Abstract
The spread of multidrug-resistant organisms (MDROs) is a global concern, and much about transmission in healthcare systems remains unknown. To reduce hospital stays, nursing facilities (NFs) have increasingly assumed care of post–acute populations. We estimate the prevalence of MDRO colonization in NF patients on enrollment and discharge to community settings, risk factors for colonization, and rates of acquiring MDROs during the stay.
We conducted a prospective, longitudinal cohort study of newly admitted patients in 6 NFs in southeast Michigan using active microbial surveillance of multiple anatomic sites sampled at enrollment, days 14 and 30, and monthly thereafter for up to 6 months.
We enrolled 651 patients and collected 7526 samples over 1629 visits, with an average of 29 days of follow-up per participant. Nearly all participants were admitted for post–acute care (95%). More than half (56.8%) were colonized with MDROs at enrollment: methicillin-resistant Staphylococcus aureus (MRSA), 16.1%; vancomycin-resistant enterococci (VRE), 33.2%; and resistant gram-negative bacilli (R-GNB), 32.0%. Risk factors for colonization at enrollment included prolonged hospitalization (>14 days), functional disability, antibiotic use, or device use. Rates per 1000 patient-days of acquiring a new MDRO were MRSA, 3.4; VRE, 8.2; and R-GNB, 13.6. MDRO colonization at discharge was similar to that at enrollment (56.4%): MRSA, 18.4%; VRE, 30.3%; and R-GNB, 33.6%.
Short-stay NF patients exhibit a high prevalence of MDROs near the time of admission, as well as at discharge, and may serve as a reservoir for spread in other healthcare settings. Future interventions to reduce MDROs should specifically target this population.
An estimated 1.7 million older Americans received post–acute care during 2.4 million Medicare-covered nursing facility (NF) stays in 2015 [1]. In 2016, one-fifth of acute hospital stays covered by Medicare resulted in discharge to an NF. As a result of an aging demographic, an increased reliance on post–acute care, and a decreasing length of hospital stay, the healthcare system in the United States has seen a tremendous increase in the volume of people entering and exiting NFs [2, 3].
Multidrug-resistant organisms (MDROs) are common in both hospitals and in NFs [4–10]. Even when not actively causing infection, MDRO colonization has the potential for transmission from patient to patient and increases the risk of clinically significant infection among those colonized [7–10]. However, the MDRO colonization status is often unknown and routine implementation of MDRO surveillance and isolation procedures is challenging and costly [11]. With the transfer of increasing numbers of patients colonized with MDROs between hospitals and NFs, current infection prevention measures may be inadequate to prevent MDRO transmission between these settings [12–16].
Nearly 25% of short-stay post–acute care patients return to the hospital [17]. How the rapid cycling of high-risk patients between the hospital and NF influences the dynamics of MDRO colonization and transmission is unknown. We conducted a prospective cohort study among patients recently admitted to 1 of 6 NFs in southeast Michigan to estimate the dynamics of MDRO colonization during their stay. We also identified the risk factors for MDRO colonization upon enrollment and discharge, and estimated the duration of MDRO colonization.
METHODS
Study Population and Design
We conducted a prospective cohort study of recently admitted NF patients between November 2013 and May 2016. Patients from 6 NFs in southeast Michigan were enrolled within 14 days of NF admission and followed for up to 6 months. We evaluated MDRO colonization prevalence upon enrollment, any new acquisitions and spontaneous losses of MDROs during their stay, and MDRO prevalence on discharge. We confirmed dates and discharge destination in the minimum data set [18]. Patients receiving end-of-life care were excluded. A written informed consent by the patient or his/her proxy was required. This research was approved by the University of Michigan Institutional Review Board.
Clinical Data Collection
Demographic data (including age, sex, race) and risk factors for MDRO colonization (including functional disability, use of indwelling devices, presence of comorbidities, prior antibiotic use, and length of hospitalization) were collected by trained research personnel for each patient. Functional disability was measured using the Physical Self-Maintenance Scale (PSMS), which ranges from 6 (full independence) to 30 (full dependence) in 6 categories of self-maintenance (bathing, dressing, feeding, ambulation, grooming, and toileting [19, 20]). We also tested specific disabilities in dressing (at least moderate assistance), bathing (unable to independently bathe more than hands and face), toileting (soiling or wetting more than once a week), or grooming (regularly needs at least moderate assistance or supervision). Device use was defined as having a feeding tube or indwelling urinary catheter in place at the time of enrollment. Prolonged hospital stay prior to the post–acute care stay was ≥14 days. The Charlson comorbidity score [21] was calculated, and high comorbidity was defined as a score of ≥3. Prior documented antibiotic use was defined as any antibiotic use within the past 30 days, including prior to NF admission.
