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2011 Guidelines for the Prevention of Intravascular Catheter-Related Infections

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Antibiotic Lock Prophylaxis, Antimicrobial Catheter Flush and Catheter Lock Prophylaxis

Recommendation

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]. Category II

Background

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 [133]. 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 [135]. 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) [135]. 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 [124]. 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) [300]. 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) [301].

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Anticoagulants

Recommendation

Do not routinely use anticoagulant therapy to reduce the risk of catheter-related infection in general patient populations [139]. Category II

Background

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 [303]. 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 [139]. 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) [306]. 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 [307] and provides an anti-thrombotic effect [308]. However, some catheters have heparin bound directly to the catheter without benzalkonium [309]. 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 [311]. Unfortunately, heparin-induced thrombocytopenia can occur and has prompted many clinicians to avoid heparin [312]. Trisodium citrate has been recommended as a catheter lock solution because it possesses both anticoagulant and antimicrobial properties [133]. 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 [313].

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 [321]. 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.

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Replacement of Peripheral and Midline Catheters

Recommendations

  1. There is no need to replace peripheral catheters more frequently than every 72–96 hours to reduce risk of infection and phlebitis in adults [36, 140, 141]. Category 1B
  2. No recommendation is made regarding replacement of peripheral catheters in adults only when clinically indicated [142–144]. Unresolved issue
  3. Replace peripheral catheters in children only when clinically indicated [32, 33]. Category 1B
  4. Replace midline catheters only when there is a specific indication. Category II

Background

Scheduled replacement of intravascular catheters has been proposed as a method to prevent phlebitis and catheter-related infections. Studies of short peripheral venous catheters indicate that the incidence of thrombophlebitis and bacterial colonization of catheters increases when catheters are left in place >72 hours [258]. However, rates of phlebitis are not substantially different in peripheral catheters left in place 72 hours compared with 96 hours [141]. Because phlebitis and catheter colonization have been associated with an increased risk for catheter-related infection, short peripheral catheter sites commonly are replaced at 72–96 hour intervals to reduce both the risk for infection and patient discomfort associated with phlebitis.

Some studies have suggested that planned removal at 72 hours vs. removing as needed resulted in similar rates of phlebitis and catheter failure [142–144]. However, these studies did not address the issue of CRBSI, and the risk of CRBSIs with this strategy is not well studied.

Midline catheters are associated with lower rates of phlebitis than short peripheral catheters and with lower rates of infection than CVCs [322–324]. In one prospective study of 140 midline catheters, their use was associated with a BSI rate of 0.8 per 1,000 catheter days [324]. No specific risk factors, including duration of catheterization, were associated with infection. Midline catheters were in place a median of 7 days, but for as long as 49 days. Although the findings of this study suggested that midline catheters could be changed only when there is a specific indication, no prospective, randomized studies have assessed the benefit of routine replacement as a strategy to prevent CRBSI associated with midline catheters.

Replacement of CVCs, Including PICCs and Hemodialysis Catheters

Recommendations

  1. Do not routinely replace CVCs, PICCs, hemodialysis catheters, or pulmonary artery catheters to prevent catheter-related infections. Category IB
  2. Do not remove CVCs or PICCs on the basis of fever alone. Use clinical judgment regarding the appropriateness of removing the catheter if infection is evidenced elsewhere or if a noninfectious cause of fever is suspected. Category II
  3. Do not use guidewire exchanges routinely for non-tunneled catheters to prevent infection. Category IB
  4. Do not use guidewire exchanges to replace a non-tunneled catheter suspected of infection. Category IB
  5. Use a guidewire exchange to replace a malfunctioning non-tunneled catheter if no evidence of infection is present. Category IB
  6. Use new sterile gloves before handling the new catheter when guidewire exchanges are performed. Category II

Background

Catheter replacement at scheduled time intervals as a method to reduce CRBSI has not lowered rates. Two trials have assessed a strategy of changing the catheter every 7 days compared with a strategy of changing catheters as needed [165, 325]. One of these studies involved 112 surgical ICU patients needing CVCs, pulmonary artery catheters, or peripheral arterial catheters [165], whereas the other study involved only subclavian hemodialysis catheters [325]. In both studies, no difference in CRBSI was observed in patients undergoing scheduled catheter replacement every 7 days compared with patients whose catheters were replaced as needed.

