Version May 2024
INTRODUCTION — Catheter-related bloodstream infection (CRBSI) is a significant cause of morbidity and mortality. Issues related to the epidemiology, microbiology, clinical manifestations, diagnosis, and treatment of CRBSI are discussed in detail separately. (See "Intravascular catheter-related infection: Epidemiology, pathogenesis, and microbiology" and "Intravascular non-hemodialysis catheter-related infection: Clinical manifestations and diagnosis" and "Intravascular non-hemodialysis catheter-related infection: Treatment".)
Types of central venous catheters (CVCs) include nontunneled catheters, tunneled catheters, and subcutaneous ports (figure 1). (See "Central venous access in adults: General principles".)
For circumstances in which catheter or port removal is not feasible and salvage is attempted (eg, retention of the catheter with administration of antimicrobial therapy), systemic antimicrobial therapy is used in conjunction with antibiotic lock therapy (ALT) [1]. ALT refers to instillation of a concentrated antibiotic solution into the catheter lumen and allowing the solution to dwell in the catheter for a set period of time with the goal of achieving a sustained drug level high enough to kill bacteria within the biofilm of the catheter.
Issues related to use of antimicrobial locks for adjunctive treatment of CRBSI in patients with CVCs (apart from hemodialysis catheters) are discussed here, as are issues related to use of antimicrobial and ethanol locks for prevention of CRBSI.
Issues related to ALT in the setting of hemodialysis catheter infection are discussed separately. (See "Central venous catheters for acute and chronic hemodialysis access and their management" and "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Management and prevention".)
Other issues related to prevention of CRBSI are discussed in detail separately. (See "Routine care and maintenance of intravenous devices" and "Central venous catheters for acute and chronic hemodialysis access and their management".)
RATIONALE — Catheter-related bloodstream infection (CRBSI) is associated with the development of biofilm on the catheter luminal surface; a biofilm is an aggregate of microorganisms encased in a matrix of self-produced exopolysaccharides that in turn adhere tightly to surfaces.
Antibiotic lock therapy (ALT) provides a concentrated antibiotic solution into the catheter lumen to achieve a drug level high enough to kill bacteria within the biofilm of the catheter.
Bacteria in a biofilm can be difficult to eradicate with systemic antibiotic administration [2-5]. Antibiotic concentrations must be 100- to 1000-fold higher to kill sessile bacteria (those adhered to a surface) within a biofilm than to kill planktonic bacteria (those floating as single cells) [4,6]. In addition, antibiotic penetration into biofilm is variable and depends on factors such as biofilm composition and antibiotic physical and biochemical properties [7].
Anticoagulants may be beneficial in ALT for treatment of CRBSI by interfering with fibrin formation and allowing increased antibiotic penetration into microbial biofilms [8,9]. However, data from other studies suggest that heparin may stimulate Staphylococcus aureus biofilm formation, although this finding is not universally accepted [10-14].
LOCK USE FOR ADJUNCTIVE CRBSI TREATMENT — For circumstances in which catheter salvage is attempted (eg, retention of the catheter with administration of antimicrobial therapy), management includes antibiotic lock therapy (ALT) in conjunction with systemic antimicrobial therapy [15,16]. (See "Intravascular non-hemodialysis catheter-related infection: Treatment", section on 'Catheter salvaged'.)
Indications — In general, ALT is used as adjunctive therapy together with systemic antibiotics for treatment of catheter-related bloodstream infection (CRBSI) in the setting of catheter salvage. Candidates for catheter salvage include patients with a long-term intravascular device (>14 days) who are hemodynamically stable with CRBSI due to a pathogen of relatively low virulence (such as coagulase-negative staphylococci or drug-susceptible Enterobacteriaceae) in the absence of complications (eg, septic thrombophlebitis, endocarditis, or metastatic musculoskeletal infection).
