Use povidone iodine antiseptic ointment or bacitracin/ gramicidin/polymyxin B ointment at the hemodialysis catheter exit site after catheter insertion and at the end of each dialysis session only if this ointment does not interact with the material of the hemodialysis catheter per manufacturer’s recommendation [59, 115–119].
A variety of topical antibiotic or antiseptic ointments have been utilized in attempts to lower the antimicrobial burden at the catheter insertion site and thus prevent infection. A number of older studies, examining primarily peripheral venous catheters, yielded varying conclusions [82, 285, 286]. In addition, the use of antibiotic ointments that have limited antifungal activity may serve to increase colonization and/or infection due to Candida species .
More recent studies have examined this approach in high-risk patients, particularly those undergoing hemodialysis [116–119]. Three randomized, controlled trials have evaluated the use of 10% povidone iodine [117–119]. A significant decrease in colonization, exit-site infection, or bloodstream infection was observed. The beneficial effect was most prominent in subjects with nasal colonization by Staphylococcus aureus [117–119].
Nasal carriers of S. aureus are more likely to experience a CRBSI than non-colonized persons [287–289]. This has prompted investigators to assess the utility of topical mupirocin, a potent anti-staphylococcal agent. Several studies have demonstrated a reduced risk of CRBSI when mupirocin ointment was applied at the catheter insertion site [117, 290–292]. Others have shown similar benefits when mupirocin was applied nasally [288, 289, 293]. However, enthusiasm for this measure has been dampened by the rapid emergence of mupirocin resistance observed at some centers [88, 294, 295], and the potential degrading effect that mupirocin has on polyurethane catheters [94, 95].
In the only study demonstrating a significant effect on mortality, the application of bacitracin/gramicidin/polymyxin B ointment at the catheter insertion site was compared with placebo in 169 hemodialysis patients . Infections were observed in more patients in the placebo group than in the bacitracin/gramicidin/polymyxin B group (34 versus 12%; relative risk, 0.35; 95% CI, .18 to .68). The number of infections per 1,000 catheter days (4.10 versus 1.02; P < .0001) and the number of bacteremia cases per 1,000 catheter days (2.48 versus .63; P = .0004) were also greater in the placebo group. Within the 6-month study period, there were 13 deaths in the placebo group as compared with three deaths in the bacitracin/gramicidin/ polymyxin B group (P = .004). Thus, there is evidence from one study in hemodialysis patients that bacitracin/gramicidin/ polymyxin B ointment can improve outcome, but no similar data exist for use in other patient populations . It should be noted that the gramicidin containing ointment is not currently available in the United States.
Antibiotic Lock Prophylaxis, Antimicrobial Catheter Flush and Catheter Lock Prophylaxis
Use prophylactic antimicrobial lock solution in patients with long term catheters who have a history of multiple CRBSI despite optimal maximal adherence to aseptic technique [120– 138].
To prevent CRBSI, a wide variety of antibiotic and antiseptic solutions have been used to flush or lock catheter lumens [120– 138]. Catheter lock is a technique by which an antimicrobial solution is used to fill a catheter lumen and then allowed to dwell for a period of time while the catheter is idle. Antibiotics of various concentrations that have been used either alone (when directed at a specific organism) or in combination (to achieve broad empiric coverage) to prophylactically flush or lock central venous catheters include vancomycin, gentamicin, ciprofloxacin, minocycline, amikacin, cefazolin, cefotaxime, and ceftazidime; while antiseptics have included alcohol, taurolidine, trisodium citrate. (Taurolidine and trisodium citrate are not approved for this use in the United States). These agents are usually combined with a compound acting as an anticoagulant, such as heparin or EDTA. Most of these studies have been conducted in relatively small numbers of high-risk patients, such as hemodialysis patients, neonates, or neutropenic oncology patients. Although most studies indicate a beneficial effect of the antimicrobial flush or lock solution in terms of prevention of catheter-related infection, this must be balanced by the potential for side effects, toxicity, allergic reactions, or emergence of resistance associated with the antimicrobial agent. The wide variety of compounds used, the heterogeneity of the patient populations studied, and limitations in the size or design of studies preclude a general recommendation for use. In addition, there are no FDA approved formulations approved for marketing, and most formulations have been prepared in hospital pharmacies. A brief overview of some of the studies follows.
At least 10 studies regarding catheter flush or lock solutions have been performed in hemodialysis patients [128, 129, 131– 138]. Three meta-analyses have all demonstrated that catheter lock solutions reduce risk of CRBSI in hemodialysis patients [297–299]. In the largest of these studies, 291 subjects were enrolled in a prospective randomized comparison of 30% trisodium citrate versus heparin . The rate of CRBSI was significantly lower in the group whose catheters were locked with trisodium citrate (4.1 BSI/1,000 CVC days vs. 1.1 BSI/1,000 CVC days, P< .001), and no significant difference in thrombosis or occlusion of the catheter was noted. However, if infused rapidly, concentrated citrate can result in serious hypocalcaemia, cardiac dysrhythmia, and death. The second largest study in hemodialysis subjects examined the effect of a catheter lock solution containing cefazolin, gentamicin, and heparin compared with control patients receiving only heparin . In 120 subjects, the rate of CRBSI was significantly lower in those receiving the antibiotic lock solution (0.44 BSI/1,000 CVC days vs. 3.12 BSI/1,000 CVC days, P = .03) . Other trials in hemodialysis patients have studied minocycline, gentamicin, EDTA, heparin, taurolidine, vancomycin, and cefotaxime.
