For the military and veteran medical communities, the field of infection control – preventing infections acquired during health care delivery – has been challenged on two fronts in the post-9/11 era: the emergence of infectious diseases, such as the bacterium Acinetobacter baumannii (A. baumannii or “Iraqibacter”) in military treatment facilities in Iraq and Afghanistan, and the spread of multidrug-resistant organisms (MDROs) across global health care networks.

In 2014, Dr. Eli Perencevich, a professor of internal medicine and epidemiology at the University of Iowa and director of the Center for Comprehensive Access & Delivery Research and Evaluation (CADRE) at the Iowa City VA Health Care System, co-wrote an overview of the problem in the journal Infection Control & Hospital Epidemiology. About 10 percent of hospitalizations, he wrote, are complicated by health care-associated infection, and up to 75 percent of those infections are from organisms that resist first-line antimicrobial treatment.

Military medical providers wage the infection control fight on the same fronts as other professionals, attempting to minimize infections resulting from contact with medical equipment such as catheters, intravenous lines, and ventilators, but their work is complicated by several factors.

At least part of the reason for this, according to Perencevich, has been worldwide complacency among the infectious disease community. “It used to be that we always had a new antibiotic,” he said. About 30 years ago, laboratories and pharmaceutical companies stopped developing such new drugs, probably because other drugs were more profitable.

The drug-resistant superbugs that have gained ground as a result of this lapse include A. baumannii, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), Klebsiella pneumoniae, Clostridium difficile (C. difficile), and others. These organisms have a tendency to hang around in health care settings; according to the Department of Veterans Affairs (VA), C. difficile can persist on inadequately cleaned surfaces for up to five months, and MRSA can survive for more than nine months.

Department of Defense (DOD) and VA professionals have developed strategies and tactics – and established institutions – to fight these organisms. When A. baumannii began spreading to patients in stateside military hospitals in 2003, medical staffs implemented strict protocols – screening every single incoming patient, isolating infected patients, and using personal protective equipment (PPE). The Defense Health Agency required infection control officers (ICOs) at each of its combat support hospitals, created or expanded infection control curricula at military medical schools and training centers, and established the Multidrug-resistant Organism Repository and Surveillance Network (MRSN) at the Walter Reed Army Institute of Research. MRSN collects and characterizes MDROs at medical facilities throughout the military in order to inform best clinical practices, influence policy, and enhance infection prevention and control efforts.

The Veterans Health Administration (VHA) – the nation’s largest integrated health care network – has undertaken similar efforts throughout its medical and residential facilities. Its National Infectious Diseases Service launched a prevention initiative that, in its first five years, drove health care-associated MRSA infections down 69 percent in acute care facilities, 81 percent in spinal cord injury units, and 49 percent in long-term care facilities. These infection rates continue to fall. The VHA built on this success by expanding the program into an MDRO Prevention Initiative targeting multiple organisms, in different modes of care. The initiative involves commonly used prevention protocols – screening, environmental management, hand hygiene, and contact precautions – tailored to setting and circumstances.

Infection control is a concept now firmly embedded, both culturally and institutionally, throughout the VHA and the military medical system – and yet, despite dramatic reductions in infection rates, health care-associated infections remain a persistent problem, often flaring up in particular environments and circumstances. The military and VA remain hyper-vigilant, crafting joint plans and responses to drug-resistant infections for patients in their care.

Battlefield Trauma:
Opening the Door to Infectious Disease

Military medical providers wage the infection control fight on the same fronts as other professionals, attempting to minimize infections resulting from contact with medical equipment such as catheters, intravenous lines, and ventilators, but their work is complicated by several factors. Many warfighters admitted to forward medical facilities have open wounds that make them more susceptible to infection, and trauma itself is known to disrupt the immune system and predispose patients to infections and inflammatory complications. When the emergence of A. baumannii was first tracked among military casualties, it was initially thought that the organism had been introduced – inoculated, in epidemiological parlance – bluntly, by the penetrating force of improvised explosive devices, bullets, or debris.

According to Dr. David Tribble, DrPH, science director of the Infectious Disease Clinical Research Program at the Uniformed Services University of the Health Sciences, this idea was first dispelled by epidemiologists from the Walter Reed Army Institute of Research, who found that the outbreak was largely due to another signature characteristic of military medicine: the different echelons of care, at different locations, received by wounded service members during the casualty-evacuation process.

