlorhexidine versus aqueous povidone-iodine, alcoholic chlorhexidine versus aqueous povidone-iodine and alcoholic chlorhexidine versus alcoholic povidone-iodine showed clear differences for catheter-related BSI or mortality (and were generally underpowered). Mortality was only reported in a single study.There was very low quality evidence that skin antisepsis with chlorhexidine may also reduce catheter colonisation relative to povidone-iodine (RR of 0.68, 95% CI 0.56 to 0.84; ARR 8%, 95% CI 3% to 12%; ; five studies, 1533 catheters, downgraded for risk of bias, indirectness and inconsistency).Evaluations of other skin antiseptic agents were generally in single, small studies, many of which did not report the primary outcome of catheter-related BSI. Trials also poorly reported other outcomes, such as skin infections and adverse events.
AUTHORS' CONCLUSIONS: It is not clear whether cleaning the skin around CVC insertion sites with antiseptic reduces catheter related blood stream infection compared with no skin cleansing. Skin cleansing with chlorhexidine solution may reduce rates of CRBSI and catheter colonisation compared with cleaning with povidone iodine. These results are based on very low quality evidence, which means the true effects may be very different. Moreover these results may be influenced by the nature of the antiseptic solution (i.e. aqueous or alcohol-based). Further RCTs are needed to assess the effectiveness and safety of different skin antisepsis regimens in CVC care; these should measure and report critical clinical outcomes such as sepsis, catheter-related BSI and mortality.
METHODS: A total of 15 PD bags (3 bags for each type of PD solution) containing meropenem and heparin and 24 PD bags (3 bags for each type of PD solution) containing PIP/TZB and heparin were prepared and stored at 4°C for 168 hours. The same bags were stored at 25°C for 3 hours followed by 10 hours at 37°C. An aliquot withdrawn before storage and at defined time points was analyzed for the concentration of meropenem, PIP, TZB, and heparin using high-performance liquid chromatography. Samples were also analysed for particle content, pH and color change, and the anticoagulant activity of heparin.
RESULTS: Meropenem and heparin retained more than 90% of their initial concentration in 4 out of 5 types of PD solutions when stored at 4°C for 168 hours, followed by storage at 25°C for 3 hours and then at 37°C for 10 hours. Piperacillin/tazobactam and heparin were found to be stable in all 8 types of PD solutions when stored under the same conditions. Heparin retained more than 98% of its initial anticoagulant activity throughout the study period. No evidence of particle formation, color change, or pH change was observed at any time under the storage conditions employed in the study.
CONCLUSIONS: This study provides clinically important information on the stability of meropenem and PIP/TZB, each in combination with heparin, in different PD solutions. The use of meropenem-heparin admixed in pH-neutral PD solutions for the treatment of PDAP should be avoided, given the observed suboptimal stability of meropenem.
METHODS: We did a randomised, controlled, assessor-masked trial at ten Australian hospitals. Our hypothesis was CRBSI equivalence for central venous access devices and non-inferiority for peripheral arterial catheters (both 2% margin). Adults and children with expected greater than 24 h central venous access device-peripheral arterial catheter use were randomly assigned (1:1; stratified by hospital, catheter type, and intensive care unit or ward) by a centralised, web-based service (concealed before allocation) to infusion set replacement every 7 days, or 4 days. This included crystalloids, non-lipid parenteral nutrition, and medication infusions. Patients and clinicians were not masked, but the primary outcome (CRBSI) was adjudicated by masked infectious diseases physicians. The analysis was modified intention to treat (mITT). This study is registered with the Australian New Zealand Clinical Trials Registry ACTRN12610000505000 and is complete.
FINDINGS: Between May 30, 2011, and Dec, 9, 2016, from 6007 patients assessed, we assigned 2944 patients to 7-day (n=1463) or 4-day (n=1481) infusion set replacement, with 2941 in the mITT analysis. For central venous access devices, 20 (1·78%) of 1124 patients (7-day group) and 16 (1·46%) of 1097 patients (4-day group) had CRBSI (absolute risk difference [ARD] 0·32%, 95% CI -0·73 to 1·37). For peripheral arterial catheters, one (0·28%) of 357 patients in the 7-day group and none of 363 patients in the 4-day group had CRBSI (ARD 0·28%, -0·27% to 0·83%). There were no treatment-related adverse events.
INTERPRETATION: Infusion set use can be safely extended to 7 days with resultant cost and workload reductions.
FUNDING: Australian National Health and Medical Research Council.
