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A combination of public health, antibiotic stewardship, and infection control efforts over the last six years have managed to beat back the devil of multidrug-resistant bacteria. Yet all still hangs in the balance.
There are surging new threats like Candida auris, the continuing emergence of carbapenem-resistant Acinetobacter and the ongoing death toll of Clostridioides difficile — about 13,000 patients in 2017, the Centers for Disease Control and Prevention (CDC) reports.1
In a 2019 update of its 2013 report on the threat of antibiotic-resistant infections, the CDC reveals some progress and much remaining peril. In a forward to the report, CDC Director Robert Redfield, MD, opens with a dire assessment of the current situation and a call to action.
“Stop referring to a coming post-antibiotic era — it’s already here,” he notes. “You and I are living in a time when some miracle drugs no longer perform miracles and families are being ripped apart by a microscopic enemy. The time for action is now and we can be part of the solution.”
Infection preventionists (IPs) have been and must remain a very large part of that solution. Four of the top five pathogens that pose an “urgent” threat — the highest level of risk — are healthcare-associated infections (HAIs). These include carbapenem-resistant Enterobacteriaceae (CRE) and the aforementioned C. auris and C. diff.
“All together, unfortunately, the U.S. toll of all the threats in the report exceed 3 million infections,” Michael Craig, MD, of the CDC’s Antibiotic Resistance Coordination and Strategy Unit, said at a recent press conference. “[However, since 2013], we’ve reduced the number of deaths from antibiotic resistance by 18% overall and by nearly 30% in hospitals alone.”
Speaking at the press conference, Redfield credited some level of success to nationwide efforts that include “using infection prevention and control to stop transmission in healthcare facilities.” However, bacteria and fungi will continue to develop resistance to the drugs designed to kill them, he warned.
For example, the gains cited in the report could be undone by the rapid global emergence of C. auris, a drug-resistant fungus that was not even on the watchlist in the 2013 report.
“To underscore the challenge we are facing, Candida auris emerged on five continents at the same time,” Redfield said. “One in three patients infected by invasive Candida auris dies, and some samples have been shown to be resistant to all three classes of antifungal drugs.”
Antibiotic resistance is multifactorial and mutable as drugs are used — often indiscriminately — on people, plants, and animals across the globe. The results can be unpredictable. In contrast to the rapid emergence of C. auris, for example, another pathogen that once was feared as the harbinger to the post-antibiotic era has fallen completely off the list of 18 pathogens in the new report. Vancomycin-resistant Staphylococcus aureus (VRSA), considered an ominous superbug when it first appeared, was listed as “concerning” in the 2013 report, and then removed in the 2019 update.
“Since 2002, 14 cases of VRSA have been identified in the United States,” the new CDC report states. “These are isolated cases and spread from patient to patient has never been documented.”
One theory is that VRSA paid a price in terms of transmissibility by acquiring resistance to vancomycin, which has been the mainstay against potentially deadly staphylococcus infections for decades. The hope is that C. auris will fade out in similar fashion, but right now it threatens to become endemic in some healthcare facilities.
“This is a pathogen we didn’t even know about when we put out the last report in 2013, and since then, it has circumnavigated the globe and caused a lot of infections and deaths as it has spread,” Craig said. “We are still trying to figure out its origins.”
Other changes in the report include carbapenem-resistant Acinetobacter, which was categorized as a “serious” threat in 2013 but has been elevated to “urgent” in 2019.
“It has been listed as a new urgent threat because it is spreading in healthcare and is often resistant to many antibiotics,” Craig said.
The number of estimated hospital infections due to this pathogen actually declined from 10,300 in 2013 to 8,500 in 2017, but this is a multiple-threat bug that can cause a lot of problems. Once called “Iraqibacter” due to infections in soldiers returning from the Gulf wars, carbapenem-resistant Acinetobacter is hard to eradicate in the healthcare environment and can carry mobile genetic plasmids that can be transferred to other bacteria.
“Some can make a carbapenemase enzyme, which makes carbapenem antibiotics ineffective and rapidly spreads resistance that destroys these important drugs,” the CDC report states. “Overall rates of carbapenem-resistant Acinetobacter cases have decreased. However, carbapenem-resistant Acinetobacter that can produce carbapenemases, which can spread to other germs and amplify the problem of resistance … appear to be increasing.”
That is a troubling sign, because some Acinetobacter strains are already resistant to nearly all antibiotics, carbapenems are a last-line choice, and few new drugs are in development. Carbapenem-resistant Acinetobacter generally strikes intensive care unit patients with pneumonia, wound, bloodstream, and urinary tract infections (UTIs), the CDC reported.
There has been some progress against C. diff, but it still causes about 220,000 infections annually. C. diff emerges as a byproduct of antibiotic use, which disturbs the microbiome in the gut and sets up the infection.
“A common strain of C. difficile (ribotype 027) that can cause more serious disease can be associated with use of certain antibiotics, such as fluoroquinolones,” the CDC report states.
Reducing fluoroquinolone use through antibiotic stewardship efforts has been shown to reduce C. diff, which can linger in the environment in spore form unless eradicated with sporicidal disinfectants.
“More than half of C. difficile cases among long-term care facility residents happen in those who were recently hospitalized,” the CDC reports. “Improving antibiotic use may have contributed to the decrease in long-term care facility-onset C. difficile cases in 10 U.S. sites [studied].”
