524049
research-article2014
AOPXXX10.1177/1060028014524049Annals of PharmacotherapyTan et al
Review Article
Ethanol Locks in the Prevention and Treatment of Catheter-Related Bloodstream Infections
Annals of Pharmacotherapy 2014, Vol. 48(5) 607–615 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028014524049 aop.sagepub.com
Marisela Tan, PharmD1, Jackie Lau, PharmD1, and B. Joseph Guglielmo, PharmD1
Abstract Objective: To evaluate the evidence regarding the use of ethanol lock therapy (ELT) for catheter-related bloodstream infection (CRBSI) prophylaxis and treatment. Data Sources: A literature search was conducted using PubMed (August 2003-January 2013) with search terms: ethanol lock, ethanol locks, ethanol lock therapy, prophylaxis, prevention, catheter-related bloodstream infection, and catheter-related infection. Additional sources were identified through a subsequent review of relevant articles. Study Selection and Data Extraction: All English-language studies with >1 patient and a primary outcome of rates of infection, clinical cure, catheter removal or line salvage were evaluated. Studies where ELT was not used for CRBSI prophylaxis or treatment, review articles, and in vitro studies were excluded. Data were abstracted through an independent review of all articles by 2 authors. Discrepancies were discussed and resolved. Data Synthesis: 13 prophylaxis studies evaluated 617 patients; all studies reported decreased rates of infection and catheter removal with ELT. The ELT regimen associated with the most consistent benefit was 70% ethanol, a 2- to 4-hour dwell time, and daily exchange for ≥1 month. 9 treatment studies evaluated 213 catheters, with 90% (192/213) cure and 84% (179/213) line salvage. ELT was always used in combination with systemic antibiotics. The most common ELT treatment regimen was 70% ethanol, a 12- to 24-hour dwell time, and a duration of 1-5 days. No serious adverse events were reported. Conclusion: The current literature suggests that prophylactic ELT decreases the rates of infection and catheter removal, and ELT treatment appears efficacious in combination with systemic antibiotics. Keywords ethanol locks, ethanol lock therapy, treatment, prevention, catheter-related bloodstream infection, review
Introduction In 2002, an estimated 250 000 health care–associated bloodstream infections and >30 000 deaths in the United States were associated with intravenous catheter infection.1 In 2009, an estimated 41 000 catheter line–associated bloodstream infections (CLABSIs) were reported in hospitalized patients in the United States.2 CLABSIs are among the most common and serious health care–associated infections in pediatric and adult patients, with a mortality rate of 12% to 25%.2-5 CLABSIs encompass catheter-related bloodstream infections (CRBSIs), which are associated with increased mortality, health care costs, and length of stay.1 The cost of a CRBSI has been estimated to be $20 647 and even greater ($33 000-$75 000) in ICU patients.6 Considering the potentially preventable mortality, morbidity, and associated health care costs, effective prophylaxis and treatment interventions are needed. CRBSIs often originate from biofilm formation on the inner surface of catheters.7 Compared with planktonic bacteria, biofilm pathogens are less susceptible to antibiotics.7
Infectious Diseases Society of America (IDSA) Guidelines for Prevention of Intravascular Catheter-Related Infections recommend the use of prophylactic antimicrobial lock solutions in patients with long-term catheters and a history of multiple CRBSIs.7 However, a hypothetical disadvantage of antibiotic locks is the potential for the development of resistance. Ethanol is a cost-effective antiseptic, with no known acquired resistance and minimal adverse effects.8,9 Although reviews of ethanol lock therapy (ELT) have been previously published, to date, there has not been a review that is inclusive of all patient populations and case reports. The objective of this review is to critically and comprehensively evaluate the current evidence regarding the use of ELT in the prevention and treatment of CRBSIs. 1
University of California, San Francisco, CA, USA
Corresponding Author: B. Joseph Guglielmo, San Francisco School of Pharmacy, University of California, C-156, Box 0622, 521 Parnassus Avenue, San Francisco, CA 94143-0622, USA. Email: [email protected]
Downloaded from aop.sagepub.com at UNIVERSITE LAVAL on July 5, 2014
608
Annals of Pharmacotherapy 48(5)
