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Molecular Epidemiology and Risk Factors for Extended-Spectrum β-Lactamase–Producing Enterobacterales in Long-Term Care Residents

Open AccessPublished:July 20, 2021DOI:https://doi.org/10.1016/j.jamda.2021.06.030

      Abstract

      Objectives

      We aimed to assess the burden of extended-spectrum β-lactamase (ESBL)-producing Enterobacterales in Swiss long-term care facilities (LTCFs) to describe the molecular epidemiology, describe the intrainstitutional and regional clusters of resistant pathogens, and identify independent institution- and resident-level factors associated with colonization.

      Design

      Cross-sectional study.

      Setting and Participants

      From August to October 2019, we performed a point prevalence study among residents from 16 LTCFs in Western and Eastern Switzerland (8 per region).

      Methods

      Residents underwent screening for ESBL-producing Enterobacterales (ESBL-E); whole-genome sequencing (WGS) was performed. We gathered institution-level (eg, number of beds, staff-resident ratio, alcoholic hand rub consumption) and resident-level [eg, anthropometric data, time in facility, dependency, health care exposure, antibiotic treatment, proton-pump inhibitor (PPI) use] characteristics. Factors associated with colonization were identified using a generalized linear model.

      Results

      Among 1185 eligible residents, 606 (51%) consented to the study. ESBL-E prevalence was 11.6% (70/606), ranging from 1.9% to 33.3% between institutions, with a median of 12.5% in the West and 6.9% in the East (P = .03). Among 59 Escherichia coli (from 58 residents), multilocus sequence type (ST) 131 was most common (n = 43/59, 73%), predominantly its subclone H30R1 (n = 37/43, 86%). WGS data identified multiple intrainstitutional and regional clusters. Independent risk factors for ESBL carriage were previous ESBL colonization [adjusted odds ratio (aOR) 23.5, 95% confidence interval (CI) 6.6-83.8, P < .001), male gender (aOR 2.6, 95% CI 1.5-4.6, P = .002), and use of PPIs (aOR 2.2, 95% CI 1.2-3.8, P = .01).

      Conclusions and Implications

      Overall ESBL-E prevalence in Swiss LTCF residents is low. Yet, we identified several clusters of residents with identical pathogens within the same institution. This implies that particularly affected institutions might benefit from targeted infection control interventions. PPI use was the only modifiable factor associated with carriage of ESBL producers. This study adds to the growing list of adverse outcomes associated with PPIs, calling for action to restrict their use in the long-term care setting.

      Keywords

      Residents of long-term care facilities (LTCFs) are at particular risk of being colonized and developing infections with antibiotic-resistant pathogens.
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      Data on extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-E) are lacking, although laboratory-based surveillance data suggest a substantial increase of ESBL-E over the past decade.
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      We aimed to assess the prevalence and describe the molecular epidemiology of ESBL-E among LTCF residents from 2 geographic regions in Switzerland. We also aimed to identify intra- and interinstitutional clusters of pathogens based on next-generation sequencing (NGS) and to assess institution- and resident-level risk factors for carriage of resistant pathogens.

      Methods

      Selection of Institutions and Residents, and Ethical Approval

      LTCFs in the cantons of Vaud (VD), Western Switzerland, and St Gallen (SG), Eastern Switzerland, with ≥40 residents were invited to participate. Residents with a life expectancy of >7 days were eligible. Local staff contacted the residents (or their next of kin in case of dementia) for participation and obtained oral informed consent. Consenting residents, who showed obvious discomfort during the screening procedure, were excluded. The study was approved by the local ethic commissions (#2019-00087).

      Study Design and Procedures

      This multicenter point prevalence study was performed between August and October 2019. Every institution was visited by at least 2 study team members; data were collected within 1-2 days. Institutional characteristics were collected according to the HALT protocol.

      European Centre for Disease Prevention and Control (ECDC). Protocol for point prevalence surveys of healthcare-associated infections and antimicrobial use in European long-term care facilities. Version 2.1. Stockholm: ECDC. 2016. Available at: https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/HALT-3-LTCF-PPS-Protocol-v2.1.pdf.

      Resident characteristics included age, sex, presence of urinary/vascular catheters, dementia, disorientation, immobility (ie, wheelchair or bedbound), presence of wounds or decubital ulcers, Katz index,
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      Studies of illness in the aged. The index of ADL: A standardized measure of biological and psychosocial function.
      day of admission, hospital admissions, endoscopic examinations and antibiotic treatment (all within 6 months before the study), use of PPIs at the time of the study, and previous (timely unrestricted) documentation of ESBL-E. Residents underwent rectal (all), urine (in case of urine catheters), or wound (if applicable) screening for ESBL-E. Screenings were performed using eSwabs (rectal and wound) or by collecting catheter urine, either by the study team or the institutional care teams. Samples from both geographic regions were sent to the same microbiology laboratory for further processing.

