HOPSITAL-ASSOCIATED INFECTSIONS: WHY ARE THEY STILL A PROBLEM?

H o s p i t a l A s s o c i a t e d I n f e c t i o n s : W h y a r e They Still a Problem?

Ana Rosu

A B S T R A C T There have been both government and hospital-led policy-based initiatives to prevent HAIs, with limited success due to lack of consistency when implementing proper sanitary procedures. Since most HAIs are caused by transmission of pathogens on the surface of a medical device, several large-scale companies and startups have attempted to create medical devices with antimicrobial surfaces. However, these technological solutions have had their challenges in clinical trials and implementation. HAIs are an issue in any country and, to properly address them, there should be an increased push and support for technological solutions from both the financial and political perspectives.

I N T R O D U C T I O N

Hospital-associated infections (HAIs) were first reported in 1846 by Hungarian doctor Ignaz Semmelweis. Semmelweis realized that doctors in his hospital were spreading puerperal fever to women giving birth because they were not washing their hands after dissecting infected cadavers (Cavaillon et al.). Since then, HAIs continue to be associated with a variety of unsanitary practices in hospitals: improper sterilization in surgeries, catheter insertions, and ventilators are just a few examples.

One in thirty-one patients will be infected by pathogens in hospitals after being admitted for treatment of another disease (Magill et al.). Most often, these HAIs will be transmitted when patients are catheterized with central lines or urinary catheters. Central line-associated bloodstream infections (CLABSI) have the highest mortality rate and monetary cost: the average CLABSI case has an 18 percent chance of death and costs 46,000 dollars. Other common HAIs include ventilator-associated pneumonia (VAP) and surgical site infections (SSI) (Zimlichman et al.). In 2013, it was estimated that the total annual costs for HAIs was 9.8 billion dollars, with SSIs contributing most to overall costs, then VAPs and catheter-associated HAIs.

Unfortunately, today, a patient’s likelihood of getting infected during their hospital stay is highly dependent upon how well their nurse or doctor follows proper sanitary procedure (“2018 National and State HealthcareAssociated Infections Progress Report”).

H O S P I T A L A S S O C I A T E D I N F E C T I O N S (H A I S) C A U S E S

HAIs are commonly caused by C. difficile, S. aureus MRSA (multidrug resistant staphylococcus aureus), E. Coli., and norovirus. MRSA is best known for its high mortality rate and resistance to drugs like penicillin, oxacillin, methicillin, and amoxicillin. In extreme cases, HAIs can lead to severe sepsis, causing organs to dysfunction. In those cases, one in four patients will die (Mayr et al.). While some HAIs are deadly, many other HAI-causing pathogens do not necessarily cause death but increase hospital stay and inhibit patient recovery from the original disease.

Catheter-associated HAIs are caused when pathogens crawl from the catheter’s insertion site to the tip of the catheter inside of the patient’s body. Once inside the body, these pathogens begin to colonize and form a biofilm, a layer of bacteria that covers itself in extracellular polymeric substances (EPS), which help pathogens adhere to the catheter and each other (Safdar et al.). Research has found that the EPS of biofilms protects bacteria from many common drugs, making the infection harder to treat (Costerton et al.; Drenkard et al.).

Surgical site infections (SSI) are caused when pathogens infect a surgical wound through contact with a contaminated surgical instrument or caregiver or spread from the air into a newly made surgical wound. Because surgeries are invasive, infections can occur at different levels within the body: superficial (skin and subcutaneous tissue), deep incisional (fascia and muscular layers), and organ or space (any part of the body opened or manipulated during the procedure that is not skin, subcutaneous tissue, fascia, or muscular layers). Although more than half of SSIs are preventable by evidence-based guidelines,

approximately 160,000-300,000 SSIs occur each year in the United States, accounting for 20 percent of all HAIs in hospitalized patients (Anderson et al.).

