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Professor of Medicine
Director, Immunocompromised Host Infectious Diseases Program
Division of Infectious Diseases
University of North Carolina
Chapel Hill, North Carolina
David van Duin, MD, PhD, FIDSA, FAST: consultant/advisor/speaker: Entasis, Merck, Pfizer, Qpex, Roche, Shionogi, Union; researcher: Merck, Shionogi.
As an infectious diseases physician who specializes in the care of immunocompromised patients, I witness the burden of extraintestinal pathogenic E coli (ExPEC) infections every day. Patient populations that I care for include those who have had a transplant, like a liver or kidney transplant, and patients who are being treated for cancer including those who have received a bone marrow transplant. With the changes in the immune system that are seen in these patients, infections unfortunately occur more frequently and tend to be more severe.
Why Are We Concerned?
Infections caused by ExPEC are increasingly frequent in the US and around the world. At the same time, we are seeing increasing rates of antibiotic resistance—including many ExPEC “superbugs” (eg, extended spectrum beta-lactamase producing E coli) that detrimentally affect our patients through community spread or acquisition from healthcare settings such as hospitals. Infections caused by multidrug-resistant (MDR) E coli are associated with worsened clinical outcomes, including prolonged hospitalizations, increased morbidity and mortality, and higher healthcare costs.
Treatment selection for infections caused by MDR E coli can be challenging as fewer effective antibiotics are available; also, there is less of a chance for healthcare professionals to select appropriate empiric therapy prior to knowing the results from patients’ cultures. Further delay in time to effective therapy can further worsen clinical outcomes—every hour delay has been associated with increased mortality risk.
Who Is at Risk?
ExPEC infections are often in the urinary tract or blood stream. Patients may be subject to recurrent urinary tract infections that pose risk to acquiring antibiotic resistance. In the hospital, patients also may have additional infections with ExPEC like pneumonia or skin infections. In babies, ExPEC may cause meningitis, as well.
Specific diseases and conditions put people at higher risk for more severe infections with ExPEC, where the bacteria are found in the blood. Some of these conditions are things I commonly see in my patients such as kidney problems requiring dialysis, diabetes, cancer, transplantation, heart disease, and other chronic diseases. Of importance, the aging American population is growing, and older adults are at risk for ExPEC infections. The proportion of people 80 years of age and older is growing even faster. Older adults are also at higher risk of dying from these infections.
Identifying risk factors for developing invasive ExPEC infection, especially infections caused by MDR E coli, may help identify patients who might benefit the most from infection prevention including a vaccine. Also, awareness of these risk factors may help minimize the time to effective therapy and subsequently reduce the risk of poor outcomes.
Two of the biggest risk factors for developing multidrug resistant E coli include prior antibiotic use and MDRO colonization and/or infection, so promoting better infection prevention and antimicrobial stewardship practices are key. Other multidrug-resistant organism infection risk factors include previous hospitalization, residence in a nursing home or other healthcare facility, presence of a medical device (eg, urinary catheter), and older age (eg, >60 years).
What Is Needed?
ExPEC has been around for a very long time and will likely remain clinically important in the foreseeable future. If we can limit the use of antibiotics to those people who will derive benefit from antibiotic treatment, that will help curtail the spread of antibiotic-resistant bacteria. Furthermore, limiting the use of antibiotics as growth enhancers in agriculture is very important.
Alternative strategies to avoid the development of ExPEC infections, including infections caused by MDR E coli, would be extremely helpful and would free us from relying solely on the judicious use of antibiotics or the development of novel therapies. Vaccines have been shown to decrease antibiotic resistance in other bacterial diseases. I hope that an ExPEC-directed vaccine may decrease the spread of resistant ExPEC in communities and limit the burden of ExPEC infections in vulnerable patients.
Which patient population do you think is at greatest risk for developing an infection caused by ExPEC? Join the discussion by posting a comment.