Methods All primary studies using ethanol locks in the prevention or treatment of CRBSIs were identified via PubMed and subsequent review of all relevant retrieved papers. Search terms included the following: ethanol lock, ethanol locks, ethanol lock therapy, prophylaxis, prevention, catheterrelated bloodstream infection, and catheter-related infection. Studies electronically published up to January 20, 2013, were included, and the overall range of publication dates was August 2003 through January 2013. Studies were excluded if they were determined to be review papers, in vitro evaluations, single-case reports, ELT utilization not for treatment or prophylaxis of CRBSIs, or focused on a primary outcome other than rate of infection/clinical cure or rate of catheter removal/line salvage. Data collected from ELT prophylaxis studies related to study population, catheter age, ELT regimen, and rates of infection and catheter removal. Data collected from ELT treatment studies related to study population, ELT regimen, and rates of clinical cure and line salvage. For ELT prophylaxis studies, the primary outcomes included rates of infection and catheter removal. Not all studies differentiated the reason for catheter removal; however, any catheter removal determined to be secondary to infection was included. Rates per 1000 catheter days were collated or calculated from reported data to allow for standardization and comparison of infection and catheter removal rates. For ELT treatment studies, the clinical cure was based on the individual study definition, and catheters were considered nonsalvageable if they were removed for any reason. Data from each study were independently validated, and rates of infection/clinical cure and catheter removal/line salvage were calculated with reported data.
Results A total of 49 unique articles were identified for CRBSI prophylaxis and 96 for treatment. After application of exclusion criteria, 13 prophylaxis and 9 treatment studies were included for analysis.
Prophylaxis Table 1 summarizes all ELT prophylaxis studies included.10-22 The respective study definitions of CRBSI varied widely, with some, but not all, studies strictly adhering to the IDSA guidelines.15,21 Other studies defined CRBSI as a positive central-line culture and positive peripheral blood culture in the presence of systemic symptoms.10,12,16,19,20 Some studies required only a single positive central-line culture without a supporting peripheral culture or other confirmed source.11,13,14,17,18,22 Subclassification of CRBSIs similarly differed, with some studies noting endoluminal infections.15,21
A total of 627 patients were included from the 13 prophylaxis studies; 8 studies were categorized as retrospective11,13,16-20,22 and 5 as prospective.10,12,14,15,21 All studies were conducted from 2007 to 2013. Patients receiving ELT prophylaxis ranged from 3-months13 to 75-years-old15; 5 studies were conducted in adults12,15,18,19,21 and 7 in children.11,13,14,16,17,20,22 Underlying concomitant disease states included short-bowel syndrome,11,16,20,22 other gastrointestinal diseases,10,13,17-19 and malignancy.12,14,15 Most studies focused on patients with a history of previous CRBSI.10,11,13,14,16-19,22 Catheter age was not recorded in the majority of studies, and among the 4 studies reporting catheter age, the range was newly placed to 2-years-old.10,12,15,21 Catheters were composed of silicone, with the exception of 1 ELT prophylaxis study including polyurethane catheters.14 The concentration of ethanol used for ELT was consistently 70%, with 1 study evaluating 25% in elderly patients.10 Most studies used a daily ELT exchange, though exchange frequency ranged from daily10-12,14-20 to weekly.13,21,22 Decreasing the frequency of exchange from daily to less often than daily was associated with an increase in the rate of infection.20 Dwell time ranged from 15 minutes15 to >48 hours.21 Those studies demonstrating a significant decrease in the rate of infection used a minimum dwell time of 2 hours.10,12,13,16,17,19,20,22 Among studies that reported significant findings, the most commonly used regimen consisted of 3 mL of 70% ethanol with a 2- to 4-hour dwell time provided daily.10,12,16,17 Some studies reported success with weekly21,22 or 3-times-weekly administration13; however, Ralls et al20 reported a statistically significant increase in the rate of infection from 0.68 to 6.16 per 1000 catheter days with administration of less-than-daily ELT. The duration of ELT prophylaxis varied, ranging from
