SYSTEMATIC REVIEW
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Antibiotic and other lock treatments for tunnelled central venous catheter-related infections in children with cancer.

BACKGROUND: The risk of developing a tunnelled central venous catheter (CVC)-related infection ranges between 0.1 and 2.3 per 1000 catheter days for children with cancer. These infections are difficult to treat with systemic antibiotics (salvage rate 24% - 66%) due to biofilm formation in the CVC. Lock treatments can achieve 100 - 1000 times higher concentrations locally without exposure to high systemic concentrations.

OBJECTIVES: Our objective was to investigate the efficacy of antibiotic and other lock treatments in the treatment of CVC-related infections in children with cancer compared to a control intervention. We also assessed adverse events of lock treatments.

SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, issue 3, 2011), MEDLINE/PubMed (1945 to August 2011) and EMBASE/Ovid (1980 to August 2011). In addition we searched reference lists from relevant articles and the conference proceedings of the International Society for Paediatric Oncology (SIOP) (from 2006 to 2010), American Society of Clinical Oncology (ASCO) (from 2006 to 2010), the Multinational Association of Supportive Care in Cancer (MASCC) (from 2006 to 2011), the American Society of Hematology (ASH) (from 2006 to 2010) and the International Society of Thrombosis and Haematology (ISTH) (from 2006 to 2011). We scanned the ISRCTN Register and the National Institute of Health Register for ongoing trials (www.controlled-trials.com) (August 2011).

SELECTION CRITERIA: Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing an antibiotic lock or other lock treatment (with or without concomitant systemic antibiotics) with a control intervention (other lock treatment with or without concomitant systemic antibiotics or systemic antibiotics alone) for the treatment of CVC-related infections in children with cancer. For the description of adverse events, cohort studies were also eligible for inclusion.

DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data and performed 'Risk of bias' assessments of included studies. Analyses were performed according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.

MAIN RESULTS: Two RCTs evaluated urokinase lock treatment with concomitant systemic antibiotics (n = 56) versus systemic antibiotics alone (n = 48), and one CCT evaluated ethanol lock treatment with concomitant systemic antibiotics (n = 15) versus systemic antibiotics alone (n = 13). No RCTs or CCTs evaluating antibiotic lock treatments were identified. All studies had methodological limitations and clinical heterogeneity between studies was present. We found no evidence of significant difference between ethanol or urokinase lock treatments with concomitant systemic antibiotics and systemic antibiotics alone regarding the number of participants cured, the number of recurrent CVC-related infections, the number of days until the first negative blood culture, the number of CVCs prematurely removed, ICU admission and sepsis. Not all studies were included in all analyses. No adverse events occurred in the five publications of cohort studies (one cohort was included in two publications) assessing this outcome; CVC malfunctioning occurred in three out of five publications of cohort studies assessing this outcome.

AUTHORS' CONCLUSIONS: No significant effect of urokinase or ethanol lock in addition to systemic antibiotics was found. However, this could be due to low power or a too-short follow-up. The cohort studies identified no adverse events; some cohort studies reported CVC malfunctioning. No RCTs or CCTs were published on antibiotic lock treatment alone. More well-designed RCTs are needed to further explore the effect of antibiotic or other lock treatments in the treatment of CVC-related infections in children with cancer.

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