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Antimicrobial stewardship: Is there a role in hemodialysis?

OBJECTIVES

After reading this article, the reader will be able to:

1. Define the term antimicrobial stewardship.

2. Describe the reasons why antimicrobial stewardship is needed in hemodialysis.

3. Evaluate the literature supporting antimicrobial stewardship in the hemodialysis population.

4. Explain which antimicrobial stewardship strategies may be effective in the hemodialysis setting.

WHAT IS ANTIMICROBIAL STEWARDSHIP?

Antimicrobial stewardship has been defined in a consensus statement from the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), and the Pediatric Infectious Diseases Society (PIDS), as "coordinated interventions designed to improve and measure the appropriate use of antimicrobial agents by promoting the selection of the optimal antimicrobial drug regimen including dosing, duration of therapy, and route of administration" (Society for Healthcare Epidemiology of America, Infectious Diseases Society of America, & Pediatric Infectious Diseases Society, 2012). Core principles of antimicrobial stewardship are to: (a) ensure patients receive timely and appropriate regimens based on indication and local susceptibility patterns; (b) de-escalate and tailor therapy based on microbiology results; (c) provide expertise and resources at point of care; and (d) monitor antimicrobial consumption transparently and continuously (Centers for Disease Control and Prevention [CDC] & Institute for Healthcare Improvement [IHI], 2012; Dellit et al., 2007; Hyun et al., 2013). The primary goal of an antimicrobial stewardship program (ASP) is to achieve best clinical outcomes related to antimicrobial use while minimizing toxicity and other adverse events (Dellit et al., 2007). The benefits of ASP include improved antimicrobial prescribing practices, improved antimicrobial susceptibility rates, and reduced adverse events, mortality and costs attributable to suboptimal antimicrobial use (Barlam et al., 2016).

WHY IS ANTIMICROBIAL STEWARDSHIP NEEDED IN HEMODIALYSIS?

There are three key reasons why antimicrobial stewardship is needed in hemodialysis (HD) units. First, the HD population is one of the most medically complex group of patients outside an acute care setting (Snyder et al., 2013). Patients on HD have multiple comorbidities and have the highest pill burden of all chronically ill patient populations with an estimated daily average of 12 medications (Chiu et al., 2009). With such a large number of medications, these patients are at increased risk of drug-drug interactions, especially when on antimicrobial therapy.

Second, the pharmacokinetics of a medication may be altered in patients on HD, which impacts their risk of adverse events with the use of antimicrobials (Smyth, Jones, & Saunders, 2016). Many antimicrobials are excreted by the kidney, and alterations in the absorption, distribution, metabolism and excretion of drugs places HD patients at increased risk of drug accumulation and toxicity (Velenosi & Urquhart, 2014).

Third, HD patients are at risk of infectious complications, including from multi-drug resistant organisms (MDROs). In Canada, infection is the second leading reason for admission to hospital, after cardiovascular disease, among patients receiving long-term dialysis (Lafrance et al., 2014). Patients on HD are prone to infection due to numerous individual and treatment-related factors including decreased immunity, dialysis-mediated immune dysfunction, repeated healthcare visits, and repetitive vascular access procedures (Lata, Girard, Parkins, & James, 2016). In a 30-month, single-centre cohort study, patients receiving HD had a higher incidence of nosocomial infection (9.1/1000 patient-days) compared to hospitalized patients not requiring dialysis (3.8/1000 patient-days; relative risk [RR], 2.4; 95% confidence interval [CI], 1.8-3.2; p < 0.001) (D'Agata, Mount, Thayer, & Schaffner, 2000). According to the U.S. Renal Data System (2010) annual report, the rates of all-cause admissions to hospital remained fairly stable between 1994 to 2008 among HD patients. However, the number of hospitalizations due to infection rose by 45.8%. Unfortunately, similar data for the HD population in Canada are unavailable (Lafrance et al., 2014).

