Antimicrobial Stewardship was raised as a serious concern by the World Health Organization and by the CDC nearly 25 years ago, which was then driven by expanding drug-resistant malaria, tuberculosis, and HIV. Since then, active microbial stewardship has often been talked about but rarely acted upon.
Today, our concern about multi-drug resistant tuberculosis has been supplanted by pan-resistant Gram negative bacteria. Instead of being concerned about resistance of a common, but not ubiquitous, pathogen, we are now concerned about one of the most common bacterium for which we have absolutely no treatment. Nonetheless, we remain inert as the danger expands in our midst—we consign antimicrobial stewardship to "paper compliance" committees or untrained employees.
Recently, my region was visited by pan-resistant Klebsiella, a Gram negative bacteria, by way of India. Only by virtue of a single, sharp hospitalist asking the right questions, did we avoid the crisis of colonization of an intensive care unit and potential public relations nightmare for the medical facility. Our community is 7,600 miles away from the source of Klebsiella—but we no longer have the luxury of two oceans to keep us safe—resistant pathogens have no borders. We cannot close our eyes and expect bad diseases and their carriers to go away. Yet, our inaction belies our true sentiment. Like a frog in slowly heated water, we do not seem to notice until it is too late.
We hear the warnings, yet ignore them, assuming that our current practices are good enough. Our splendid isolation on an "island of tranquility" should nary be ruffled by alarmists.
This particular crisis was dealt with swiftly, and indeed most of the nation's attention is on such one-off events occurring randomly in major urban areas of the United States. But we are blind to the larger threat that is present.
The analogy I often use is that focusing on a single clinical case is like focusing on the lichen on tree bark when the rest of the forest is on fire. I used this analogy before in 2009, to describe the focus of the Centers for Disease Control and Prevention on less than a handful of type A/H1N1 influenza cases in California and Texas while we were tracking a massive signature of lethal influenza in several areas of Mexico. Antimicrobial drug resistance has evolved to the point that we need to shift our attention to both a higher level of granularity and a larger context. We need to closely monitor the trees and the forest.
The issue in Reno, Nevada is not the rare importation of pan-resistant bacteria. It is the "boiling frog" phenomenon that we have documented in every acute and long-term care center in our region—the entire population of Escherichia coli ("E. coli") is showing evidence of rapidly increasing resistance, and we are seeing little evidence of successful antimicrobial stewardship.
E. Coli is the single most common bacterium isolated by clinical laboratories in the U.S. health care system and permeates our healthcare infrastructure. This is the bacterium that lives in our gut that helps us digest food and defends us from pathogenic bacteria. It is the bacterium that protects us from Clostridium difficile. It is also the bacterium that can be found on our toilets and bathroom sinks, and causes urinary tract infections that occasionally lead to sepsis.
In our community, we are seeing E. coli resistance to amoxicillin-clavulanate, first and second generation cephalosporins, trimethoprim-sulfamethoxazole, ciprofloxacin, and levofloxacin. Our team is forecasting that third generation cephalosporins will be severely lacking in effectiveness in 15 years. When we sit down with our pharmacists and infectious disease physicians to discuss prescribing guidelines that will appear in the electronic medical record, we soon realize that we have already lost nearly all of our options. We no longer have the ability to swap out a drug with a higher level of resistance for one with a lower level. We can only pray the pharmaceutical industry can make something new. However, there is a limit to what the pharmaceutical industry can do. This is real, it is happening now, and it is common.
In one hospital our team surveyed, the emergency department clinicians aggressively treat asymptomatic bacteriuria—to the point that intravenous antibiotics, by all appearances, is a requirement for admission to the hospital. These are typically elderly patients with a long list of other mostly more serious diagnoses. The Infectious Disease Society of America (IDSA) does not recommend treating asymptomatic bacteriuria because of concerning trends in resistance that have been observed nationwide (and worldwide as well). But, as often noted by physicians and laypeople, we live in a litigious society where defensive medicine is practiced routinely- often to the detriment of good, evidence-based medicine.
In this particular emergency room, ciprofloxacin is the leading antibiotic used to treat urinary tract infections, in part due to aggressive pharmaceutical marketing, generic pricing, and ready availability. The antibiogram (data summarizing the percent of individual bacterial pathogens susceptible to different antimicrobial agents) produced by this hospital's clinical microbiology staff, is ignored. There is a stewardship committee, but physician attendance is poor, and the pharmacy recommendations are ignored. The hospital administrators, reluctant to antagonize the very physicians who often admit the most patients, do not enforce compliance with antibiogram-informed guidance. Infectious disease specialists drop in to provide only the occasional patient-specific consult, however neither their mission nor their focus is on sustainable antimicrobial stewardship.
