Welcome to the Briar Patch: Ethics of Antibiotic Stewardship
‘We’re not fortune tellers. What sounds good now may have significant future harms’
Applying ethical concepts to infection control and infectious disease issues, helps infection preventionists (IPs) and ID physicians reframe problems and develop “moral resilience” to make tough choices, said Olivia Kates, MD, MA, an infectious disease professor and director of research ethics at Johns Hopkins University in Baltimore.
“Infectious diseases are communicable, and we deal with exceptionally personal and intimate risk factors,” she said at the recent IDWeek 2023 meeting in Boston. “A lot of infectious diseases are stigmatized and infections or interventions like vaccines seem to be popular subjects of entrenched misconceptions and coordinated misinformation. In fact, the public seems to love thinking and talking and arriving at conclusions about infectious diseases topics almost as much as we do.”
Justice and equity are cornerstones of medical ethics, as difficult as these principles may be to resolve in actual infectious disease situations.
“I think that a lot of us entered the field looking for opportunities to move the needle on health equity because we know that infectious diseases disproportionately affect disadvantaged populations,” Kates said. “We have to reckon with a history that’s fraught with examples of injustice and untrustworthy practices. Tuskegee was a study of syphilis and infectious disease. Willowbrook was a study of hepatitis A and infectious disease.”
In both these infamous incidents an unsuspecting human population was exploited and studied for disease progression without medical intervention.1,2
Thus, the enduring segment of public skepticism and reluctance to trust public health measures for an infectious disease.
“Infectious disease practice is inherently interdisciplinary and collaborative,” Kates said. “Often, someone else is running the show and calling us for help. You can’t give chemo without an oncologist, but pretty much anybody can give antibiotics, so that raises some ethical questions.”
As infectious diseases evolve and emerge, a nimble approach to ethics is necessary.
“Where we do have a little bit of power and responsibility is in our organizational quality initiatives like infection prevention and control and antimicrobial stewardship,” she said. “Those bring up ethical issues too because pathogens evolve and change, all infectious disease treatments are scarce resources — limited resources that can be exhausted by overuse.”
Embracing an ethical approach helps the clinician recognize and reframe recurrent issues.
“Build your vocabulary for describing these issues,” Kates said. “Articulating your own moral resilience is your ability to understand and master moral stressors, whether it’s shock, disgust, or outrage. Then we know where we want to stand relative to that event, and we act in accordance with those moral ideas.”
Four Ethical Principles
A co-speaker at the same session, Christina Yen, MD, MBE, medical director of antimicrobial stewardship at Maine Medical Center, said some of these bedrock ethical touchstones include the so-called four principles:3
• Autonomy: Respect for the patient’s right to self-determination;
• Beneficence: The duty to do good;
• Non-Maleficence: The duty to not do bad;
• Justice: To treat all people equally and equitably.
“What’s nice about this framework is it’s easy to remember — it’s four things,” she said. “It quickly allows us to kind of categorize or figure out what are the things I need to consider in balance to make an ethical or fair decision.”
As her title suggests, Yen is interested in the ethical issue of antibiotic stewardship, more specifically stopping antibiotic treatment when feasible for patients on end-of-life care. She was careful to say every case is different, but cited the following findings from the literature:4-8
• 87% of hospitalized patients with cancer-related deaths receive antibiotics;
• 20% of patients discharged on hospice are on antibiotics;
• 27% of hospice patients receive one or more antibiotics during the last week of life.
“And what I think, to me, makes these numbers more concerning is that there was a recent meta-analysis of 72 studies that found over 50% of patients near the end of life receiving antimicrobials across healthcare settings that had insufficient evidence of a bacterial infection,” she said.9 “We are uniquely positioned to act on this data through our practice or stewardship efforts. We’re taking time away from a patient, asking them to take an unnecessary antimicrobial and deal with side effects when they don’t have time left to give. Seeing all this as an ethical nuance is how we can transform awareness into action.”
Prolonging Life or Prolonging Death?
Moreover, another meta-analysis of studies on sepsis patients found that “inappropriate empirical antibiotic treatment is significantly associated with all-cause mortality in prospective studies. The estimated effect of appropriate empirical antibiotic treatment on mortality reported in observational studies is highly variable.”10
In general, antibiotic use always has been a kind of ethical, philosophical question about the one and the many. Does the physician treat the patient in front of her at the risk of spurring drug resistance that may infect others? With the primacy of the sick patient outweighing abstractions of the burgeoning problem of multidrug-resistant bacteria, few could deny antimicrobials, although they certainly may look for the best drug on the narrowest spectrum.
“Decision making regarding antibiotic treatment is unique,” the authors of the aforementioned meta-analysis concluded. “On one hand, no treatment equals the efficacy of antibiotics. On the other hand, there is no other instance in medicine where treatment given to the individual patient affects other patients and the society at large. In an era of increasing antibiotic resistance, prescription of an antibiotic to one patient might mean no available treatment for future patients.”