Scheduled guidewire exchange of CVCs is another proposed strategy for preventing CRBSI. The results of a meta-analysis of 12 randomized, controlled trials assessing CVC management failed to demonstrate any reduction of CRBSI rates through routine replacement of CVCs by guidewire exchange compared with catheter replacement on an as needed basis [326]. Thus, routine replacement of CVCs is not necessary for catheters that are functioning and have no evidence of causing local or systemic complications.

Catheter replacement over a guidewire has become an accepted technique for replacing a malfunctioning catheter or exchanging a pulmonary artery catheter for a CVC when invasive monitoring no longer is needed. Catheter insertion over a guidewire is associated with less discomfort and a significantly lower rate of mechanical complications than are those percutaneously inserted at a new site [327]. In addition, this technique provides a means of preserving limited venous access in some patients. Replacement of temporary catheters over a guidewire in the presence of bacteremia is not an acceptable replacement strategy because the source of infection is usually colonization of the skin tract from the insertion site to the vein [37, 327]. However, in selected patients with tunneled hemodialysis catheters and bacteremia, catheter exchange over a guidewire, in combination with antibiotic therapy, is an alternative as a salvage strategy in patients with limited venous access [328–331].

Because of the increased difficulty obtaining vascular access in children, attention should be given to the frequency with which catheters are replaced in these patients. In a study in which survival analysis techniques were used to examine the relation between the duration of central venous catheterization and complications in pediatric ICU patients, all of the patients studied (n = 397) remained uninfected for a median of 23.7 days [250]. In addition, no relation was found between duration of catheterization and the daily probability of infection (r = 0.21; P > .1), suggesting that routine replacement of CVCs likely does not reduce the incidence of catheter-related infection [250].

Vascular access sites can be even more limited among neonates. Four randomized trials (n = 368) summarized in a recent Cochrane Database Systemic Review compared the effects of giving parenteral nutrition through percutaneous central venous catheters vs. peripheral intravenous catheters. Fewer painful procedures (venipunctures) were required in neonates randomized to percutaneously placed CVCs, and there was no evidence for increased risk of BSIs [332].

CVC occlusion due to thrombus formation is one of the most common reasons for CVC removal in neonates. Various methods have been tried to prevent catheter occlusion. Recently, a randomized trial (n = 201) evaluated whether a continuous heparin infusion (0.5 units/kg/hour) could effectively prolong the duration of catheterization when compared with a placebo infusion. The rate of catheter occlusion requiring catheter removal was lower in the heparin group (6% vs. 31%, P = .001: NNT = 4). Rates of CRBSI were similar, although the study was not powered to evaluate CRBSI rate differences. Heparin associated antibody levels were not routinely measured [333].

Hemodialysis Catheters. The use of catheters for hemodialysis is the most common factor contributing to bacteremia in dialysis patients [334, 335]. The relative risk for bacteremia in patients with dialysis catheters is sevenfold the risk for patients with arteriovenous (AV) fistulas [336]. AV fistulas and grafts are preferred over hemodialysis catheters in patients with chronic renal failure, due to their lower associated risk of infection. If temporary access is needed for dialysis, a tunneled cuffed catheter is preferable to a non-cuffed catheter, even in the ICU setting, if the catheter is expected to stay in place for >3weeks [59].

Pulmonary Artery Catheters. Pulmonary artery catheters are inserted through a Teflon® introducer and typically remain in place an average of 3 days. The majority of pulmonary artery catheters are heparin bonded, which reduces not only catheter thrombosis but also microbial adherence to the catheter [307]. Meta-analysis indicates that the CRBSI rate associated with pulmonary artery catheterization is 3.7 per 1,000 catheter days and somewhat higher than the rate observed for unmedicated and non-tunnelled CVCs (2.7 per 1,000 catheter days)[6, 45].