Furthermore, the outpatient HD unit is a high-risk setting for the acquisition of MDROs, as a result of extensive antimicrobial exposure. A six-month prospective study in an outpatient dialysis unit identified that 16% of the 85 chronic HD patients were colonized with MDROs (Pop-Vicas, Strom, Stanley, & D'Agata, 2008). The increased risk of MDROs represents a significant source of morbidity, potential mortality, and cost in the care of patients on HD (Snyder & D'Agata, 2012; Snyder et al., 2013). Therefore, minimizing exposure to unnecessary antimicrobials through multifaceted antimicrobial stewardship interventions is crucial for curtailing the ongoing rise of infections due to MDROs in this population (D'Agata, 2013).

It is evident from the reasons outlined above that antimicrobial stewardship is warranted in the HD population. Adverse events associated with antimicrobial exposure, such as drug-drug interactions, drug toxicity, and emergence of resistance may be more common in dialysis settings. Hence, it is imperative to implement an ASP in the HD unit to help guide the appropriate prescribing of antimicrobials to maximize benefit while minimizing harm to patients.

WHAT IS THE EVIDENCE FOR ANTIMICROBIAL STEWARDSHIP IN HEMODIALYSIS?

There is a paucity of data pertaining to antimicrobial use among the outpatient HD population. A study by Snyder et al. (2013) quantified and characterized parenteral antimicrobial prescribing among the HD population at two outpatient dialysis units in the United States. Over the 35-month retrospective study period, the rate of parenteral antimicrobial use was 32.9 doses per 100 patient-months. Vancomycin was the most commonly prescribed antimicrobial in the study, followed by cefazolin and third- or fourth-generation cephalosporins.

In the 12-month prospective component of the same study, investigators followed 278 patients among whom a total of 1,003 antimicrobial doses were prescribed. Among the 926 (92.3%) doses for which an indication for administration was available, approximately 276 (30%) were classified as inappropriate. The authors defined inappropriate administration as occasions when: (a) criteria for infection based on national guidelines were not met; (b) narrow-spectrum antimicrobials were not chosen on the basis of culture data; or (c) indications for surgical prophylaxis were not met, including prolonged duration of antimicrobial use ([greater than or equal to] 24 hours after the procedure). According to the results of the study, the most common reason for inappropriate administration was that the criteria for infection were not met, accounting for about 50% (146/276) of all inappropriate doses. A presumed bloodstream infection that did not meet criteria was the most common inappropriate indication and accounted for 48.6% (71/146) of doses in the study. Failure to choose a more narrow-spectrum agent represented another 25% of inappropriate doses. Snyder et al. (2013) found that approximately two-thirds of these doses represented administration of vancomycin instead of a beta ([beta])-lactam antimicrobial despite available antimicrobial susceptibility data and absence of a [beta]-lactam allergy. In addition, they noted that the most common inappropriately prescribed antimicrobials were vancomycin and third- or fourth-generation cephalosporins. A limitation of this study is that the investigators only evaluated parenteral antimicrobial use and, therefore, the overall burden of both oral and parenteral antimicrobial exposure in the outpatient HD population remains yet to be defined.

In a follow-up study, Snyder et al. (2016) presented additional data describing the characteristics of HD patients at higher risk of receiving antimicrobials. They found that patients with tunnelled catheter access, a history of colonization or infection with a MDRO in the year preceding enrollment, and receiving HD sessions during daytime shifts were more likely to receive antimicrobials. In summary, based on evidence from the existing literature, it is apparent that antimicrobial use is common among the outpatient HD population and may represent an important antimicrobial stewardship opportunity.

WHICH ANTIMICROBIAL STEWARDSHIP STRATEGIES MAY BE EFFECTIVE IN THE HEMODIALYSIS SETTING?