research-article2014
AOPXXX10.1177/1060028014524049Annals of PharmacotherapyTan et al
Review Article
Ethanol Locks in the Prevention and Treatment of Catheter-Related Bloodstream Infections
Annals of Pharmacotherapy 2014, Vol. 48(5) 607–615 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028014524049 aop.sagepub.com
Marisela Tan, PharmD1, Jackie Lau, PharmD1, and B. Joseph Guglielmo, PharmD1
Abstract Objective: To evaluate the evidence regarding the use of ethanol lock therapy (ELT) for catheter-related bloodstream infection (CRBSI) prophylaxis and treatment. Data Sources: A literature search was conducted using PubMed (August 2003-January 2013) with search terms: ethanol lock, ethanol locks, ethanol lock therapy, prophylaxis, prevention, catheter-related bloodstream infection, and catheter-related infection. Additional sources were identified through a subsequent review of relevant articles. Study Selection and Data Extraction: All English-language studies with >1 patient and a primary outcome of rates of infection, clinical cure, catheter removal or line salvage were evaluated. Studies where ELT was not used for CRBSI prophylaxis or treatment, review articles, and in vitro studies were excluded. Data were abstracted through an independent review of all articles by 2 authors. Discrepancies were discussed and resolved. Data Synthesis: 13 prophylaxis studies evaluated 617 patients; all studies reported decreased rates of infection and catheter removal with ELT. The ELT regimen associated with the most consistent benefit was 70% ethanol, a 2- to 4-hour dwell time, and daily exchange for ≥1 month. 9 treatment studies evaluated 213 catheters, with 90% (192/213) cure and 84% (179/213) line salvage. ELT was always used in combination with systemic antibiotics. The most common ELT treatment regimen was 70% ethanol, a 12- to 24-hour dwell time, and a duration of 1-5 days. No serious adverse events were reported. Conclusion: The current literature suggests that prophylactic ELT decreases the rates of infection and catheter removal, and ELT treatment appears efficacious in combination with systemic antibiotics. Keywords ethanol locks, ethanol lock therapy, treatment, prevention, catheter-related bloodstream infection, review
Introduction In 2002, an estimated 250 000 health care–associated bloodstream infections and >30 000 deaths in the United States were associated with intravenous catheter infection.1 In 2009, an estimated 41 000 catheter line–associated bloodstream infections (CLABSIs) were reported in hospitalized patients in the United States.2 CLABSIs are among the most common and serious health care–associated infections in pediatric and adult patients, with a mortality rate of 12% to 25%.2-5 CLABSIs encompass catheter-related bloodstream infections (CRBSIs), which are associated with increased mortality, health care costs, and length of stay.1 The cost of a CRBSI has been estimated to be $20 647 and even greater ($33 000-$75 000) in ICU patients.6 Considering the potentially preventable mortality, morbidity, and associated health care costs, effective prophylaxis and treatment interventions are needed. CRBSIs often originate from biofilm formation on the inner surface of catheters.7 Compared with planktonic bacteria, biofilm pathogens are less susceptible to antibiotics.7
Infectious Diseases Society of America (IDSA) Guidelines for Prevention of Intravascular Catheter-Related Infections recommend the use of prophylactic antimicrobial lock solutions in patients with long-term catheters and a history of multiple CRBSIs.7 However, a hypothetical disadvantage of antibiotic locks is the potential for the development of resistance. Ethanol is a cost-effective antiseptic, with no known acquired resistance and minimal adverse effects.8,9 Although reviews of ethanol lock therapy (ELT) have been previously published, to date, there has not been a review that is inclusive of all patient populations and case reports. The objective of this review is to critically and comprehensively evaluate the current evidence regarding the use of ELT in the prevention and treatment of CRBSIs. 1
University of California, San Francisco, CA, USA
Corresponding Author: B. Joseph Guglielmo, San Francisco School of Pharmacy, University of California, C-156, Box 0622, 521 Parnassus Avenue, San Francisco, CA 94143-0622, USA. Email: [email protected]
Downloaded from aop.sagepub.com at UNIVERSITE LAVAL on July 5, 2014
608
Annals of Pharmacotherapy 48(5)
