The Basics of Infection Prevention in Research

Overview

Understanding the potential for infection is strategic in determining what level of infection prevention activities should be used in research settings. In some circumstances, clinical investigators may work in tandem with infection control or epidemiology department specialists to help determine if unique strategies should be implemented.

The spread of bacteria in clinical settings can occur easily through various vehicles, which can sometimes lead to sepsis, a life-threatening complication. Additionally, bacterial contamination in the healthcare setting is common. One Ethiopian hospital-based study featuring cultures taken from 212 non-critical medical devices used by different health professionals, including 187 stethoscopes and 25 sphygmomanometers, found an overall bacterial contamination prevalence of 53.8%. Staphylococcus aureus was the most identified bacteria. Though the study was conducted outside of the United States, it does provide a glimpse into how non-critical healthcare tools can transmit resistant-bacterial strains to patients, contributing to elevated risks of HAIs (hospital-acquired infections). [i]

Preventative measures to mitigate the portal of entry and exit infections were realized on a global scale during our recent pandemic. To address the public health threat, special guidance and considerations were issued to clinical investigation teams to help keep trial participants safe. [ii] Mitigation strategies included the mandatory use of face shields and masks (personal protective equipment, or PPE) in public health spaces, along with other heightened disinfection protocols.

Following the COVID-19 public health emergency, many public health professionals emerged with a fresh take on infection control practices. Clinical investigator teams continue to work diligently to enforce disinfection protocols for instrumentation and devices, PPE, handwashing, ventilation, and isolation practices for infected persons to minimize incidences that could threaten the lives of the clinical trial participants.

Risk Factors for Multidrug-Resistant Organisms in Clinical Trials

Preventative strategies are prioritized against infectious threats because, on a national level, statistics show the estimated cost related to treating MDROs in inpatient hospital settings can range between 2.3 – 3.4 billion dollars. [iii]

A significant concern surrounding infection control is the transmission of multidrug-resistant organisms (MDRO), which are becoming more problematic in healthcare settings. They are most often spread through contact with a contaminated source. For example, touching contaminated bedside rails and tables and then eating might present an opportunity for a resistant pathogen to enter the body and begin to multiply. There are also evidence-based risk factors that place certain patient populations at risk, such as patients with a history of prolonged antibiotic use or underlying health conditions such as diabetes, kidney disease, or open wounds. [iv]

Screening is a strong point of mitigation for clinical investigators, especially since many trial participants present with issues that place them at elevated risk for contracting or transmitting infectious organisms. The CDC discusses on its guidance webpage how some clinical investigators look to artificial intelligence to help find solutions by factoring in statistical data taken from molecular genotyping and clinical microbiology findings to help calculate MDRO risk factors.

Understanding the Chain of Infection in Research Clinical Settings

Disrupting the chain of infection hinges on the ability to identify and mitigate the potential for infectious points of entry. Six known vulnerable areas present above-average risks for transmission [vi]:

Infectious Agents

Infectious agents are the first link in the chain of infection. Examples of the four main types of pathogens or infectious agents include viruses (e.g., influenza), bacteria (e.g., Lyme disease), fungi (e.g., Candida), and parasites (e.g., Amebiasis).

Mode of Transmission

Based on improved understanding about how pathogens invade host environments, a scholarly article indicates three major routes of transmission [vii]:

• Spray: Transmission occurs through propelled droplets in the air such as by sneezing.
• Inhalation: Transmission occurs by inhaling pathogenic aerosols in the air.
• Touch: Transmission likely occurs by touching an infected surface such as restroom fixtures or by shaking hands with an infected person.

Reservoir

Reservoir is the term that references the source of the transmittable pathogen. The source or host acts as a sort of incubator by allowing an infectious pathogen to flourish and multiply. Animals, humans, and other suitable environments all harbor the potential to act as a reservoir for infections. In some cases, a human host can harbor a deadly pathogen without any strong indicators and is termed asymptomatic.

