Getting to zero: Current and emerging strategies and technologies to reduce catheter-related bloodstream infections

About 150 million intravascular devices are used every year in the United States.[i] Intravascular catheters are essential for delivering fluids, medications, blood and blood products, and parenteral nutrition. Intravascular catheters, even when inserted using perfect sterile technique, can provide an incidental route for bacteria and fungi to move from the skin to the bloodstream. Every year, an estimated total of 250,000 catheter-related bloodstream infections occur across American hospitals[ii], with annual costs between 670 million to 2.68 billion dollars in the United States.[iii] In 2011, the CDC reported: "Of patients who get a bloodstream infection from having a central line, up to 1 in 4 die." [iv]

The high incidence, mortality, morbidity and cost associated with CRBSIs have created considerable interest by healthcare providers, insurers, regulators, and patient advocates in further reducing the incidence of these infections. Implementation of guideline based care, such as the CDC recommendations listed below, has dramatically improved care of chronically placed intravascular catheters over the past decade. However, CRBSI rates have not dropped below 0.5 to 2.39 per 1,000 patient days despite rigorous attention to cleanliness and early signs of infection.[v] [vi] While it may not be possible to prevent 100 percent of CRBSIs with current evidence-based prevention strategies, implementation of currently available strategies could prevent as many as 65-70 percent of these infections.[vii] Emerging strategies and technologies have the potential to further improve these numbers. In this article, we will provide an overview on the current and possible future best practices in diagnosis, treatment and prevention of these infections.

A CRBSI is defined as a primary bloodstream infection that develops in a patient with a catheter that is not related to infection at another site. Confirmation of a CRBSI requires specific laboratory testing to identify the catheter as the source of the bloodstream infection, such as culturing the catheter tip. The most common clinical signs and symptoms of CRBSI are inflammation or purulence at the catheter site, as well as the acute onset of fever, chills, and hypotension with no other apparent source of infection but the catheter.

Potential risk factors for CRBSI include: underlying disease, method of catheter insertion, site of catheter insertion and duration, and purpose of catheterization. Local risk factors, such as poor personal hygiene, occlusive transparent dressing, moisture around the exit site, S. aureus nasal colonization, and contiguous infections support the role of bacterial colonization in the pathogenesis of CRBSI.[viii]

Reduction of CRBSI rates has been a multidisciplinary effort, involving healthcare professionals who order the insertion and removal of CVCs, personnel who insert and maintain central lines, infection control personnel, healthcare managers including the chief executive officer and those who allocate resources, and patients who are capable of assisting in the care of their catheters.

The CDC recommends that facilities:

  • Use CDC-recommended infection control guidelines every time a central line is put in and for central line care.
  • Use central lines for hemodialysis only when other options are not available.
  • Use data for action. Track infection rates and germ types with CDC's National Healthcare Safety Network to learn where and why infections are happening, target actions to stop them, and track progress.
  • Recognize staff members or units that work hard to prevent central line infections.
  • Join state and local health department prevention programs, quality improvement projects, and state-based partnerships to foster best practices.

While doctors and nurses can:

  • Use CDC-recommended infection control steps every time a central line is put in and used.
  • Remove central lines as soon as they are no longer needed.
  • Be sure that all people taking care of the patient follow the right steps.
  • Speak up if someone is not following the right steps.[ix]

The next evolution of improvements could be assisted by emerging products that have the potential to enhance the effectiveness of public guidelines. New antiseptic impregnated transparent dressings may assist in suppressing bacterial growth and allow inspection of exit sites without removal of the dressing.[x] Antiseptic impregnated port protectors may also assist in suppressing bacterial growth at the site of entry.[xi] Certain catheters and cuffs that are coated or impregnated with antimicrobial or antiseptic agents may decrease the risk for CRBSI and potentially decrease hospital costs associated with treating CRBSIs.[xii] Potential downsides of these products include the additional acquisition cost of antimicrobial/antiseptic impregnated catheters and the rare incidence of allergic reactions to the antiseptic agent[xiii]

Independent of improvements in devices, we may see a transition from saline and heparin based "lock solutions" to antimicrobial lock solutions. Multiple lock solutions have been studied in small studies of narrowly selected patients. This information has shown that the concept of antimicrobial lock solutions lowering the CRBSI rate is valid. Though gentamicin containing solutions showed efficacy, the prevalence of gentamicin resistant pathogens requires the selection of a different effective product with an appropriate spectrum of antimicrobial activity and a nonspecific mechanism such that development of pathogen resistance is unlikely. Seventy percent ethanol is such a product and has shown success in a small study,[xiv] but the high concentration may have rare unintended local effects such as endothelial dysfunction and thrombosis. Taurolidine, which has received CE Mark certification for commercial sale in the European Union and is currently not approved in the U.S., has both an appropriate spectrum of activity and the mechanism of action is generally accepted to be bacterial and fungal cell wall degradation. One post-marketing study of a taurolidine-based product approved in Europe found that the product was associated with 96.0 percent reduction in the rate of CRBSI and 96.6 percent reduction in thrombosis compared to published historical benchmarks of 3.5 CRBSIs and 2-3 episodes of thrombosis per 1,000 catheter days.[xv]

The next step will be to demonstrate the efficacy of antimicrobial lock solutions in a sufficiently large population to allow the evaluation of benefit versus risk for FDA approval and Infection Control and Quality Improvement policy making. One such study is a U.S. Phase 3 clinical trial exploring the efficacy of a Taurolidine based solution on reducing CRBSIs in Hemodialysis patients with chronic cuffed central venous catheters which can be found on clinicaltrials.gov.