Microbiologic Methods
Microbiological samples were collected from patients’ hands, nares, oropharynx, enteral feeding tube insertion site, suprapubic catheter site, groin, perianal area, and wounds to assess MDRO colonization on the day of enrollment, day 14, day 30, and then monthly for up to 6 months. Samples were collected using sterile swabs in transport media (BactiSwab, Remel, Lenexa, Kansas) and cultured on mannitol salt agar, MacConkey agar, and bile-esculin plates with 6 μg/mL vancomycin. Hand swabs were enriched overnight in brain heart infusion broth at 36°C before culturing. Staphylococcus aureus, vancomycin-resistant enterococci (VRE), and gram-negative bacilli (GNB) were identified using standard microbiologic testing described previously [12]. Antimicrobial susceptibility testing for S. aureus and GNB isolates was performed by disk diffusion per Clinical and Laboratory Standards Institute guidelines, including screening for extended-spectrum β-lactamases (ESBLs) [22]. For S. aureus, methicillin resistance was determined by disk diffusion method using 30-μg cefoxitin disks. For GNB, the following antibiotics were tested: ceftazidime (30 μg), ceftazidime/clavulanic acid (30/10 μg), ciprofloxacin (5 μg), and imipenem (10 μg); resistance to 1 or more these was considered resistant GNB (R-GNB). We identified the species of VRE (ie, Enterococcus faecalis, Enterococcus faecium, other enterococci) using the multiplex polymerase chain reaction assay [23]. Results of microbiological testing were not disclosed to NF staff or administrators during the study period.
Statistical Analysis
We estimated the prevalence of MDRO colonization overall and by specific MDRO at enrollment and discharge by anatomic site and across all anatomic sites sampled for each patient at each visit. We also stratified our analyses by additional clinical characteristics. First, MDRO prevalence was estimated among patients admitted to the facility following a prolonged (>14 days) vs short hospital stay. Second, we compared MDRO colonization between patients discharged to the community vs back to an acute care facility.
To analyze MDROs present on enrollment, we used the entire sample of patients. To estimate both new MDRO acquisition during the NF stay and colonization status prior to discharge, we limited the analysis to patients with >1 sampling event. For the acquisition analysis by MDRO, we further excluded those colonized on enrollment with that MDRO. For the acquisition analysis of any MDRO, we excluded those colonized on enrollment with all 3 MDROs. The acquisition rate was defined as new acquisition events per 1000 patient-days.
We first tested for risk factors of VRE, MRSA, or R-GNB colonization on enrollment and discharge, using logistic regression. Significant risk factors (P < .05) were then included in multivariate regression models. We used Poisson regression to ascertain new acquisition. Having a risk factor for MDRO colonization was strongly correlated with longer exposure in the NF (due to longer antibiotic and rehabilitation courses). Several risk factors were collinear with longer NF stays and therefore not further tested in acquisition models. Recruiting subjects strictly within 3 days of admission to nursing facilities (as per hospital surveillance practices) was impractical due to (1) our frail study population, who often required communication with their proxy, which can delay obtaining consent to participate, and (2) the study requiring frequent travel by study team across a large metropolitan area to 6 separate facilities. We thus performed sensitivity analyses to understand the impact of enrolling new participants beyond 3 days of their admission. First, we analyzed whether the number of days between each patient’s admission and enrollment sampling affected their MDRO status at admission. Second, we assessed whether the number of days between the last sampling and each patient’s discharge affected their MDRO status in the discharge analysis. All regression analyses were clustered by NF. Data were analyzed using Stata software version 13 (StataCorp, College Station, Texas).