Catheter salvage should not be attempted in patients with a condition warranting catheter removal (table 1). In addition, catheter salvage, even with ALT, should not be attempted in the setting of persistent or relapsed CRBSI following appropriate antimicrobial therapy. Issues related to deciding between catheter salvage and catheter removal are discussed further separately. (See "Intravascular non-hemodialysis catheter-related infection: Treatment", section on 'Selecting a catheter management strategy'.)
In the setting of bloodstream infection (BSI) associated with a subcutaneous port, indications for adjunctive ALT are the same as the indications for adjunctive ALT in the setting of other CRBSI [1].
Antibiotic lock solutions
Selection — An "antibiotic lock" is a highly concentrated antibiotic solution, often combined with an anticoagulant such as heparin, administered in a volume sufficient to fill and dwell in the catheter lumen when the catheter is not in use. When catheters are needed for intravenous access, the antibiotic lock solution must be withdrawn to avoid systemic exposure to toxic high concentrations of antibiotics and/or anticoagulants [17,18]. (See 'Preparation, instillation, and dwell time' below.)
Ideally, the antimicrobial lock solution should be chemically stable, compatible with anticoagulants or other additives (if applicable), active against the organisms in the biofilm, have a low risk of adverse events and toxicity, and a low potential for inducing resistance.
The optimal approach to antibiotic selection or dosing for ALT is uncertain; thus far, there have been no rigorous studies comparing the efficacy and safety of various types of antibiotic lock solutions. Antibiotic selection for ALT should be guided by the antimicrobial susceptibility of the infecting organism, the available dwell time between venous access, and individual patient factors. Commonly used antibiotics that are compatible with heparin and remain active and stable for prolonged periods include vancomycin, cefazolin, ceftazidime, and gentamicin. These and other ALT solutions are summarized in the table (table 2). Alternative agents not listed in the preceding table have been used for ALT, but we do not recommend these agents for routine use [1,19-30]. (See 'Limitations of other lock types' below.)
In vitro studies have consistently shown that high antibiotic concentrations are required to kill bacteria within a biofilm; thus antibiotic concentrations in lock solutions should exceed the minimum inhibitory concentration of the known or suspected infecting organism by 1000-fold [31,32]. The agent used for ALT should be one to which the organism is susceptible, even though the high antibiotic concentrations in ALT may overcome certain mechanisms of resistance. This is further underscored by studies that suggest a decreasing antibiotic concentration gradient across the length of the catheter in ALT, with small quantities of drug diffusing from the distal catheter into the bloodstream [33,34].
In general, we add heparin to our ALT solutions to help maintain catheter patency; heparin may also facilitate antibiotic penetration into some biofilms by interfering with fibrin formation [8,9]. However, heparin should not be used in ALT solutions in individuals with a history of heparin-induced thrombocytopenia (HIT) or in patients for whom large systemic doses of heparin would be dangerous if the lock solution were inadvertently flushed, such as infants (see "Heparin and LMW heparin: Dosing and adverse effects"). In addition, heparin is incompatible with certain antibiotics (table 2) [18,35]. There are no comparative clinical studies demonstrating that ALT solutions containing heparin are more effective than solutions without heparin.
Administration — ALT should be used in conjunction with systemic antibiotics. Issues related to selection of systemic antibiotic therapy are discussed separately. (See "Intravascular non-hemodialysis catheter-related infection: Treatment", section on 'Catheter salvaged'.)
Preparation, instillation, and dwell time — The catheter lumen fill volume should be determined in order to identify the volume of lock solution needed to fill the lumen but not spill into the systemic circulation. A common method used to determine the fill volume is to flush the line with normal saline, attach a new 5 mL syringe to the catheter, and aspirate slowly until blood appears at the syringe tip; the amount of saline in the syringe is the "fill volume" of lock solution that should be administered to the patient. Notably, as the internal end of the catheter is open, some diffusion of lock solution into the circulation is inevitable and of an unpredictable amount; moreover, there exists the risk for accidental flushing of the lock solution into the systemic circulation.
