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.
To our knowledge, this is the first comprehensive, prospective study to describe the quantity, type, and pattern of antimicrobials prescribed and the indication for therapy among patients with advanced dementia in the long-term care setting. Earlier studies that focused on the treatment of specific infections (ie, pneumonia) in advanced dementia were retrospective or cross-sectional in design, examined hospitalized patients, or studied only a single institution.2–5,21,22
Despite these differences, our study corroborates that antimicrobial agents are commonly prescribed in advanced dementia and extends these findings by demonstrating a marked increase in antimicrobial use as death becomes imminent. Terminally ill patients with cancer in palliative care settings also frequently receive antimicrobial therapy.13,14
White et al13
reported that approximately 30% of hospice recipients with advanced cancer are prescribed antibiotics. Although a urinary tract infection was the most frequent indication for treatment among patients with cancer who were dying, a respiratory tract infection was the most common diagnosis in our cohort with end-stage dementia.
Treatment decisions for infections in advanced dementia can be difficult for family members and care-givers. The 2 purported reasons to administer antimicrobials are life prolongation and symptom control. Limited observational studies4,5,22
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.23
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.5
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.24
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
Moreover, parenteral administration, which was common in our cohort, can be an uncomfortable procedure in advanced dementia.6
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.10,28
In particular, up to 40% of residents living in nursing homes harbor at least 1 species of antimicrobial-resistant bacteria.29–31
Once admitted to the hospital, these nursing home residents contribute substantially to the influx and spread of antibiotic-resistant bacteria.28,29
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.31–33
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.
Future initiatives aimed at optimizing antimicrobial use will require standardized units of measurement. In this study, a DOT value was used to quantify antimicrobial utilization. The DOT quantifies the mean duration of therapy adjusted for the total time that the population was observed and does not take into consideration the actual dose administered. The DOT value was developed as an alternative to the defined daily dose measure.20,34
The daily defined dose assumes that all patients receive standard antimicrobial doses, and therefore does not take into consideration unique patient characteristics that require dosage adjustments. This limitation is especially relevant to elderly patients, who often require alternative dosing to adjust for low body mass and renal insufficiency.25
Measures of antimicrobial DOT have not been previously reported for patients with advanced dementia. Thus, the DOT values found in this study provide a benchmark for future research in this area and for comparing prescribing practices between institutions.
This study has limitations that warrant comment. First, this prospective cohort study did not include a comparison group. Therefore, we do not know whether the pattern of antimicrobial use observed in our subjects with advanced dementia differs from that of other long-term care residents. Second, data were not collected to determine the presence of antimicrobial-resistant bacteria. Thus, although our study raises concerns that nursing home residents with advanced dementia are reservoirs of antimicrobial-resistant organisms, this supposition remains to be proved. Finally, this observational study was not designed to study the outcomes of antimicrobial therapy in advanced dementia, despite the fact that many subjects died shortly after receiving treatment.
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.23
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.