      Microbiology Processing

      For ESBL-E screening, 10 μL of the preservation liquid of an eSwab (or urine) were inoculated into enrichment broth (trypticase soy broth). Following 24-hour incubation, chromID ESBL (enabling growth of ESBL-producing gram-negatives) were inoculated with 10 μL enriched trypticase soy broth. In case of bacterial growth after 19-hour incubation at 36° C, identification at the species level was done with MALDI-ToF mass spectrometry (MALDI Biotyper Smart System, Bruker Daltonics, Bremen, Germany), using the BDAL 9.0 database. Depending on the actual susceptibility test patterns reported by the BD Phoenix M50 (Becton Dickinson, Sparks, MD), further confirmation tests were performed (E-test ESBL confirmation with specific E-test stripes, purchased from bioMérieux, Marcy l'Etoile, France).

      Whole Genome Sequencing and Definition of Clusters

      For further molecular characterization, isolates identified as ESBL-E were sent to the Clinical Bacteriology Laboratory of the University Hospital Basel. DNA was extracted using the EZ1, Qiacube robotic system (Qiagen, Hilden, Germany) followed by library preparation using Nexteraflex (Illumina, San Diego, CA) and sequencing on a NextSeq500 platform (Illumina) in the ISO 17025–accredited facility. All were sequenced to a mean coverage over 20×, and following assembly with Unicycler v0.3.0 b,
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      all genomes passed the Ridom Seqsphere+ (Jünemann, Updating benchtop sequencing performance comparison) criterion of possessing >90% of the core genome MLST targets (https://www.cgmlst.org/ncs/schema/5064703/). Clusters were defined as ≥2 isolates from different patients with a genetic difference of ≤10 cgMLST alleles. We assessed patient clusters within institutions, but also clusters between institutions of the same geographic region (ie, regional clusters). MLST sequence types were determined within Ridom Seqsphere + according to the Warwick scheme. FimH typing of ST131 genomes was performed using FimTyper,
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      and H30Rx isolates were defined according to previously published criteria.
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      The epidemic of extended-spectrum-β-lactamase-producing Escherichia coli ST131 is driven by a single highly pathogenic subclone, H30-Rx. Parkhill J, ed.

      Data Analysis and Statistics

      Baseline characteristics of screened and nonscreened residents were compared using descriptive statistics. Categorical variables were compared using chi-square or Fisher exact test, as appropriate; continuous variables were compared with the Mann-Whitney U test. The prevalence of positive screenings was calculated for every institution, with the number of screened individuals as denominator.
      For univariable analysis, institutional characteristics were compared between institutions with high (above median) and low (below median) ESBL-E prevalence. Resident-level characteristics were analyzed regarding their association with ESBL-E colonization using logistic regression. For both institution- and resident-level variables, those reaching statistical significance in univariable analyses were entered into a multivariable model. Collinearity was tested calculating the variance inflation factor (cut off >5). We used a generalized linear mixed model adjusting for random effects on the institutional level. In a subgroup analysis, resident-level characteristics between those colonized with E coli ST131 vs other sequence types were compared using descriptive statistics. Two-sided P values ≤ .05 were considered statistically significant; statistical analyses were performed using R, version 3.5.2 (R Foundation for Statistical Computing, Vienna, Austria).

      Results

      Institutions and Residents

      We included 8 LTCFs in Western and 8 in Eastern Switzerland with a mean of 73 and 75 residents, respectively (Supplementary Figure 1, Supplementary Table 1). Among 1185 eligible residents, 606 (51.1%) underwent screening for resistant pathogens (Table 1). The mean number of screened residents across LTCFs was 38 (range 16-56). Screened residents were more likely to be male (32% vs 26%, P = .04), to have a urinary catheter (14% vs 5%, P < .001), and to be located in the East (55% vs 44% in the West, P < .001). Of note, 35% and 36%, respectively, of screened and nonscreened residents were treated with a PPI on the day of the survey (P = .79).
      Table 1Baseline Characteristics of Long-Term Care Residents Undergoing and Those Not Undergoing Screening (Factor Present/Not Present at Time of the Study if Not Specified Otherwise)
      CharacteristicsScreening (n = 606)No Screening (n = 579)P Value
      West (canton of Vaud)265 (43.7)320 (55.3)<.001
      Age, y, mean (SD)84.1 (11)84.9 (33).57
      Female411 (67.8)426 (73.6).035
      Urinary catheter83 (13.7)28 (4.8)<.001
      Incontinence396 (65.3)364 (62.9).41
      Decubitus22 (3.6)17 (2.9).61
      Other wound52 (8.6)43 (7.4).53
      Disoriented325 (53.6)303 (52.3).70
      Dementia270 (44.6)275 (47.5).34
      Wheelchair or bedbound225 (37.1)185 (32.0).07
      Surgery previous 30 d7 (1.2)4 (0.7).60
      Proton-pump inhibitor210 (34.6)206 (35.6).79
      Antibiotic treatment16 (2.6)18 (3.1).76
      SD, standard deviation.
      Values are n (%) if not stated otherwise.
      P values <.05 are given in bold.