Methods All primary studies using ethanol locks in the prevention or treatment of CRBSIs were identified via PubMed and subsequent review of all relevant retrieved papers. Search terms included the following: ethanol lock, ethanol locks, ethanol lock therapy, prophylaxis, prevention, catheterrelated bloodstream infection, and catheter-related infection. Studies electronically published up to January 20, 2013, were included, and the overall range of publication dates was August 2003 through January 2013. Studies were excluded if they were determined to be review papers, in vitro evaluations, single-case reports, ELT utilization not for treatment or prophylaxis of CRBSIs, or focused on a primary outcome other than rate of infection/clinical cure or rate of catheter removal/line salvage. Data collected from ELT prophylaxis studies related to study population, catheter age, ELT regimen, and rates of infection and catheter removal. Data collected from ELT treatment studies related to study population, ELT regimen, and rates of clinical cure and line salvage. For ELT prophylaxis studies, the primary outcomes included rates of infection and catheter removal. Not all studies differentiated the reason for catheter removal; however, any catheter removal determined to be secondary to infection was included. Rates per 1000 catheter days were collated or calculated from reported data to allow for standardization and comparison of infection and catheter removal rates. For ELT treatment studies, the clinical cure was based on the individual study definition, and catheters were considered nonsalvageable if they were removed for any reason. Data from each study were independently validated, and rates of infection/clinical cure and catheter removal/line salvage were calculated with reported data.
Results A total of 49 unique articles were identified for CRBSI prophylaxis and 96 for treatment. After application of exclusion criteria, 13 prophylaxis and 9 treatment studies were included for analysis.
Prophylaxis Table 1 summarizes all ELT prophylaxis studies included.10-22 The respective study definitions of CRBSI varied widely, with some, but not all, studies strictly adhering to the IDSA guidelines.15,21 Other studies defined CRBSI as a positive central-line culture and positive peripheral blood culture in the presence of systemic symptoms.10,12,16,19,20 Some studies required only a single positive central-line culture without a supporting peripheral culture or other confirmed source.11,13,14,17,18,22 Subclassification of CRBSIs similarly differed, with some studies noting endoluminal infections.15,21
A total of 627 patients were included from the 13 prophylaxis studies; 8 studies were categorized as retrospective11,13,16-20,22 and 5 as prospective.10,12,14,15,21 All studies were conducted from 2007 to 2013. Patients receiving ELT prophylaxis ranged from 3-months13 to 75-years-old15; 5 studies were conducted in adults12,15,18,19,21 and 7 in children.11,13,14,16,17,20,22 Underlying concomitant disease states included short-bowel syndrome,11,16,20,22 other gastrointestinal diseases,10,13,17-19 and malignancy.12,14,15 Most studies focused on patients with a history of previous CRBSI.10,11,13,14,16-19,22 Catheter age was not recorded in the majority of studies, and among the 4 studies reporting catheter age, the range was newly placed to 2-years-old.10,12,15,21 Catheters were composed of silicone, with the exception of 1 ELT prophylaxis study including polyurethane catheters.14 The concentration of ethanol used for ELT was consistently 70%, with 1 study evaluating 25% in elderly patients.10 Most studies used a daily ELT exchange, though exchange frequency ranged from daily10-12,14-20 to weekly.13,21,22 Decreasing the frequency of exchange from daily to less often than daily was associated with an increase in the rate of infection.20 Dwell time ranged from 15 minutes15 to >48 hours.21 Those studies demonstrating a significant decrease in the rate of infection used a minimum dwell time of 2 hours.10,12,13,16,17,19,20,22 Among studies that reported significant findings, the most commonly used regimen consisted of 3 mL of 70% ethanol with a 2- to 4-hour dwell time provided daily.10,12,16,17 Some studies reported success with weekly21,22 or 3-times-weekly administration13; however, Ralls et al20 reported a statistically significant increase in the rate of infection from 0.68 to 6.16 per 1000 catheter days with administration of less-than-daily ELT. The duration of ELT prophylaxis varied, ranging from