RESULTS
Study Group Characteristics
The 6 participating NFs were privately owned and ranged in size from 72 to 143 beds (average, 105 beds), with an average of 28 beds (range, 8–54 beds) occupied by short-stay patients (expected stay ≤90 days) (Supplementary Table 1). The Average Nursing Home Compare 5-star rating (Centers for Medicare and Medicaid Services quality measure [24]) was 3.7 (range, 2–5). All 6 NFs admit patients from multiple hospitals (range, 11–19 hospitals). Average length of stay ranged from 33.5 to 60.2 days (Supplementary Table 1).
We enrolled 651 (47%) recently admitted patients of 1384 potentially eligible patients (Figure 1). The main reasons for nonenrollment were patient refusal (n = 458 [31.9%]), family or legal guardian refusal (n = 172 [12.0%]), and inability to obtain consent within 14 days of admission (n = 84 [5.9%]). Most patients (78%) were enrolled within 7 days of NF admission (mean, 5.6 days; standard deviation [SD], 3.0 days; range, 1–14 days), and nearly all (95%) were admitted directly from a hospital. Four patients were admitted from home (0.6%), 28 were admitted from another nursing or rehabilitation facility (4.3%), and 1 was discharged from an inpatient hospice due to improved prognosis. Most patients were anticipated to have a short stay at the NF (602/651 [92.5%]) at the time of admission. Of the 651 patients enrolled, 195 were discharged after the enrollment sampling. Patients were followed for 1629 total visits. In all, 7526 microbiological samples were collected from various anatomic sites. The average length of follow-up time was 29 days (SD, 44.1 days).
Patient enrollment. Flow of data from eligible to final enrolled analytic sample. Among the 456 patients with follow-up, 446 were seen on day 14, 248 on day 30, 96 on day 60, 67 on day 90, 46 on day 120, 39 on day 150, and 36 on day 180. Total days of follow-up for the sample of 456 patients was 18717 days.
The average age of patients was 74.7 years (SD, 12.2 years); 42.2% were male and 62.4% were white (Table 1). The average PSMS score at enrollment was 14.5 (SD, 4.6; range, 6–30), and 75.0% had at least 1 disability: ambulation (63.4%), dressing (60.2%), bathing (53.0%), toileting (32.9%), grooming (28.1%), or feeding (6.9%) (Table 1). One-third of patients had incontinence episodes at least once a week. One-tenth (10.3%) of patients had an indwelling urinary catheter or feeding tube at enrollment; 7.1% had a urinary catheter, 1.8% had a feeding tube, and 0.9% had both. A majority (61.7%) had a history of antibiotic use within 30 days of enrollment. The most commonly prescribed antibiotics were cephalosporins, quinolones, and glycopeptides (Supplementary Table 2). Nearly half (44.7%) had ≥3 chronic conditions [21]. Approximately one-tenth (9.3%) of patients were admitted following a hospital stay of ≥14 days.
Characteristics of Post–acute Care Nursing Facility Patients on Enrollment
| Patient Characteristics | Colonized With Any MDRO (n = 370) | Not Colonized With an MDRO (n = 281) | All Patients (n = 651) | P Value |
|---|---|---|---|---|
| Age, y, mean (SD) | 74.7 (11.8) | 74.6 (12.7) | 74.7 (12.2) | .8950 |
| Male sex, No. (%) | 163 (44.1) | 112 (40.0) | 275 (42.2) | .283 |
| Non-Hispanic white, No. (%) | 230 (62.2) | 176 (62.6) | 406 (62.4) | .902 |
| Device use | 50 (13.5) | 17 (6.1) | 67 (10.3) | .002 |
