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Original Investigation
July 12, 2021

The Trial to Reduce Antimicrobial Use in Nursing Home Residents With Alzheimer Disease and Other Dementias (TRAIN-AD): A Cluster Randomized Clinical Trial

Author Affiliations
  • 1Hebrew SeniorLife, Hinda and Arthur Marcus Institute for Aging Research, Boston, Massachusetts
  • 2Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  • 3Division of Infectious Diseases, Brown University, Providence, Rhode Island
  • 4Palliative Care Program, Division of Geriatric Medicine, University of North Carolina at Chapel Hill, Chapel Hill
  • 5Division of Primary Care Medicine, University Hospitals of Geneva, Geneva, Switzerland
  • 6School of Nursing, University of North Carolina at Chapel Hill, Chapel Hill
  • 7Department of Public Health Sciences, Pennsylvania State College of Medicine, Hershey
  • 8Frank Statistical Consulting LLC, Vashon, Washington
JAMA Intern Med. 2021;181(9):1174-1182. doi:10.1001/jamainternmed.2021.3098
Key Points

Question  Can a multicomponent intervention integrating best practices in infectious diseases and palliative care reduce antimicrobial and burdensome intervention use for suspected urinary and lower respiratory tract infections among nursing home residents with advanced dementia?

Findings  In this pragmatic cluster randomized clinical trial among 426 nursing home residents with advanced dementia, there was a nonsignificant reduction in antimicrobial use in the intervention arm. Chest radiography use was significantly lower in the intervention arm, but other burdensome procedures were unchanged.

Meaning  An intervention to improve infection management did not significantly reduce antimicrobial use among nursing home residents with advanced dementia.


Importance  Antimicrobials are extensively prescribed to nursing home residents with advanced dementia, often without evidence of infection or consideration of the goals of care.

Objective  To test the effectiveness of a multicomponent intervention to improve the management of suspected urinary tract infections (UTIs) and lower respiratory infections (LRIs) for nursing home residents with advanced dementia.

Design, Setting, and Participants  A cluster randomized clinical trial of 28 Boston-area nursing homes (14 per arm) and 426 residents with advanced dementia (intervention arm, 199 residents; control arm, 227 residents) was conducted from August 1, 2017, to April 30, 2020.

Interventions  The intervention content integrated best practices from infectious diseases and palliative care for management of suspected UTIs and LRIs in residents with advanced dementia. Components targeting nursing home practitioners (physicians, physician assistants, nurse practitioners, and nurses) included an in-person seminar, an online course, management algorithms (posters, pocket cards), communication tips (pocket cards), and feedback reports on prescribing of antimicrobials. The residents’ health care proxies received a booklet about infections in advanced dementia. Nursing homes in the control arm continued routine care.

Main Outcomes and Measures  The primary outcome was antimicrobial treatment courses for suspected UTIs or LRIs per person-year. Outcomes were measured for as many as 12 months. Secondary outcomes were antimicrobial courses for suspected UTIs and LRIs when minimal criteria for treatment were absent per person-year and burdensome procedures used to manage these episodes (bladder catherization, chest radiography, venous blood sampling, or hospital transfer) per person-year.

Results  The intervention arm had 199 residents (mean [SD] age, 87.7 [8.0] years; 163 [81.9%] women; 36 [18.1%] men), of which 163 (81.9%) were White and 27 (13.6%) were Black. The control arm had 227 residents (mean [SD] age, 85.3 [8.6] years; 190 [83.7%] women; 37 [16.3%] men), of which 200 (88.1%) were White and 22 (9.7%) were Black. There was a 33% (nonsignificant) reduction in antimicrobial treatment courses for suspected UTIs or LRIs per person-year in the intervention vs control arm (adjusted marginal rate difference, −0.27 [95% CI, −0.71 to 0.17]). This reduction was primarily attributable to reduced antimicrobial use for LRIs. The following secondary outcomes did not differ significantly between arms: antimicrobials initiated when minimal criteria were absent, bladder catheterizations, venous blood sampling, and hospital transfers. Chest radiography use was significantly lower in the intervention arm (adjusted marginal rate difference, −0.56 [95% CI, −1.10 to −0.03]). In-person or online training was completed by 88% of the targeted nursing home practitioners.

Conclusions and Relevance  This cluster randomized clinical trial found that despite high adherence to the training, a multicomponent intervention promoting goal-directed care for suspected UTIs and LRIs did not significantly reduce antimicrobial use among nursing home residents with advanced dementia.

Trial Registration  ClinicalTrials.gov Identifier: NCT03244917

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    1 Comment for this article
    Response to “The Trial to Reduce Antimicrobial Use in Nursing Home Residents With Alzheimer Disease and Other Dementias (TRAIN-AD)”
    Jiakun Yu, BSc(Hons) | Imperial College London, School of Medicine
    To the editor: I have read with great interest the recent study published by Mitchell et al.1 The authors showed a reduction in antimicrobial use in nursing home residents with Alzheimer's disease and other dementias by implementing the most recent infectious diseases and palliative care guidelines, although the adjusted marginal rate was not statistically significant. Nevertheless,  it is important to discuss the limitations of this study and would like to share our suggestions.
    Despite the authors’ endeavour to create a matched study cohort, a number of non-controlled variables can still challenge the validity of the paper. The clinical management guidelines,
    such as criteria for hospitalization, and threshold for further investigation (chest radiograph) for suspected lower respiratory tract infections (LTIs) and urinary tract infections (UTIs), may differ between nursing homes. Thompson et al. showed the prevalence of antimicrobial use can vary up to 10-fold between different nursing homes.2 The inconsistency in clinical practice between nursing homes can attribute to the different rate of antimicrobial use between intervention and control groups. This was further highlighted by higher utilization rate of chest radiography in the control group, further research is warranted to explore this statistically significant finding. I suggest adapting a longitudinal approach in addition to the cross-sectional study, where the intervention group is observed prior to intervention to establish a baseline.
    Furthermore, debilitating side-effects, such as antibiotic-associated-diarrhoea, are common amongst nursing home residents taking antibiotics for pneumonia.3 Literature also recognises the high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in nursing homes in United States which can be influenced by facility characteristics like the frequency of antibiotic use.4,5 However, delayed use of antibiotics when necessary can lead to more invasive management and further infections with worse outcomes.5 Therefore, I suggest exploring patient outcome and public health in nursing homes before and after implementing the intervention, using markers such as the rate of hospital admission for UTI/LRI and multi-drug resistant bacteria burden (such as MRSA). Thus, providing a better understanding of the long-term effect of the intervention outlined in this study.

    Antimicrobial overuse in nursing homes remains a widespread problem, recognising physical deterioration in patients with reduced mental state can be challenging. The intervention in this study has the potential to be widely implemented in nursing homes to tackle these problems. However, further research is needed to evaluate the effectiveness of the outlined multicomponent intervention.

    Jiakun Yu, BSc(Hons); Sihan Chen, BSc(Hons); Sa-Bin Hong, BSc(Hons)