Data from prospective studies indicate that the risk of significant catheter colonization and CRBSI increases the longer the catheter remains in place. In general, the risk of significant catheter colonization increases after 4 days of catheterization [75, 337, 338], whereas the risk of CRBSI increases beyond 5-7 days of catheterization [75, 84, 166]. Efforts must be made to differentiate between infection related to the introducer and that related to the pulmonary artery catheter. Significant colonization of the introducer occurs earlier than that of the pulmonary artery catheter [337, 339]. However, no studies indicate that catheter replacement at scheduled time intervals is an effective method to reduce risk of CRBSI [165, 327, 339]. In patients who continue to require hemodynamic monitoring, pulmonary artery catheters do not need to be changed more frequently than every 7 days [339]. No specific recommendation can be made regarding routine replacement of catheters that need to be in place for >7 days.

Pulmonary artery catheters are usually packaged with a thin plastic sleeve that prevents touch contamination when placed over the catheter. In a study of 166 catheters, patients who were randomly assigned to have their catheters self-contained within this sleeve had a reduced risk for CRBSI compared with those who had a pulmonary artery catheter placed without the sleeve (P = .002) [81].

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Umbilical Catheters

Recommendations

  1. Remove and do not replace umbilical artery catheters if any signs of CRBSI, vascular insufficiency in the lower extremities, or thrombosis are present [145]. Category II
  2. Remove and do not replace umbilical venous catheters if any signs of CRBSI or thrombosis are present [145]. Category II
  3. No recommendation can be made regarding attempts to salvage an umbilical catheter by administering antibiotic treatment through the catheter. Unresolved issue
  4. Cleanse the umbilical insertion site with an antiseptic before catheter insertion. Avoid tincture of iodine because of the potential effect on the neonatal thyroid. Other iodine-containing products (e.g., povidone iodine) can be used [146– 150]. Category IB
  5. Do not use topical antibiotic ointment or creams on umbilical catheter insertion sites because of the potential to promote fungal infections and antimicrobial resistance [88, 89]. Category IA
  6. Add low-doses of heparin (0.25–1.0 U/ml) to the fluid infused through umbilical arterial catheters [151–153]. Category IB
  7. Remove umbilical catheters as soon as possible when no longer needed or when any sign of vascular insufficiency to the lower extremities is observed. Optimally, umbilical artery catheters should not be left in place >5 days [145, 154]. Category II
  8. Umbilical venous catheters should be removed as soon as possible when no longer needed, but can be used up to 14 days if managed aseptically [155, 156]. Category II
  9. An umbilical catheter may be replaced if it is malfunctioning, and there is no other indication for catheter removal, and the total duration of catheterization has not exceeded 5 days for an umbilical artery catheter or 14 days for an umbilical vein catheter. Category II

Background

Although the umbilical stump becomes heavily colonized soon after birth, umbilical vessel catheterization often is used for vascular access in newborn infants. Umbilical vessels can be cannulated easily and permit both collection of blood samples and measurement of hemodynamic status. The incidences of catheter colonization and BSI are similar for umbilical vein catheters and umbilical artery catheters. In several studies, an estimated 40%–55% of umbilical artery catheters were colonized and 5% resulted in CRBSI; umbilical vein catheters were associated with colonization in 22%–59% of cases [147, 148, 340] and with CRBSI in 3%–8% of cases [148]. Although CRBSI rates are similar for umbilical catheters in the high position (i.e, above the diaphragm) compared with the low position (i.e, below the diaphragm and above the aortic bifurcation), catheters placed in the high position result in a lower incidence of vascular complications without an increase in adverse sequelae [148].

Risk factors for infection differ for umbilical artery and umbilical vein catheters. In one study, neonates with very low birth weight who also received antibiotics for >10 days were at increased risk for umbilical artery CRBSIs [148]. In comparison, those with higher birth weight and receipt of parenteral nutrition fluids were at increased risk for umbilical vein CRBSI. Duration of catheterization was not an independent risk factor for infection of either type of umbilical catheter.