| Antibiotic use in past 30 d | 248 (68.3) | 144 (52.9) | 392 (61.7) | <.001 |
| History of MRSA (n = 642)a | 21 (5.8) | 7 (2.5) | 28 (4.4) | .047 |
| History of VRE (n = 639)a | 14 (3.9) | 0 (0.0) | 14 (2.2) | .001 |
| History of R-GNB (n = 626)a | 30 (8.6) | 7 (2.5) | 37 (5.9) | .001 |
| Charlson comorbidity score >2 | 171 (46.2) | 120 (42.7) | 291 (44.7) | .372 |
| Length of preadmission hospitalization, No. (%) | ||||
| 0–3 d | 87 (23.7) | 86 (30.7) | 173 (26.7) | <.001 |
| 4–7 d | 144 (39.2) | 123 (43.9) | 267 (41.3) | |
| 8–14 d | 87 (23.7) | 60 (21.4) | 147 (22.7) | |
| >14 d | 49 (13.4) | 11 (3.9) | 60 (9.3) | |
| Functional disabilitiesb on enrollment, No. (%) | ||||
| Ambulation | 249 (67.3) | 164 (58.4) | 413 (63.4) | .019 |
| Dressing | 239 (64.6) | 153 (54.5) | 392 (60.2) | .009 |
| Bathing | 216 (58.4) | 129 (45.9) | 345 (53.0) | .002 |
| Toileting | 144 (38.9) | 70 (24.9) | 214 (32.9) | <.001 |
| Grooming | 118 (31.9) | 65 (23.1) | 183 (28.1) | .014 |
| Feeding | 32 (8.7) | 13 (4.6) | 45 (6.9) | .045 |
| Patient Characteristics | Colonized With Any MDRO (n = 370) | Not Colonized With an MDRO (n = 281) | All Patients (n = 651) | P Value |
|---|---|---|---|---|
| Age, y, mean (SD) | 74.7 (11.8) | 74.6 (12.7) | 74.7 (12.2) | .8950 |
| Male sex, No. (%) | 163 (44.1) | 112 (40.0) | 275 (42.2) | .283 |
| Non-Hispanic white, No. (%) | 230 (62.2) | 176 (62.6) | 406 (62.4) | .902 |
| Device use | 50 (13.5) | 17 (6.1) | 67 (10.3) | .002 |
| Antibiotic use in past 30 d | 248 (68.3) | 144 (52.9) | 392 (61.7) | <.001 |
| History of MRSA (n = 642)a | 21 (5.8) | 7 (2.5) | 28 (4.4) | .047 |
| History of VRE (n = 639)a | 14 (3.9) | 0 (0.0) | 14 (2.2) | .001 |
| History of R-GNB (n = 626)a | 30 (8.6) | 7 (2.5) | 37 (5.9) | .001 |
| Charlson comorbidity score >2 | 171 (46.2) | 120 (42.7) | 291 (44.7) | .372 |
| Length of preadmission hospitalization, No. (%) | ||||
| 0–3 d | 87 (23.7) | 86 (30.7) | 173 (26.7) | <.001 |
| 4–7 d | 144 (39.2) | 123 (43.9) | 267 (41.3) | |
| 8–14 d | 87 (23.7) | 60 (21.4) | 147 (22.7) | |
| >14 d | 49 (13.4) | 11 (3.9) | 60 (9.3) | |
| Functional disabilitiesb on enrollment, No. (%) | ||||
| Ambulation | 249 (67.3) | 164 (58.4) | 413 (63.4) | .019 |
| Dressing | 239 (64.6) | 153 (54.5) | 392 (60.2) | .009 |
| Bathing | 216 (58.4) | 129 (45.9) | 345 (53.0) | .002 |
| Toileting | 144 (38.9) | 70 (24.9) | 214 (32.9) | <.001 |
| Grooming | 118 (31.9) | 65 (23.1) | 183 (28.1) | .014 |
| Feeding | 32 (8.7) | 13 (4.6) | 45 (6.9) | .045 |
Abbreviations: MDRO, multidrug-resistant organism; MRSA, methicillin-resistant Staphylococcus aureus; R-GNB, resistant gram-negative bacilli; SD, standard deviation; VRE, vancomycin-resistant enterococci.
aDue to data missing on admission, the following total sample sizes apply: history of MRSA, n = 642; history of VRE, n = 639; history of R-GNB, n = 626.
bFunctional disabilities are defined as (1) ambulation: ambulates with assistance of another person, uses a wheelchair with help getting in and out, or cannot move without help; (2) dressing: requires at least moderate assistance with dressing; (3) bathing: unable to independently bathe more than hands and face; (4) toileting: soiling or wetting more than once a week; (5) grooming: regularly needs at least moderate assistance or supervision in grooming; (6) feeding: eats with moderate assistance and is untidy.