      Prevalence, Coresistances, and Molecular Epidemiology

      Among 606 screened residents, 70 (11.6%) had at least 1 positive screening result for ESBL-E. Among the 70 residents, 68 had positive rectal screening, 1 had a positive urine (declined rectal screening), and 1 a positive wound swab (negative rectal screening). Most residents with ESBL-E were colonized with E coli (n = 62; 89%), followed by K pneumoniae (n = 5; 7%). One resident was colonized with 2 different E coli STs (Supplementary Table 2). On the institutional level, ESBL-E prevalence ranged from 1.9% to 33.3% (Figure 1), with a median of 12.5% in the West and 6.9% in the East (P = .03). Institutional characteristics were similar between facilities with high and those with low prevalence (Supplementary Table 1).
      Figure thumbnail gr1
      Fig. 1ESBL prevalence (y axis) among residents in 16 Swiss long-term care facilities (dots represent institutional prevalence; bars, 95% CIs) and overall prevalence (red line represents overall prevalence; red band, 95% CI). x axis: Long-term care facilities from the West start with the abbreviation VD (Vaud), those from the East with SG (St Gallen); 2-digit numbers denote the different facilities. ID, identifier.
      NGS was performed on 67 nonduplicated ESBL-E (59 E coli and 8 non-E coli) from 66 residents. Of the 59 E coli, the most commonly detected ST was ST131 (n = 43, 73%), with a higher proportion in the West (91%) than in the East (54%) (Supplementary Table 2, Supplementary Figure 2). All the isolates possessing the type 1 fimbriae FimH30 allele (n = 24/43, 56%) were resistant to ciprofloxacin (H30R). ST131 most commonly harbored blaCTX-M-14 (n = 23/43; 53%) or blaCTX-M-27 (n = 14/43, 33%) (H30R1), and 4 (9%) carried blaCTX-M-15 (H30Rx). Among the 4 K pneumoniae isolates sequenced, 3 different STs were found, none of them belonging to any high-risk clone (Supplementary Table 2).

      Clustering of ESBL-E Within and Between LTCFs

      We identified 7 (2 in VD, 5 in SG) intrainstitutional ESBL–E coli clusters (range of 2-7 residents); 2 large clusters caused by ST131 (6 residents) and ST69 (6 residents) (with 1 resident being colonized with both ST131 and ST69) were detected in 1 single LTCF in SG. We detected 3 (all in VD) interinstitutional clusters (2 with 2 patients, respectively, and 1 with 11 patients from 6 institutions). This large cluster was caused by blaCTX-M-14-producing E coli ST131 (H30R1), and no common link (eg, spatiotemporal overlap in acute care hospital or endoscopy at the same center) was evident for these residents (Figure 2). No clustering between geographic regions was observed. For ESBL–K pneumoniae, we found 1 putative intrainstitutional cluster involving 2 patients.
      Figure thumbnail gr2
      Fig. 2Results of next-generation sequencing showing extended spectrum β-lactamase producing Escherichia coli isolates from (A) the Western and (B) the Eastern part of Switzerland. Colors followed by 2-digit numbers denote long-term care facilities for each region; facilities from the West start with the abbreviation VD (Vaud), those from the East with SG (St Gallen); the 3-digit number at the end stands for individual residents. Numbers on lines between colored circles show number of single-nucleotide polymorphisms (ie, genetic distance between isolates). Cluster defined as distance of 10 single-nucleotide polymorphisms or less.

      Risk Factors for ESBL-E and for ESBL–E coli ST131

      In univariable analysis, previous ESBL-E colonization was the strongest risk factor for ESBL-E [odds ratio (OR) 29.6, 95% confidence interval (CI) 9.0-97.2, P < .001]. PPI use was documented for 175 of 536 (32.6%) of ESBL-negative, and for 35 of 70 (50%) ESBL-positive residents, translating into an OR of 2.2 (95% CI 1.3-3.6, P = .003). No collinearity was detected between variables entered in multivariable analysis. Independent risk factors for ESBL-E were previous ESBL colonization with an adjusted OR (aOR) of 23.5 and a 95% CI of 6.6-83.8 (P < .001), male gender (aOR = 2.6, 95% CI 1.5-4.6, P = .001), and current PPI use (aOR = 2.2, 95% CI 1.2-3.8, P = .007) (Table 2).
      Table 2Univariable and Multivariable Analysis of Risk Factors Between ESBL-E-Negative and ESBL-E-Positive Residents
      CharacteristicsESBL Negative (n = 536)ESBL Positive (n = 70)Univariable Logistic RegressionMultivariable Logistic Regression
      OR (95% CI)P ValueOR (95% CI)P Value
      Western Switzerland227 (42.4)38 (54.3)1.8 (0.8-3.9).13NANA
      Age, y, median (IQR)87 (80-92)84.5 (70-89)0.97 (0.95-0.99).0060.99 (0.96-1.00).46
      Male sex157 (29.3)38 (54.3)3.0 (1.8-5.0)<.0012.6 (1.5-4.6).001
      Urinary catheter67 (12.5)16 (22.9)1.7 (0.9-3.3).10NANA
      Decubitus18 (3.4)4 (5.7)1.5 (0.5-4.6).53NANA
      Wound47 (8.8)5 (7.1)0.8 (0.3-2.1).66NANA
      Wheelchair or bedbound193 (36.0)32 (45.7)1.4 (0.8-2.4).22NANA
      Incontinence346 (64.6)50 (70.4)1.4 (0.8-2.4).27NANA
      Disorientation291 (54.3)34 (47.9)0.9 (0.5-1.5).64NANA
      Dementia240 (44.8)30 (42.3)1.0 (0.6-1.7).91NANA
      Years in facility, median (IQR)2 (1-5)2.5 (1-5)1.0 (0.9-1.1).66NANA
      Katz-Score, median (IQR)16 (10-20)17 (13-21)1.03 (0.98-1.08).21NANA
      Proton-pump inhibitor175 (32.6)35 (50.0)2.2 (1.3-3.6).0032.2 (1.2-3.8).007
      Previous ESBL detection5 (0.9)12 (17.1)29.6 (9.0-97.2)<.00123.5 (6.6-83.8)<.001
      Previous hospital admission88 (16.4)17 (24.3)1.6 (0.9-3.0).13NANA
      Previous endoscopy8 (1.5)1 (1.4)1.3 (0.2-10.8).84NANA
      Previous antibiotic treatment175 (32.6)33 (47.1)1.7 (1.0-2.9).041.2 (0.7-2.1).57
      IQR, interquartile range; NA, not available.
      Values are n (%) if not stated otherwise. OR, 95% CI, and P values are from logistic regression analysis.
      P values <.05 are given in bold.
      In the subgroup of residents colonized with ESBL-E, the only risk factor associated with ESBL–E coli ST131 was residence in Western Switzerland (Supplementary Table 3).