With the release of the CDC report, The Joint Commission underscored its standards on antibiotic stewardship, including Medication Management (MM) standard MM.09.01.01, which requires “hospitals, critical access hospitals, and nursing care center organizations to have an antimicrobial stewardship program based on current scientific literature.” (See editor’s note.) Also, effective Jan. 1, 2020, standard MM.09.01.03 will apply to accredited ambulatory care settings. This standard may impact some infection preventionists with outpatient responsibilities, as it specifies that “the organization identifies an individual(s) responsible for developing, implementing, and monitoring activities to promote appropriate antimicrobial medication prescribing practices.”2
The CDC-recommended actions for healthcare providers in the report include the following:
• Follow infection prevention and control recommendations, including screening at-risk patients when indicated.
• Ask patients if they recently received care in another facility or traveled to another country.
• Alert receiving facilities when transferring patients colonized or infected with antibiotic-resistant pathogens.
• Educate patients on ways to prevent spread.
• Follow clinical and antibiotic treatment guidelines.
• Consider fungal infections for patients with respiratory infections who do not respond to antibiotics.
• Watch for signs and symptoms of sepsis. If you suspect sepsis, start antibiotics as soon as possible and reassess antibiotic therapy.
• Perform appropriate diagnostic tests to guide antibiotic therapy, including correct drug, dose, and duration.
• Be aware of infections and resistance patterns in your facility and community. Ensure you are notified by the lab immediately when antibiotic-resistance pathogens are identified.
• Know when to report cases and submit resistant isolates to public health.
Beyond the hospital, there are resistant threats in the community that include increasing extended spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, which was previously found more often in healthcare, Craig said.
“It is one of the leading causes of death from resistant germs, and is making common infections like UTIs harder to treat,” he said. The report cites 197,400 estimated cases in 2017, including 9,100 deaths.
“ESBLs are enzymes that break down commonly used antibiotics, such as penicillins and cephalosporins, making them ineffective,” the CDC report explains. “[They] often cause infections in otherwise healthy people. About one quarter of patients with these infections had no known underlying health conditions.”
The Enterobacteriaceae “family” of microorganisms includes Escherichia coli. “Certain strains of E. coli, such as ST131, have quickly spread in the community and among healthcare settings,” the CDC reported. “These strains often cause more severe infections and spread more easily. Additionally, a particular ESBL enzyme, called CTX-M, appears to be spreading in the United States and around the world.”
This enzyme can be transferred genetically to different types of Enterobacteriaceae. “When CTX-M and ST131 combine, they are a dangerous combination that can rapidly spread resistance,” the CDC notes. “Almost half of ESBL-producing Enterobacteriaceae infections occur in people who have not had recent inpatient healthcare exposure or an invasive medical procedure.”
Of course, that no longer remains the case when patients infected in the community present for care. The level of drug resistance in some normally routine infections like UTIs can be hard to treat at outpatient facilities, Craig said.
“With the ESBLs we’re seeing, harder-to-treat ultimately means these patients have to be hospitalized,” he said. “They go on to more aggressive, stronger antibiotics that might have more side effects, and that can be very challenging.”
Another urgent threat in the community is drug-resistant Neisseria gonorrhoeae, a sexually transmitted pathogen that has developed resistance to all but one class of antibiotics. Given this panoply of threats, Craig emphasized baseline prevention.
“Infection prevention and control in healthcare facilities works,” he said. “Improving the use of antibiotics we already have works. Proper food handling works. Safe sex works. Vaccines and keeping hands clean works.”
“This report is dedicated to the 48,700 families who lose a loved one each year to antibiotic resistance or C. difficile, and the countless healthcare providers, public health experts, innovators, and others who are fighting back with everything they have,” the CDC states.
One element of the report that caused some confusion at the press conference is that the CDC updated the 2013 “conservative estimate” of mortality with better data, finding that the original estimate of 23,000 deaths from antibiotic-resistant germs was a severe undercount. Recalculating the data revealed that the 2013 report should have listed 44,000 deaths, Craig said. The CDC highly values messaging, and one can only speculate if the higher number would have redoubled prevention efforts as well as mortality.
“There were nearly twice as many deaths,” Craig said. “When we look at the trends of that data, moving forward, we see actually, though, that we’ve made progress. That 44,000 number from 2013 for overall antibiotic resistance deaths has declined to around 35,900 today.”
Craig estimated that 85% of the deaths were caused by HAIs. While the previous report was based on extrapolations from 180 hospitals, the new data comes from more than 700 hospitals and represents millions of patient records.
However, the 35,900 number apparently does not include C. diff, which usually is not resistant to antibiotics, but arguably is most harmful to antibiotic use.
Editor’s note: Joint Commission antibiotic stewardship standards and resources are available at https://bit.ly/2rYBLdo.
Financial Disclosure: Peer Reviewer Patrick Joseph, MD, reports that he is a consultant for Genomic Health, Siemens, and CareDx. Senior Writer Gary Evans, Editor Jason Schneider, Editor Journey Roberts, Nurse Planner Patti Grant, RN, BSN, MS, CIC, and Editorial Group Manager Leslie Coplin report no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study.