Antimicrobial lock solutions should be prepared using aseptic technique under sterile conditions immediately prior to instillation into the catheter lumen by mixing the appropriate solutions in a single syringe. The solutions should be prepared using proper protocols for injection safety [36].
In general, the catheter should be locked with ALT solution whenever the catheter is not otherwise being used (eg, for infusion of systemic antibiotics, other medications, intravenous fluids, or nutrition). When feasible, alternative intravenous access should be used for administration of agents other than antimicrobial therapy.
Ideally ALT should be instilled at least once daily. The optimal dwell time is unknown; dwell times may range from hours to days, depending on stability of the lock solution and the amount of time available when the catheter is not in use. Some studies support a minimum dwell time of 8 to 12 hours [7]. In one prospective study including 30 patients, successful catheter salvage was observed with once daily ALT instillation with a dwell time as short as two hours [37]. Given the available data, we favor a minimum ALT dwell time of two hours.
Maximum dwell times for antibiotic lock solutions (based on their physical and chemical stability) are summarized in the table (table 2). In general, we favor limiting the dwell time to 24 to 48 hours, since antibiotic concentrations in the catheter can fall to subtherapeutic levels over time [1,33].
For multilumen catheters, instillation of ALT into all lumens is preferred when feasible; it may be necessary to rotate lumens every 12 to 24 hours in order to administer other intravenous fluids or medications. If a significant number of intravenous therapies are needed, the agents should be reviewed for Y-site compatibility to optimize ALT dwell time in the infected catheter; alternatively, administration of intravenous therapies via peripheral vein access could be considered.
At the end of the dwell time or when the catheter is required for alternate use, the ALT should be withdrawn (not flushed into the vein) and discarded, to avoid systemic exposure to the antimicrobial and/or anticoagulant.
Duration of therapy — In general, the duration of ALT is the same as the duration of systemic antibiotic therapy, which depends on the organism and other patient factors [1]. Issues related to duration of therapy are discussed further separately. (See "Intravascular non-hemodialysis catheter-related infection: Treatment", section on 'Catheter salvaged'.)
Monitoring — When adjunctive ALT is used as CRBSI treatment, monitoring of serum levels of vancomycin and gentamicin is not required (unless these antibiotics are also being given parenterally) because systemic exposure from lock therapy is minimal and treatment courses are relatively short.
Issues related to monitoring during management of CRBSI via catheter salvage are discussed separately. (See "Intravascular non-hemodialysis catheter-related infection: Treatment", section on 'Monitoring and indications for catheter removal'.)
Efficacy — Limited data suggest that ALT is associated with reductions in rates of subsequent catheter removal and complications. Most studies on the efficacy of ALT for adjunctive treatment of CRBSI were small, observational, and/or lacked contemporary controls [37-39]. Furthermore, interpretation of available data is challenging given variability in CRBSI definitions, catheter types, ALT agents, outcomes reported, and duration of follow-up.
In a 2011 meta-analysis that included eight (one randomized and seven observational) studies and more than 390 patients with CRBSI, catheter replacement was needed less frequently among patients treated with systemic antibiotics plus ALT than among patients with systemic antibiotics alone (10 versus 33 percent; odds ratio 0.20, 95% CI 0.10-0.39) [39]. In a 2016 observational study that included outcomes of 90 patients with CRBSI who were enrolled prospectively and treated with ALT and systemic therapy and then compared with historical controls, the rate of infectious complications (septic thrombophlebitis, deep-seated infection) was lower among the patients treated with ALT than among the control group (0 versus 12 percent) [37].
Common contexts for use of ALT include patients with catheters for receiving chemotherapy and parenteral nutrition [15,24,26,37,38,40-54].
