Risk Factors for Community Colonization With Extended-Spectrum Cephalosporin-Resistant Enterobacterales (ESCrE) in Botswana: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: The epidemiology of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in low- and middle-income countries (LMICs) is poorly described. Identifying risk factors for ESCrE colonization is critical to inform antibiotic resistance reduction strategies because colonization is typically a precursor to infection. METHODS: From 15 January 2020 to 4 September 2020, we surveyed a random sample of clinic patients at 6 sites in Botswana. We also invited each enrolled participant to refer up to 3 adults and children. All participants had rectal swabs collected that were inoculated onto chromogenic media followed by confirmatory testing. Data were collected on demographics, comorbidities, antibiotic use, healthcare exposures, travel, and farm and animal contact. Participants with ESCrE colonization (cases) were compared with noncolonized participants (controls) to identify risk factors for ESCrE colonization using bivariable, stratified, and multivariable analyses. RESULTS: A total of 2000 participants were enrolled. There were 959 (48.0%) clinic participants, 477 (23.9%) adult community participants, and 564 (28.2%) child community participants. The median (interquartile range) age was 30 (12-41) and 1463 (73%) were women. There were 555 cases and 1445 controls (ie, 27.8% of participants were ESCrE colonized). Independent risk factors (adjusted odds ratio [95% confidence interval]) for ESCrE included healthcare exposure (1.37 [1.08-1.73]), foreign travel [1.98 (1.04-3.77]), tending livestock (1.34 [1.03-1.73]), and presence of an ESCrE-colonized household member (1.57 [1.08-2.27]). CONCLUSIONS: Our results suggest healthcare exposure may be important in driving ESCrE. The strong links to livestock exposure and household member ESCrE colonization highlight the potential role of common exposure or household transmission. These findings are critical to inform strategies to curb further emergence of ESCrE in LMICs.

A National Registry for People With All Stages of Kidney Disease: The National Kidney Foundation (NKF) Patient Network.

RATIONALE & OBJECTIVE: The National Kidney Foundation (NKF) launched the first national US kidney disease patient registry, the NKF Patient Network, that is open to patients throughout the continuum of chronic kidney disease (CKD). The Network provides individualized education and will facilitate patient-centered research, clinical care, and health policy decisions. Here, we present the overall design and the results of a feasibility study that was conducted July through December 2020. STUDY DESIGN: Longitudinal observational cohort study of patient-entered data with or without electronic health care record (EHR) linkage in collaboration with health systems. SETTING & PARTICIPANTS: People with CKD, age≥18 years, are invited through their provider, NKF communications, or national outreach campaign. People self-enroll and share their data through a secure portal that offers individualized education and support. The first health system partner is Geisinger. EXPOSURE: Any cause and stage of CKD, including dialysis and kidney transplant recipients. OUTCOME: Feasibility of the EHR data transfer, participants' characteristics, and their perspectives on usability and content. ANALYTICAL APPROACH: Data were collected and analyzed through the registry portal powered by the Pulse Infoframe healthie 2.0 platform. RESULTS: During the feasibility study, 80 participants completed their profile, and 42 completed a satisfaction survey. Mean age was 57.5 years, 51% were women, 83% were White, and 89% were non-Hispanic or Latino. Of the participants, 60% were not aware of their level of estimated glomerular filtration rate and 91% of their urinary albumin-creatinine ratio. LIMITATIONS: Challenges for the Network are lack of awareness of kidney disease for many with CKD, difficulty in recruiting vulnerable populations or those with low digital readiness, and loss to follow-up, all leading to selection bias. CONCLUSIONS: The Network is positioned to become a national and international platform for real-world data that can inform the development of patient-centered research, care, and treatments.

A behavioral economics-based telehealth intervention to improve aspirin adherence following hospitalization for acute coronary syndrome.

PURPOSE: A significant number of patients with acute coronary syndrome (ACS) are nonadherent to aspirin after hospital discharge, with an associated increased risk of subsequent cardiovascular events. The purpose of this pilot study was to test the efficacy of a telehealth intervention based on behavioral economics to improve aspirin adherence following hospitalization for ACS. METHODS: We enrolled 130 participants (c¯X = 58 ± 10.7 years of age, 38% female, 45% black) from two hospitals. Patients were eligible if they owned a smartphone and were admitted to the hospital for ACS, prescribed aspirin at discharge, and responsible for administering their own medications. Consenting participants were randomized to the intervention or usual care group. The intervention group was eligible to receive up to $50 per month if they took their medicine daily, with $2 per day deducted if a dose was missed. All participants received an electronic monitoring (EM) pill bottle containing a 90-day supply of aspirin, which was used to measure adherence calculated as the proportion of prescribed drug taken using the EM device. Based on the skewness in the adherence distribution, quantile regression was used to evaluate the effect of the intervention on median adherence over time. RESULTS: After 90 days, adherence fell in the control group but remained high in the intervention group (median adherence 81% vs 90%, P = .18). Rehospitalization was higher in the control group (24% vs 13%, P = .17). CONCLUSION: A loss aversion behavioral economics-based telehealth intervention is a promising approach to improving aspirin adherence following hospitalization for ACS.