Dr. Reidenberg earned both his undergraduate (biochemistry, cum laude) and medical degrees from Cornell University. He did Pediatric Residency at The New York Hospital (currently New York Presbyterian Hospital) and fellowships at Rockefeller University (Microbiology) and Mt Sinai Hospital (Infectious Diseases). Dr. Reidenberg has been a project physician within the Pharmaceutical industry for many experimental medicines and is an inventor on 16 patents.

Since 2008, Dr. Reidenberg has divided his time between pharmaceutical consulting and clinical care. Dr. Reidenberg also currently serves on the Scientific Advisory Board of CorMedix, Inc. and volunteers with the World Health Organization Expert Panel for Essential Medicines and the Marathon Medical Team of the New York City Road Runners Club.

 


[i] 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 Disease Society of America. Clin Infectious Dis. 2009;49(1):1–45

[ii] Maki DG, Kluger DM and Crnich CJ. The risk of bloodstream infection in adults with different intravascular devices: a systematic review of 200 published prospective studies. Mayo Clin Proc 2006;81:1159-71.

[iii] https://www.cdc.gov/hai/pdfs/hai/scott_costpaper.pdf

[iv] https://www.cdc.gov/vitalsigns/pdf/2011-03-vitalsigns.pdf

[v] Liu H, Liu H, Deng J, Chen L, Yuan L, Wu Y. Preventing catheter-related bacteremia with taurolidine-citrate catheter locks: a systematic review and meta-analysis. Blood Purif. 2014;37(3):179-87. doi: 10.1159/000360271. Epub 2014 Apr 26.

[vi] Youssouf S, Nache A, Wijesekara C, Middleton RJ, Lewis D, Shurrab AE, O'Riordan E, Lappin LP, O'Donoghue D, Kalra PA, Hegarty J. Effect of a Quality Improvement Program to Improve Guideline Adherence and Attainment of Clinical Standards in Dialysis Care: Report of Outcomes in Year 1. Nephron. 2017 Feb 25. doi: 10.1159/000450890. [Epub ahead of print]

[vii] Umscheid CA, Mitchell MD, Doshi JA, Agarwal R, Williams K, Brennan PJ. Estimating the proportion of healthcare-associated infections that are reasonably preventable and the related mortality and costs. Infect Control Hosp Epidemiol. 2011 Feb;32(2):101-14.

[viii] Sachdev A, Gupta D, Soni A, Chugh K. Central venous catheter colonization and related bacteremia in pediatric intensive care unit. Indian Pediatr. 2002;39:752–60.

[ix] https://www.cdc.gov/vitalsigns/pdf/2011-03-vitalsigns.pdf

[x] Apata IW, Hanfelt J, Bailey JL1, Niyyar VD. Chlorhexidine-impregnated transparent dressings decrease catheter-related infections in hemodialysis patients: a quality improvement project. J Vasc Access. 2017 Feb 4:0. doi: 10.5301/jva.5000658. [Epub ahead of print]

[xi] Martino A, Thompson L, Mitchell C, Trichel R, Chappell W, Miller J, Allen D, Mann-Salinas E. Efforts of a Unit Practice Council to implement practice change utilizing alcohol impregnated port protectors in a burn ICU. Burns. 2017 Jan 27. pii: S0305-4179(17)30022-0. doi: 10.1016/j.burns.2017.01.010. [Epub ahead of print]

[xii] Lorente L, Lecuona M, Jiménez A, Cabrera J, Santacreu R, Lorenzo L, Raja L, Mora ML. Chlorhexidine-silver sulfadiazine-impregnated venous catheters are efficient even at subclavian sites without tracheostomy. Am J Infect Control. 2016 Dec 1;44(12):1526-1529.

[xiii] Raad I, Darouiche R, Dupuis J, et al. Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections. A randomized, double-blind trial. The Texas Medical Center Catheter Study Group. Ann Intern Med. 1997;127:267–74.

[xiv] Sofroniadou S, Revela I, Kouloubinis A, Makriniotou I, Zerbala S, Smirloglou D, Kalocheretis P, Drouzas A, Samonis G, Iatrou C. Ethanol combined with heparin as a locking solution for the prevention of catheter related blood stream infections in hemodialysis patients: A prospective randomized study. Hemodial Int. 2017 Jan 11. doi: 10.1111/hdi.12524. [Epub ahead of print]

[xv] Hollenbeck M, et al A Novel Taurolidine Containing Catheter Lock Solution (CLS) Without Reported Antimicrobial Resistance, Reduces the Rates of Infection and Thrombosis in Hemodialysis Patients Enrolled in a Post-Approval Surveillance Study. AJKD 2016 May;67(5): A54.

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