●For patients with CRBSI in the setting of solid tumor or hematologic malignancy, available data from small, observational studies suggest that adding ALT to standard systemic antibiotic therapy may increase catheter salvage rates [26,37,48,49]. A retrospective study of 24 hematopoietic stem cell transplant patients with CRBSI found that catheter salvage rates were higher among patients who received ALT plus systemic antibiotics versus systemic therapy alone (86 versus 55 percent) [49].
●In adults requiring parenteral nutrition, small observational studies of ALT have reported catheter salvage rates of 25 to 100 percent [15,50-54]. However, none of the lock solutions contained heparin, and there was substantial variability in antibiotic choice, dwell time, duration of therapy, and use of concomitant systemic antibiotics. A systematic review of CRBSI management in adults receiving home parenteral nutrition reported a higher rate of catheter salvage with ALT plus systemic therapy versus systemic antibiotics alone, but only 1 of the 28 included studies involved direct comparison of these two groups [55].
Data on ALT in patients with port-related BSI are limited and reported success rates range from 18 to 100 percent [44-47].
Available studies in children are largely limited to retrospective case series [56,57]. In children, host factors may influence the probability of catheter salvage with ALT. In a small series of pediatric oncology patients, younger age was associated with a higher risk of treatment failure during lock therapy [58].
Adverse effects of ALT as therapy — Potential adverse effects of ALT for treatment of CRBSI include systemic toxicity associated with the agents in the lock solution, emergence of antibiotic resistance, and secondary candidemia.
Potential adverse effects of heparin include risk of bleeding from inadvertent systemic anticoagulation and risk of HIT. Heparin should not be used in ALT for individuals with a history of HIT. The rate of adverse events is likely lower with ALT than with systemic heparin administration since ALT solutions are not flushed, but direct comparative data are not available [18,35].
Diffusion of medication from the locked catheter lumen into the systemic circulation can occur [33]. However, no reports of significant toxicity associated with ALT for adjunctive treatment of CRBSI have been described.
Data on emergence of antibiotic resistance associated with ALT are limited. One retrospective study found no increased risk of resistance when 662 hemodialysis patients treated with systemic antibiotic therapy and ALT were compared to 265 historical controls treated with systemic therapy alone [59].
Secondary candidemia has been observed among patients receiving ALT for CRBSI [15,19]. In one prospective study including 79 patients on hemodialysis with CRBSI treated with systemic antibiotic therapy and ALT, treatment failure occurred in 49 percent of cases. Positive surveillance cultures were observed in 15 patients, including nine patients with secondary candidemia [19].
Limitations of other lock types — Given concern that use of antibiotic locks may promote antimicrobial resistance, alternative agents have been evaluated. However, data are too limited to support their routine use.
●Ethanol has been proposed as an alternative lock solution as it is bactericidal and fungicidal against a broad range of microorganisms. However, ethanol locks should not be used routinely for treatment of CRBSI pending further study because available data are limited by small sample sizes and study heterogeneity. In small observational studies (particularly in pediatric populations), ethanol locks have demonstrated comparable efficacy to antibiotic locks [37,60-65].
Use of ethanol locks may promote release of polymer components from polyurethane catheters and increase the risk for catheter occlusion or breakage; this is less of a concern with silicone catheters [66-68]. Ethanol is incompatible with heparin; therefore, heparin should never be added to ethanol lock solutions. In addition, ethanol locks should not be used in patients with a history of alcohol use disorder or patients on metronidazole (given the possibility of disulfiram-like reaction).
●Taurolidine is a derivative of the amino acid taurine that exhibits antimicrobial properties against gram-positive cocci, Enterobacteriaceae, and Candida species. In a case series of adults with cancer and CRBSI treated with 2% taurolidine locks for five days along with systemic antimicrobials, treatment was successful in 25 of 26 patients, and no adverse events were reported [69]. However, this agent is not widely available, and a paucity of data preclude its routine use at this time.
