Abstract
Annual prevalences of antimicrobial resistance among urine Escherichia coli (n=3,913) and Klebsiella pneumoniae (n=1,736) isolates from home-based primary care patients with dementia were high between 2014–2018 (ciprofloxacin:18–23% and 5–7%, respectively; multidrug-resistance, 9–11% and 5–6%, respectively). Multidrug-resistance varied by region. Additional studies of antimicrobial resistance in home care settings are needed.
Keywords: Home care services, antimicrobial resistance, urinary tract infections, Escherichia coli, Klebsiella pneumoniae
Background
Urinary tract infection (UTI) is one of the most commonly diagnosed and treated infections in older adults. The microbial etiology of UTIs is well described, with Escherichia coli and Klebsiella pneumoniae being the predominant organisms isolated.[1–2] Antimicrobial resistance is a major public health threat, and existing literature regarding antimicrobial resistance among UTIs in older adults has largely focused on nursing homes. Recent data from 243 nursing homes indicate that a substantial portion of UTIs due to E. coli and K. pneumoniae are multidrug-resistant.[2]
In the United States, the population of homebound older adults is over 1.5 times larger than the nursing home population.[3] Similar to nursing home residents, homebound older adults often have dementia and are prone to UTI. Little is known regarding antimicrobial resistance among urine isolates from home care settings. Home-based primary care (HBPC) offers one method for homebound older adults to receive comprehensive care in their home.[4] This study evaluated antimicrobial resistance among urine E. coli and K. pneumoniae isolates from a national sample of homebound older adults with dementia who were enrolled in HBPC.
Methods
This was a retrospective cohort study of persons aged ≥65 years with a diagnosis of dementia from whom a urine E. coli or K. pneumoniae isolate was collected after enrollment in HBPC between January 1, 2014 and December 31, 2018 through the U.S. Veterans Affairs (VA) healthcare system. Enrollment in HBPC occurred after receiving ≥2 in-person home visits by a physician or advanced practice provider within a calendar year. Additional inclusion criteria are described elsewhere.[5] In 2018, HBPC programs served >55,000 homebound patients across 130 VA medical centers. This study was deemed exempt from review by the institutional review boards at VA Connecticut Healthcare System and Yale University.
Data were obtained from the VA Corporate Data Warehouse. Patients with urine isolates with reported identification of E. coli or K. pneumoniae from inpatient (e.g., hospital) or outpatient (e.g., emergency department, home) locations and a susceptibility result were included. For both E. coli and K. pneumoniae, urine isolates collected after the initial in-person home visit by a physician or advance practice provider between 2014–2018 were evaluated.
Demographics and comorbidities were recorded at the time of the initial in-person home visit by a physician or advance practice provider. Data collected from urine isolates included the organism (E. coli or K. pneumoniae), collection date, and susceptibility to antibiotics and antibiotic groups that were prespecified based on clinical relevance and drug utilization in HBPC.[5] Antimicrobial resistance among urine isolates was defined as nonsusceptibility (resistant or intermediate susceptibility) to one or more of the following: ampicillin/sulbactam, 3rd generation cephalosporins, ciprofloxacin, gentamicin, piperacillin/tazobactam, meropenem, or trimethoprim-sulfamethoxazole. Multidrug-resistant was defined as isolates with nonsusceptibility to 3 or more of the prespecified antibiotics or antibiotic groups.[2]
For E. coli and K. pneumoniae, the annual proportions of urine isolates that were nonsusceptible to prespecified antibiotics or antibiotic groups were determined using the first urine isolate collected per patient per year between 2014–2018.[6] Characteristics of persons with and without multidrug-resistance detected from any urine isolate collected after the initial in-person home visit by a physician or advance practice provider were compared using Fisher’s exact tests. Results were categorized by organism. Analyses were conducted using SAS 9.4 (Cary, NC, USA).
Results
When evaluating the first urine isolate collected per patient per year, 3,913 E. coli isolates and 1,736 K. pneumoniae isolates were examined. Mean annual prevalence of nonsusceptibility among urine E. coli and K. pneumoniae isolates was 21% and 6% for ciprofloxacin, 17% and 8% for ampicillin/sulbactam, 15% and 6% for trimethoprim-sulfamethoxazole, 7% and 6% for 3rd generation cephalosporins, 5% and 2% for gentamicin, and 2% and 4% for piperacillin/tazobactam, respectively (Figure 1). Less than 1% of urine E. coli and K. pneumoniae isolates were non-susceptible to meropenem. Overall, multidrug-resistance was detected in 9–11% of urine E. coli isolates and 5–6% of urine K. pneumoniae isolates (Supplement).
Figure 1.
