Repertoire Magazine – August 2021
The hand sanitizer healthcare providers choose is critical to both their hand hygiene and patient safety programs.
Hand hygiene is foundational to infection prevention programs in healthcare. Alcohol-based hand rubs (ABHR) are recommended as the primary means of hand hygiene in healthcare settings on the basis of demonstrated superiority to hand washing with respect to antimicrobial efficacy, skin tolerance, convenience/accessibility and clinical effectiveness.1,2 Few, if any, products are used as frequently and by as many caregivers, patients and visitors in a healthcare facility than those used for hand hygiene. It is critical that healthcare products are designed to meet the rigorous efficacy requirements set forth by the Food and Drug Administration (FDA).
Why in vitro is not the same as in vivo
The FDA requires both in vitro (in a test tube) and in vivo (on hands) testing of hand sanitizer products. For in vitro testing, also known as time-kill testing, bacteria along with the test product (ABHR) are placed together in a test tube. Because this test is performed in a test tube the alcohol does not evaporate and can easily surround and interact with the bacteria. In vitro tests are designed to demonstrate broad-spectrum kill only, often using 5 mL – 10 mL of product, in this lab-based test. In this environment, ABHR products with greater than 60% ethanol will typically kill these organisms in 15 seconds. Further, in vitro tests are not meant to demonstrate performance on hands, so it is important for decision makers to understand the FDA requirements and not accept in vitro laboratory test results as the only proof of product efficacy.
The FDA requires that all healthcare hand sanitizers, or ABHR products, pass the Healthcare Personnel Handwash test (HCPHW), ASTM E1174. This in vivo test method is designed to evaluate how effectively products inactivate transient bacteria over all surfaces of the hands and fingers using a process that simulates bacterial exposure in clinical settings. It is important to recognize that the FDA requirements for passing the HCPHW test do not dictate “volume” of product to predict efficacy, they dictate actual “germ reduction”. Germ reduction is spoken in terms of “log reduction”. The word “log” stands for logarithm, and log reduction is a mathematical term referring to the reduction of germs compared to a starting baseline level. A 1-log10 reduction means that the number of germs is 10 times smaller than the baseline measurement or 90% reduction of bacteria. A 2-log10 reduction is 100x smaller or 99% reduction and 3-log10 is 1,000x smaller or 99.9% reduction of bacteria. It is important to understand log reduction as it relates to the FDA’s requirements for product efficacy.
ASTM E1174, or HCPHW test, is conducted on hands using one marker organism, Serratia marcescens. Hands are contaminated with a specific level of S. marcescens at baseline and the antimicrobial product (sanitizer) is applied repeatedly with sampling throughout the process as outlined in the method. The FDA requires that products achieve a 2-log10 reduction (99% reduction of bacteria) after the 1st application of product, and a 3-log10 reduction (99.9% reduction of bacteria) after the 10th application.
Product formulation determines the amount of volume of ABHR needed to achieve the FDA-required log reductions with ASTM E1174. This is why it’s important to ask the manufacturer at what volume of product do they pass ASTM E1174 and get data for both the 1st and the 10th application. The 3-log10 (99.9%) reduction after the 10th application is critical. In healthcare, unlike consumer settings, products are often applied repeatedly in succession. Excipient ingredients such as those providing skincare benefits can negatively impact efficacy over time. Product formulation determines the overall antimicrobial efficacy of ABHR and is more important than alcohol concentration alone.
Previous studies evaluating the efficacy of ABHR products have used application volumes of 3 mL – 5 mL or more.3 However, such large volumes are seldom used in clinical practice in U.S. healthcare settings. In a seminal publication, the efficacy of two novel ABHR formulations containing 70% ethanol were evaluated via ASTM E1174 and compared head-to-head against 7 representative commercially available ABHRs and two World Health Organization (WHO) recommended formulations containing alcohol concentrations of 60% to 90%. The novel ABHR formulations met efficacy requirements for HCPHW when tested at application volumes at a more realistic 2 mL dose. In contrast, the commercial ABHRs and WHO formulations failed to meet HCPHW ASTM E1174 requirements using a 2 mL application (see graph above). This is why ASTM E1174 is required and is so important: because it is meant to mimic exposure and efficacy in the real world.
The Centers for Disease Control and Prevention (CDC) guidelines state that if hands are dry after 15 seconds, an insufficient volume of product was likely applied. In fact, the CDC guidelines tell healthcare facilities to follow manufacturer recommendations for the correct volume of product to use to meet FDA efficacy requirements. This is important again as most products, with the volume required to meet FDA efficacy requirements, take well over 15 seconds to dry. If the correct volume of product is applied, it is often way too much volume of product, therefore not a clinically acceptable dose, and takes well over 30 seconds to dry.4
The hand sanitizer healthcare providers choose is critical to both their hand hygiene and patient safety programs. Do not accept in vitro (test tube) laboratory results as a substitute for in vivo (ASTM E1174) results. In vitro results alone are not enough to pass FDA requirements for hand sanitizers used in healthcare settings. Healthcare workers are increasingly burdened with additional responsibilities and want hand hygiene to be as efficient as possible. If ABHR isn’t formulated properly, healthcare personnel are not achieving proper efficacy and patient safety could be impacted.
1. Boyce JM, Pittet D; Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America. Guidelines for hand hygiene in health-care settings: recommendations fo the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. MMWR Recomm Rep 2002;51(RR-16):1-45
2. World Health Organization (WHO) WHO Guidelines on Hand Hygiene in Health Care. Geneva: WHO, 2009
3. Rotter ML. Hand washing and hand disinfection. In: Mayhal CG, ed. Hospital Epidemiology and Infection Control. 4th ed. Philadelphia; Lippincot Williams & Wilkins, 2011:1365-1383.
4. Macinga DR; Infection Control and Hospital Epidemiology. Efficacy of Novel Alcohol-Based Hand Rub Products at Typical In-Use Volumes 2013;34(3):299-301