Portal of entry

This describes the process of a susceptible host coming into direct contact with the infectious agent by way of respiratory droplets, a skin cut, or other open route to inside the body, such as through catheterization. These are referred to as the point of entry, whereas an infectious organism can travel directly into the host’s body.

Portal of Exit

The portal of exit references the avenue in which an infectious organism or agent leaves the host. Like the infectious point of entry, these areas include infected reservoir areas such as mucous membranes, skin wounds, gastrointestinal fluids (vomit, saliva), infected tubing, devices, or instrumentation.

Susceptible Host

The susceptible host is the recipient of the infectious organism and the last link within the chain of infection. Susceptibility is determined by a range of factors such as age, health history, and current health. Because many clinical trial participants might be inherently vulnerable, investigators may choose to use susceptibility data in conjunction with a comprehensive risk-benefit analysis. [viii]

Investigator Considerations for Infection Control

Clinical investigator teams are often tasked with using risk assessment tools to mitigate the transmission of infectious diseases. One of the tools used to apply infection control best practices is the Spaulding Criteria, a system developed by Eerie Spaulding in 1957. The Spaulding system is a sterilization classification scheme that places patient care items into three distinct levels of germicidal activity: non-critical, semi-critical, and critical.

Non-critical care items normally fall into a non-invasive type of category of clinical contact items and include things like bedpans, wheelchairs, crutches, and stethoscopes and require an intermediate level of disinfection. Non-critical care items have the lowest risk factors because they are not intended to be placed inside the body or come into direct contact with bodily fluids but are still considered clinically high-touch items.

Semi-critical care items have contact with mucous membranes and carry a moderate risk of transmitting disease. Semi-critical care items include medical devices like endoscopes, anesthesia equipment, probes, and diaphragm fittings that must undergo high-level disinfection practices.

Critical care items reference those medical devices with the highest level of contamination risk. They must be completely sterile before entering any part of the human body cavity, tissue, or vascular system. Examples of critical care products falling into this category include surgical tools and devices and multiple types of catheters because they present the highest risk of carrying bacteria from patient to patient.

Basic Pain Points for Preventing Infection in Research Settings

[x] [xi]

• Proper hand washing and hygiene protocols
• Enforcing the use of personal protective equipment (e.g., gloves, masks, eyewear) when appropriate
• Respiratory droplet control; cough, respiratory distress hygiene.
• Containment measures for sharps
• Patient surveillance
• Safe injection practices
• Sterilization techniques and training
• Patient screening, assessments, and placement
• Environmental and facilities management
• Equipment maintenance and cleaning
• Housekeeping supply management (e.g., patient linens, towels, blankets)
• Infection management for body fluids

Managing a Breach in Infection Control

The CDC outlines six key steps for handling an outbreak or infectious breach in the scope of a clinical research trial.

Identification of the breach involves gaining a complete understanding of all the details concerning the breach, including the source, route of transmission, and a detailed assessment of the decontamination techniques used. Corrective action and mitigation planning are also expected at this step.

Data collection efforts mandate meticulous reviewing and documentation of the incident along with any correlative health data of all affected persons.

Notifications to the stakeholders, affected health care workers, regulatory officials, risk management, and state and local authorities.

Qualitative assessment and classification of the breach:

• Category A = gross error or demonstrated high-risk practice
• Category B = breach with a lower likelihood of blood exposure

Testing, public risk assessments and information, and the decision to notify patients must get underway as soon as possible. This involves implementing a plan for testing procedures, locations, and frequency and consulting with epidemiologist experts to assess public health risk factors. The decision to notify the patients falls under the duty to warn and should commence with best practice notification scenarios. [xiii]

Communications and logistics detail any aspects of public information requests, media and press statements, and expert analytics towards any post-exposure concerns and risks.

