SUPPLEMENT ARTICLE
Advances in Prevention and Management of Central Line–Associated Bloodstream Infections in Patients With Cancer Issam Raad and Anne-Marie Chaftari Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston
Keywords. central venous catheters; catheter-related infections; central line–associated bloodstream infections; prevention and management; cancer patients.
Central venous catheters (CVCs) have become the lifeline for cancer patients. Of the >13 million patients living with invasive cancer in the United States [1], at least 4 million have a long-term CVC (LTCVC). A large surveillance study conducted at The University of Texas MD Anderson Cancer Center found that nontunneled, non–surgically implantable LTCVCs were placed on average for approximately 200 consecutive days. However, in cancer patients, the dwell time of implantable venous ports often extends beyond 200 days. We therefore estimate that on an annual basis the total number of LTCVC days in cancer patients is at least 800 million. The National Healthcare Safety Network reports a rate of 1.5 central line–associated bloodstream infections (CLABSIs) per 1000 CVC-days in the United States [2], with a mortality rate of 12%–25% [3, 4]. If we assume a more conservative rate of 0.5 CLABSI per 1000 CVC-days in patients with cancer, we estimate that at least 400 000 episodes of CLABSI occur every year in cancer patients. A recent report estimated the cost of a single CLABSI episode to be $45 814, making CLABSI the most costly healthcare-associated infection.
Correspondence: Issam Raad, MD, The University of Texas MD Anderson Cancer Center, Department of Infectious Diseases, Infection Control & Employee Health, 1515 Holcombe Blvd, Houston, TX 77030 ([email protected]). Clinical Infectious Diseases® 2014;59(S5):S340–3 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected]. DOI: 10.1093/cid/ciu670
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Based on these figures, the total annual US cost of CLABSI in patients with cancer is estimated to exceed $18 billion [5]. Colonization by pathogens may occur as early as 1 day after CVC insertion. For short-term CVCs (2 days from the date of bacteremia onset or the day before. However, the CLABSI definitions often lack specificity in cancer patients.
Downloaded from http://cid.oxfordjournals.org/ at Dalhousie University on November 12, 2014
Central lines, which are essential for treating cancer, are associated with at least 400 000 episodes of bloodstream infection in patients with cancer every year in the United States. Effective novel interventions for preventing and managing these infections include antimicrobial-coated catheters and antimicrobial lock solutions.
PREVENTION The institution of a bundle of aseptic techniques—such as barrier precautions, application of chlorhexidine during insertion, hand hygiene, avoidance of femoral sites, and removal of CVC when it is not needed—was shown to decrease the risk of CLABSI with short-term catheters, which are used mostly in critical care patients with a dwell time of 5-fold [12]. Another large prospective study, comparing antimicrobial-impregnated nontunneled LTCVCs to tunneled uncoated LTCVCs, showed that antimicrobial impregnation significantly decreased the risk of CRBSI and alleviated the need for LTCVC tunneling to prevent infection [13]. The success of M/R impregnation in preventing LTCVC-associated
infections in patients with cancer was most likely related to the fact that both the external and the internal surfaces are impregnated with the antimicrobial with an indwelling durability of approximately 50 days [13]. In contrast, chlorhexidine/silver sulfadiazine (CHX/SS)–coated catheters with an antimicrobial durability of about 7 days failed to show any benefit in patients with cancer, with a mean catheter dwell time of approximately 20 days [14]. The challenge would be to prevent infections when the dwell time of M/R-impregnated CVC exceeds 50 days, particularly as the antibiotics elute from the surface of the catheters (especially the lumen) during this time period. Therefore, antimicrobial lock solutions have been proposed as a mode of preventing intraluminal CLABSI in LTCVCs that are projected to remain in place beyond 7–8 weeks as outlined below. The M/Rimpregnated and CHX/SS-coated CVCs are US Food and Drug Administration (FDA)–approved and available for clinical use. 2. Antimicrobial lock: Chelator (citrate or ethylenediaminetetraacetic acid [EDTA]) antimicrobial locks were developed to replace heparin-based intraluminal locks given the fact that they have equivalent anticoagulant activity to heparin, and they have a complementary antimicrobial and antibiofilm