OBJECTIVE: Peritoneal dialysis (PD)-related infection is a common cause of catheter loss and the main reason for PD drop-out. Exit-site infection (ESI) is a pathway to developing tunnel infection and peritonitis, hence rigorous exit-site care has always been emphasized in PD therapy. The aim of this study was to evaluate the effect of exit-site dressing vs non-dressing on the rate of PD-related infection. ♦
METHODS: A prospective randomized controlled study was conducted in prevalent PD patients at the Hospital Tuanku Jaafar Seremban, Negeri Sembilan, Malaysia, from April 2011 until April 2013. All patients were required to perform daily washing of the exit site with antibacterial soap during a shower. In the dressing group (n = 54), patients were required to clean their exit site using povidone-iodine after drying, followed by topical mupirocin antibiotic application to the exit site. The exit site was then covered with a sterile gauze dressing and the catheter immobilized with tape. In the non-dressing group (n = 54), patients were not required to do any further dressing after drying. They were only required to apply mupirocin cream to the exit site and then left the exit site uncovered. The catheter was immobilized with tape. The primary outcome was ESI. The secondary outcomes were evidence of tunnel infection or peritonitis. ♦
RESULTS: A total of 97 patients completed the study. There were a total of 12 ESI episodes: 4 episodes in 4 patients in the dressing group vs 8 episodes in 4 patients in the non-dressing group. This corresponds to 1 episode per 241.3 patient-months vs 1 episode per 111.1 patient-months in the dressing and non-dressing groups respectively. Median time to first ESI episode was shorter in the non-dressing than in the dressing group, but not significant (p = 0.25). The incidence of gram-positive ESI in both groups was similar. There were no gram-negative ESI in the non-dressing group compared with 2 in the dressing group. The peritonitis rate was 1 per 37.1 patient-month in the dressing group and 1 per 44.4 patient-months in the non-dressing group. Median time to first peritonitis episode was significantly shorter in the dressing group compared to non-dressing (p = 0.03). There was no impact of dressing disruptions in the occurrence of major PD catheter-related infection. ♦
CONCLUSION: Use of a non-dressing technique with only prophylactic topical mupirocin cream application is effective in preventing PD-related infection. The non-dressing technique is more cost-effective and convenient for PD patients, with fewer disposables.
OBJECTIVES: We assessed the effectiveness and safety of antimicrobial (antiseptic or antibiotic) dressings in reducing CVC-related infections in newborn infants. Had there been relevant data, we would have evaluated the effects of antimicrobial dressings in different subgroups, including infants who received different types of CVCs, infants who required CVC for different durations, infants with CVCs with and without other antimicrobial modifications, and infants who received an antimicrobial dressing with and without a clearly defined co-intervention.
SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group (CNRG). We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2015, Issue 9), MEDLINE (PubMed), EMBASE (EBCHOST), CINAHL and references cited in our short-listed articles using keywords and MeSH headings, up to September 2015.
SELECTION CRITERIA: We included randomised controlled trials that compared an antimicrobial CVC dressing against no dressing or another dressing in newborn infants.
DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the CNRG. Two review authors independently assessed the eligibility and risk of bias of the retrieved records. We expressed our results using risk difference (RD) and risk ratio (RR) with 95% confidence intervals (CIs).