Incorporating patient-centered factors into heart failure readmission risk prediction: A mixed-methods study.

BACKGROUND: Capturing and incorporating patient-centered factors into 30-day readmission risk prediction after hospitalized heart failure (HF) could improve the modest performance of current models. METHODS: Using a mixed-methods approach, we developed a patient-centered survey and evaluated the additional predictive utility of the survey compared to a traditional readmission risk model (the Krumholz et al. model). Area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow goodness-of-fit statistic quantified the performance of both models. We measured the amount of model improvement with the addition of patient-centered factors to the Krumholz et al. model with the integrated discrimination improvement (IDI). In an exploratory analysis, we used hierarchical clustering algorithms to identify groups with similar survey responses and tested for differences between clusters using standard descriptive statistics. RESULTS: From 3/24/2014 to 3/12/2015, 183 patients hospitalized with HF were enrolled from an urban, academic health system and followed for 30days after discharge. The Krumholz et al. plus patient-centered factors model had similar-to-slightly lower performance (AUC [95%CI]:0.62 [0.52, 0.71]; goodness-of-fit P=.10) than the Krumholz et al. model (AUC [95%CI]:0.66 [0.57, 0.76]; goodness-of-fit P=.19). The IDI (95%CI) was 0.003 (-0.014,0.020). We identified three patient clusters based on patient-centered survey responses. The clusters differed with respect to gender, self-rated health, employment status, and prior hospitalization frequency (all P<.05). CONCLUSIONS: The addition of patient-centered factors did not improve 30-day readmission model performance. Rather than designing interventions based on predicted readmission risk, tailoring interventions to all patients, based on their characteristics, could inform the design of targeted, readmission reduction strategies.

Performance of CHROMagar ESBL media for the surveillance of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) from rectal swabs in Botswana.

Introduction. Lack of laboratory capacity hampers consistent national antimicrobial resistance (AMR) surveillance. Chromogenic media may provide a practical screening tool for detection of individuals colonized by extended-spectrum beta-lactamase (ESBL)-producing organisms.Hypothesis. CHROMagar ESBL media represent an adequate screening method for the detection of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE), isolated from rectal swabs.Aim. To evaluate the performance of CHROMagar ESBL media to accurately identify ESCrE isolates from rectal swab samples attained from hospitalized and community participants.Methodology. All participants provided informed consent prior to enrolment. Rectal swabs from 2469 hospital and community participants were inoculated onto CHROMagar ESBL. The performance of CHROMagar ESBL to differentiate Escherichia coli and Klebsiella spp., Enterobacter spp. and Citrobacter spp. (KEC spp.) as well as select for extended-spectrum cephalosporin resistance were compared to matrix-assisted laser desorption/ionization-time-of-flight MS (MALDI-TOF-MS) and VITEK-2 automated susceptibility testing.Results. CHROMagar ESBL had a positive and negative agreement of 91.2 % (95 % CI, 88.4-93.3) and 86.8 % (95 % CI, 82.0-90.7) for E. coli and 88.1 % (95 % CI 83.2-92.1) and 87.6 % (95 % CI 84.7-90.2) for KEC spp. differentiation, respectively, when compared to species ID by MALDI-TOF-MS. When evaluated for phenotypic susceptibilities (VITEK-2), 88.1 % (714/810) of the isolates recovered on the selective agar exhibited resistance to third-generation cephalosporins.Conclusion. The performance characteristics of CHROMagar ESBL media suggest that they may be a viable screening tool for the identification of ESCrE from hospitalized and community participants and could be used to inform infection prevention and control practices in Botswana and potentially other low-and middle-income countries (LMICs). Further studies are required to analyse the costs and the impact on time-to-result of the media in comparison with available laboratory methods for ESCrE surveillance in the country.

Development of an Electronic Algorithm to Target Outpatient Antimicrobial Stewardship Efforts for Acute Bronchitis and Pharyngitis.