activity with other antimicrobial agents vs heparin, which enhances biofilm formation [15–18]. These chelator-based antimicrobial locks have been widely studied and shown to be highly effective in hemodialysis patients with LTCVCs [19–21], as well as pediatric cancer patients. The combination of minocycline/EDTA in particular has been highly effective in patients with cancer as well as hemodialysis patients with LTCVCs [16, 17, 19]. In a large prospective, randomized trial, 70% ethanol failed to decrease the intraluminal CLABSI rate [22] and was associated with adverse events, including dizziness and drowsiness. The use of >30% ethanol lock has been associated with serum protein precipitation and incompatibility with the polyurethane catheter polymer [23]. More recently, the addition of 25% ethanol to a minocycline/EDTA lock solution demonstrated high efficacy in eradicating pathogens in biofilm and high clinical efficacy in salvaging CVCs. Nonantibiotic chelator lock solutions such as nitroglycerin citrate lock have also shown high efficacy in eradicating microbial organisms embedded in biofilm on catheter surfaces [24]. Although antimicrobial locks are well studied, currently there are no FDA-approved, commercially available antimicrobial catheter locks. MANAGEMENT The strategies for managing CLABSI vary by pathogen. 1. Coagulase-negative staphylococci: Neither CVC retention nor treatment >7 days had an effect on resolution of bacteremia, but CVC retention was a significant risk factor for recurrence [25]. However, the recurrence of the bacteremia is unlikely to be
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Downloaded from http://cid.oxfordjournals.org/ at Dalhousie University on November 12, 2014
The CDC recently developed a new definition termed “mucosal barrier injury–laboratory-confirmed bloodstream infection” (MBI-LCBI) [6]. It applies to bacteremic patients with central lines (suspected CLABSI) who could have a gastrointestinal source for the bacteremia associated with mucosal injury related to postchemotherapy neutropenia or graft-vs-host disease [6]. However, exclusion of all MBI-LCBIs from CLABSI wrongly assumes that CLABSI cannot occur in cancer patients with MBI. Hence, for cases of MBI, it might be prudent to rely on the definition of catheter-related bloodstream infection (CRBSI) by the Infectious Diseases Society of America (2009 guidelines). CRBSI is a more specific and stringent definition that identifies the CVC as the source of the bacteremia and requires specific laboratory testing such as quantitative catheter cultures, simultaneous quantitative blood cultures, or differential time to positivity [7, 8].
Notes Financial support. Funding for this conference was supported in part by the National Institutes of Health and the Agency for Healthcare Research and Quality (grant number R13 HS021599).
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Supplement sponsorship. This article appeared as part of the supplement “The Third Infections in Cancer Symposium,” sponsored by the National Institute of Health, Agency for Healthcare Research and Quality. Potential conflicts of interest. I. R. is coinventor of technology related to minocycline and rifampin-coated catheters, licensed to Cook, Inc; and is coinventor of technology related to minocycline-EDTA Lock, licensed to Novel Anti-infective Technology and Leonard-Meron Biosciences, Inc. A.-M. C. reports no potential conflicts. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References 1. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975–2010. Bethesda, MD: National Cancer Institute. Available at: http://seer.cancer.gov/csr/1975_2010/. Accessed 6 February 2014. 2. Edwards JR, Peterson KD, Mu Y, et al. National Healthcare Safety Network (NHSN) report: data summary for 2006 through 2008, issued December 2009. Am J Infect Control 2009; 37:783–805. 3. Centers for Disease Control and Prevention. Vital signs: central lineassociated blood stream infections—United States, 2001, 2008, and 2009. MMWR Morb Mortal Wkly Rep 2011; 60:243–8. 4. Pronovost P, Needham D, Berenholtz S, et al. An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 2006; 355:2725–32. 5. Dimick JB, Pelz RK, Consunji R, Swoboda SM, Hendrix CW, Lipsett PA. Increased resource use associated with catheter-related bloodstream infection in the surgical intensive care unit. Arch Surg 2001; 136:229–34. 6. National Healthcare Safety Network. Central line–associated bloodstream infection (CLABSI) event. Available at: http://www.cdc.gov/ nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf. Accessed 18 April 2014. 7. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 49:1–45. 