Other proposed lock additives include N-acetylcysteine (which may be capable of degrading biofilm matrices) [70,71], ion chelators (such as citrate and ethylenediaminetetraacetic acid) [7,37], and lock solutions containing chelators as well as antimicrobials [72]. Pending further study, there is no role for routine use of these agents.
LOCK USE FOR CRBSI PREVENTION — Issues related to use of locks for secondary prevention of catheter-related bloodstream infection (CRBSI) in patients with long-term catheters (apart from hemodialysis catheters) and a history of recurrent CRBSI are discussed below. Other issues related to CRBSI prevention are discussed separately. (See "Routine care and maintenance of intravenous devices".)
Issues related to locks for prevention of CRBSI in hemodialysis catheters are discussed separately. (See "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Management and prevention" and "Central venous catheters for acute and chronic hemodialysis access and their management", section on 'Access, flushing, and catheter locking'.)
Indications — We do not routinely use antibiotic locks for prevention of CRBSI. However, for patients with long-term non-hemodialysis catheters and a history of recurrent CRBSI despite adherence to other routine infection prevention measures, we suggest use of antibiotic locks for prevention of CRBSI. This approach is in agreement with the 2011 Infectious Disease Society of America guidelines and the 2014 Society for Healthcare Epidemiology of America guidelines [73,74].
Data on the efficacy of antibiotic locks for prevention of CRBSI include randomized trials and meta-analyses [75-81]. In one meta-analysis of 23 randomized trials including more than 2800 patients with indwelling catheters (mostly adults on hemodialysis but also including adult and pediatric oncology patients, critically ill neonates, and patients receiving total parenteral nutrition), use of antibiotic locks for prevention of CRBSI was associated with a 69 percent relative reduction in rates of CRBSI (absolute risk reduction 0.11 percent; relative risk [RR] 0.31; 95% CI 0.24-0.40) [79]. Among adults and children with cancer, a meta-analysis of six randomized controlled trials reported that antibiotic-heparin locks or flushes reduced the risk of gram-positive CRBSI by 53 percent (95% CI 15-74) compared with heparin locks or flushes alone [80]. These studies were heterogeneous (eg, catheter type, antibiotic and concentration, duration of central venous catheter [CVC] placement, infection definitions were variable), and only two of the studies evaluated lock therapy.
Ethanol locks are an alternative to antibiotic locks for prevention of CRBSI; data regarding their use are limited. Prophylactic ethanol locks may be considered on a case-by-case basis for patients in certain circumstances as discussed below. (See 'Alternative lock solutions' below.)
Antibiotic lock solutions
Selection and administration — The choice of antibiotic lock solution for prevention of CRBSI should be guided by the microbiology of prior CRBSI episodes.
Antibiotic concentrations for prevention of CRBSI differ from those used for adjunctive treatment of CRBSI:
●For secondary prevention of CRBSI among patients with recurrent infection due to gram-positive organisms, we favor the combination of vancomycin (25 mcg/mL) and heparin (10 units/mL); this is the best-studied antibiotic lock solution for prevention [75-77].
●For secondary prevention of CRBSI among patients with recurrent infection due to gram-negative organisms, we favor the combination of gentamicin and heparin; the optimal dose is uncertain. Gentamicin (5 mg/mL) and heparin (5000 units/mL) has been used successfully (primarily in patients with hemodialysis catheters); successful prophylactic gentamicin concentrations have ranged from 0.32 to 5 mg/mL [82-85]. In some patients receiving prophylactic high-concentration gentamicin locks, detectable systemic levels of gentamicin have been associated with vestibular symptoms (in the absence of hearing loss) [85]. Alternative agents to gentamicin include cephalosporins (such as ceftazidime or cefepime) or fluoroquinolones; however, data regarding prophylactic dosing of these agents are limited.
