Tackling the still unmet crisis of hospital-acquired infections 

I will never forget the day I lost my sister, Sheila Sokol, after a series of hospital infections that complicated her courageous battle with leukemia. That was 14 years ago.  While there is more awareness and better protocols, healthcare-acquired infection (HAI) remains an unsolved challenge that takes millions of lives worldwide every year. Add to this, newly reported data indicating antimicrobial resistance continues to grow.  Already, AMR has mitigated many of the gains of modern medicine, and we now face a future where antibiotics may be largely ineffective. Deaths from infectious disease are projected to be the leading cause of death by 2050.   

Consider the advances in the treatment of various cancers.  While new therapeutics have improved survival, many patients develop respiratory failure related to infectious and non-infectious processes during treatment which often includes support with mechanical ventilation.  Ventilator-associated pneumonia may occur in a significant number of lung cancer patients intubated for 48 hours.  VAP is the second most frequent ICU-acquired infection, and the one associated with the highest mortality rate. In many cases cancer patients don’t die from cancer, but from infections.

Any patient who is immune compromised — the elderly, neonates and those taking immune suppressive medications—are at high risk for potentially lethal hospital acquired infections.  If we don’t act now, as UK former Chief Medical Officer, Dame Sally Davies once said, “any of us could go into hospital in 20 years for minor surgery and die because of an ordinary infection.”    

Where will the solution be found?  

The conventional wisdom is that the answer is a new antibiotic. Yet, there is little reason to believe this to be a near term solution given the pace of antibiotic development has slowed and a number of  pharmaceutical companies have exited infectious disease development. 

 Even if a new antibiotic becomes available, hospital formularies may force second-line use after first trying less costly generics.  Additionally, new antimicrobial resistant strains emerge rapidly. Antibiotics in development today may not be a cure for the infections of tomorrow, or as many as eight years from now when the new treatment may become available.

 An alternative approach is to address one of the root causes of infection:  the formation of biofilms on indwelling medical devices.  Biofilms are a slimy layer of bacteria that sticks to surfaces and is inherently resistant to antibiotics.  Any medical device in contact with a patient for more than eight hours (such as endotracheal tubes) allow the robust growth of bacteria, fungi and even viruses, which can form biofilms inherently resistant to antibiotics.   Biofilm fouled medical devices are responsible for as much as 65% of all hospital-acquired infections and result in the need for extended stays and antibiotics.  If medical devices can be made safer, it could be possible to safely intubate patients without exposing them to as high a risk of infection.  

Technology can help

Antimicrobial coating strategies have been reported to effectively inhibit bacterial adhesion and are currently used on various biomedical implants used in orthopedics, dentistry, and cardiology.  For application to indwelling devices, antimicrobial peptides already found in the human body are an attractive target as anti-fouling agents.

Paul Savage, Ph.D., Reed M. Izatt Professor of Chemistry and Biochemistry at BYU, has done extensive development of ceragenins non-peptide mimics of antimicrobial peptides that form the cornerstone of our own bodies’ innate immune system and are recognized  for their broad-spectrum antibacterial and antifungal activities including the ability to both prevent and eradicate biofilms.  Ceragenins have long been considered attractive potential therapeutics for persistent infections in the lung and trachea.   Working with Dr. Savage and international collaborators, we have developed a ceragenin-based platform technology, with a biofilm-resistant ceragenin-coated endotracheal tube as the first application.  Findings from clinical studies indicate reduced infection using this approach and confirm its effectiveness and safety.  

Steps forward 

A practical first step could be to look beyond pharmaceutical development to new technology as a nearer-term answer.  This could lead to improvements such as safer medical devices used in hospitals everyday around the world and the potential addition of antimicrobial UV-C-emitting devices to standard cleaning protocols.  

On the policy side, benefit could be realized by modifying the GAIN Act to extend coverage beyond therapeutics to include medical devices that have clinical evidence that show infection reduction and reduces the need for antibiotics. Use of Priority Review Vouchers for HAI innovations, including medical devices, is also warranted.   

My sister’s experience is still fresh in my mind. It provides a visceral reminder that the healthcare system must do better for patients, and we need to do it now.