8. Raad I, Hanna HA, Alakech B, Chatzinikolaou I, Johnson MM, Tarrand J. Differential time to positivity: a useful method for diagnosing catheter-related bloodstream infections. Ann Intern Med 2004; 140:18–25. 9. Furuya EY, Dick A, Perencevich EN, Pogorzelska M, Goldmann D, Stone PW. Central line bundle implementation in US intensive care units and impact on bloodstream infections. PLoS One 2011; 6:e15452. 10. Raad II, Hohn DC, Gilbreath BJ, et al. Prevention of central venous catheter-related infections by using maximal sterile barrier precautions during insertion. Infect Control Hosp Epidemiol 1994; 15(4 pt 1): 231–8. 11. Hanna HA, Raad I. Blood products: a significant risk factor for longterm catheter-related bloodstream infections in cancer patients. Infect Control Hosp Epidemiol 2001; 22:165–6. 12. Hanna H, Afif C, Alakech B, et al. Central venous catheter-related bacteremia due to gram-negative bacilli: significance of catheter removal in preventing relapse. Infect Control Hosp Epidemiol 2004; 25:646–9. 13. Darouiche RO, Berger DH, Khardori N, et al. Comparison of antimicrobial impregnation with tunneling of long-term central venous catheters: a randomized controlled trial. Ann Surg 2005; 242:193–200. 14. Logghe C, Van Ossel C, D’Hoore W, Ezzedine H, Wauters G, Haxhe JJ. Evaluation of chlorhexidine and silver-sulfadiazine impregnated central venous catheters for the prevention of bloodstream infection in leukaemic patients: a randomized controlled trial. J Hosp Infect 1997; 37:145–56. 15. Shanks RM, Sargent JL, Martinez RM, Graber ML, O’Toole GA. Catheter lock solutions influence staphylococcal biofilm formation on abiotic surfaces. Nephrol Dial Transplant 2006; 21:2247–55. 16. Bleyer AJ, Mason L, Russell G, Raad II, Sherertz RJ. A randomized, controlled trial of a new vascular catheter flush solution (minocyclineEDTA) in temporary hemodialysis access. Infect Control Hosp Epidemiol 2005; 26:520–4.
Downloaded from http://cid.oxfordjournals.org/ at Dalhousie University on November 12, 2014
associated with a deep-seated infection (such as endocarditis) in the absence of an indwelling prosthetic device (such as prosthetic valve). Hence, often the CVC is retained and antimicrobial lock therapy is initiated. Treatment duration has not been defined, but 5- to 7-day treatment with vancomycin is considered acceptable for uncomplicated cases. Daptomycin is an alternative. 2. Staphylococcus aureus: A large study involving 299 cancer patients with S. aureus CLABSI, conducted by our group, showed that 67% of the cases were complicated and associated with either deep-seated infections or persistent fever and bacteremia. Early removal of the CVC (within the first 3 days) was associated with an improved outcome. A treatment course of 10–14 days was considered acceptable in the remaining 33% of patients without complications [26]. When the CVC cannot be removed because no other intravascular sites are available or because of problems such as neutropenia, the patient should either receive antibiotic lock therapy, ( particularly in CVC with dwell time of > 30 days) [27], or have the CVC exchanged over guidewire using an antimicrobial CVC along with systemic antibiotic therapy. If the fever and bacteremia persist for >72 hours or the patient has a deep-seated infection, therapy should be extended to 4–6 weeks. 3. Candida: The 2009 guidelines of the Infectious Diseases Society of America recommend removing the CVC in cases of catheter-related candidemia on the basis of a large body of evidence from patients with cancer and those without cancer [7]. More recent evidence supports this recommendation for cancer patients [28]. Treatment could include fluconazole or one of the echinocandins, particularly in hospitals with a high rate of infection with fluconazole-resistant Candida glabrata or Candida krusei. Recommended duration of therapy is 2 weeks from the last positive blood culture [7]. 4. Gram-negative bacilli: CLABSIs due to gram-negative bacilli require prompt removal of the CVC (within 72 hours) [12] with appropriate antimicrobial systemic therapy. The gramnegative bacilli most commonly involved in CLABSI are those that form biofilms and include Enterobacter, Stenotrophomonas, Klebsiella, Pseudomonas, and Acinetobacter species [12, 29] Treatment with a systemic antibiotic over a 7-day period appears to resolve the infection. 5. Gram-positive bacilli: Gram-positive bacilli such as Bacillus species may cause CLABSI and often require removal of the catheter [25]. However, CLABSIs caused by non–group JK corynebacteria do not necessarily require removal of the CVC, particularly if a nonglycopeptide is used with a lock solution. Vancomycin, in general, remains the drug of choice [30].