The bias in Western medical practice is to prescribe drugs in response to public demand. Patients have been conditioned by ubiquitous, aggressive marketing from pharmaceutical companies to expect a drug for every problem, medical or not. Pills are available everywhere, from gas stations to the Internet. We have widespread evidence of prescription medications in our sewage systems. Meanwhile, physicians are fearful of low patient satisfaction scores as they may negatively influence compensation. As a result, the public has yet another mechanism to reinforce their demand for antibiotics, whether they are needed or not.
A mom walks into an urgent care clinic with a crying baby. She had been up all night because the child was uncomfortable and running a low grade fever. She is sleep-deprived, had to take the day off from work, and is now waiting to be seen in a busy waiting room. She wants an antibiotic and wants to go home. After the healthcare provider evaluates her, he tells her the child does not need an antibiotic because there is no evidence of a bacterial infection. She then proceeds to post a negative online review and a negative customer satisfaction survey with the hospital. Soon, the healthcare provider receives a phone call from an administrator of the hospital that employs him. The administrator asks him to find a way to improve their customer satisfaction scores. There is even encouragement to provide trial antibiotics until culture results are returned. The net result is that the healthcare provider, not wanting to be penalized by his employer, is now going to give an antibiotic to the next child, who displayed symptoms no different than the previous child. This is the reality for the majority of healthcare providers who want to do the right thing but are not supported by their employers.
If you talk to infection control experts or pharmacists, they will tell you they are tired of fighting physicians on appropriate antimicrobial use. If you talk to hospital administrators, they will tell you nearly the same thing. In contrast, many prescribing physicians and clinicians, when faced with possible customer disapprobation and litigation, as well as conditioned by repetitive practice, choose to ignore the warnings and advisories. The reality is the majority of physicians do not keep up with the peer-reviewed literature on antimicrobial resistance, and they are conditioned to believe their prescribing behavior is correct and justifiable. As the front line of medical practice and the party responsible for the well-being of the patient, they are often highly defensive of their practice and refuse to consider the possibility that they have harmed many more patients than they have helped. Perhaps they have even contributed to their patient's unnecessary admission to an intensive care unit or worse. Some members of the long term care community have told us they are seeing a rise in demand for dialysis and most ominously, a rise in demand for ventilated, dialyzed patients. They wonder if this rise is due to the abuse of antibiotics and other drugs that damage the kidney. In our state, there is no specialized medical facility that will accept ventilated, dialyzed patients for long-term care. Meanwhile, the patients who do not get the antibiotic they want from one physician, simply walk down the street until they find a doctor who will prescribe what they want.
The Centers for Medicaid and Medicare Services (CMS), in partnership with the CDC, have recently proposed guidelines for antimicrobial stewardship. The White House intends to enforce compliance and have called for hospitals to decrease their rates of hospital-acquired multi-drug resistant infections by 50% in 2010. This will not happen without real and accountable action by medical system leadership. The indicators that CMS has chosen to focus on have been roundly criticized for not being sufficiently specific to truly hold medical facilities accountable for antimicrobial stewardship. For example, there is no current mechanism to examine, in real time, the appropriateness of specific prescriptions. The result is confusion and a wholesale effort to dodge meaningful compliance. Many healthcare institutions have chosen to create "paper committees" that conform to the "letter" of CMS and the Joint Commission, but not the intent to actively institute meaningful antimicrobial stewardship. Consequently, we have yet to meet a single medical center CEO (whether a physician or not) who is willing to establish stewardship as a truly urgent objective and demands absolute compliance by their provider staff.
To be fair, medical center executives are besieged with a mind-numbing array of CMS requirements, all enforced with the threat of losing federal funding. The management of a healthcare facility is nothing like running a Toyota automobile assembly plant. It is extremely difficult to be proactive or responsive in an agile manner under such conditions. Some CEOs have told me, "This issue is not our fault. We do not see how we are responsible." This would be true if the healthcare facility operated in isolation from all other outpatient, urgent care, long term or other facilities where inappropriate prescribing occurs. The current healthcare economy is increasingly moving toward a mass acquisition of all modes of healthcare by a single corporate entity. They now have the opportunity to address stewardship from primary care all the way to the intensive care unit. This underscores the fact that healthcare is not an "island" but a highly interconnected ecosystem with other care providers in the community and region.