Effective ASP strategies outlined by D'Agata (2013) include: (a) education, (b) guidelines and clinical pathways, (c) antimicrobial order sets, (d) de-escalation therapy, and (e) prospective audit and feedback. In the dialysis setting, clinician education on the treatment of common infections and antimicrobial resistance rates in this population should be considered an essential component of an ASP (D'Agata, 2013). Despite compelling reasons to use antimicrobials judiciously in the HD population, it can be challenging due to the lack of antimicrobial prescribing guidelines specific to these patients. Hemodialysis patients comprise a small population in clinical trials, and guidelines by expert groups such as the IDSA do not provide recommendations for this specific population, limiting evidence-based prescribing. Therefore, implementation of clinical practice guidelines and algorithms for the most common infections and most commonly prescribed antimicrobials in HD patients is an effective strategy that can help standardize prescribing practices (D'Agata, 2013). In addition, antimicrobial order sets that outline when and what agents should be utilized for specific infections may help minimize excessive and suboptimal antimicrobial use (Cunha & D'Agata, 2016). Another key strategy described by D'Agata (2013) is de-escalation of therapy by changing to a more narrow-spectrum antimicrobial when culture and susceptibility data are available to reduce inappropriate antimicrobial use and associated costs. This strategy is especially relevant to dialysis units, as one of the main areas of inappropriate prescribing is the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infections with vancomycin instead of cefazolin in the absence of contraindications to [beta]-lactam antimicrobials (Green, Schulman, Haas, Schaffner, & D'Agata, 2000). Awareness of antimicrobial prescribing practices and improvements by tracking, reporting, and providing feedback to prescribers is another important core element of ASP. This strategy involves reviewing clinicians' prescribing of antimicrobials, identifying areas for improvement, and then providing an intervention, such as education, with either verbal or written feedback to the prescriber.

CONCLUSION

Hemodialysis patients are at high risk for infections (including those caused by multi-drug resistant organisms), because of frequent healthcare access and increased use of antimicrobials. Thus, optimizing antimicrobial prescribing would have a substantial impact on their care. Antimicrobial stewardship programs (ASPs) aim to improve, advocate, and measure appropriate use of antimicrobials through coordinated interventions. While additional studies are needed in this area, successful implementation of an ASP will require full engagement of the dialysis care team. Developing an effective ASP requires a complete understanding of specific areas of antimicrobial prescribing practices that need improvement and careful attention to which strategies will be most effective for a particular dialysis unit.

REFERENCES

Barlam, T.F., Cosgrove, S.E., Abbo, L M., MacDougall, C., Schuetz, A.N., Septimus, E.J., ... Trivedi, K.K. (2016). Implementing an antibiotic stewardship program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clinical Infectious Diseases, ciw118.

Centers for Disease Control and Prevention (CDC) & Institute for Healthcare Improvement (IHI). (2012). Antimicrobial stewardship driver and change package. Retrieved from http://www.cdc.gov/getsmart/healthcare/pdfs/Antibiotic_Stewardship_Change_Package.pdf

Chiu, Y.W., Teitelbaum, I., Misra, M., De Leon, E.M., Adzize, T., & Mehrotra, R. (2009). Pill burden, adherence, hyperphosphatemia, and quality of life in maintenance dialysis patients. Clinical Journal of the American Society of Nephrology, 4(6), 1089-1096.

Cunha, C.B., & D'Agata, E.M. (2016). Implementing an antimicrobial stewardship program in out-patient dialysis units. Current Opinion in Nephrology and Hypertension, 25(6), 551-555.

D'Agata, E.M., Mount, D.B., Thayer, V., & Schaffner, W. (2000). Hospital-acquired infections among chronic hemodialysis patients. American Journal of Kidney Diseases, 35(6), 1083-1088.

D'Agata, E.M. (2013). Antimicrobial use and stewardship programs among dialysis centers. Seminars in Dialysis, 26(4), 457-64.

Dellit, T.H., Owens, R.C., McGowan, J.E., Gerding, D.N., Weinstein, R.A., Burke, J.P., ... Hooton, T.M. (2007). Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clinical Infectious Diseases, 44(2), 159-177.

Green, K., Schulman, G., Haas, D.W., Schaffner, W., & D'Agata, E.M. (2000). Vancomycin prescribing practices in hospitalized chronic hemodialysis patients. American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation, 35(1), 64-8.