24. Rosenblatt J, Reitzel R, Dvorak T, Jiang Y, Hachem RY, Raad II. Glyceryl trinitrate complements citrate and ethanol in a novel antimicrobial catheter lock solution to eradicate biofilm organisms. Antimicrob Agents Chemother 2013; 57:3555–60. 25. Raad I, Kassar R, Ghannam D, Chaftari AM, Hachem R, Jiang Y. Management of the catheter in documented catheter-related coagulase-negative staphylococcal bacteremia: remove or retain? Clin Infect Dis 2009; 49:1187–94. 26. El Zakhem A, Chaftari AM, Bahu R, et al. Central line-associated bloodstream infections caused by Staphylococcus aureus in cancer patients: clinical outcome and management. Ann Med 2014; 46:163–8. 27. Mermel LA. What is the predominant source of intravascular catheter infections? Clin Infect Dis 2011; 52:211–2. 28. Garnacho-Montero J, Diaz-Martin A, Garcia-Cabrera E, Ruiz Perez de Pipaon M, Hernandez-Caballero C, Lepe-Jimenez JA. Impact on hospital mortality of catheter removal and adequate antifungal therapy in Candida spp. bloodstream infections. J Antimicrob Chemother 2013; 68:206–13. 29. Cairo J, Hachem R, Rangaraj G, Granwehr B, Raad I. Predictors of catheter-related gram-negative bacilli bacteraemia among cancer patients. Clin Microbiol Infect 2011; 17:1711–6. 30. Ghide S, Jiang Y, Hachem R, Chaftari AM, Raad I. Catheter-related Corynebacterium bacteremia: should the catheter be removed and vancomycin administered? Eur J Clin Microbiol Infect Dis 2010; 29:153–6.
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17. Campos RP, do Nascimento MM, Chula DC, Riella MC. MinocyclineEDTA lock solution prevents catheter-related bacteremia in hemodialysis. J Am Soc Nephrol 2011; 22:1939–45. 18. Maki DG, Ash SR, Winger RK, Lavin P. A novel antimicrobial and antithrombotic lock solution for hemodialysis catheters: a multi-center, controlled, randomized trial. Crit Care Med 2011; 39:613–20. 19. Chatzinikolaou I, Zipf TF, Hanna H, et al. Minocycline-ethylenediaminetetraacetate lock solution for the prevention of implantable port infections in children with cancer. Clin Infect Dis 2003; 36:116–9. 20. Ferreira Chacon JM, Hato de Almeida E, de Lourdes Simoes R, et al. Randomized study of minocycline and edetic acid as a locking solution for central line ( port-a-cath) in children with cancer. Chemotherapy 2011; 57:285–91. 21. Handrup MM, Moller JK, Schroder H. Central venous catheters and catheter locks in children with cancer: a prospective randomized trial of taurolidine versus heparin. Pediatr Blood Cancer 2013; 60: 1292–8. 22. Slobbe L, Doorduijn JK, Lugtenburg PJ, et al. Prevention of catheterrelated bacteremia with a daily ethanol lock in patients with tunnelled catheters: a randomized, placebo-controlled trial. PLoS One 2010; 5: e10840. 23. Schilcher G, Schlagenhauf A, Schneditz D, et al. Ethanol causes protein precipitation—new safety issues for catheter locking techniques. PLoS One 2013; 8:e84869.