As with therapeutic lock therapy, heparin should not be included in prophylactic lock solutions in individuals with a history of heparin-induced thrombocytopenia (HIT) or in individuals for whom large systemic doses of heparin would be dangerous if the lock solution were inadvertently flushed, such as infants. (See "Heparin and LMW heparin: Dosing and adverse effects".)
The optimal approach to frequency of administration of lock prophylaxis is uncertain. We favor administration daily or every other day with dwell times of one hour; in small studies, this approach has been associated with reduced rates of CRBSI [75,76].
The catheter lumen fill volume should be determined in order to identify the volume of lock solution needed to fill the lumen but not spill into the systemic circulation. One method to determine the fill volume is to flush the line with normal saline, attach a new 5 mL syringe to the catheter, and aspirate slowly until blood appears at the syringe tip; the amount of saline in the syringe is the "fill volume" of lock solution that should be administered to the patient.
Antimicrobial lock solutions should be prepared using aseptic technique under sterile conditions immediately prior to instillation into the catheter lumen by mixing the appropriate solutions in a single syringe. The solutions should be prepared using proper protocols for injection safety [36].
For multilumen catheters, instillation of antibiotic lock therapy (ALT) into all lumens is preferred when feasible; it may be necessary to rotate lumens in order to administer other intravenous fluids or medications.
At the end of the dwell time, the ALT should be withdrawn (not flushed into the vein) and discarded, to avoid systemic exposure to the antimicrobial and/or anticoagulant.
Duration and monitoring — The optimal duration for lock prophylaxis is uncertain. For patients with recurrent CRBSI in the setting of malignancy who are receiving myelosuppressive chemotherapy, it may be reasonable to use lock prophylaxis during periods of neutropenia [75]. For other patients, lock prophylaxis may be needed for the duration of catheter retention.
For patients receiving ALT as prophylaxis, monitoring of serum levels of vancomycin or gentamicin is not typically required because systemic exposure from locks is minimal. However, it may be reasonable to periodically monitor levels if a patient experiences symptoms of toxicity, has underlying renal insufficiency or advanced age, or is on concurrent nephrotoxic agents. The rationale for this approach is discussed below. (See 'Adverse effects of ALT as prevention' below.)
Patients receiving aminoglycoside ALT should be educated to report the onset of vestibular symptoms or changes in hearing. If long-term use is anticipated, baseline audiology testing is warranted.
Adverse effects of ALT as prevention — Although antimicrobial locks used for CRBSI prevention are used for longer periods of time than when used for treatment, the risk of systemic toxicity from the agents in the lock solution (such as ototoxicity from aminoglycoside locks) remains low. However, detectable gentamicin levels have been reported in some hemodialysis patients on prophylactic ALT, along with some reports of dizziness (no vertigo or hearing loss were reported) [85]. A case report described sudden hearing loss in a patient receiving amikacin locks for prophylaxis, but this case was confounded by the prior use of several courses of systemic amikacin therapy [17].
Data on whether prophylactic ALT induces antibiotic resistance are inconclusive [86]. In one meta-analysis including 11 trials and more than 900 patients who received prophylactic ALT, development of antibiotic resistance was documented in one patient [87]. In a subsequent study including more than 1400 patients who received a gentamicin-heparin lock for prevention of CRBSI over a four-year period, 24 episodes of CRBSI due to a gentamicin-resistant organism were observed; outcomes included four deaths, two cases of septic shock requiring intensive care unit admission, and four cases of endocarditis [88].
Heparin in prophylactic lock solutions can cause the same adverse effects as heparin in therapeutic lock solutions, namely inadvertent bleeding or HIT. Further information is found above. (See 'Adverse effects of ALT as therapy' above.)
Alternative lock solutions
●Ethanol locks – Data for use of ethanol locks for CRBSI prophylaxis are emerging; this remains an area of ongoing investigation. Prophylactic ethanol locks may be used on a case-by-case basis in patients meeting the following criteria, after considering risks and alternative strategies:
•Patients with prior CRBSI episodes due to different organisms, for which a single prophylactic antibiotic agent may not be effective.