      Discussion

      In this multicenter point prevalence study among 606 residents from 16 Swiss LTCFs, we found an ESBL-E prevalence of 11.6%. ESBL–E coli ST131 (mostly H30R1) was the most common ST. The only modifiable risk factor for ESBL-E carriage was treatment with a PPI. The large sample size, inclusion of institutions from 2 geographical areas, and the use of NGS are particular strengths of the study.
      The ESBL-E prevalence of 11.6% is similar to other Middle European countries. Data from LTCFs in Germany and Austria have shown an ESBL-E prevalence of 15% and 13%, respectively.
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      In a systematic review from 2017, global ESBL-E prevalence among LTCF residents was estimated at 18% (range 5%-70% between countries).
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      These results suggest that Swiss LTCFs are not (yet) a hotspot of antibiotic resistance. However, we observed multiple clusters of ESBL-E in several LTCFs, which suggests that basic infection prevention measures are not rigorously followed. For example, almost one-third of residents in an LTCF from Eastern Switzerland were colonized with ESBL-E. In this institution, a workshop was held after communication of the results, and potential breaches in hygiene were discussed with the local infection control and prevention nurse. This example suggests that if infection prevention measures are to be improved in the long-term care setting, a customized approach considering the epidemiology of the respective institution could be the most efficient strategy.
      NGS has been shown to be an extraordinarily valuable tool in the detection of outbreaks and transmission of resistant gram-negative pathogens.
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      NGS results showed that E coli ST131 was the most common ST in our study. Spread of ESBL–E coli ST131 in LTCFs has been described from many countries.
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      In our study, ST131 strain H30R was most common, carrying predominantly blaCTX-M-14 and blaCTX-M-27 (ie, H30R1), whereas blaCTX-M-15 (associated with H30Rx strains) was less common.
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      The epidemic of extended-spectrum-β-lactamase-producing Escherichia coli ST131 is driven by a single highly pathogenic subclone, H30-Rx. Parkhill J, ed.
      Indeed, ST131 carrying blaCTX-M-27 has been suggested to be more transmissible than those with blaCTX-M-15, which might explain its successful spread.
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      Transmission dynamics of ESBL-producing Escherichia coli clones in rehabilitation wards at a tertiary care centre.
      Of note, the interfacility spread of ST131 among residents without any common epidemiologic link in the Western part of Switzerland was caused by H30R1-carrying blaCTX-M-14, which suggests that this subclone is not confined to health care settings but is endemic in the region. The scarcity of data on the molecular epidemiology of ESBL-producing E coli in Switzerland makes it difficult to put our data into context. However, an analysis of acute care patient isolates from Geneva (Western Switzerland) has shown an ST131 prevalence of 38% among ESBL E coli, most of them belonging to the blaCTX-M-27-carrying C1/H30R1 subclone,
      • Merino I.
      • Hernández-García M.
      • Turrientes M.C.
      • et al.
      Emergence of ESBL-producing Escherichia coli ST131-C1-M27 clade colonizing patients in Europe.
      which was also the second most common subclone in our study. To increase our rather limited knowledge about the molecular epidemiology of antibiotic-resistant pathogens in community and health care settings, NGS should be performed more broadly and more systematically in Switzerland.
      We identified PPI use to be independently associated with ESBL-E carriage. Similar findings have been published before, mostly from studies performed in acute care patients,
      • Huizinga P.
      • van den Bergh M.K.
      • van Rijen M.
      • et al.
      Proton pump inhibitor use is associated with extended-spectrum β-lactamase–producing enterobacteriaceae rectal carriage at hospital admission: A cross-sectional study.
      but also from a Belgian LTCF,
      • Latour K.
      • Huang T.-D.
      • Jans B.
      • et al.
      Prevalence of multidrug-resistant organisms in nursing homes in Belgium in 2015.
      and from the general population.
      • Søgaard M.
      • Heide-Jørgensen U.
      • Vandenbroucke J.P.
      • et al.
      Risk factors for extended-spectrum β-lactamase-producing Escherichia coli urinary tract infection in the community in Denmark: A case-control study.
      In a recent meta-analysis, the OR for ESBL colonization was estimated at 1.7 for patients under gastric acid–suppressive treatment,