Characteristics of Post–acute Care Nursing Facility Patients on Enrollment
| Patient Characteristics | Colonized With Any MDRO (n = 370) | Not Colonized With an MDRO (n = 281) | All Patients (n = 651) | P Value |
|---|---|---|---|---|
| Age, y, mean (SD) | 74.7 (11.8) | 74.6 (12.7) | 74.7 (12.2) | .8950 |
| Male sex, No. (%) | 163 (44.1) | 112 (40.0) | 275 (42.2) | .283 |
| Non-Hispanic white, No. (%) | 230 (62.2) | 176 (62.6) | 406 (62.4) | .902 |
| Device use | 50 (13.5) | 17 (6.1) | 67 (10.3) | .002 |
| Antibiotic use in past 30 d | 248 (68.3) | 144 (52.9) | 392 (61.7) | <.001 |
| History of MRSA (n = 642)a | 21 (5.8) | 7 (2.5) | 28 (4.4) | .047 |
| History of VRE (n = 639)a | 14 (3.9) | 0 (0.0) | 14 (2.2) | .001 |
| History of R-GNB (n = 626)a | 30 (8.6) | 7 (2.5) | 37 (5.9) | .001 |
| Charlson comorbidity score >2 | 171 (46.2) | 120 (42.7) | 291 (44.7) | .372 |
| Length of preadmission hospitalization, No. (%) | ||||
| 0–3 d | 87 (23.7) | 86 (30.7) | 173 (26.7) | <.001 |
| 4–7 d | 144 (39.2) | 123 (43.9) | 267 (41.3) | |
| 8–14 d | 87 (23.7) | 60 (21.4) | 147 (22.7) | |
| >14 d | 49 (13.4) | 11 (3.9) | 60 (9.3) | |
| Functional disabilitiesb on enrollment, No. (%) | ||||
| Ambulation | 249 (67.3) | 164 (58.4) | 413 (63.4) | .019 |
| Dressing | 239 (64.6) | 153 (54.5) | 392 (60.2) | .009 |
| Bathing | 216 (58.4) | 129 (45.9) | 345 (53.0) | .002 |
| Toileting | 144 (38.9) | 70 (24.9) | 214 (32.9) | <.001 |
| Grooming | 118 (31.9) | 65 (23.1) | 183 (28.1) | .014 |
| Feeding | 32 (8.7) | 13 (4.6) | 45 (6.9) | .045 |
| Patient Characteristics | Colonized With Any MDRO (n = 370) | Not Colonized With an MDRO (n = 281) | All Patients (n = 651) | P Value |
|---|---|---|---|---|
| Age, y, mean (SD) | 74.7 (11.8) | 74.6 (12.7) | 74.7 (12.2) | .8950 |
| Male sex, No. (%) | 163 (44.1) | 112 (40.0) | 275 (42.2) | .283 |
| Non-Hispanic white, No. (%) | 230 (62.2) | 176 (62.6) | 406 (62.4) | .902 |
| Device use | 50 (13.5) | 17 (6.1) | 67 (10.3) | .002 |
| Antibiotic use in past 30 d | 248 (68.3) | 144 (52.9) | 392 (61.7) | <.001 |
| History of MRSA (n = 642)a | 21 (5.8) | 7 (2.5) | 28 (4.4) | .047 |
| History of VRE (n = 639)a | 14 (3.9) | 0 (0.0) | 14 (2.2) | .001 |
| History of R-GNB (n = 626)a | 30 (8.6) | 7 (2.5) | 37 (5.9) | .001 |
| Charlson comorbidity score >2 | 171 (46.2) | 120 (42.7) | 291 (44.7) | .372 |
| Length of preadmission hospitalization, No. (%) | ||||
| 0–3 d | 87 (23.7) | 86 (30.7) | 173 (26.7) | <.001 |
| 4–7 d | 144 (39.2) | 123 (43.9) | 267 (41.3) | |
| 8–14 d | 87 (23.7) | 60 (21.4) | 147 (22.7) | |
| >14 d | 49 (13.4) | 11 (3.9) | 60 (9.3) | |
| Functional disabilitiesb on enrollment, No. (%) | ||||
| Ambulation | 249 (67.3) | 164 (58.4) | 413 (63.4) | .019 |
| Dressing | 239 (64.6) | 153 (54.5) | 392 (60.2) | .009 |
| Bathing | 216 (58.4) | 129 (45.9) | 345 (53.0) | .002 |
| Toileting | 144 (38.9) | 70 (24.9) | 214 (32.9) | <.001 |
| Grooming | 118 (31.9) | 65 (23.1) | 183 (28.1) | .014 |
| Feeding | 32 (8.7) | 13 (4.6) | 45 (6.9) | .045 |
Abbreviations: MDRO, multidrug-resistant organism; MRSA, methicillin-resistant Staphylococcus aureus; R-GNB, resistant gram-negative bacilli; SD, standard deviation; VRE, vancomycin-resistant enterococci.