•Patients with prior CRBSI episodes caused by drug-resistant pathogens; in such cases, use of an ethanol lock serves as an alternative to use of broad-spectrum antibiotics.
The data informing the benefit of ethanol locks are mixed, with some studies supporting and other studies suggesting no benefit. Data supporting use of ethanol locks for prevention of CRBSI in the setting of malignancy (solid tumor or hematologic malignancy) and parenteral nutrition include:
•In one trial including 64 adults with hematologic malignancies, patients were randomly assigned to receive a 70% ethanol lock (daily for two hours) or a heparinized saline lock (control); the rate of CRBSI was lower among the patients who received the ethanol lock (9 versus 37 percent) [89]. The rate of CRBSI in patients in the control arm was higher than rates of CRBSI reported at other centers, raising uncertainty about the relative efficacy of this procedure at institutions with low baseline rates of CRBSI. In a subsequent randomized trial including 85 adults with hematologic malignancies, use of ethanol locks (daily for two hours) or heparinized saline locks was associated with comparable rates of CRBSI (6 versus 4 percent) [90].
•Data on use of ethanol locks for CRBSI prevention among children with cancer are conflicting. In one study including 94 children randomly assigned to CRBSI prevention with ethanol lock or placebo, the rate of CRBSI was similar (43 versus 44 percent; RR 1.0, 95% CI 0.6-1.6) [91]. However, in an earlier randomized trial including more than 300 children with cancer, patients received a 70% ethanol lock (dwell time two hours, administered once weekly to once every six weeks) or heparin; the rate of CRBSI was lower among those who received ethanol locks (0.77 versus 1.46 per 1000 catheter days) [92].
•In a meta-analysis including four retrospective studies and 53 children receiving parenteral nutrition, use of ethanol lock prophylaxis was associated with an 81 percent reduction in CRBSI relative to heparin locks [93].
Most studies of ethanol locks for prevention of CRBSI have used daily administration of a 70% solution with dwell times of at least two to four hours [89,92,94-96]. Lower concentrations (eg, 30%) may not provide adequate protection against infection and should be avoided [97].
Contraindications to use of ethanol locks (for prevention or treatment) are discussed above. (See 'Limitations of other lock types' above.)
Adverse effects associated with ethanol lock flushing include nausea, dysgeusia, alcoholic taste, dizziness, and skin flushing [92,98,99]. In addition, use of ethanol locks for prevention of CRBSI has been associated with an increased risk of catheter thrombosis [66,100,101]; in an observational study including seven patients with a single-lumen silicone central line exposed to both heparin lock (in the absence of antibiotic lock) as well as ethanol lock therapy, the number of thrombotic events was 1 and 12 on heparin lock and ethanol lock therapy, respectively (rate 0.46 versus 3.27 per 1000 catheter days) [101].
In some regions, high costs and limited availability of ethanol locks hinder the wide implementation of this practice [102].
●Locks containing chelation agents – Chelating agents (such as ethylenediaminetetraacetic acid or citrate) have been investigated for the prevention of CRBSI, primarily in hemodialysis patients. The reported efficacy has been conflicting. Potential adverse effects include catheter dysfunction and reduced patency [72,103-105]. Pending further study, there is no role for routine use of these agents.
●Taurolidine locks – Lock solutions containing taurolidine have been associated with reduction in CRBSI incidence; this agent is not available in many countries, including the United States [106-112]. In a systematic review of four trials including 162 adults receiving parenteral nutrition, the cumulative proportion of CRBSI-free patients using taurolidine, saline, and heparin after one year was 88, 56, and 14 percent, respectively [109]. In children, a randomized trial of 129 catheters in 112 cancer patients found that the rate of CRBSI was lower with taurolidine locks versus heparin locks (incident rate ratio, 0.26; 95% CI 0.09-0.61) [106]. Data for taurolidine are limited by variability in concentrations, frequency of administration, and dwell times. Adverse effects reported with taurolidine locks include dysgeusia and paresthesias [106,109].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Venous access".)