Summary

The landscape for discoveries in clinical research is at a momentous phase. As more research findings become available surrounding infection transmission and other virulence factors, the therapeutic and infection control strategies towards serious pathogens like one of our greatest threats, Staphylococcus aureus, are likely to become more streamlined and definitive. [xiv]  Current approaches to infection control rest primarily with diligent sterilization, decontamination controls, antimicrobial stewardship, [xv] and surveillance. However, clinical investigators are now equipped with many artificial intelligence-driven resources [xvi] to assist them in navigating the potential for infectious outbreaks, which will help drive more favorable clinical trial results.

References

[i] Weldegebreal, Fitsum, Desalegn Admassu, Dereje Meaza, and Mulatu Asfaw. 2019. “Non-critical healthcare tools as a potential source of healthcare-acquired bacterial infections in eastern Ethiopia: A hospital-based cross-sectional study.” SAGE Open Medicine 7:2050312118822627.

[ii] U.S. Food and Drug Administration (FDA). 2023. “FDA Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency.” Accessed August 17, 2023.

[iii] Johnston, Kenton J., Kenneth E. Thorpe, Jesse T. Jacob, and David J. Murphy. “The incremental cost of infections associated with multidrug-resistant organisms in the inpatient hospital setting—A national estimate.” Health Services Research 54(4):782-92.

[iv] Blanco, Natalia, Lyndsay M. O’Hara, and Anthony D. Harris. “Transmission pathways of multidrug-resistant organisms in the hospital setting: a scoping review.” Infection Control & Hospital Epidemiology 40(4):447-56.

[v] U.S. Centers for Disease Control and Prevention (CDC). 2015. “MDRO Prevention and Control.” Accessed August 17, 2023.

[vi] van Seventer, Jean Maguire, and Natasha S. Hochberg. 2017. “Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control.” In International Encyclopedia of Public Health. Accessed August 17, 2023.

[vii] Marr, Linsey C., and Julian W. Tang. 2021. “A Paradigm Shift to Align Transmission Routes With Mechanisms.” Clinical Infectious Diseases 73(10):1747-9.

[viii] Casadevall, Arturo, and Liise-anne Pirofski. 2018. “What Is a Host? Attributes of Individual Susceptibility.” Infection and Immunity 86(2):e00636-17.

[ix] U.S. Centers for Disease Control and Prevention (CDC). 2016. “A Rational Approach to Disinfection and Sterilization.” Accessed August 17, 2023.

[x] Habboush, Yacob, Siva Naga S. Yarrarapu, and Nilmarie Guzman. 2023. “Infection Control.” Accessed August 17, 2023.

[xi] Godfrey, Catherine, and Jeffrey T. Schouten. 2014. “Infection Control Best Practices in Clinical Research in Resource-Limited Settings.” Journal of Acquired Immune Deficiency Syndrome 65(0 1):S15-8.

[xii] U.S. Centers for Disease Control and Prevention (CDC). 2012. “Steps for Evaluating an Infection Control Breach.” Accessed August 17, 2023.

[xiii] Schaefer, Melissa K., Kiran M. Perkins, Ruth Link-Gelles, Alexander J. Kallen, Priti R. Patel, and Joseph F. Perz. 2020. “Outbreaks and infection control breaches in health care settings: Considerations for patient notification.” American Journal of Infection Control 48(6):718-24.

[xiv] Tong, Steven Y.C., Luke F. Chen, and Vance G. Fowler, Jr. 2012. “Colonization, Pathogenicity, Host Susceptibility and Therapeutics for Staphylococcus aureus: What is the Clinical Relevance?” Seminars in Immunopathology 34(2):185-200.

[xv] Nguyen, Hoa Q., Declan T. Bradley, Michael M. Tunney, and Carmel M. Hughes. 2021. “Development of a core outcome set for clinical trials aimed at improving antimicrobial stewardship in care homes.” Antimicrobial Resistance & Infection Control 10(52).

[xvi] Fitzpatrick, Fidelma, Aaron Doherty, and Gerard Lacey. 2020. “Using Artificial Intelligence in Infection Prevention.” Current Treatment Options in Infectious Diseases 12(2):135-44.