aDue to data missing on admission, the following total sample sizes apply: history of MRSA, n = 642; history of VRE, n = 639; history of R-GNB, n = 626.
bFunctional disabilities are defined as (1) ambulation: ambulates with assistance of another person, uses a wheelchair with help getting in and out, or cannot move without help; (2) dressing: requires at least moderate assistance with dressing; (3) bathing: unable to independently bathe more than hands and face; (4) toileting: soiling or wetting more than once a week; (5) grooming: regularly needs at least moderate assistance or supervision in grooming; (6) feeding: eats with moderate assistance and is untidy.
MDRO Colonization at Enrollment
More than half of the patients (56.8%) were colonized with an MDRO at enrollment: 16.1% with MRSA, 33.2% with VRE (57% E. faecium, 36% E. faecalis, and 7% other), and 32.0% with R-GNB (Figure 2). The most common anatomic sites for MRSA colonization were nares (10.3%) and hands (10.0%); perianal area (30.1%) and hands (16%) for VRE; and perianal (24.8%) and groin (15.4%) for R-GNB (Figure 3). Those with prolonged hospitalization (odds ratio [OR], 3.24; 95% confidence interval [CI], 1.99–5.27; P < .001), functional disability (OR, 1.82; 95% CI, 1.46–2.27; P < .001), prior use of antibiotics (OR, 1.81; 95% CI, 1.40–2.34; P < .001), or indwelling device (OR, 1.69; 95% CI, 1.45–1.97; P < .001) were more likely to be colonized at enrollment. In fact, nearly 82% (49/60) of patients with prolonged hospitalizations were colonized with MDRO. Most patient characteristics did not differ when analyzed by number of days from NF admission to study enrollment except for age and functional disability. A greater number of days to enrollment did not increase the likelihood of detecting an MDRO (Supplementary Table 3).
Colonization with multidrug-resistant organisms on enrollment and discharge. A, Bars indicate proportion of patients colonized at enrollment and discharge among all 651 patients enrolled in the study. For those who were discharged after only 1 visit, the enrollment visit is considered in both the enrollment and discharge samples. The capped error bars indicate 95% confidence interval (CI). B, Bars and 95% CI error bars indicate proportion of patients colonized at enrollment and discharge, but among only those patients with >1 visit, allowing distinct admission and discharge samples (n = 456). Abbreviations: MDRO, multidrug-resistant organism; MRSA, methicillin-resistant Staphylococcus aureus; R-GNB, resistant gram-negative bacilli; VRE, vancomycin-resistant enterococci.
Colonization at sampled body sites on enrollment. Circles representing each body site are sized and shaded proportionately to colonization prevalence at that body site, using a multiplier of 1.5 to determine diameter and color saturation.
New Acquisition and Spontaneous Loss of MDROs
To estimate new MDRO acquisition, we limited the analysis to the 456 patients with 1 or more follow-up sampling visits. Of these, 21 patients were colonized with all 3 MDROs at enrollment and thus not considered at risk of acquiring a new MDRO resulting in 435 patients (with 1358 visits) at risk of acquiring 1 or more MDROs. Patients frequently acquired a new MDRO: MRSA (12.7% of 386 at-risk patients), VRE (25.7% of 296 at-risk patients), and R-GNB (35.8% of 296 at-risk patients), with an average time to new acquisition being 24.6 days (range, 10–176 days). The incidence rate per 1000 patient-days was 3.4, 8.2, and 13.6 for MRSA, VRE, and R-GNB, respectively (Supplementary Table 4).
