Bacteria

A microbiologist examines bacteria from a tube.

By Gonzalo Bearman and Richard P. Wenzel

Every year 700,000 inpatients in the U.S., 3% of all hospitalized people, suffer a health care-associated infection. Although rates of infections in health care settings continue to decline, alarming increases in drug-resistant pathogens, the dwindling pipeline of new antibiotics and the shortage of infectious disease specialists pose ongoing threats. An aging population and the growing use of immune-suppressive drugs mean that more vulnerable patients are at risk for health care-associated infections, with not only reduced coping responses but also few antibiotic treatment options. The outcomes for these patients are markedly worse, with significant increases in 30- and 90-day mortality. The estimated direct costs of health care-associated infections in the U.S., currently $9 billion annually, are poised to increase.

The modern practice of infection prevention minimizes the risk of transmission of bacteria within the hospital. The assumption behind the goal is that with the control of exogenous sources of infection, transmitted via health care worker hands, invasive devices and the hospital environment, such risks would be eliminated. This strategy has significantly reduced the rate of infections. Today, however, the vast majority of remaining health care-associated infections are endogenous — caused by the patients’ own bacteria and drug-resistant organisms.

The personal microbiome defines our symbiotic, well-balanced bacterial community of organisms living in harmony on the skin, nose, mouth and gastrointestinal tract. These “good” bacteria protect us from colonization and infection from more aggressive, harmful organisms. An imbalance in the personal microbiome, termed “dysbiosis,” results from the overuse of antibiotics or alterations of the immune system. An unrestrained overgrowth of good bacteria can result in invasive disease. Antibiotic overuse further selects for drug-resistant organisms.

For example, in high-risk intensive care units, the overuse of anti-infectives is linked with the emergence of drug resistant bacteria such as Carbapenem-resistant enterobacteriaceae (CRE). Such organisms often are susceptible to a single antibiotic and sometimes to none. Transplant recipients are at particular risk for CRE, with up to 10% of patients having a CRE infection with an associated 70%, 30-day mortality.

Even in low-risk wards, the widespread use of antimicrobials further results in intestinal dysbiosis and disease from Clostridiodes difficile, a drug-resistant bacterium associated with diarrheal infection, severe colon inflammation, relapse and elevated morbidity and mortality. Fecal transplants are now performed, effectively restoring the normal intestinal microbiome for patients with Clostridiodes difficile infection, ending all symptoms.

We know much less about how to control the personal microbiome for broad infection prevention. Preliminary studies suggest that perioperative control of the microbiome through topical nasal and skin decontamination can limit the rate of surgical site infections. However, some bacteria exist below the epidermis, where topical antiseptics do not penetrate, posing a challenge to surgical risk reduction.

Unfortunately, a limited pipeline exists for the development of new antimicrobials to treat drug-resistant bacteria. Scientific, regulatory and economic barriers make the development of novel antibiotics unprofitable to the pharmaceutical industry. The net present value (NPV) of new antibiotics, or sum of all development investment costs and expected value of future revenues, is significantly less than that of drugs to treat chronic conditions such as diabetes and heart disease. This is a major financial disincentive for new antibiotic drug development. Sustainable public-private partnerships are required to spur development of new antibiotics.

Further, there is a growing shortage of infectious disease specialists and even fewer hospital epidemiologists. A combination of rising tuitions, growing reliance on student loans and modest increases in reimbursement for services result in a recruitment disincentive, with medical graduates seeking higher-paying subspecialties. Medical student debt forgiveness might be a useful new incentive.

Adequate funding is required to support infection prevention programs. Hospital epidemiologists drive research efforts to define patient-specific factors, invasive devices, immune modifying treatments, hospital environments, microbiome and antimicrobial use practices that heighten the risk of health care-associated infections. Infection prevention programs define optimal strategies for reliably implementing risk reduction processes to scale across health care systems.

Antimicrobial stewardship programs to reduce the emergence of Clostridiodes difficile and other drug-resistant pathogens are in early development. Greater research is needed to define appropriate antimicrobial use across diverse patient populations with strategies to curtail overuse, to minimize dysbiosis, prevent the development of resistance and improve patient outcomes.

Some colleagues envision the end of health care-associated infections, a “getting to zero” program. But with the existing knowledge of the microbiome, the emergence of drug-resistant bacteria and the fragile immune system of patients, this currently is impossible. Failure to communicate the health care infection risk accurately undermines the public trust. The long-term view to success requires aligning funding to ensure new antibiotic drug development, improved antimicrobial stewardship, adequate infectious diseases expertise and staffing of infection prevention programs. An energetic effort to further understand the biology of the microbiome is urgently needed. This defines the pathway for modern control of health care-associated infections.

Gonzalo Bearman, M.D., is a hospital epidemiologist and professor of medicine and division chair of infectious diseases at Virginia Commonwealth University. Contact him at gonzalo.bearman@vcuhealth.org.

Richard P. Wenzel, M.D., is a hospital epidemiologist, former president of the Society for Healthcare Epidemiology of America and professor emeritus at Virginia Commonwealth University. Contact him at richard.wenzel@vcuhealth.org.

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