Ventilator-associated pneumonia (VAP) is specific to patients that are mechanically ventilated. Clinical surveys suggest that VAP occurs in 5-15 percent of ventilated patients, causing between 250,000 and 300,000 cases per year in the United States (Klompas et al.). It’s suspected that VAP occurs when ventilators are improperly sterilized or placed in the supine position in patients. Another potential cause is the inhalation of bacteria through the ventilator circuit (Koenig et al.).

P R E V E N T I N G H A I S W I T H P O L I C Y

In 2008, the United States government enacted policies that penalized hospitals with high rates of HAIs. The Centers for Medicare and Medicaid Services denied payment for HAIs but restricted patients from having to pay more if their stay or treatment was increased because of HAIs, forcing hospitals to pay from their own budget.

In response, hospitals implemented various programs to bring down HAI rates (Stone et al.). Many used the Comprehensive Unit-based Safety Program (CUSP) developed by Johns Hopkins Hospital, which was tested iwn 100 Michigan intensive care units and resulted in a 41 percent reduction in the rate of CLABSI (“Eliminating CLABSI, A National Patient Safety Imperative”). CUSP requires special training and ensures regular use of checklists for the most common procedures associated with HAIs. These checklists include simple steps such as washing hands, sanitizing patients’ skin with antiseptic, and wearing sterile masks, hats, gowns, and gloves.

Some hospitals implemented individualized programs responding to HAI patterns specific to their institution. The Haukeland University Hospital in Norway performed a 17- year study analyzing the results of their systematic infection control program, which included training healthcare workers and introducing evidencebased checklists, and found that they were able to reduce their HAI rate from 8.3 percent in 1994 to 7.1 percent in 2010 (Koch et al.). The University of Mississippi Medical Center was able to reduce HAIs in neonatal intensive care units through coaching initiatives where colleagues privately tell one another to wash hands, rotating groups of employees secretly observing hand hygiene practices of their coworkers, and repeated training (Norwood, 2016).

In the United States, due to the implementation of both nationwide and individual hospital policies, HAI rates have gone down significantly. In the case of CLABSI, in the period between 2006 and 2016, the rate of infection almost halved (“Data Summary of HAIs in the US: Assessing Progress 2006-2016”). However, despite this, there are many instances of both medical professionals and hospitals ignoring the designated checklists and training, due to overcrowded hospitals and too little time. Thus, due to human error, HAIs remain a persistent problem. To address this, both small and large companies have developed technological solutions to HAIs in the form of antimicrobial catheters, countertops, dialysis machines, and more.

P R E V E N T I N G H A I S W I T H A N T I M I C R O B I A L M E D I C A L D E V I C E S

Although HAIs happen when medical professionals do not properly follow sterilization and sanitation procedures, there are points in the infection chain where the spread of bacteria can be prevented through technology. Most solutions to HAIs are based on making medical devices or surfaces where HAI-causing bacteria typically colonize antimicrobial.

To keep biofilms from adhering to catheters, companies such as Bard, Arrow International, and Cook Critical Care produce antibiotic-coated and antiseptic catheters. Cook Critical Care’s catheters use a combination of the antibiotics rifampin and minocycline to create an antimicrobial surface that kills bacteria before they can adhere and colonize (Zenios, 2009). Rifampin and minocycline inhibit protein synthesis: minocycline binds to the 30S subunit of bacterial ribosomes, preventing translation of RNA to proteins, and rifampin binds to beta subunits of DNA-dependent RNA polymerase, preventing the creation of RNA (Ye et al.; Deck, 2015). Unfortunately, rifampin/minocycline catheters can unintentionally select for bacteria that have ribosomal and RNA polymerase subunit designs resistant to binding, creating drugresistant bacterial strains. Studies have shown minocycline/rifampin catheters to be ineffective against new strains of S. Epidermis and Candida species (Raad et al.; Bonne et al.).