New MDRO acquisition in the study population was balanced by spontaneous decolonization. Overall, 68 of 456 (14.9%) patients with multiple visits were not colonized with an MDRO on enrollment, then acquired and were discharged with a new MDRO. By contrast, 17.3% of patients were colonized at enrollment but spontaneously decolonized by discharge (Figure 4). Thus, new acquisition and spontaneous decolonization was a dynamic process for all MDROs. The average time until detected clearance of MRSA, VRE, and R-GNB was 27.6 days (SD, 33.0 days), 39.9 days (SD, 45.5 days), and 28.6 days (SD, 36.3 days), respectively.
Longitudinal changes in multidrug-resistant organism colonization status. Each “n” indicates the number of patients with a given colonization status on study enrollment. Arrow bars indicate patients’ colonization status change from admission to discharge. For example, 70 patients who had multiple visits were colonized with methicillin-resistant Staphylococcus aureus at enrollment. Of those, 64.3% (n = 45) remained colonized at discharge, represented by the top horizontal arrow. The remaining 37.5% (n = 25) spontaneously decolonized and clear on discharge, represented by the arrow originating in the top left corner (colonized, enrollment) and terminating in the bottom right (not colonized, discharge). Abbreviations: MDRO, multidrug-resistant organism; MRSA, methicillin-resistant Staphylococcus aureus; R-GNB, resistant gram-negative bacilli; VRE, vancomycin-resistant enterococci.
MDRO Colonization at Discharge
For the discharge analyses, we limited the analysis to the 456 patients with >1 sampling visit. Of these, 328 (71.9%) were discharged to the community and 86 (18.9%) were readmitted to the hospital or another institution. Overall, more than half of the patients (56.4%) were colonized with 1 or more MDROs at discharge. More than half (52.4%) of patients discharged to the community and 70.9% of those readmitted to the hospital were colonized with an MDRO. This finding did not differ by length of stay. Of 456 patients with >1 sampling visit, 379 had NF stays of ≤90 days. Of these, 57.8% were colonized with an MDRO at enrollment and 54.9% were colonized at discharge.
The most common MDRO colonization at discharge was R-GNB (33.6%), followed by VRE (30.3%) and MRSA (18.4%) (Figure 2). Using multivariate logistic regression, antibiotic use (OR, 1.50; 95% CI, 1.23–1.83; P < .001), device use (OR, 3.27; 95% CI, 1.46–7.28, P = .004), and prolonged hospital stay of ≥14 days prior to NF admission (OR, 2.36; 95% CI, 1.27–4.36; P = .006) were significant predictors of MDRO colonization at discharge (Supplementary Table 5). Among patients discharged from the NF within 2 days of their last study visit, colonization on the last visit (53%) did not differ significantly from the rest of the sample (57%).
We found that 21.4% of patients (139/651) were colonized with imipenem-resistant GNB at enrollment and 31.6% (144/456) newly acquired imipenem-resistant GNB after enrollment. Of these, 18.9% and 27.9% were colonized with imipenem-resistant Enterobacteriaceae at enrollment and during follow-up, respectively. Twenty-nine (4.5%) patients screened positive for ESBL-producing Enterobacteriaceae at enrollment, and 40 (8.8%) during follow-up (Supplementary Table 6).
Ninety-nine patients had no MDRO on enrollment, during follow-up, or at discharge. These patients had fewer risk factors than those who were colonized at some point during the study. Specifically, this group of patients had significantly fewer prolonged hospitalizations and lower antibiotic use.
DISCUSSION
In this prospective, longitudinal cohort study of 651 patients newly admitted to 6 NFs in southeast Michigan, nearly all were admitted for short-stay post–acute care. At enrollment, 56.8% were colonized with at least 1 MDRO and new acquisition was frequent. Although there was a spontaneous loss of MDRO colonization among some participants, the loss was offset by new MDRO acquisitions. Our study, for the first time, shows that nearly half of the participants were discharged back to the community with an MDRO. Our results suggest that NF patients transitioning to the community can potentially transmit MDROs to community healthcare settings such as ambulatory care medical clinics, dialysis, rehabilitation centers, and procedure units.