Advances in Prevention and Management of Central Line–Associated Bloodstream Infections in Patients With Cancer Issam Raad and Anne-Marie Chaftari Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston
Keywords. central venous catheters; catheter-related infections; central line–associated bloodstream infections; prevention and management; cancer patients.
Central venous catheters (CVCs) have become the lifeline for cancer patients. Of the >13 million patients living with invasive cancer in the United States [1], at least 4 million have a long-term CVC (LTCVC). A large surveillance study conducted at The University of Texas MD Anderson Cancer Center found that nontunneled, non–surgically implantable LTCVCs were placed on average for approximately 200 consecutive days. However, in cancer patients, the dwell time of implantable venous ports often extends beyond 200 days. We therefore estimate that on an annual basis the total number of LTCVC days in cancer patients is at least 800 million. The National Healthcare Safety Network reports a rate of 1.5 central line–associated bloodstream infections (CLABSIs) per 1000 CVC-days in the United States [2], with a mortality rate of 12%–25% [3, 4]. If we assume a more conservative rate of 0.5 CLABSI per 1000 CVC-days in patients with cancer, we estimate that at least 400 000 episodes of CLABSI occur every year in cancer patients. A recent report estimated the cost of a single CLABSI episode to be $45 814, making CLABSI the most costly healthcare-associated infection.
Correspondence: Issam Raad, MD, The University of Texas MD Anderson Cancer Center, Department of Infectious Diseases, Infection Control & Employee Health, 1515 Holcombe Blvd, Houston, TX 77030 ([email protected]). Clinical Infectious Diseases® 2014;59(S5):S340–3 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected]. DOI: 10.1093/cid/ciu670
S340
•
CID 2014:59 (Suppl 5)
•
Raad and Chaftari
Based on these figures, the total annual US cost of CLABSI in patients with cancer is estimated to exceed $18 billion [5]. Colonization by pathogens may occur as early as 1 day after CVC insertion. For short-term CVCs (2 days from the date of bacteremia onset or the day before. However, the CLABSI definitions often lack specificity in cancer patients.
Downloaded from http://cid.oxfordjournals.org/ at Dalhousie University on November 12, 2014
Central lines, which are essential for treating cancer, are associated with at least 400 000 episodes of bloodstream infection in patients with cancer every year in the United States. Effective novel interventions for preventing and managing these infections include antimicrobial-coated catheters and antimicrobial lock solutions.
PREVENTION The institution of a bundle of aseptic techniques—such as barrier precautions, application of chlorhexidine during insertion, hand hygiene, avoidance of femoral sites, and removal of CVC when it is not needed—was shown to decrease the risk of CLABSI with short-term catheters, which are used mostly in critical care patients with a dwell time of 5-fold [12]. Another large prospective study, comparing antimicrobial-impregnated nontunneled LTCVCs to tunneled uncoated LTCVCs, showed that antimicrobial impregnation significantly decreased the risk of CRBSI and alleviated the need for LTCVC tunneling to prevent infection [13]. The success of M/R impregnation in preventing LTCVC-associated
infections in patients with cancer was most likely related to the fact that both the external and the internal surfaces are impregnated with the antimicrobial with an indwelling durability of approximately 50 days [13]. In contrast, chlorhexidine/silver sulfadiazine (CHX/SS)–coated catheters with an antimicrobial durability of about 7 days failed to show any benefit in patients with cancer, with a mean catheter dwell time of approximately 20 days [14]. The challenge would be to prevent infections when the dwell time of M/R-impregnated CVC exceeds 50 days, particularly as the antibiotics elute from the surface of the catheters (especially the lumen) during this time period. Therefore, antimicrobial lock solutions have been proposed as a mode of preventing intraluminal CLABSI in LTCVCs that are projected to remain in place beyond 7–8 weeks as outlined below. The M/Rimpregnated and CHX/SS-coated CVCs are US Food and Drug Administration (FDA)–approved and available for clinical use. 2. Antimicrobial lock: Chelator (citrate or ethylenediaminetetraacetic acid [EDTA]) antimicrobial locks were developed to replace heparin-based intraluminal locks given the fact that they have equivalent anticoagulant activity to heparin, and they have a complementary antimicrobial and antibiofilm activity with other antimicrobial