Hyun, D.Y., Hersh, A.L., Namtu, K., Palazzi D.L., Maples H.D., Newland J.G., & Saiman L. (2013). Antimicrobial stewardship in pediatrics: How every pediatrician can be a steward. Journal of the American Medical Association Pediatrics, 167(9), 859-866.

Lafrance, J., Rahme, E., Iqbal, S., Elftouh, N., Laurin, L., & Vallee, M. (2014). Trends in infection-related hospital admissions and impact of length of time on dialysis among patients on long-term dialysis: A retrospective cohort study. Canadian Medical Association Journal Open, 2(2), E109-E114.

Lata, C., Girard, L., Parkins, M., & James, M.T. (2016). Catheter-related bloodstream infection in end-stage kidney disease: A Canadian narrative review. Canadian Journal of Kidney Health and Disease, 3(1), 24.

Pop-Vicas, A., Strom, J., Stanley, K., & D'Agata, E.M. (2008). Multidrug-resistant gram-negative bacteria among patients who require chronic hemodialysis. Clinical Journal of the American Society of Nephrology, 3(3), 752-758.

Smyth, B., Jones, C., & Saunders, J. (2016). Prescribing for patients on dialysis. Australian Prescriber, 39(1), 21.

Snyder, G.M., & D'Agata, E.M. (2012). Novel antimicrobial-resistant bacteria among patients requiring chronic hemodialysis. Current Opinion in Nephrology & Hypertension, 21(2), 211-215.

Snyder, G.M., Patel, P.R., Kallen, A.J., Strom, J.A., Tucker, J.K., & D'Agata, E.M. (2013). Antimicrobial use in outpatient hemodialysis units. Infection Control and Hospital Epidemiology, 34(4), 349-57.

Snyder, G.M., Patel, P.R., Kallen, A.J., Strom, J.A., Tucker, J.K., & D'Agata, E.M. (2016). Factors associated with the receipt of antimicrobials among chronic hemodialysis patients. American Journal of Infection Control, 44(11), 1269-1274.

Society for Healthcare Epidemiology of America, Infectious Diseases Society of America, & Pediatric Infectious Diseases Society. (2012). Policy statement on antimicrobial stewardship by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), and the Pediatric Infectious Diseases Society (PIDS). Infection Control and Hospital Epidemiology, 33(4), 322-327.

U.S. Renal Data System. (2010). USRDS 2010 annual data report: Atlas of chronic kidney disease and end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease. Retrieved from https://www.usrds.org/atlas10.aspx

Velenosi, T.J., & Urquhart, B.L. (2014). Pharmacokinetic considerations in chronic kidney disease and patients requiring dialysis. Expert Opinion on Drug Metabolism & Toxicology, 10(8), 1131-1143.

By Sylvia Sivarajahkumar, BscPhm, Miranda So, PharmD, and Marisa Battistella, PharmD, ACPR

ABOUT THE AUTHORS

Sylvia Sivarajahkumar, BScPhm, Pharmacy Resident, University Health Network, Toronto, ON

Miranda So, PharmD, Pharmacotherapy Specialist - Sinai Health System-University Health Network Antimicrobial Stewardship Program, University Health Network, Assistant Professor (Status-Only), Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON

Marisa Battistella, PharmD, ACPR, Clinician Scientist, Assistant Professor, Leslie Dan Faculty of Pharmacy, University of Toronto, Pharmacy Clinician Scientist, Clinical Pharmacist--Nephrology, University Health Network, Toronto, ON

Address for correspondence: Marisa Battistella, University Health Network, 200 Elizabeth Street, EB 214,Toronto, ON M5G 2C4

Email: marisa.battistella@uhn.ca
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Title Annotation:CONTINUING EDUCATION SERIES
Author:Sivarajahkumar, Sylvia; So, Miranda; Battistella, Marisa
Publication:CANNT Journal
Geographic Code:1CANA
Date:Apr 1, 2017
Words:2393
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