Tuesday, March 04, 2008

Are antibiotics futile for nursing home patients with advanced dementia?

Today's New York Times has a piece about a recent article in the Archives of Internal Medicine in which the authors question the use of antibiotics to treat infections in nursing home patients with advanced dementia. The study concludes:

This prospective cohort study demonstrates that antimicrobial exposure among nursing home residents with advanced dementia is extensive and steadily increases toward the end of life. During the follow-up period (mean follow-up, 322 days), two-thirds of the subjects were prescribed at least 1 course of antimicrobial therapy and, on average, a total of 4 courses. Among the residents who died, 42.4% received antimicrobials during the last 2 weeks of life, often via a parenteral route. The proportion of residents taking antimicrobials was 7 times greater in the last 2 weeks of life compared with 6 to 8 weeks before death. This extensive use of antimicrobials and pattern of antimicrobial management in advanced dementia raises concerns not only with respect to individual treatment burden near the end of life but also with respect to the development and spread of antimicrobial resistance in the nursing home setting. . . .

Treatment decisions for infections in advanced dementia can be difficult for family members and caregivers. The 2 purported reasons to administer antimicrobials are life prolongation and symptom control. Limited observational studies have failed to demonstrate that antimicrobial treatment achieves either outcome in this frail population; however, randomized trials have not been conducted. Our findings further support that antimicrobials may not meaningfully extend the life of patients with advanced dementia for whom infections are frequently a terminal event. Palliation is often the main goal of care in this condition. It is difficult to assess the extent to which infections cause suffering in patients with advanced dementia. Previous work demonstrates that pneumonia is an uncomfortable experience for these patients and suggests that antimicrobial therapy may improve symptoms. However, it remains unclear whether antimicrobial therapy promotes symptomatic relief beyond what can be achieved by high-quality palliative treatment with more conservative modalities (eg, oxygen and acetaminophen). Finally, it is also important to minimize inappropriate antimicrobial exposure. For example, up to one-third of antimicrobials prescribed in nursing homes are for asymptomatic bacteriuria, for which treatment is not indicated. Antimicrobial administration has associated risks in the frail elderly population that merit consideration. Older persons are particularly susceptible to the adverse effects of antimicrobials owing to altered pharmacokinetics, polypharmacy, dosing errors, and an increased risk of Clostridium difficile infections. Moreover, parenteral administration, which was common in our cohort, can be an uncomfortable procedure in advanced dementia. Thus, from the individual patient's perspective, the balance of advantages and disadvantages of antimicrobial treatment of infections in advanced dementia remains unclear, regardless of the primary goal of care.

On a broader level, the emergence and spread of antimicrobial-resistant bacteria is a major public health concern. Older persons account for one of the largest patient reservoirs of these organisms. In particular, up to 40% of residents living in nursing homes harbor at least 1 species of antimicrobial-resistant bacteria. Once admitted to the hospital, these nursing home residents contribute substantially to the influx and spread of antibiotic-resistant bacteria. Exposure to antibiotics is strongly associated with the development of antibiotic resistance. Quinolones and third-generation cephalosporins were the most frequently prescribed antimicrobials in our cohort. Several studies have reported that more than 50% of isolates recovered from nursing home residents are resistant to these 2 classes of drugs. These observations and the extensive use of antibiotics found in this study raise the serious concern that nursing home residents with advanced dementia may be contributing to the emergence and spread of antimicrobial-resistant bacteria, posing health risks that extend beyond the individual being treated. . . .

Infections and febrile episodes are a hallmark of end-stage dementia. The extensive antimicrobial use demonstrated in this study is concerning given the lack of demonstrable benefits and the potential burdens of treatment in this terminally ill population for whom the goal of care is often palliation. Moreover, we believe that the widespread use of antibiotics in advanced dementia may pose a potential public health risk through the emergence of antibiotic resistance. This hypothesis requires further research. Meanwhile, from individual and societal perspectives, our study supports the development of programs and guidelines designed to reduce the use of antimicrobial agents in advanced dementia.

The accompanying editorial in Archives explictly frames the study in terms of medical ethics generally and "futility" in particular. The editorial poses this question: "If antibiotics are not required to restore comfort to an infected patient (either because the patient is in no distress or because palliation can be achieved by other means) and cannot be expected to enhance duration or quality of life, might not their use be considered futile?," which it then answers, "Prior investigators have indeed come to this conclusion" [footnote omitted]. So far, so good. If the purposes for which antibiotics would be prescribed are not likely to be attained, their use lacks a pathophysiologic rationale, a classic "futility" rationale. This is especially so because there are some negative consequences for the elderly and the overuse of antiobiotics in this population (as in any other) contributes to some degree in the development of antiobiotic resistant bacteria, a significant source of morbidity and mortality in hospitals.

But then the editorialist continues: "Even if antibiotics may prolong life, should they be used if they will not enhance quality of life?" This is a fair question only if it is separated from the issue of "futility." In common parlance, invocation of the "futility" label confers upon the practitioner the moral right to withhold or withdraw a medical intervention, even over the objections of the patient or the patient's surrogate decision maker. If the intervention does have a pathophysiologic rationale (prolongation of life), I would argue that "futility" is no longer the proper ethical framework for the discussion. As with any other intervention that may prolong life without necessarily increasing the quality of life, a discussion with the patient or the surrogate is certainly appropriate. A unilateral decision to withhold the drug(s) (or the discussion) is not. The editorial writer appears to agree with this: "The solution is not to categorically deny antibiotics to the severely demented elderly, or even to impose limits on their use or their spectrum as a matter of policy. Such decisions, in addition to being ethically untenable, would run counter to the expressed wishes of patients and their families. We must, however, begin to consider every decision to use antibiotics in this population as we would decisions regarding other treatment modalities, including resuscitation and major surgery."

According to the Times, Prof. Paul Appelbaum at Columbia sees things the same way: “The apparent suggestion that we should not be treating persons with dementia when they develop infections rests on a normative judgment — that does not flow from these data — that their lives are worth less than the unknown degree of risk of contributing to antibiotic resistance. Although one cannot ask the patients themselves how they feel about this judgment, many of their family members and caregivers would disagree, and our society — fortunately, in my view — has not yet reached the point where it is willing to embrace it.”

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