agents vs heparin, which enhances biofilm formation [15–18]. These chelator-based antimicrobial locks have been widely studied and shown to be highly effective in hemodialysis patients with LTCVCs [19–21], as well as pediatric cancer patients. The combination of minocycline/EDTA in particular has been highly effective in patients with cancer as well as hemodialysis patients with LTCVCs [16, 17, 19]. In a large prospective, randomized trial, 70% ethanol failed to decrease the intraluminal CLABSI rate [22] and was associated with adverse events, including dizziness and drowsiness. The use of >30% ethanol lock has been associated with serum protein precipitation and incompatibility with the polyurethane catheter polymer [23]. More recently, the addition of 25% ethanol to a minocycline/EDTA lock solution demonstrated high efficacy in eradicating pathogens in biofilm and high clinical efficacy in salvaging CVCs. Nonantibiotic chelator lock solutions such as nitroglycerin citrate lock have also shown high efficacy in eradicating microbial organisms embedded in biofilm on catheter surfaces [24]. Although antimicrobial locks are well studied, currently there are no FDA-approved, commercially available antimicrobial catheter locks. MANAGEMENT The strategies for managing CLABSI vary by pathogen. 1. Coagulase-negative staphylococci: Neither CVC retention nor treatment >7 days had an effect on resolution of bacteremia, but CVC retention was a significant risk factor for recurrence [25]. However, the recurrence of the bacteremia is unlikely to be
CLABSI in Cancer Patients
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CID 2014:59 (Suppl 5)
•
S341
Downloaded from http://cid.oxfordjournals.org/ at Dalhousie University on November 12, 2014
The CDC recently developed a new definition termed “mucosal barrier injury–laboratory-confirmed bloodstream infection” (MBI-LCBI) [6]. It applies to bacteremic patients with central lines (suspected CLABSI) who could have a gastrointestinal source for the bacteremia associated with mucosal injury related to postchemotherapy neutropenia or graft-vs-host disease [6]. However, exclusion of all MBI-LCBIs from CLABSI wrongly assumes that CLABSI cannot occur in cancer patients with MBI. Hence, for cases of MBI, it might be prudent to rely on the definition of catheter-related bloodstream infection (CRBSI) by the Infectious Diseases Society of America (2009 guidelines). CRBSI is a more specific and stringent definition that identifies the CVC as the source of the bacteremia and requires specific laboratory testing such as quantitative catheter cultures, simultaneous quantitative blood cultures, or differential time to positivity [7, 8].
Notes Financial support. Funding for this conference was supported in part by the National Institutes of Health and the Agency for Healthcare Research and Quality (grant number R13 HS021599).
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Raad and Chaftari
Supplement sponsorship. This article appeared as part of the supplement “The Third Infections in Cancer Symposium,” sponsored by the National Institute of Health, Agency for Healthcare Research and Quality. Potential conflicts of interest. I. R. is coinventor of technology related to minocycline and rifampin-coated catheters, licensed to Cook, Inc; and is coinventor of technology related to minocycline-EDTA Lock, licensed to Novel Anti-infective Technology and Leonard-Meron Biosciences, Inc. A.-M. C. reports no potential conflicts. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References 1. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975–2010. Bethesda, MD: National Cancer Institute. Available at: http://seer.cancer.gov/csr/1975_2010/. Accessed 6 February 2014. 2. Edwards JR, Peterson KD, Mu Y, et al. National Healthcare Safety Network (NHSN) report: data summary for 2006 through 2008, issued December 2009. Am J Infect Control 2009; 37:783–805. 3. Centers for Disease Control and Prevention. Vital signs: central lineassociated blood stream infections—United States, 2001, 2008, and 2009. MMWR Morb Mortal Wkly Rep 2011; 60:243–8. 4. Pronovost P, Needham D, Berenholtz S, et al. An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 2006; 355:2725–32. 5. Dimick JB, Pelz RK, Consunji R, Swoboda SM, Hendrix CW, Lipsett PA. Increased resource use associated with catheter-related bloodstream infection in the surgical intensive care unit. Arch Surg 2001; 136:229–34. 6. National Healthcare Safety Network. Central line–associated bloodstream infection (CLABSI) event. Available at: http://www.cdc.gov/ nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf. Accessed 18 April 2014. 7. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 49:1–45. 