      • Willems R.P.J.
      • van Dijk K.
      • Ket J.C.F.
      • Vandenbroucke-Grauls C.M.J.E.
      Evaluation of the association between gastric acid suppression and risk of intestinal colonization with multidrug-resistant microorganisms: A systematic review and meta-analysis.
      which is perfectly in line with our data. Owing to potential residual confounding, causality cannot be inferred between PPI use and risk for ESBL-E colonization based on our cross-sectional study design. However, the purported mechanism—which is that PPI might facilitate the colonization of the gastrointestinal tract by Enterobacterales through disruption of the gastric acid barrier—seems plausible. Of note, PPIs have also been associated with recurrent Clostridioides difficile infection,
      • Mehta P.
      • Nahass R.G.
      • Brunetti L.
      Acid suppression medications during hospitalization as a risk factor for recurrence of Clostridioides difficile infection: Systematic review and meta-analysis.
      health care–acquired pneumonia,
      • Herzig S.J.
      • Howell M.D.
      • Ngo L.H.
      • Marcantonio E.R.
      Acid-suppressive medication use and the risk for hospital-acquired pneumonia.
      and even increased mortality.
      • Xie Y.
      • Bowe B.
      • Yan Y.
      • et al.
      Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: Cohort study.
      The proportion of residents being treated with a PPI was 35% in our study, which is almost as high as the 45% reported from a Belgian study.
      • Latour K.
      • Huang T.-D.
      • Jans B.
      • et al.
      Prevalence of multidrug-resistant organisms in nursing homes in Belgium in 2015.
      Although we did not evaluate if PPIs were indeed indicated, these high numbers suggest that PPIs are being overprescribed in this population, as shown by others.
      • Delcher A.
      • Hily S.
      • Boureau A.S.
      • et al.
      Multimorbidities and overprescription of proton pump inhibitors in older patients.
      In a previous study in 22 LTCFs from the United States, almost 80% of residents were given a PPI at the time of admission, more than half without an indicated diagnosis.
      • Burdsall D.P.
      • Flores H.C.
      • Krueger J.
      • et al.
      Use of proton pump inhibitors with lack of diagnostic indications in 22 midwestern US skilled nursing facilities.
      Based on these data, we think that antibiotic stewardship programs should not only focus on reducing antibiotic use but also on reducing acid suppression therapy.
      • Rohde A.M.
      • Gastmeier P.
      Optimizing proton pump inhibitor use to reduce antimicrobial resistance rates?.
      Previous efforts to do so have shown that reducing PPI use is challenging. Although PPI usage declined after implementation of a PPI deprescribing guideline in LTCFs in Ontario, Canada, the effect could not be maintained over time.
      • Thompson W.
      • Hogel M.
      • Li Y.
      • et al.
      Effect of a proton pump inhibitor deprescribing guideline on drug usage and costs in long-term care.
      This study has several limitations. First, the selection of LTCF might not be representative for all institutions in Switzerland. LTCF with a particular interest in the topic are probably overrepresented, which could lead to both over- and underestimation of the prevalence. Second, only about 50% of residents consented to participate in the study. Men and those with urinary catheters were more likely to consent, which might have led to an overestimation of the prevalence. Third, the frequency of ESBL–E coli STs and subtypes, as described in our study, is determined by the epidemiology in the participating LTCFs. Nevertheless, the overall predominance of ST131 H30 and the interfacility spread of blaCTX-M-14-carrying ST131 in Western Switzerland give us valuable insights into this hitherto surprisingly understudied area. Fourth, previous antibiotic use was not independently associated with ESBL-E detection. Although collinearity was formally not detected, adjustment for the variable “previous ESBL detection,” which might itself be associated with higher antibiotic exposure, could account for the nonsignificant effect of antibiotic use in multivariable analysis. However, because antibiotic use has been found as a risk factor for antibiotic resistance in many other studies, we still believe that antibiotic use plays an important role in the promotion of AMR in LTCFs. Fifth, as outlined above, residual confounding is possible. For instance, variables not captured in our questionnaires include adherence to hand hygiene and use of PPE at the institution level and duration of previous hospital stays or exposure to ESBL-colonized roommates at the resident level.