Prolonged hospitalization (≥14 days) was strongly associated with MDRO colonization at NF enrollment; also associated were recent antibiotic use, presence of indwelling devices, and functional impairment [25–27]. Patients with these risk factors should be appropriate targets for interventions. MDRO colonization increases the risk of MDRO infection [4–6, 15, 16], but is typically amenable to interventions [28–34]. Current standard interventions for MDRO reduction (eg, curbing antibiotic use and discontinuing indwelling devices) and patients’ improving health status throughout the post–acute care stay have been thought to be sufficient reasons to presume that MDROs would decolonize by the time of discharge to the community. However, our study shows that patients are equally as likely to acquire an MDRO as to spontaneously decolonize from one during their post–acute care stay. Furthermore, our study reveals a greater risk of acquiring R-GNB, followed by VRE and MRSA, suggesting pathogen-level differences in new acquisition.
Emerging literature underscores the potential for transmission of an MDRO between institutional settings [35]. Our data support that hypothesis: Participants readmitted back to a hospital had a higher MDRO prevalence than those returning home. Described as a “revolving door,” about one-fifth of post–acute care patients will return back to a hospital within 30 days of admission to an NF, sepsis and other infections being the most common reason [17, 36]. Therefore, interventions are urgently needed to significantly reduce and eliminate MDROs before and after going through the revolving door in order to break the chain of transmission. Our data suggest that such an intervention would need to be rapidly implemented on admission to the NF and should be targeted at patients with prolonged hospitalization. Such interventions, if effective, can have the upstream effect of reducing transmission to hospitals and downstream impact of reducing MDROs upon discharge to the community. Furthermore, predischarge surveillance should be considered as an important outcome to evaluate the effectiveness of any intervention.
Our study has several limitations. First, as all participating NFs were located in metropolitan Detroit; the results may not be generalizable to other regions of the country. However, epidemiological investigations in NFs across the nation have also shown a high prevalence and new acquisition of MDROs [7, 8, 14–16]. Second, as none of these facilities are physically connected to a hospital and because informed consent was required, our study protocol permitted us to obtain enrollment and discharge samples for a period longer than the standard 3-day window required in acute care MDRO research. Results of sensitivity testing of samples taken later in the enrollment window and earlier within the discharge window suggest that a 1-week window is an acceptable proxy for a patient’s true admission and discharge MDRO status, and a 2-week window is likely adequate. We believe that these results have substantial methodologic implications for future prospective longitudinal surveillance studies in these settings.
We note several strengths. First, this is one of the largest microbial surveillance studies of recently discharged post–acute care patients who are in a facility for brief periods of time before being discharged to the community. Second, we made multiple visits to patients shortly after admission, which helped us to understand trajectories and colonization dynamics at critical points of the patients’ stay. Third, we swabbed multiple anatomic sites which, coupled with extensive clinical metadata collected by trained research personnel, provided a unique comprehensive picture of patient colonization with MDROs.
In summary, MDRO colonization at or near the time of NF admission and new acquisition during their stay results in high rates of MDRO colonization among those returning to the community, and even higher rates among those requiring hospitalization. Patients with long prior hospitalizations and other risk factors are more likely to be colonized with MDROs, suggesting that subpopulations of patients who are at risk of infection and rehospitalization with MDROs should be targets for aggressive MDRO preventive efforts.
Supplementary Data
Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.
Notes
Author contributions. L. Mody, L. Min, B. F., S. B., S. M., and B. L. designed the study. S. M., B. L., and K. G. collected data. K. G. and M. C. conducted microbiological testing. J. M. and L. Min assembled and analyzed data. L. Mody, L. Min, B. F., S. B., J. M., and C. A. interpreted analyses and wrote the manuscript. All authors read and provided feedback to the manuscript, and approved the submitted version. L. Mody, M. C., J. M. and L. Min had full access to all data and had final responsibility for the decision to submit for publication.
Acknowledgments. We thank the patients and their families who participated in this study.
Financial support. This work was supported by the National Institutes of Health (grant numbers RO1 AG041780 to L. Mody, M. C., and L. Min; K24 AG050685 to L. Mody); Pepper Center (pilot grant number AG024824 to M. C.); the Michigan Institute for Clinical and Health Research (grant number UL1TR002240 to L. Mody and M. C.); and the National Institute on Aging (grant number P30 AG024824 to L. Mody). L. Mody and L. Min are also supported by the Geriatrics Research, Education and Clinical Centers, Veterans Affairs Ann Arbor Healthcare System.
Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