This decision would seem intuitive for patients on end-of-life care, particularly if the prescribed antibiotics interact and cause adverse effects with pain medication. The meta-analysis authors continued, reminding that one of the main goals of hospice and palliative care is letting patients “die with dignity. Because of this, many have argued that the primary goal of antibiotic therapy in hospice and palliative care settings should be symptom relief. Antibiotics are not universally effective at achieving this goal.”
Studies also differ on whether antibiotics prolong life in palliative care, or to put it a more ghoulish way, prolong death in a process “incongruent with a short life expectancy and goals of care.”11
For her part, Yen argues for alternatives, if possible, of symptoms that otherwise might be treated with antibiotics.“We all know symptom relief from antibiotics is rarely immediate,” she told IDWeek attendees. “For fever reduction and cough suppression, there are other medications, such as non-steroidal anti-inflammatory drugs and antitussives. Consider alternatives to antibiotics if there are some.”
Go back to your ethical principles, she advised — in this case, beneficence.
“Beneficence is not just doing good,” she said. “I think, for a lot of us in infectious diseases, [we] fear missing an opportunity to do good. In this case, do antimicrobials really allow us to help this patient in a substantial way and what other benefits does it provide? You’re not trying to withhold treatment. You’re trying to do good. We all want to do good for this patient.”
Much Ado About Nothing?
Chen said some audience members may think this is quibbling — a few antibiotics at the end of a patient’s life is not going to drive widespread resistance.
Maybe so, but it should be noted that the much-feared vancomycin-resistant Staphylococcus aureus (VRSA) — which some thought would herald the beginning of a post-antibiotic era — finally occurred in 2002 in a dialysis patient co-infected with vancomycin-resistant Enterococcus (VRE).
Although VRSA really has never emerged as feared, the take-home point is that it obtained vancomycin resistance from a plasmid transfer from VRE. It is not possible to predict with any semblance of certainty what resistance will appear in a given patient, even one taking antibiotics for a short period under end-of-life care. Although unlikely in this case, antibiotic treatment adds selective pressure for resistant bacteria to thrive by killing off drug-susceptible strains. Both gram-negative and gram-positive bacteria can transfer and receive antibiotic plasmids, usually through what are called conjugation events involving close contact
“I know we’re quibbling,” Chen said. “What’s a few antibiotics at the end of life? But I would challenge us to think of this issue as not just an individual problem, but as a collective problem. Listen, we’re infectious diseases physicians, pharmacists, nurses, whatnot — we are infectious disease folks, but we’re not fortune tellers. What sounds good now may have significant future harms.”
- McVean A. 40 years of human experimentation in America: The Tuskegee Study. McGill University Office for Science and Society. Published Jan. 25, 2019. https://www.mcgill.ca/oss/article/history/40-years-human-experimentation-america-tuskegee-study
- BuBois JM. Hepatitis studies at the Willowbrook State School for Children. Bioethics Research Center, Washington University in St. Louis. https://bioethicsresearch.org/resources/case-studies/hepatitis-studies-at-the-willowbrook-state-school-for-children/
- Medical Protection. The four pillars of medical ethics. Last updated June 6, 2023. https://www.medicalprotection.org/uk/articles/essential-learning-law-and-ethics#:~:text=The%20four%20pillars%20of%20medical%20ethics%20are%20defined%20as%3A,all%20people%20equally%20and%20equitably
- Lee S, Datta R. Frontiers in antimicrobial stewardship: Antimicrobial use during end-of-life care. Antimicrobial Stewardship and Healthcare Epidemiology. Published Oct. 2, 2023. https://www.cambridge.org/core/journals/antimicrobial-stewardship-and-healthcare-epidemiology/article/frontiers-in-antimicrobial-stewardship-antimicrobial-use-during-endoflife-care/00EF7FA98DA20844956DB510779F65DB
- Thompson AJ, Silveira MJ, Vitale CA, Malani PN. Antimicrobial use at the end of life among hospitalized patients with advanced cancer. Am J Hosp Palliat Care 2012;29:599-603.
- Oh DY, Kim JH, Kim DW, et al. Antibiotic use during the last days of life in cancer patients. Eur J Cancer Care 2006;15:74-79.
- Albrecht JS, McGregor JC, Fromme EK, et al. A nationwide analysis of antibiotic use in hospice care in the final week of life. J Pain Symptom Manage 2013;46:483-490.
- Furuno JP, Noble BN, Horne KN, et al. Frequency of outpatient antibiotic prescription on discharge to hospice care. Antimicrob Agents Chemother 2014;58:5473-5477.
- Marra AR, Puig-Asensio M, Balkenende E, et al. Antibiotic use during end-of-life care: A systematic literature review and meta-analysis. Infect Control Hosp Epidemiol 2021;42:523-529.
- Mical P, Shani V, Muchtar E, et al. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother 2010;54:4851-4863.
- Ford PJ, Fraser TG, Davis MP, Kodish E. Anti-infective therapy at the end of life: Ethical decision-making in hospice-eligible patients. Bioethics 2005;19:379-392.
Applying ethical concepts to infection control and infectious disease issues, helps infection preventionists and infectious disease physicians reframe problems and develop “moral resilience” to make tough choices, said Olivia Kates, MD, MA, an infectious disease professor and director of research ethics at Johns Hopkins University in Baltimore.
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