SUMMARY AND RECOMMENDATIONS
●Definition – Antibiotic lock therapy (ALT) refers to instillation of a concentrated antibiotic solution into a catheter lumen and allowing the solution to dwell within the catheter for a set period of time with the goal of achieving a drug level high enough to kill bacteria within the biofilm of the catheter. (See 'Introduction' above and 'Rationale' above.)
●Treatment of CRBSI using ALT
•Indications – For patients with catheter-related bloodstream infection (CRBSI) in whom catheter salvage is appropriate, we suggest using ALT in conjunction with systemic antibiotic therapy rather than using systemic antibiotics alone (Grade 2C). Observational studies suggest that ALT is associated with higher rates of catheter salvage. (See 'Efficacy' above.)
Catheter salvage should not be attempted in patients with a condition that warrants catheter removal; indications for catheter removal are described in detail elsewhere (table 1). (See 'Indications' above and "Intravascular non-hemodialysis catheter-related infection: Treatment", section on 'Selecting a catheter management strategy'.)
•Selection of antimicrobials – Commonly used antibiotics for ALT solutions include vancomycin, cefazolin, and gentamicin (table 2). (See 'Selection' above.)
Systemic antibiotics should be given concurrently with ALT; details regarding systemic therapy are found elsewhere. (See "Intravascular non-hemodialysis catheter-related infection: Treatment", section on 'Empiric antibiotic therapy' and "Intravascular non-hemodialysis catheter-related infection: Treatment", section on 'Directed systemic antibiotic therapy and duration'.)
•Dwell time, frequency, and duration – We favor minimal dwell times of two hours; maximal dwell times depend on the antibiotic used (table 2). Ideally, fresh ALT solution should be instilled at least once daily. ALT is usually continued for the duration of systemic antimicrobial therapy. (See 'Preparation, instillation, and dwell time' above and 'Duration of therapy' above.)
•Monitoring response – Persistent symptoms or positive blood cultures 72 hours after initiation of appropriate antibiotics are indications of clinical failure. In this situation, the catheter should be removed and evaluation for complications (including suppurative thrombophlebitis, endocarditis, and metastatic foci of infection) should be pursued. (See "Intravascular non-hemodialysis catheter-related infection: Treatment", section on 'Monitoring and indications for catheter removal'.)
●ALT technique
•Preparation of ALT solution – ALT solutions should be prepared immediately prior to installation by mixing the appropriate solutions using aseptic technique under sterile conditions. We suggest adding heparin to ALT solutions unless the patient has a contraindication to heparin (table 2) (Grade 2C). (See 'Preparation, instillation, and dwell time' above and 'Selection' above.)
•Administration – ALT solutions should be administered via a single syringe in a volume sufficient to fill the catheter lumen but not spill into the systemic circulation. (See 'Preparation, instillation, and dwell time' above.)
At the end of the dwell time or when the catheter needs to be used, the ALT solution should be withdrawn and discarded. It should not be flushed into the vein. (See 'Preparation, instillation, and dwell time' above.)
●Prevention of CRBSI using ALT – We do not routinely use ALT for prevention of CRBSI. However, we suggest preventative ALT (without systemic antibiotics) for patients who have recurrent CRBSI despite adherence to proper infection prevention measures in whom catheter salvage is preferred (Grade 2C). Antibiotic selection depends on the causative organisms of prior CRBSI episodes. (See 'Lock use for CRBSI prevention' above.)
●Adverse effects – These appear to be rare and include systemic toxicity associated with the agents in the lock solution, emergence of antibiotic resistance, and secondary candidemia. (See 'Adverse effects of ALT as therapy' above and 'Adverse effects of ALT as prevention' above.)
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