Annual prevalence of antimicrobial nonsusceptibility when evaluating the first urine E. coli isolate (A) and first urine K. pneumoniae isolate (B) collected per patient per year from homebound older adults with dementia who received home-based primary care through the Veterans Affairs Healthcare System, 2014–2018. Number of first urine E. coli isolates and first urine K. pneumoniae isolates collected per year: 2014, n=573 and n=259; 2015, n=724 and n=302; 2016, n=822 and n=383; 2017, n=862 and n=383; 2018, n=932 and n=409, respectively. Abbreviations: E. coli, Escherichia coli; K. pneumoniae, Klebsiella pneumoniae; CIP, ciprofloxacin; AMS, ampicillin/sulbactam, TRS, trimethoprim-sulfamethoxazole; 3GC, 3rd generation cephalosporins; GEN, gentamicin; PIT, piperacillin/tazobactam; MER, meropenem; MDR, multidrug.
When evaluating all urine E. coli (n=5,684) and K. pneumoniae (n=2,337) isolates collected after the initial in-person home visit by a physician or advance practice provider, 364 patients had a multidrug-resistant urine E. coli isolate, and 89 patients had a multidrug-resistant K. pneumoniae isolate (Table). Detection of multidrug-resistance from urine isolates was associated with region for E. coli (p=0.0003) and K. pneumoniae (p=0.007). Greater proportions of patients with versus without multidrug-resistant urine isolates were identified in the Northeast and South for E. coli (14.6% vs 8.9% and 36.3% vs 33.0%, respectively) and K. pneumoniae (18.0% vs 10.2% and 41.6% vs 35.2%, respectively).
Table.
Patient-level characteristics of homebound older adults with dementia from whom a urine Escherichia coli or Klebsiella pneumoniae isolate was collected after enrollment in home-based primary care, 2014–2018.
| Patients with urine | Patients with urine | |||||
|---|---|---|---|---|---|---|
| Escherichia coli isolate | Klebsiella pneumoniae isolate | |||||
| Characteristica | Non-MDRb | MDRc | P | Non-MDR | MDR | P |
| n=2,791 | n=364 | Value | n=1,396 | n=89 | Value | |
| No. (%) | No. (%) | No. (%) | No. (%) | |||
| Age, years | 0.23 | 0.44 | ||||
| 65–74 | 545 (19.5) | 83 (22.8) | 327 (23.4) | 26 (29.2) | ||
| 75–84 | 894 (32.0) | 104 (28.6) | 501 (35.9) | 28 (31.5) | ||
| ≥85 | 1,352 (48.4) | 177 (48.6) | 568 (40.7) | 35 (39.3) | ||
| Sex | 0.07 | 0.44 | ||||
| Male | 2,579 (92.4) | 346 (95.1) | 1,327 (95.1) | 87 (97.8) | ||
| Female | 212 (7.6) | 18 (5.0) | 69 (4.9) | 2 (2.3) | ||
| Race | 0.46 | 0.06 | ||||
| White | 1,944 (69.7) | 255 (70.1) | 953 (68.3) | 52 (58.4) | ||
| Black | 612 (21.9) | 87 (23.9) | 338 (24.2) | 33 (37.1) | ||
| Other | 62 (2.2) | 6 (1.7) | 24 (1.7) | 1 (1.1) | ||
| Unknown | 173 (6.2) | 16 (4.4) | 81 (5.8) | 3 (3.4) | ||
| Ethnicity | 0.07 | 0.20 | ||||
| Non-Hispanic | 2,515 (90.1) | 339 (93.1) | 1,241 (88.9) | 83 (93.3) | ||
| Hispanic | 247 (8.9) | 22 (6.0) | 142 (10.2) | 5 (5.6) | ||
| Unknown | 29 (1.0) | 3 (0.8) | 13 (1.0) | 1 (1.1) | ||
| Comorbidities | ||||||
| Diabetes | 1,148 (41.1) | 158 (43.4) | 0.43 | 662 (47.4) | 41 (46.1) | 0.83 |
| Lung Disease | 890 (31.9) | 125 (34.3) | 0.37 | 434 (31.1) | 25 (28.1) | 0.64 |
| Vascular Disease | 590 (21.1) | 85 (23.4) | 0.34 | 330 (23.6) | 24 (27.0) | 0.52 |
| Heart Failure | 530 (19.0) | 78 (21.4) | 0.29 | 288 (20.6) | 23 (25.8) | 0.28 |
| BPHd | 524 (18.8) | 77 (22.2) | 0.29 | 251 (18.0) | 19 (21.4) | 0.40 |
| Prostate Cancer | 370 (13.3) | 44 (12.1) | 0.56 | 203 (14.5) | 8 (9.0) | 0.16 |
| Region | 0.0003 | 0.007 | ||||
| Northeast | 247 (8.9) | 53 (14.6) | 143 (10.2) | 16 (18.0) | ||
| Mid-Atlantic | 725 (26.0) | 80 (22.0) | 371 (26.6) | 25 (28.1) | ||
| South | 921 (33.0) | 132 (36.3) | 492 (35.2) | 37 (41.6) | ||
| Midwest | 496 (17.8) | 67 (18.4) | 238 (17.1) | 8 (9.0) | ||
| West | 402 (14.4) | 32 (8.8) | 152 (10.9) | 3 (3.8) | ||
Patient-level characteristics at the time of their first in-person home visit by a physician or advance practice provider
Patients without multidrug-resistance (non-MDR) detected from any urine isolate when evaluating all urine isolates collected after the date of the first in-person home visit by a physician or advance practice provider
Patients with multidrug-resistance (MDR) detected from at least 1 urine isolate when evaluating all urine isolates collected after the date of the first in-person home visit by a physician or advance practice provider
Benign prostatic hypertrophy
Discussion