      Conclusion and Implications

      The prevalence of ESBL-E in Swiss LTCFs is comparable to other middle European countries; E coli ST131, and its subclone H30R1, is the predominant ST, as shown in many other long-term care settings across the globe. We observed multiple clusters of residents with identical pathogens in certain institutions, calling for targeted interventions to revise and improve infection control policies in affected institutions. Such interventions may include efforts to increase adherence to hand hygiene, instructions for the correct use of personal protective equipment, and strategies to reduce prescription of antibiotics. Use of PPI represents an independent risk factor for ESBL-E carriage, which is why reducing PPI use should be considered as part of any antibiotic stewardship programs in long-term care.

      Acknowledgments

      We thank the employees of the participating LTCF for aiding in the collection of resident data and screening of residents. We thank Christine Kiessling, Magdalena Schneider, Elisabeth Schultheiss, Clarisse Straub, and Rosa-Maria Vesco (University Hospital Basel) for excellent technical assistance with next-generation sequencing. We also thank the Robert-Koch Institute for providing us with the German version of the HALT protocol.

      Supplementary Data

      Supplementary Table 1Organizational Characteristics of Included Long-Term Care Facilities Stratified by Those With High and Low Prevalence of ESBL-Producing Escherichia coli
      CharacteristicsHigh Prevalence

      (Median 13.4%)

      (n = 8)
      Low Prevalence

      (Median 6.9%)

      (n = 8)
      P Value
      General information
       Western Switzerland6 (75.0)2 (25.0).13
       Ownership.80
      Public1 (12.5)2 (25.0)
      Not for profit5 (62.5)4 (50.0)
      For profit2 (25.0)2 (25.0)
       Occupied beds at time of survey73.50 (21.99)75.00 (14.71).88
       Qualified nursing care available 24 h3 (37.5)1 (12.5).56
       FTE nursing assistants, %, mean (SD)44.13 (11.70)50.08 (11.43).32
       FTE per occupied bed, mean (SD)0.36 (0.20)0.55 (0.24).11
       Single beds, %, mean (SD)76.39 (23.63)64.58 (23.97).34
       Medical care.27
      Both5 (62.5)3 (37.5)
      Personal general practitioners (GPs)1 (12.5)4 (50.0)
      Medical staff employed by the facility2 (25.0)1 (12.5)
      Residents
       Katz score, median (IQR)16.50 (3.04)15.12 (2.63).35
       Age >85 y, %, mean (SD)55.58 (25.87)55.44 (13.95).99
       Consent for screening, %, mean (SD)46.71 (10.54)55.28 (10.17).12
      Infection control practice
       Trained persons in infection control and prevention8 (100.0)8 (100.0)NA
       Infection prevention training for nurses1 (12.5)1 (12.5)>.99
       Infection prevention training for non-nurses6 (75.0)2 (25.0).13
       Infection control committee6 (75.0)3 (37.5).31
       Hand hygiene training2 (25.0)0 (0.0).45
       Liters of alcohol rub solution in 2018/bed, mean (SD)3.70 (2.15)6.94 (5.39).17
      Antimicrobial policy
       Therapeutic guidelines available2 (25.0)5 (62.5).31
       Pharmacist advice for antimicrobials5 (62.5)7 (87.5).56
       Microbiology laboratory in charge of institution.14
      One5 (62.5)4 (50.0)
      More than 12 (25.0)0 (0.0)
      None, this is done directly by the GP1 (12.5)4 (50.0)
      FTE, full-time equivalent; GP, general practitioner; IQR, interquartile range; NA, not available; SD, standard deviation.
      Values are n (%) if not stated otherwise.
      Supplementary Table 2Phenotypic Resistance (n = 71) and Next-Generation Sequencing (n = 67) Results of ESBL-Producing Enterobacterales (From 70 Residents)
      IDSpeciesAMCTZPCAZFEPATMIMIMERAMTBMNORCIPLVXFOSNFSXTSTβ-Lactamase-

      Gene
      bla-Class A

      Genes (I)
      bla-Class A

      Gene (II)
      bla-Class D

      Gene
      bla-misc.