At least five studies have been conducted in pediatric oncology patients [120, 121, 124, 126, 127]. In the largest trial, 126 subjects were enrolled in a prospective, randomized, double blind study comparing vancomycin/ciprofloxacin/heparin (VCH) to vancomycin/heparin (VH) to heparin (H) alone . The time to CVC-related infection was significantly longer in the VCH or VH arms of the study compared with heparin, and the rate of infection was significantly lower with either of the antibiotic containing solutions compared with heparin alone (1.72/1,000 CVC days [H] vs. 0.55/1,000 CVC days [VCH] vs. 0.37/1,000 CVC days [VH]).
In a meta-analysis of seven randomized, controlled trials examining the utility of vancomycin containing lock or flush solutions compared with heparin alone, the risk ratio for
vancomycin/heparin solutions was 0.49 (95% CI .26–.95, P = .03) . Use of the catheter lock technique appeared to have greater benefit than simply flushing vancomycin through the catheter.
Recently, a prospective, double blind, randomized trial compared the utility of 70% ethanol lock versus heparinized saline for the prevention of primary CRBSI in oncology patients. Patients receiving the ethanol lock preventive therapy were significantly less likely to experience a primary CRBSI (0.60/ 1,000 CVC days vs. 3.11/1,000 CVC days; OR 0.18, 95% CI .05.65, P5 .008) .
Do not routinely use anticoagulant therapy to reduce the risk of catheter-related infection in general patient populations .
Shortly after insertion, intravascular catheters are coated with a conditioning film, consisting of fibrin, plasma proteins, and cellular elements, such as platelets and red blood cells [213, 302]. Microbes interact with the conditioning film, resulting in colonization of the catheter . There is a close association between thrombosis of central venous catheters and infection [221, 304, 305]. Therefore, anticoagulants have been used to prevent catheter thrombosis and presumably reduce the risk of infection.
In a meta-analysis evaluating the benefit of heparin prophylaxis (3 units/mL in parenteral nutrition, 5,000 units every 6 or 12 hours flush or 2,500 units low molecular weight heparin subcutaneously) in patients with short-term CVCs, the risk for catheter-related central venous thrombosis was reduced with the use of prophylactic heparin . However, no substantial difference in the rate of CRBSI was observed. In a more recent prospective, randomized trial, 204 patients with non-tunneled catheters were assigned to receive a continuous infusion of heparin (100 units/kg/ d) or saline (50 mL/d) . The rate of CRBSI was significantly decreased in the group receiving heparin (2.5 BSI/1,000 CVC days vs. 6.4 BSI/1,000 CVC days). Because the majority of heparin solutions contain preservatives with antimicrobial activity, whether any decrease in the rate of CRBSI is a result of the reduced thrombus formation, the preservative, or both is unclear. The majority of pulmonary artery, umbilical, and central venous catheters are available as heparin-bonded devices. The majority of catheters are heparin bonded with benzalkonium, which provides the catheters with antimicrobial activity  and provides an anti-thrombotic effect . However, some catheters have heparin bound directly to the catheter without benzalkonium . Studies have shown that heparin bonded catheters reduce risk of thrombosis and risk of CRBSI [306, 308– 310], but are less effective at reducing catheter colonization than catheters impregnated with chlorhexidine/silver sulfadiazine . Unfortunately, heparin-induced thrombocytopenia can occur and has prompted many clinicians to avoid heparin . Trisodium citrate has been recommended as a catheter lock solution because it possesses both anticoagulant and antimicrobial properties . In a prospective, randomized, double blind study in hemodialysis patients, use of interdialytic heparin (5,000 U/mL) was associated with a significantly greater rate of CRBSIs compared with use of 30% trisodium citrate (4.1 BSI/ 1,000 CVC days vs. 1.1BSI/1,000 CVC days .
Warfarin has been evaluated as a means to reduce CVC thrombus formation and, hence, infection [314–318]. In patients with long-term CVCs, low dose warfarin (i.e., 1 mg/day) reduced the incidence of catheter thrombus [142, 143]. However, other studies have not confirmed reduced thrombosis and still others have found untoward interactions in patients receiving 5-FU [319, 320]. Data are limited; although low dose warfarin decreases the risk of thrombus formation in cancer patients, it has not been shown to reduce infectious complications. Over 20% of patients in some studies develop prolonged prothrombin times and required dosage adjustment . Other anticoagulants, such as factor Xa inhibitors or direct thrombin inhibitors, have not been adequately assessed in terms of reducing the risk of catheter-associated infection.