Some healthcare executives believe that making a floor nurse the "infection control" officer, with responsibility for "antimicrobial stewardship", is enough. Rarely are these nurses certified for infection control duties or trained to manage the complexity of antimicrobial stewardship- especially in rural medical facilities. Most importantly, many are already overworked, have enormous clinical responsibilities, and are entirely lacking in authority, clinical, budgetary, or otherwise. They are set up to fail before they even start, or worse yet, designated as the scapegoat if the program fails. In our experience, this kind of an implementation universally fails. Any program that depends on a nurse, regardless of their experience, to police physicians is doomed to fail because of the inherent resistance of physicians to nursing leadership.
Others believe that the solution is to charge an infectious disease physician with responsibility for "antimicrobial stewardship." Often, their situation is parallel to nurses as these physicians are responsible for the clinical workload of the infectious disease specialist, often distracted with complex patients, and unwilling to confront their fellow physicians with poor performance. Worse, we have witnessed infectious disease specialists falling prey to pharmaceutical marketing similar to the public, where drugs that have newly entered the market are used in preference to far cheaper drugs for which resistance is not an issue yet.
Antimicrobial stewardship requires the undivided attention of all outpatient healthcare facilities, urgent care centers, and emergency departments, along with the inpatient wards and intensive care units. It requires absolute attention by specialized nursing and long-term care facilities. All of these facilities must be communicating and sharing data with each other openly. In our experience, we have yet to see an outpatient group or specialized nursing and long-term care facility staff that know what an antibiogram is, much less have the staff, policies and procedures in place to respond to its recommendations.
So where does this leave us? The level of drug resistance in this country shows persistent ignorance of the problem and continual deterioration of drug efficacy. However, there is the occasional bright spot.
Recently we spoke with Dr. Mitchell Rubinstein, a cardiothoracic surgeon and former Vice President of Medical Affairs (VPMA) at a busy full service hospital in New Jersey. He shared with us how his former hospital was able to create an effective antimicrobial stewardship program. This was made possible by the strong support of the CEO/COO, effective collaboration between the VPMA, the infectious disease personnel, and the pharmacy, and finally their ability to convince key medical staff leaders of the importance of such a program.
The program itself encompassed three processes. The first was real time decision support. The infectious disease specialist on the project created approximately 40 order sets, which were embedded in the hospital's electronic medical record system. With these order sets, a prescriber could click on the clinical entity they were planning to treat, and would be given a selection of the most appropriate antibiotics based on the hospitals antibiogram, patient allergies, and other key factors. The second step was a process of ongoing surveillance. Every day a pharmacist reviewed all antibiotics in use, and compared them with culture results and other key patient characteristics in order to identify opportunities to de-escalate the antibiotic use. Finally, based on the de-escalation opportunities identified, an infectious disease specialist would change the antibiotic selection. Based on prior Medical Executive Committee action, this antibiotic change did not require the approval of the treating physician. While some may argue that this program infringes on a physician's autonomy, this hospital's Medical Executive Committee took the position that inappropriate treatment choices should not be a physician's prerogative.
Simultaneously, the hospital took one other step to help reduce the number of hospital-acquired multi drug resistant organism (MDRO) infections it was seeing. They purchased and deployed several ultraviolet light machines to disinfect hospital room surfaces and thus reduce the ambient environmental burden of colonized organisms. The result of these two steps was a 30% reduction in antibiotic utilization, and a 40% reduction in the hospital's rate of nosocomial MDRO infections. While the hospital's $600,000 investment in equipment and staff might at first seem onerous, it was repaid within three years, not only with improved patient outcomes, but with a very positive return on investment.
This example illustrates success with two arms of the Healthcare Triple Aim; improving patient outcomes and doing so at a reduced cost structure. It clearly shows what can be accomplished when the appropriate stakeholders are actively committed to taking action. The upfront financial, personnel, or training commitment is truly modest compared to the high risk and cost of doing "business as usual."
In my career as a pediatrician who worked for the intelligence community, I was responsible for providing guidance and warnings on laboratory accidents, biological terrorism, Ebola, the 2009 H1N1 influenza pandemic, and the accidental introduction of cholera to Haiti that killed over 10,000 people. I will tell you without hesitation that this "boiling frog" disaster of drug resistance is more concerning to me than any national security issue that I have encountered in my career, mostly because the issue is not that we do not know what to do, but that we are unwilling to do it. My plea to every healthcare executive who reads this, is to lead rather than procrastinate, engage rather than resist, champion rather than entomb in toothless committees.
James M Wilson V, MD
Fellow, American Academy of Pediatrics
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