Using a national sample of homebound older adults with dementia who were enrolled in HBPC, this work identified a high prevalence of antimicrobial nonsusceptibility among urine E. coli and K. pneumoniae isolates between 2014–2018. Among 3,913 urine E. coli isolates, annual prevalence of nonsusceptibility was greatest for ciprofloxacin, ranging from 18–23%, and multidrug-resistance was detected in 9–11% of isolates. In contrast, annual prevalence of nonsusceptibility among 1,736 urine K. pneumoniae isolates was greatest for ampicillin/sulbactam, ranging from 7–9%, and multidrug-resistance was detected in 5–6% of isolates. For both organisms, carbapenem-resistance, as measured by meropenem nonsusceptibility, was rare (0–1%), and detection of multidrug-resistance varied by region.
This study suggests that the prevalence of multidrug-resistance among urine E. coli and K. pneumoniae isolates in HBPC programs is comparable to estimates from nursing homes. Among 2,539 E. coli UTIs and 776 K. pneumoniae/oxytoca UTIs reported from U.S. nursing homes between 2013–2017, 9.4% and 5.9% were multidrug-resistant.[2] It is important to note that patients from these nursing homes had signs and symptoms suggestive of UTI, whereas clinical features of UTI among patients in the current study were not assessed. Patterns of antimicrobial resistance from the current work are also similar to those reported from other nursing home studies.[7,8]
Notably, guidelines for the evaluation and management of UTI in home care settings are lacking. Existing recommendations do not address the unique challenges that clinicians face in diagnosing and treating infection among homebound patients who receive home care.[9] The current study identified regional differences in the detection of multidrug-resistance among urine isolates. Many factors likely contributed to this finding, such as geographic variation in healthcare utilization, host factors, and antimicrobial use in HBPC.[5] Collectively, these data support the role for local urine antibiograms that include aggregate nonsusceptibility data among programs to inform empiric antibiotic use in home care settings like HBPC.[10]
Study limitations include a lack of data regarding the indication for urine specimen collection, potential contamination of urine specimens, and susceptibility to other commonly prescribed antibiotics. Urine specimens collected in non-VA locations and differences between VA microbiology laboratories were not evaluated. Finally, the current work was limited to Veterans, who are predominantly male, and involved homebound patients who received interdisciplinary, longitudinal HBPC.[4,5] These results may lack generalizability to non-Veterans or to homebound patients in other home care settings who receive problem-focused, episodic care.[4] Nevertheless, this work shows a high prevalence of antimicrobial resistance among urine E. coli and K. pneumoniae that limit the effectiveness of empiric treatment options for UTI in HBPC. This study addresses a gap in the scientific literature, which lacks surveillance data for antimicrobial resistance among uropathogens in home care, and supports the rationale for further investigation of multidrug-resistant organisms in home care settings.
Supplementary Material
Acknowledgements
This work was supported with resources from and the use of facilities at the Hospital Epidemiology and Infection Prevention Program at the Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
Financial support.
Dr. Datta was supported by a career development award from the National Institute of Aging (NIA) of the National Institutes of Health (NIH) under Award Number U54AG063546, which funds the NIA Imbedded Pragmatic Alzheimer’s Disease and AD-Related Dementias Clinical Trials Collaboratory (NIA IMPACT Collaboratory). This publication was made possible by CTSA Grant Award UL1 TR001863 from the National Center for Advancing Translational Science (NCATS), a component of the NIH, the Operations Core of the Claude D. Pepper Older Americans Independence Center at Yale School of Medicine (P30AG021342), the Yale Physician-Scientist Development Award, and the Society for Healthcare Epidemiology of America Epidemiology Competition Award. Dr. Zullo was supported in part by NIA grants R21AG061632, R01AG065722, RF1AG061221, and R24AG064025. Dr. Cohen was supported in part by NIA grant K76AG059987.
Role of the funding source.
The funders had no role in the study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
Footnotes
Disclaimer. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs.
Prior Presentations: None
Potential conflicts of interest. All authors report no conflicts of interest relevant to this article.
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