Arrow International impregnates catheter surfaces with chlorhexidinesilver sulfadiazine, making them antiseptic. Silver sulfadiazine releases silver ions that bind to microbial DNA, allowing sulfadiazine to interfere with microbial metabolic processes (Gallagher, 2012). Chlorhexidine, a positively charged molecule, binds with the negatively charged phospholipids that comprise bacterial cell walls, causing them to rupture (Mangram et al.). In the lab, chlorhexidine and silver sulfadiazine work synergistically to create a slightly hydrophobic surface on catheters that is toxic to fungi and bacteria, prevents bacterial adhesion, and inhibits bacterial colony growth (Monzillo et al.). However, in clinical practice, numerous studies have found chlorhexidine silver sulfadiazine impregnated catheters to be ineffective, and in a few cases, toxic to patients (Wassil et al.).

In a discussion with the Chief of Infection Prevention Control, at a Midwestern Hospital, it was revealed that hospitals avoid using current antimicrobial catheters at a large scale because of unconvincing clinical data of their efficacy and their increased cost (Susan Ruwe, personal communication, March 13, 2019).

Light Line Medical (originally Veritas Medical LLC), a startup company founded by researchers at the University of Utah, is developing a set of catheters that utilize electromagnetic light therapy to eliminate bacterial colonies. A conductive line transfers light with a wavelength of 405 nm

from an electromagnetic power source throughout the whole catheter (Rhodes et al.). Light Line Medical urinary catheters, respiratory catheters, and central lines have been expected to achieve FDA/ CE clearance for hospital use by 2018, 2020, and 2022, respectively.

One Johns Hopkins-based startup, Relavo, has come up with a novel way to sterilize dialysis machines. They are particularly common in patients receiving at-home dialysis treatment. By changing the structure of the dialysis machine, Relavo forces patients and medical professionals to follow sanitary procedure, preventing infection (Hub staff report, 2019; Tantibanchachai, 2019).

Last of all, some hospitals like Memorial Sloan Kettering have replaced steel countertops, armrests, and doorknobs in with copper, a well-known antimicrobial metal. After implementation, HAI rates were reduced by 58 percent (Salgado et al.). hospital is, the time that nurses have for each patient, how much experience the medical professional has, etc.).

Unfortunately, not many technological solutions have been developed to prevent SSI and VAP, primarily because of the large number of potential factors influencing infection rates and lack of specific understanding of how exactly infection is caused, respectively.

C O N C L U S I O N

While there have been attempts to address HAIs with both hospital and nationwide policy, as well as new technologies, each approach has its own drawbacks. Although proper training and procedure checklists are essential, their efficacy will always be limited by the attention and time medical professionals give them, which depends on many factors that cannot always be controlled (how crowded a

“Approximately 160,000-300,000 SSIs occur each year in the United States, accounting for 20 percent of all HAIs in hospitalized patients.”

A seemingly more convenient alternative to addressing HAIs would be coming up with medical devices that can prevent infection—either through the material they are made out of, their length of use, or their forced alteration of procedure. However, as with the development of any technological solution to a problem, for an ideal technology to appear, there must be adequate funding and desire for it. Unfortunately, many hospitals are understandably reluctant to admit that they have issues with infection control, which inhibits the rate at which new technological solutions to HAIs are implemented. In addition, because at the national level in comparison with other health problems, the number of reported deaths due to HAIs is less, it does not make the research and development of new technologies a priority for funding.

Thus, HAIs—preventable infections that have had a known cause since the 1800s—are still a common problem in hospitals. However, HAIs are not only a national problem. In poor countries developing and implementing policies for sanitization is much more challenging than in western countries. New technological solutions could offer solutions to be easily delivered and implemented worldwide.

R E F E R E N C E S

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ANA ROSU

Class of 2023. Ana is a freshman from Champaign, Illinois majoring in Biomedical Engineering. Her research interests include translational sciences as well as tissue and immunoengineering. She hopes to pursue a career in clinical research.