Walter Reed researchers, said Tribble, “provided evidence that a lot of these cases are health care-associated infections acquired through the chain of medical evacuation, where people are coming from a downrange facility, usually what we call the ‘Role 2’ forward surgical hospitals, or from the larger field hospitals like Bagram or Kandahar. And they were frequently air evacuated to Landstuhl, in Germany, and then sent for definitive care in the United States. And of course, many of them would then go on to VA hospitals for care. So there’s a lot of opportunity for health care-associated infection transmission among these very seriously injured personnel.”

About nine years ago, Tribble and colleagues with both DOD and VA developed a project for tracking short- and long-term infectious disease outcomes following deployment-related traumatic injuries among service members. The resulting Trauma Infectious Disease Outcomes Study has yielded even more data about the considerable burden trauma-associated infections place on the military health system. Around a quarter to a third of wounded service members, they found, were contracting trauma-associated infections. Interestingly, researchers found geographic differences among the organisms causing these infections. In Afghanistan, trauma-associated infections are more likely to be caused not by A. baumannii but by Escherichia coli and the group of organisms known as the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), which are the leading cause of health care-associated infections worldwide. These pathogens – primarily gram-negative bacteria, whose outer membranes protect them from many antibiotics – create most of the problems for forward-deployed medical providers.

Tribble and colleagues are still investigating the problem of trauma-associated infection. “We’re trying to better understand what leads to an increased risk of these infections, and how best to prevent them,” he said. “We look at some of the measures, in medical and surgical care, used to prevent them. And we’re also studying how to get optimal results: When you do get an infection, what’s the best way to treat it?”

Attacking the Unknowns

Over the past decade or so, DOD facilities reduced infection rates with two main tactical adjustments: pre-deployment training specific to infection control for health care professionals, and stationing infection control practitioners farther forward in Iraq and Afghanistan, up to “Role 3” hospitals.

“We saw some very dramatic declines in ventilator-associated pneumonia rates,” Tribble said, “as there was kind of a re-emphasis of proper techniques, and trying to apply them as best as possible in a forward setting. We saw the Acinetobacter infections that were so common in those earlier years in Iraq go down to very low rates.”

Despite all the medical community has learned and applied so far in the 21st century, Tribble said there are important things practitioners still don’t know about health care-associated infection that need further investigation. Health care providers still don’t have a good handle on how to use antibiotics in a way that’s both effective and doesn’t increase an already virulent organism’s resistance. “There’s not a lot of guidance out there on managing some of these complex types of patients, like these combat trauma patients who’ve suffered polytrauma and are injured at different sites,” said Tribble. “When we see wound infections, the majority of them are polymicrobial.” We know that using broad-spectrum antibiotics against these infections is a bad idea, Tribble said, but we don’t have a lot of better ones yet.

Another area in need of further research is how pathogens are transmitted from one patient to another in health care settings. “In today’s world, people often don’t stay in the hospital long,” Tribble said. “They move in and out. There’s a lot of mobility in health care – and because of that, the organisms have mobility too, and that increases risk.”

A recently unveiled vision for the future of the VA’s infection control research echoes Tribble’s concerns. In 2016, Perencevich and about three dozen of his VA colleagues – infectious disease experts, epidemiologists, implementation experts, operational partners, and leaders such as Dr. Martin Evans, director of the MRSA/MDRO Program – convened in Iowa City to chart a course for research into existing “knowledge gaps” in preventing and treating MDRO infection. The four areas of research they determined to be most necessary for exploration were:

• Transmission dynamics. VA experts cited a lack of data about how MDROs are transmitted in acute-care settings, and future studies should investigate the best and most cost-effective strategies for reducing transmission, such as hand hygiene, environmental cleaning, isolation measures, and active surveillance. Some future studies should also examine adherence issues – not only policies and protocols, but also whether these practices are universally adopted.
• Antimicrobial stewardship. Every VA facility has an antimicrobial stewardship mandate: a specific plan for reducing unnecessary use of antibiotics, which can strengthen a pathogen’s drug resistance. But not every VA facility has an infectious disease specialist. VA experts are calling for studies examining optimal strategies in both inpatient and outpatient settings, and the establishment of standard metrics that can assess, in the absence of expert judgment, changes in resistance and appropriate prescribing. “We’re definitely reducing prescribing, but we don’t have the ideal target yet,” said Perencevich. “There are really no standard ways to monitor antimicrobial stewardship. There is no metric. So, our colleagues here in Iowa City are developing automated ways to monitor prescribing.”
• The microbiome. It’s a new concept – the human organism as an ecosystem comprising interacting microorganisms – and research in this area is in its infancy. The VA anticipates ways to manipulate the human microbiome to eliminate or prevent colonization by MDROs, but also recognizes there’s no existing framework for such research, nor criteria for prioritizing study designs such as longitudinal studies or clinical trials. VA experts recommend further exploration of the effectiveness of fecal transplants as therapy (some studies have shown transplants to be effective at eradicating C. difficile), and of additional research into microbiota outside the gastrointestinal tract.
• Special populations. Many of the VA’s first MDRO initiatives were aimed squarely at the acute-care setting: large VA medical centers serving vast numbers of inpatients. The success of these early efforts has allowed VA researchers to drill down to different settings, populations, and variables that may complicate a one-size-fits-all approach. For example, a study reported last year in the American Journal of Infection Control revealed that while hospital-acquired cases of C. difficile continued to decrease throughout the VHA from 2003-2014, the infection rates in long-term care facilities actually increased over the same period. VA experts envision research into specific care settings or circumstances that should be prioritized, including long-term care, spinal cord injury, rehabilitation, mental health care, ambulatory care, and home-based care.

The work of professionals in these settings has shown that an infection control approach adapted to patients and their circumstances can yield remarkable results. In 2012, residents of the 120-bed community living center at the W.G. (Bill) Hefner VA Medical Center in Salisbury, North Carolina, were experiencing an unprecedented prevalence of MRSA: 70 percent of residents had been colonized by the bacteria, meaning they had the organism on their skin or in their noses. Nineteen residents were infected.

Long-term residents differ from hospital patients, of course, in several ways, and the center adopted a program to supplement the existing MDRO prevention protocols while maximizing interaction and mobility. Residents were screened and then “decolonized” with both a topical antiseptic and a nasal antibiotic, every day for five days, and then tested again a week later. Rooms were cleaned thoroughly with antiseptic and ultraviolet light.

Lanette Hughes, RN, the center’s MDRO prevention coordinator, said the program’s success was due to the staff’s decision to play offense. “We were monitoring this MRSA, but we weren’t really stopping it because we were continuing to get new patients in. We weren’t doing any decolonization.” Over the next four years, the MRSA infection rate among residents dropped 89 percent – and not only that, said Hughes, but rates of infection from every other drug-resistant organism decreased, including Klebsiella,
E. coli, VRE, C. difficile, and the Enterobacter genus known as CRE/CPE.

A VA/CDC Partnership

As the Salisbury program demonstrates, the failure or success of infection control isn’t necessarily determined by the mode of attack, but by how well, and how consistently, that attack is implemented. Five years ago, the VA, a leader in implementation science, established a 10-hospital Infection Control Research Network, which focused exclusively on studies of strategies to prevent the spread of MRSA in VA facilities.

This network was recently expanded in several important ways: In fall 2017, the VA and U.S. Centers for Disease Control and Prevention (CDC) announced their partnership to fund a practice-based network of 15 hospitals (the original 10, plus five) and their associated community-based outpatient clinics.

Several research initiatives, aimed at the knowledge gaps recently identified by VA experts, will be implemented among these facilities to compare infection control processes and outcomes. Heather Reisinger, Ph.D., the implementation specialist who works with Perencevich as associate director of the CADRE, traveled with an implementation research team that visited each of the original 10 facilities in the network, observing and interviewing staff, but said this new partnership will allow the VA to build capacity and train research teams at each of the sites. “Right now we’ve established that we’re going to be looking at the environmental services in the VA, the staff who do the cleaning of patient rooms, and looking at how different places do that – and then how we can standardize that across the board.” Other studies are likely to look at transmission dynamics and the use of antibiotics. These implementation studies will be funded and designed by the VA, Reisinger said, while “the CDC is covering the nuts and bolts – research coordinators and people gathering statistics and pulling data from the VA electronic medical records.”

The new partnership is an exciting new phase in infection control research, said Reisinger, a holistic attempt to not only gather data on who’s infected, and where, and when – but also how and why. “What we’re trying to do now is not only perform that data collection process, but to actually try to understand the implementation process and get a better sense of what the barriers are, specific to facilities, so that we can help them overcome those barriers. There has been work with infection control nurses, determining what types of interventions are best, but there really hasn’t been a focus on the science of implementation, and how we get that integrated into infection control practices. This is kind of the first step in trying to see if we can do that.”

This article was first published in the Veterans Affairs & Military Medicine Outlook 2018 Spring publication.