Infection and Intravenous Drug Delivery: A Long and Tumultuous Relationship Eric Wenzler, PharmD, BCPS, AAHVIP Assistant Professor University of Illinois at Chicago
Disclosures I have no actual or potential conflicts of interest in relation to the content of this presentation
Objectives Review the history of infectious complications associated with sterile preparations and the associated regulations Discuss how the risk of infection can be mitigated Describe recent and future changes to guidelines
Background Intravenous drug delivery and compounding medications are fundamental to pharmacy practice All persons involved in the process are responsible for accuracy and sterility Well known that patient morbidity and mortality have resulted from contamination
History Long and tumultuous history of infectious complications: 1970 - Nationwide epidemic of septicemia due to contaminated IV products 1984-5 patients die after receiving compounded cardioplegia contaminated with E. cloacae 1990-2005 - At least 12 incidents involving over 19,000 patients and 15 deaths
History 2004 - USP 797 first introduced Aimed at reducing infectious contamination of pharmacy-prepared sterile products (CSPs) 2004-16 patients acquire hepatitis C from contaminated radioisotope solution 2005 - S. marcescens outbreak from compounded magnesium sulfate 2007 - S. paucimobilis outbreak from compounded fentanyl
History 2008 - USP revises chapter 797 Left many facilities unable to meet standards 2012 survey: Just 8 states require USP 797 compliance 65% of hospitals adhere to clean room requirements 17% compliant with all recommendations 2011-2012: 4 serious contamination incidents harming >244 patients
https://www.google.com/url?sa=i&source=images&cd=&cad=rja&uact=8&ved=2ahukewimuvznmbleahvuqomkhudpcnsqjrx6bagbeau&url=https%3a%2f%2fw ww.cbsnews.com%2fnews%2fjudge-approves-200-million-settlement-over-meningitis-outbreak%2f&psig=aovvaw38wvzh2w- Fv_PW3ms5mftX&ust=1541127495129193
History 2013 - Mold-contaminated magnesium sulfate in Connecticut hospital 2013-2 patients die and 15 infected from contaminated calcium gluconate 2014 - Duke outbreak of Burkholderia contaminans from contaminated fentanyl
Present Frequent drug shortages has challenged hospitals ability to obtain adequate supply of safely prepared medications Inability to comply with USP 797 has forced them to compound in-house or outsource
Solution When proper aseptic technique is used and 797 is followed, contamination rate can be reduced to 0.2-0.3% Even in uncontrolled environment Appropriate risk stratification is key Identify high risk areas 22% (7%-44%) contamination rate for nurses compounding in ICU using standard precautions 1% for pharmacy technicians following USP
Solution Many of these processes or bundles should be analogous to those used to prevent HAIs like CLABSIs USP 797 - Pharmaceutical compounding sterile preparations (general information chapter 797). In: The United States Pharmacopeia, 36th rev., and the National Formulary, 31 ed. Rockville, MD: The United States Pharmacopeial Convention; 2013: 361 98.
Solution https://www.ajicjournal.org/article /S0196-6553(13)00574-9/pdf
Solution Pharmacists/technician checklist: Perform a time out and review all orders and ingredient packages to ensure that the identity and amounts of ingredients are correct Garb from dirtiest to cleanest: Don shoe covers, hair net, beard cover, and mask Wash hands with chlorhexidine/soap for 30 seconds Don gown and apply persistent antimicrobial scrub After hands have dried, put on sterile gloves
Solution Understand the elements of first air: First air is the air exiting the HEPA filter in a unidirectional air stream and is virtually free of particulate contaminants All critical manipulations must be carried out in the unobstructed first air zone in the direct path of the HEPA filter discharge Proper product and process placement with respect to the supply and discharge of first air will provide a contamination-free compounding area
Solution Disinfect the work surface before and after each CSP Disinfect all components with sterile 70% isopropyl alcohol prior to placement in the ISO Disinfect all critical sites for 10 seconds with sterile 70% isopropyl alcohol Routinely disinfect gloved hands with sterile 70% isopropyl alcohol and inspect gloves for holes or tears. Replace as necessary Visually inspect CSPs to ensure the absence of particulate matter in solutions, the absence of leakage from vials and bags, and the accuracy and thoroughness of labeling
https://www.pppmag.com/documents/sopc_09/compounding%20fte%27s.pdf
http://www.criticalpoint.info/statemap/story_html5.html
Solution https://www.pppmag.com/digitalmag/main.php?magno=210&pageno=24#page/7
http://outsourcingassessment.org/
Solution https://www.pppmag.com/digitalmag/main.php?magno=210&pageno=24#page/7
Solution 2013 Drug Quality Safety and Security Act Forced large-scale compounders to register with FDA as outsourcing facilities Subject to FDA oversight and inspection Must comply with GMP 2015: CMS announced that hospitals must comply with 797 as condition of participation
Where 797 fails No method to ensure sterility No method to test for sterility Contamination can be unpredictable and sporadic Often low organism bioburden Contaminating organisms are often fastidious Insensitivity of direct inoculation method Limited effort or ability to comply and/or investigate outbreaks Medical-legal implications
When 797 fails If a contamination event occurs: Do sterility testing of product Identify patients that received product Consult ID and infection control Disclose to treating physician and patients Screen potentially affected patients Sequester remaining compounded drug Reinforce aseptic technique Double check monitoring parameters On site observations of personnel practices and monitoring of environment
Future directions Extent to which asepsis needs to be confirmed is controversial Test all products for sterility? Nationwide surveillance system Still 5 state boards that don t mention need to adhere to 797 Revisions to 797 expected in December 2019 Consolidate risk categories into 1 and 2 In-use time Frequency of viable air tests Additional training and competency for technicians
Future directions https://www.pppmag.com/digitalmag/main.php?magno=210&pageno=24#page/7
Summary Frequent CSP contamination events throughout history leading to tremendous patient morbidity and mortality Drug shortages led to increase in in-house compounding and outsourcing of CSPs Recent events have spurred important change and reinforced importance of good infection prevention and compliance with USP 797 When good aseptic technique is used, contamination rate is virtually 0% Purchase commercially-available products from pharmaceutical manufacturers whenever possible
Infection and Intravenous Drug Delivery: A Long and Tumultuous Relationship Eric Wenzler, PharmD, BCPS, AAHVIP Assistant Professor University of Illinois at Chicago