8. Raad I, Hanna HA, Alakech B, Chatzinikolaou I, Johnson MM, Tarrand J. Differential time to positivity: a useful method for diagnosing catheter-related bloodstream infections. Ann Intern Med 2004; 140:18–25. 9. Furuya EY, Dick A, Perencevich EN, Pogorzelska M, Goldmann D, Stone PW. Central line bundle implementation in US intensive care units and impact on bloodstream infections. PLoS One 2011; 6:e15452. 10. Raad II, Hohn DC, Gilbreath BJ, et al. Prevention of central venous catheter-related infections by using maximal sterile barrier precautions during insertion. Infect Control Hosp Epidemiol 1994; 15(4 pt 1): 231–8. 11. Hanna HA, Raad I. Blood products: a significant risk factor for longterm catheter-related bloodstream infections in cancer patients. Infect Control Hosp Epidemiol 2001; 22:165–6. 12. Hanna H, Afif C, Alakech B, et al. Central venous catheter-related bacteremia due to gram-negative bacilli: significance of catheter removal in preventing relapse. Infect Control Hosp Epidemiol 2004; 25:646–9. 13. Darouiche RO, Berger DH, Khardori N, et al. Comparison of antimicrobial impregnation with tunneling of long-term central venous catheters: a randomized controlled trial. Ann Surg 2005; 242:193–200. 14. Logghe C, Van Ossel C, D’Hoore W, Ezzedine H, Wauters G, Haxhe JJ. Evaluation of chlorhexidine and silver-sulfadiazine impregnated central venous catheters for the prevention of bloodstream infection in leukaemic patients: a randomized controlled trial. J Hosp Infect 1997; 37:145–56. 15. Shanks RM, Sargent JL, Martinez RM, Graber ML, O’Toole GA. Catheter lock solutions influence staphylococcal biofilm formation on abiotic surfaces. Nephrol Dial Transplant 2006; 21:2247–55. 16. Bleyer AJ, Mason L, Russell G, Raad II, Sherertz RJ. A randomized, controlled trial of a new vascular catheter flush solution (minocyclineEDTA) in temporary hemodialysis access. Infect Control Hosp Epidemiol 2005; 26:520–4.
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associated with a deep-seated infection (such as endocarditis) in the absence of an indwelling prosthetic device (such as prosthetic valve). Hence, often the CVC is retained and antimicrobial lock therapy is initiated. Treatment duration has not been defined, but 5- to 7-day treatment with vancomycin is considered acceptable for uncomplicated cases. Daptomycin is an alternative. 2. Staphylococcus aureus: A large study involving 299 cancer patients with S. aureus CLABSI, conducted by our group, showed that 67% of the cases were complicated and associated with either deep-seated infections or persistent fever and bacteremia. Early removal of the CVC (within the first 3 days) was associated with an improved outcome. A treatment course of 10–14 days was considered acceptable in the remaining 33% of patients without complications [26]. When the CVC cannot be removed because no other intravascular sites are available or because of problems such as neutropenia, the patient should either receive antibiotic lock therapy, ( particularly in CVC with dwell time of > 30 days) [27], or have the CVC exchanged over guidewire using an antimicrobial CVC along with systemic antibiotic therapy. If the fever and bacteremia persist for >72 hours or the patient has a deep-seated infection, therapy should be extended to 4–6 weeks. 3. Candida: The 2009 guidelines of the Infectious Diseases Society of America recommend removing the CVC in cases of catheter-related candidemia on the basis of a large body of evidence from patients with cancer and those without cancer [7]. More recent evidence supports this recommendation for cancer patients [28]. Treatment could include fluconazole or one of the echinocandins, particularly in hospitals with a high rate of infection with fluconazole-resistant Candida glabrata or Candida krusei. Recommended duration of therapy is 2 weeks from the last positive blood culture [7]. 4. Gram-negative bacilli: CLABSIs due to gram-negative bacilli require prompt removal of the CVC (within 72 hours) [12] with appropriate antimicrobial systemic therapy. The gramnegative bacilli most commonly involved in CLABSI are those that form biofilms and include Enterobacter, Stenotrophomonas, Klebsiella, Pseudomonas, and Acinetobacter species [12, 29] Treatment with a systemic antibiotic over a 7-day period appears to resolve the infection. 5. Gram-positive bacilli: Gram-positive bacilli such as Bacillus species may cause CLABSI and often require removal of the catheter [25]. However, CLABSIs caused by non–group JK corynebacteria do not necessarily require removal of the CVC, particularly if a nonglycopeptide is used with a lock solution. Vancomycin, in general, remains the drug of choice [30].