Background: A major challenge for antibiotic stewardship programs is the lack of accurate and accessible electronic data to target interventions. We developed and validated separate electronic algorithms to identify inappropriate antibiotic use for adult outpatients with bronchitis and pharyngitis. Methods: We used International Classification of Diseases, 10th Revision, diagnostic codes to identify patient encounters for acute bronchitis and pharyngitis at outpatient practices between 3/15/17 and 3/14/18. Exclusion criteria included immunocompromising conditions, complex chronic conditions, and concurrent infections. We randomly selected 300 eligible subjects each with bronchitis and pharyngitis. Inappropriate antibiotic use based on chart review served as the gold standard for assessment of the electronic algorithm, which was constructed using only data in the electronic data warehouse. Criteria for appropriate prescribing, choice of antibiotic, and duration were based on established guidelines. Results: Of 300 subjects with bronchitis, 167 (55.7%) received an antibiotic inappropriately based on chart review. The electronic algorithm demonstrated 100% sensitivity and 95.3% specificity for detection of inappropriate prescribing. Of 300 subjects with pharyngitis, 94 (31.3%) had an incorrect prescribing decision. Among 29 subjects with a positive rapid streptococcal antigen test, 27 (93.1%) received an appropriate antibiotic and 29 (100%) received the correct duration. The electronic algorithm demonstrated very high sensitivity and specificity for all outcomes. Conclusions: Inappropriate antibiotic prescribing for bronchitis and pharyngitis is common. Electronic algorithms for identifying inappropriate prescribing, antibiotic choice, and duration showed excellent test characteristics. These algorithms could be used to efficiently assess prescribing among practices and individual clinicians. Interventions based on these algorithms should be tested in future work.

Colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) in healthcare and community settings in Botswana: an antibiotic resistance in communities and hospitals (ARCH) study.

OBJECTIVES: Although extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) are a global challenge, data on these organisms in low- and middle-income countries are limited. In this study, we sought to characterize colonization data critical for greater antibiotic resistance surveillance efforts. METHODS: This study was conducted in three hospitals and six clinics in Botswana. We conducted ongoing surveillance of adult patients in hospitals and clinics and adults and children in the community. All participants underwent rectal swab sampling to identify ESCrE and CRE. RESULTS: Enrollment occurred from January 15, 2020, to September 4, 2020, but paused from April 2, 2020, to May 21, 2020, because of a countrywide COVID-19 lockdown. Of 5088 individuals approached, 2469 (49%) participated. ESCrE colonization prevalence was 30.7% overall (43% for hospital participants, 31% for clinic participants, 24% for adult community participants, and 26% for child community participants) (P <0.001). A total of 42 (1.7%) participants were colonized with CRE. CRE colonization prevalence was 1.7% overall (6.8% for hospital participants, 0.7% for clinic participants, 0.2% for adult community participants, and 0.5% for child community participants) (P <0.001). ESCrE and CRE prevalence varied substantially across regions and was significantly higher prelockdown versus postlockdown. CONCLUSIONS: ESCrE colonization was high in all settings in Botswana. CRE prevalence in hospitals was also considerable. Colonization prevalence varied by region and clinical setting and decreased after a countrywide lockdown.

SARS-CoV-2 Variants Associated with Vaccine Breakthrough in the Delaware Valley through Summer 2021.

The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here, we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed 3-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of1.25-3.18). This study thus overviews viral evolution and vaccine breakthroughs in the Delaware Valley and introduces a rigorous statistical approach to interrogating enrichment of breakthrough variants against a changing background. IMPORTANCE SARS-CoV-2 vaccination is highly effective at reducing viral infection, hospitalization and death. However, vaccine breakthrough infections have been widely observed, raising the question of whether particular viral variants or viral mutations are associated with breakthrough. Here, we report analysis of 2621 surveillance isolates from people diagnosed with COVID-19 in the Delaware Valley in southeastern Pennsylvania, allowing rigorous comparison to 159 vaccine breakthrough case specimens. Our best estimate is a 3-fold enrichment for some lineages of delta among breakthroughs, and enrichment of a notable spike substitution, N501Y. We introduce statistical methods that should be widely useful for evaluating vaccine breakthroughs and other viral phenotypes.

SARS-CoV-2 variants associated with vaccine breakthrough in the Delaware Valley through summer 2021.

The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed three-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of 1.25-3.18). This study thus provides a detailed picture of viral evolution in the Delaware Valley and a geographically matched analysis of vaccine breakthroughs; it also introduces a rigorous statistical approach to interrogating enrichment of viral variants.