      Groups
      fim Type
      SG-01-007Proteus mirabilisRSRRSRRSSRRRSn.a.R35blaCTX-M-36
      SG-01-046Klebsiella pneumoniaeRSRRRSSSSRRISn.a.R1190blaCTX-M-15blaSHV-106blaTEM-1
      SG-02-012Citrobacter farmeriRSSSRSSSSSSSSn.a.SblaSED
      SG-02-014Escherichia coliRSIRRSSSSSSSSSR38blaEC-8blaCTX-M-9
      SG-02-052E coliSSIIISSSSRRRSSR131blaEC-5blaCTX-M-27fimH30
      SG-02-057E coliSSIIISSSSRRRSSR131blaEC-5blaCTX-M-27fimH30
      SG-02-091E coliSSIIISSSSRRRSSR131blaEC-5blaCTX-M-27fimH41
      SG-02-093E coliSSIIISSSSRRRSSR131blaEC-5blaCTX-M-27fimH41
      SG-03-058E coliRSIRRSSSRRRRSSS131blaEC-5blaCTX-M-14blaTEM-1fimH30
      SG-03-066E coliSSRIRSSSSRRRSSRunkblaEC-5blaCTX-M-27
      SG-03-086E coliSSIRRSSSRRRRSSR131blaEC-5blaCTX-M-27fimH30
      SG-03-089E coliSSIRRSSSSISSSSS38blaEC-8blaCTX-M-15
      SG-04-028Klebsiella oxytocaSSRSRSSSSSSSSn.a.S224blaOXY-6-1blaSHV-12
      SG-05-062E coliRSIRRSSSSSSSSSS53blaEC-18blaCTX-M-1
      SG-05-063E coliRSIIISSSSRRRSSS131blaEC-5blaCTX-M-1blaTEM-1fimH412
      SG-06-055E coliRSSIISSSSIIISSR10blaECblaCTX-M-14
      SG-06-061E coliRIRRRSSSRRRRSSR3643blaEC-15blaTEM-40
      SG-07-030K pneumoniaeRSRRRSSSRRRRRn.a.S307blaCTX-M-15blaSHV-106blaOXA-1blaTEM-1
      SG-07-034K pneumoniaeRSRIRSSSRRRRRn.a.S307blaCTX-M-15blaSHV-106blaOXA-1blaTEM-1
      SG-08-008E coliSSIIRSSSSSSSSSS69blaEC-8blaCTX-M-15
      SG-08-010E coliSSRRRSSSSRRRSSR501blaEC-8blaCTX-M-15
      SG-08-016E coliSSIRRSSSSRRRSSR131blaEC-5blaCTX-M-27fimH30
      SG-08-032E coliRSIRRSSSSSSSSSS69blaEC-8blaCTX-M-15
      SG-08-033E coliRSSRISSSRRRRSSR131blaEC-5blaCTX-M-14blaTEM-1fimH30
      SG-08-037E coliRSIRRSSSSSSSSSS69blaEC-8blaCTX-M-15
      SG-08-041E coliRSIRRSSSSSSSSSS69blaEC-8blaCTX-M-15
      SG-08-042E coliRSIRISSSRRRRSSR131blaEC-5blaCTX-M-14blaTEM-1fimH30
      SG-08-045E coliSSRRRSSSSSSSSSS69blaEC-8blaCTX-M-15
      SG-08-047E coliRSIRRSSSRRRRSSS131blaEC-5blaCTX-M-14blaTEM-1fimH30
      SG-08-055E coliRSSIISSSRRRRSSR131blaEC-5blaCTX-M-14blaTEM-1fimH30
      SG-08-058E coliRSIRISSSRRRRSSR131blaEC-5blaCTX-M-14fimH30
      SG-08-059
      Same patient with 2 different STs.
      E coliRSIRISSSRRRRSSS69blaEC-5blaCTX-M-14
      SG-08-059
      Same patient with 2 different STs.
      E coliRSIRISSSRRRRSSR131blaEC-5blaCTX-M-14fimH30
      VD-01-001E coliRSRRRSSSSRRRSSS131blaEC-5blaCTX-M-15blaTEM-1fimH30
      VD-01-014E coliRSRRRSSSSIIISSS131blaEC-5blaCTX-M-55fimH41
      VD-01-063E coliRSRRRSSSRRRRSn.d.R131blaEC-5blaCTX-M-15blaTEM-1fimH41
      VD-01-078K pneumoniaeRSRSRSSSSRRRSn.a.SblaSHV-33
      VD-01-096E coliSSRRRSSSSRRRSSS131blaEC-5blaCTX-M-27fimH30
      VD-02-015E coliRSRIRSSSSRRRSSS131blaEC-5blaCTX-M-27fimH30
      VD-02-026E coliSSRIRSSSSRRRSRR131blaEC-5blaCTX-M-27fimH30
      VD-02-033E coliSSIIRSSSSRRRSSR131blaEC-5blaCTX-M-27fimH30
      VD-02-068E coliRSIIRSSSRIISSSR131blaEC-5blaCTX-M-14blaTEM-1fimH89
      VD-02-083E coliRSIRRSSSRIISSSR131blaEC-5blaCTX-M-14blaTEM-1fimH89
      VD-02-092E coliSSIIRSSSSRRRSSS131blaEC-5blaCTX-M-27fimH30
      VD-03-042E coliSSIRRSSSSRRRSSSndnd
      VD-03-050E coliSSIIRSSSSRRRSSRndnd
      VD-04-008E coliRSSSSSSSSSSSSSSndnd
      VD-04-016E coliRSIIRSSSRIISSSR131blaEC-5blaCTX-M-14blaTEM-1fimH89
      VD-04-027E coliSSRIRSSSSRRRSSR131blaEC-5blaCTX-M-27fimH30
      VD-04-035E coliSSRIRSSSSRRRSSS131blaEC-5blaCTX-M-27fimH30
      VD-04-071E coliRSIIRSSSRIIISSS131blaEC-5blaCTX-M-14blaTEM-1fimH89
      VD-05-002E coliRSIRISSSSSSSSSS131blaEC-5blaCTX-M-14fimH41-like