24. Rosenblatt J, Reitzel R, Dvorak T, Jiang Y, Hachem RY, Raad II. Glyceryl trinitrate complements citrate and ethanol in a novel antimicrobial catheter lock solution to eradicate biofilm organisms. Antimicrob Agents Chemother 2013; 57:3555–60. 25. Raad I, Kassar R, Ghannam D, Chaftari AM, Hachem R, Jiang Y. Management of the catheter in documented catheter-related coagulase-negative staphylococcal bacteremia: remove or retain? Clin Infect Dis 2009; 49:1187–94. 26. El Zakhem A, Chaftari AM, Bahu R, et al. Central line-associated bloodstream infections caused by Staphylococcus aureus in cancer patients: clinical outcome and management. Ann Med 2014; 46:163–8. 27. Mermel LA. What is the predominant source of intravascular catheter infections? Clin Infect Dis 2011; 52:211–2. 28. Garnacho-Montero J, Diaz-Martin A, Garcia-Cabrera E, Ruiz Perez de Pipaon M, Hernandez-Caballero C, Lepe-Jimenez JA. Impact on hospital mortality of catheter removal and adequate antifungal therapy in Candida spp. bloodstream infections. J Antimicrob Chemother 2013; 68:206–13. 29. Cairo J, Hachem R, Rangaraj G, Granwehr B, Raad I. Predictors of catheter-related gram-negative bacilli bacteraemia among cancer patients. Clin Microbiol Infect 2011; 17:1711–6. 30. Ghide S, Jiang Y, Hachem R, Chaftari AM, Raad I. Catheter-related Corynebacterium bacteremia: should the catheter be removed and vancomycin administered? Eur J Clin Microbiol Infect Dis 2010; 29:153–6.
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17. Campos RP, do Nascimento MM, Chula DC, Riella MC. MinocyclineEDTA lock solution prevents catheter-related bacteremia in hemodialysis. J Am Soc Nephrol 2011; 22:1939–45. 18. Maki DG, Ash SR, Winger RK, Lavin P. A novel antimicrobial and antithrombotic lock solution for hemodialysis catheters: a multi-center, controlled, randomized trial. Crit Care Med 2011; 39:613–20. 19. Chatzinikolaou I, Zipf TF, Hanna H, et al. Minocycline-ethylenediaminetetraacetate lock solution for the prevention of implantable port infections in children with cancer. Clin Infect Dis 2003; 36:116–9. 20. Ferreira Chacon JM, Hato de Almeida E, de Lourdes Simoes R, et al. Randomized study of minocycline and edetic acid as a locking solution for central line ( port-a-cath) in children with cancer. Chemotherapy 2011; 57:285–91. 21. Handrup MM, Moller JK, Schroder H. Central venous catheters and catheter locks in children with cancer: a prospective randomized trial of taurolidine versus heparin. Pediatr Blood Cancer 2013; 60: 1292–8. 22. Slobbe L, Doorduijn JK, Lugtenburg PJ, et al. Prevention of catheterrelated bacteremia with a daily ethanol lock in patients with tunnelled catheters: a randomized, placebo-controlled trial. PLoS One 2010; 5: e10840. 23. Schilcher G, Schlagenhauf A, Schneditz D, et al. Ethanol causes protein precipitation—new safety issues for catheter locking techniques. PLoS One 2013; 8:e84869.