MAIN RESULTS: Out of 173 articles screened, three studies were included. There were two comparisons: chlorhexidine dressing following alcohol cleansing versus polyurethane dressing following povidone-iodine cleansing (one study); and silver-alginate patch versus control (two studies). A total of 855 infants from level III neonatal intensive care units (NICUs) were evaluated, 705 of whom were from a single study. All studies were at high risk of bias for blinding of care personnel or unclear risk of bias for blinding of outcome assessors. There was moderate-quality evidence for all major outcomes.The single study comparing chlorhexidine dressing/alcohol cleansing against polyurethane dressing/povidone-iodine cleansing showed no significant difference in the risk of CRBSI (RR 1.18, 95% CI 0.53 to 2.65; RD 0.01, 95% CI -0.02 to 0.03; 655 infants, moderate-quality evidence) and sepsis without a source (RR 1.06, 95% CI 0.75 to 1.52; RD 0.01, 95% CI -0.04 to 0.06; 705 infants, moderate-quality evidence). There was a significant reduction in the risk of catheter colonisation favouring chlorhexidine dressing/alcohol cleansing group (RR 0.62, 95% CI 0.45 to 0.86; RD -0.09, 95% CI -0.15 to -0.03; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 7 to 33; 655 infants, moderate-quality evidence). However, infants in the chlorhexidine dressing/alcohol cleansing group were significantly more likely to develop contact dermatitis, with 19 infants in the chlorhexidine dressing/alcohol cleansing group having developed contact dermatitis compared to none in the polyurethane dressing/povidone-iodine cleansing group (RR 43.06, 95% CI 2.61 to 710.44; RD 0.06, 95% CI 0.03 to 0.08; number needed to treat for an additional harmful outcome (NNTH) 17, 95% CI 13 to 33; 705 infants, moderate-quality evidence). The roles of chlorhexidine dressing in the outcomes reported were unclear, as the two assigned groups received different co-interventions in the form of different skin cleansing agents prior to catheter insertion and during each dressing change.In the other comparison, silver-alginate patch versus control, the data for CRBSI were analysed separately in two subgroups as the two included studies reported the outcome using different denominators: one using infants and another using catheters. There were no significant differences between infants who received silver-alginate patch against infants who received standard line dressing in CRBSI, whether expressed as the number of infants (RR 0.50, 95% CI 0.14 to 1.78; RD -0.12, 95% CI -0.33 to 0.09; 1 study, 50 participants, moderate-quality evidence) or as the number of catheters (RR 0.72, 95% CI 0.27 to 1.89; RD -0.05, 95% CI -0.20 to 0.10; 1 study, 118 participants, moderate-quality evidence). There was also no significant difference between the two groups in mortality (RR 0.55, 95% CI 0.15 to 2.05; RD -0.04, 95% CI -0.13 to 0.05; two studies, 150 infants, I² = 0%, moderate-quality evidence). No adverse skin reaction was recorded in either group.
AUTHORS' CONCLUSIONS: Based on moderate-quality evidence, chlorhexidine dressing/alcohol skin cleansing reduced catheter colonisation, but made no significant difference in major outcomes like sepsis and CRBSI compared to polyurethane dressing/povidone-iodine cleansing. Chlorhexidine dressing/alcohol cleansing posed a substantial risk of contact dermatitis in preterm infants, although it was unclear whether this was contributed mainly by the dressing material or the cleansing agent. While silver-alginate patch appeared safe, evidence is still insufficient for a recommendation in practice. Future research that evaluates antimicrobial dressing should ensure blinding of caregivers and outcome assessors and ensure that all participants receive the same co-interventions, such as the skin cleansing agent. Major outcomes like sepsis, CRBSI and mortality should be assessed in infants of different gestation and birth weight.
Methods: We searched 4 electronic databases (Medline, the Cochrane Central Register of Controlled Trials, Embase, CINAHL) and internet sources for randomized controlled trials, ongoing clinical trials, and unpublished studies up to August 2016. Studies that assessed CVCs with antimicrobial impregnation with nonimpregnated catheters or catheters with another impregnation were included. Primary outcomes were clinically diagnosed sepsis, catheter-related bloodstream infection (CRBSI), and all-cause mortality. We performed a network meta-analysis to estimate risk ratio (RR) with 95% confidence interval (CI).
Results: Sixty studies with 17255 catheters were included. The effects of 14 impregnations were investigated. Both CRBSI and catheter colonization were the most commonly evaluated outcomes. Silver-impregnated CVCs significantly reduced clinically diagnosed sepsis compared with silver-impregnated cuffs (RR, 0.54 [95% CI, .29-.99]). When compared to no impregnation, significant CRBSI reduction was associated with minocycline-rifampicin (RR, 0.29 [95% CI, .16-.52]) and silver (RR, 0.57 [95% CI, .38-.86]) impregnations. No impregnations significantly reduced all-cause mortality. For catheter colonization, significant decreases were shown by miconazole-rifampicin (RR, 0.14 [95% CI, .05-.36]), 5-fluorouracil (RR, 0.34 [95% CI, .14-.82]), and chlorhexidine-silver sulfadiazine (RR, 0.60 [95% CI, .50-.72]) impregnations compared with no impregnation. None of the studies evaluated antibiotic/antiseptic resistance as the outcome.
Conclusions: Current evidence suggests that the minocycline-rifampicin-impregnated CVC appears to be the most effective in preventing CRBSI. However, its overall benefits in reducing clinical sepsis and mortality remain uncertain. Surveillance for antibiotic resistance attributed to the routine use of antimicrobial-impregnated CVCs should be emphasized in future trials.