      VD-05-017E coliRSRRRSSSSRRRSSS131blaEC-5blaCTX-M-15blaTEM-1fimH30
      VD-05-023E coliRSSRISSSSRRRSSS131blaEC-5blaCTX-M-14blaTEM-1fimH30
      VD-05-026E coliRSSRISSSSRRRSSS131blaEC-5blaCTX-M-14blaTEM-1fimH30
      VD-05-035E coliRSIIRSSSRIIISSS131blaEC-5blaCTX-M-14blaTEM-1fimH89
      VD-05-042K pneumoniaeRIRRRSSSRRRRSn.a.R235blaLAP-2blaCTX-M-15blaSHV-145blaOXA-1
      VD-05-043E coliSSSIISSSRSSSSSS131blaEC-5blaCTX-M-14blaTEM-1fimH41-like
      VD-05-059E coliRIRRRSSSRRRRSRR6938blaEC-15blaCTX-M-15blaTEM-1
      VD-05-065E coliSSRRRSSSSIISSSR69blaEC-8blaCTX-M-15blaTEM-1?
      VD-06-040E coliRSIRRSSSSRIISSS131blaEC-5blaCTX-M-14blaTEM-1fimH89
      VD-06-048E coliRSIIRSSSRIIISSR131blaEC-5blaCTX-M-14blaTEM-1fimH89
      VD-06-061E coliRSIIRSSSRIISSSR131blaEC-5blaCTX-M-14blaTEM-1fimH89
      VD-07-011E coliRSIRRSSSSISSSSS131blaEC-5blaCTX-M-14blaTEM-1fimH89
      VD-07-025E coliRSRRRSSSRRRRSSS131blaEC-5blaCTX-M-15blaOXA-1fimH30
      VD-07-035E coliRSRRRSSSRRRRSSR8347blaEC-5blaCTX-M-15blaOXA-1blaTEM-1
      VD-08-031E coliSSRRRSSSSRRRSSS131blaEC-5blaCTX-M-27fimH30
      VD-08-032E coliRSIIRSSSRIISSSS131blaEC-5blaCTX-M-14blaTEM-1fimH89
      VD-08-058E coliRSIRRSSSRIISSSR131blaEC-5blaCTX-M-14blaTEM-1fimH89
      VD-08-067E coliRSIIRSSSRIISSSS131blaEC-5blaCTX-M-14blaTEM-1fimH89
      VD-08-068E coliRSIIRSSSSIISSSRndnd
      AM, amikacin; AMC, amoxicillin; ATM, aztreonam; CAZ, ceftazidime; CIP, ciprofloxacin; FEP, cefepime; FOS, fosfomycin; ID, identifier; IMI, imipenem; LVX, levofloxacin; MER, meropenem; NF, nitrofurantoin; NOR, norfloxacin; ST, sequence type; SXT, sulfamethoxazole; TBM, tobramycin; TZP, tazobactam; unk, unknown.
      Same patient with 2 different STs.
      Supplementary Table 3Risk Factors Compared Between Residents
      Resident with co-colonization (ST131 and ST69) excluded from analysis.
      With Extended Spectrum β-Lactamase (ESBL)–Producing Escherichia coli ST131 and ESBL E coli of Other STs
      CharacteristicsST131 (n = 42)Other ST (n = 14)P Value
      Western Switzerland29 (69.0)2 (14.3).001
      Age, median (IQR)85 (69-91)84 (75-87).59
      Female sex17 (40.5)9 (64.3).22
      Urinary catheter10 (23.8)2 (14.3).71
      Incontinence32 (76.2)9 (64.3).60
      Decubitus4 (9.5)0 (0.0).55
      Wound4 (9.5)0 (0.0).55
      Disorientation23 (54.8)4 (28.6).17
      Dementia18 (42.9)5 (35.7).88
      Wheelchair or bedbound21 (50.0)5 (35.7).54
      Proton-pump inhibitor22 (52.4)8 (57.1)>.99
      Previous endoscopy0 (0.0)0 (0.0)NA
      Previous hospital admission9 (21.4)3 (21.4)>.99
      Previous ESBL8 (19.0)0 (0.0).19
      Previous antibiotic treatment19 (45.2)4 (28.6)>.99
      Years in facility, median (IQR)3 (1-4)1.5 (1.5-7.5).88
      Katz-score, median (IQR)18 (16-21)18 (8-21).34
      ESBL, extended-spectrum β-lactamase; IQR, interquartile range.
      Values are n (%) if not indicated otherwise.
      P values <.05 are given in bold.
      Resident with co-colonization (ST131 and ST69) excluded from analysis.
      Figure thumbnail fx1
      Supplementary Figure 1Geographical location of participating institutions in the west and in the east of Switzerland.
      Figure thumbnail fx2
      Supplementary Figure 2Results of next-generation sequencing of extended spectrum β-lactamase producing Escherichia coli from Swiss nursing home residents by sequence type. SG isolates are from Eastern Switzerland and VD isolates from Western Switzerland.

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