More than two-thirds of children and adults receiving chemotherapy for cancer have long-term central venous catheters (CVCs) implanted for the delivery of chemotherapeutics, intravenous fluids, blood products, and other medications. The use of long-term CVCs is limited by the risk of infection and blood clot formation, with the risk of infection ranging from 1.4 to 2.2 infections per 1000 catheter days. Oncology patients are at increased risk of infection because of the immunosuppressive effects of their treatment, their disease, or both. Overall, approximately one-third of patients with a long-term CVC will experience an infection, and 70% of the cultured bacteria are gram-positive. Antimicrobial treatment lasts from 7 to 21 days, and although success rates of between 60% and 91% are reported, often the CVC needs to be removed.
To reduce catheter-related infections, guidelines exist for catheter insertion, care and handling, the number of times the catheter is opened per day, hand hygiene, skin antisepsis, catheter site selection, and assessment of CVC necessity. Standard maintenance of long-term CVCs includes flushing the catheter lumen with saline following access, or closing the catheter with a locking solution until the next use.
Delivering antibiotics prophylactically may reduce episodes of catheter-related infection. Antibiotics may be administered intravenously before insertion of a CVC or may be added to the flushing solution in an attempt to prevent bacterial biofilm formation. This review was needed to address the uncertainty regarding whether antibiotic prophylaxis is beneficial to adults and children who are at high risk of CVC-related infection.
The objectives of this review1 were to determine the efficacy of administering antibiotics prior to the insertion of long-term CVCs, or flushing, locking, or both flushing and locking the long-term CVC with a combined antibiotic and heparin solution, to prevent gram-positive catheter-related infections in adults and children receiving treatment for cancer.
Eleven randomized controlled trials with a total of 828 participants were included in the review. Sample sizes ranged from 27 to 108 participants. Participants were exclusively adults (5 studies), children (4 studies), or a mixture of adults and children (2 studies), with hematologic malignancy only (2 studies), solid tumors only (1 study), or a combination of patients with either hematologic malignancy or solid tumors (8 studies). Most studies included patients with tunneled CVCs (TCVCs), with 2 studies including patients with totally implanted devices, and 1 study using both. Five studies investigated the use of the antibiotics vancomycin, teicoplanin, and ceftazidime prior to CVC insertion. Six studies investigated flushing or locking TCVCs with an antibiotic and heparin solution. Antibiotics used in these studies were vancomycin, vancomycin and amikacin, and taurolidine. Outcomes of interest were catheter-related sepsis (CRS) or proxy outcomes, including catheter-related bloodstream infections. Results from studies were pooled by meta-analysis, where possible.
The included studies were mostly of a reasonable quality; however, the sample sizes were considered small. All trials randomized participants to treatment groups, and most studies adequately described allocation concealment. Six trials blinded participants to the treatment received; 5 trials did not blind participants, and 5 trials did not blind outcome assessors.
Antibiotics Before Long-term CVC Insertion
The results from 5 studies (360 participants) all conducted in adults were combined, with no significant difference found in the risk of CRS between antibiotic and control groups (placebo or no antibiotic). Subgroup analysis of the different antibiotics did not show any statistically significant differences in CRS events between antibiotic and control groups.
Antibiotic and Heparin Flush or Lock Solutions Compared With Heparin-Only Solutions
Six studies involving mainly children were combined, with the results showing that there were significantly less CRS events in the antibiotic group than in the heparin-only control group (risk ratio, 0.47; 95% confidence interval, 0.28–0.80; P = .005; 468 participants). To prevent CRS in 1 patient, the number needed to treat was determined to be 12 participants. Subgroup analysis on studies involving children only showed similar results (risk ratio, 0.41; 95% confidence interval, 0.18–0.89; P not given; 321 participants), with significantly less CRS in the group receiving combined antibiotic and heparin solution compared with heparin alone.
Administering prophylactic antibiotics prior to insertion of long-term CVCs did not reduce the risk of subsequent catheter-related infections. Flushing and locking catheters with a solution containing both antibiotics and heparin approximately halved the risk of subsequent catheter-related infection.
Implications for Practice
Flushing and locking long-term CVCs with an antibiotic and heparin solution appear to reduce gram-positive catheter-related infection in people at risk of neutropenia through chemotherapy or disease. There were insufficient data to state whether this applies equally to TCVCs and totally implanted devices, or to children and adults. The use of an antibiotic and heparin solution may be of value in high-risk people and where baseline CVC infection rates are high; however, routine antibiotic use is likely to increase microbial resistance.
1. van de Wetering MD, van Woensel JBM, Lawrie TA. Prophylactic antibiotics for preventing gram positive infections associated with long-term central venous catheters in oncology patients. Cochrane Database Syst Rev. 2013(11):CD003295.