A recent randomized trial (n = 210) evaluated whether long-term umbilical venous catheterization (up to 28 days) would result in the same or fewer CRBSIs when compared with neonates who were randomized to short-term umbilical venous catheterization for 7–10 days followed by percutaneous central venous catheterization. CRBSI rate was higher (20%) among long term catheterized neonates when compared with short term catheterized neonates (13%). The difference was not statistically significant (P = .17), although the study was underpowered. The study was not powered to evaluate differences in venous thrombosis rates [341].

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Peripheral Arterial Catheters and Pressure Monitoring Devices for Adult and Pediatric Patients

Recommendations

  1. In adults, use of the radial, brachial or dorsalis pedis sites is preferred over the femoral or axillary sites of insertion to reduce the risk of infection [46, 47, 157, 158]. Category IB
  2. In children, the brachial site should not be used. The radial, dorsalis pedis, and posterior tibial sites are preferred over the femoral or axillary sites of insertion [46]. Category II
  3. A minimum of a cap, mask, sterile gloves and a small sterile fenestrated drape should be used during peripheral arterial catheter insertion [47, 158, 159]. Category IB
  4. During axillary or femoral artery catheter insertion, maximal sterile barriers precautions should be used. Category II
  5. Replace arterial catheters only when there is a clinical indication. Category II
  6. Remove the arterial catheter as soon as it is no longer needed. Category II
  7. Use disposable, rather than reusable, transducer assemblies when possible [160–164]. Category IB
  8. Do not routinely replace arterial catheters to prevent catheter-related infections [165, 166, 167, 168]. Category II
  9. Replace disposable or reusable transducers at 96-hour intervals. Replace other components of the system (including the tubing, continuous-flush device, and flush solution) at the time the transducer is replaced [37, 161]. Category IB
  10. Keep all components of the pressure monitoring system (including calibration devices and flush solution) sterile [160, 169–171]. Category IA
  11. Minimize the number of manipulations of and entries into the pressure monitoring system. Use a closed flush system (i.e, continuous flush), rather than an open system (i.e, one that requires a syringe and stopcock), to maintain the patency of the pressure monitoring catheters [163, 172]. Category II
  12. When the pressure monitoring system is accessed through a diaphragm, rather than a stopcock, scrub the diaphragm with an appropriate antiseptic before accessing the system [163]. Category IA
  13. Do not administer dextrose-containing solutions or parenteral nutrition fluids through the pressure monitoring circuit [163, 173, 174]. Category IA
  14. Sterilize reusable transducers according to the manufacturers’ instructions if the use of disposable transducers is not feasible [163, 173–176]. Category IA

Background

Arterial catheters are usually inserted into the radial or femoral artery and permit continuous blood pressure monitoring and blood gas measurements. The risk of CRBSI for arterial catheters is lower than that associated with non-coated, uncuffed, non-tunneled short term CVCs (1.7 versus 2.7 per 1,000 catheter days) [6]. However, risk of CRBSI rates are comparable between arterial catheters and coated, uncuffed, non-tunneled short term CVCs [6]. Unlike CVCs, use of full barrier precautions during arterial cannulaton does not appear to reduce the risk of arterial CRBSI [158, 159]. Nonetheless, when arterial catheters are inserted using a protocol which includes maximum barrier precautions, a very low risk of CRBSI (0.41/1,000 catheter days) can be achieved [47]. Although a meta-analysis failed to discern a difference in rates of CRBSI among three sites of insertion (radial, femoral, and axillary) [342], colonization of catheters inserted in the femoral site occurs more often [158]. In addition, a prospective observational study of over 2,900 arterial catheters that were inserted using maximum barrier precautions demonstrated an almost 8-fold increase in the incidence of CRBSI when the femoral site was used compared with the radial site [343]. Furthermore, there is a greater risk of CRBSI caused by gram-negative bacteria when the femoral site is used [343]. The rates of catheter colonization and CRBSI appear similar between the radial and dorsalis pedis sites [157]. The risk of developing a CRBSI increases with the duration of catheterization [166, 344]; however, the routine changing of arterial catheters at scheduled times does not result in a diminution of the risk of CRBSI [165]. Catheters that need to be in place for >5 days should not be routinely changed if no evidence of infection is observed.

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