Impact of deceased organ donor marijuana use on donor culture positivity and solid organ transplant recipient outcomes.

With the increasing prevalence of marijuana use in the US, many deceased organ donors have a history of marijuana use, raising concerns about infectious risks to transplant recipients. We performed a multicenter retrospective cohort study in which exposed donors were those with recent marijuana use (in the prior 12 months) and unexposed donors were those with no recent marijuana use. Primary outcomes included the following: (1) positive donor cultures for bacteria or fungi, (2) recipient infection due to bacteria or fungi within 3 months posttransplant, and (3) recipient graft failure or death within 12 months posttransplant. Multivariable regression was used to evaluate the relationship between donor marijuana use and each outcome. A total of 658 recipients who received organs from 394 donors were included. Recent marijuana use was not associated with donor culture positivity (aOR: 0.84, 95% CI: 0.39-1.81, P = .65), recipient infection (aHR: 1.02, 95% CI: 0.76-1.38, P = .90), or recipient graft failure or death (aHR: 1.65, 95% CI: 0.90-3.02, P = .11). Our data suggest that organs from donors with a history of recent marijuana use do not pose significant infectious risks in the early posttransplant period.

Patient-Related Metadata Reported in Sequencing Studies of SARS-CoV-2: Protocol for a Scoping Review and Bibliometric Analysis.

Background: There has been an unprecedented effort to sequence the SARS-CoV-2 virus and examine its molecular evolution. This has been facilitated by the availability of publicly accessible databases, the Global Initiative on Sharing All Influenza Data (GISAID) and GenBank, which collectively hold millions of SARS-CoV-2 sequence records. Genomic epidemiology, however, seeks to go beyond phylogenetic analysis by linking genetic information to patient characteristics and disease outcomes, enabling a comprehensive understanding of transmission dynamics and disease impact.While these repositories include fields reflecting patient-related metadata for a given sequence, inclusion of these demographic and clinical details is scarce. The extent to which patient-related metadata is reported in published sequencing studies and its quality remains largely unexplored. Methods: The NIH's LitCovid collection will be used for automated classification of articles reporting having deposited SARS-CoV-2 sequences in public repositories, while an independent search will be conducted in PubMed for validation. Data extraction will be conducted using Covidence. The extracted data will be synthesized and summarized to quantify the availability of patient metadata in the published literature of SARS-CoV-2 sequencing studies. For the bibliometric analysis, relevant data points, such as author affiliations and citation metrics will be extracted. Discussion: This scoping review will report on the extent and types of patient-related metadata reported in genomic viral sequencing studies of SARS-CoV-2, identify gaps in this reporting, and make recommendations for improving the quality and consistency of reporting in this area. The bibliometric analysis will uncover trends and patterns in the reporting of patient-related metadata, including differences in reporting based on study types or geographic regions. Co-occurrence networks of author keywords will also be presented. The insights gained from this study may help improve the quality and consistency of reporting patient metadata, enhancing the utility of sequence metadata and facilitating future research on infectious diseases.

Risk Factors for Recurrence of Community-Onset Urinary Tract Infections Caused by Extended-Spectrum Cephalosporin-Resistant Enterobacterales.

Background: Extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) are an increasingly important cause of community-onset urinary tract infections (UTIs), including recurrent infections. We evaluated risk factors for recurrence among patients with community-onset ESCrE UTI. Methods: This retrospective cohort study included adults with community-onset ESCrE UTI in the Duke University Health System from April 2018 through December 2021. ESCrE UTI recurrence by the same species was assessed 14-180 days (ie, 6 months) after completion of antibiotic treatment. We evaluated the relationships between candidate risk factors and time to recurrence using Cox proportional hazards regression models. Results: Among 1347 patients with community-onset ESCrE UTI, 202 (15.0%) experienced recurrent infection during the 6-month follow-up period. Independent risk factors for recurrence included neurogenic bladder (adjusted hazard ratio [aHR], 1.8 [95% confidence interval {CI}, 1.2-2.6]; P = .005), prior history of UTI (aHR, 2.4 [95% CI, 1.7-3.3]; P < .001), and fluoroquinolone nonsusceptibility of the index UTI (aHR, 1.5 [95% CI, 1.1-2.1]; P = .02). Klebsiella pneumoniae infection was associated with recurrence in univariate analysis (HR, 1.6 [95% CI, 1.1-2.1]; P = .007) but not multivariate analysis (aHR, 1.4 [95% CI, 1.0-1.9]; P = .06). Inappropriate initial or definitive antibiotic therapy was not predictive of ESCrE UTI recurrence. Conclusions: Recurrence of community-onset ESCrE UTI was common and associated with several patient and pathogen-level risk factors. Future studies should evaluate microbial risk factors for recurrence and improve the management of ESCrE UTI.

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.

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.

Efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections associated with low procalcitonin: a randomised, placebo-controlled, double-blind, non-inferiority trial.

BACKGROUND: Lower respiratory tract infections are frequently treated with antibiotics, despite a viral cause in many cases. It remains unknown whether low procalcitonin concentrations can identify patients with lower respiratory tract infection who are unlikely to benefit from antibiotics. We aimed to compare the efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections in patients with low procalcitonin. METHODS: We conducted a randomised, placebo-controlled, double-blind, non-inferiority trial at five health centres in the USA. Adults aged 18 years or older with clinically suspected non-pneumonia lower respiratory tract infection and symptom duration from 24 h to 28 days were eligible for enrolment. Participants with a procalcitonin concentration of 0·25 ng/mL or less were randomly assigned (1:1), in blocks of four with stratification by site, to receive over-encapsulated oral azithromycin 250 mg or matching placebo (two capsules on day 1 followed by one capsule daily for 4 days). Participants, non-study clinical providers, investigators, and study coordinators were masked to treatment allocation. The primary outcome was efficacy of azithromycin versus placebo in terms of clinical improvement at day 5 in the intention-to-treat population. The non-inferiority margin was -12·5%. Solicited adverse events (abdominal pain, vomiting, diarrhoea, allergic reaction, or yeast infections) were recorded as a secondary outcome. This trial is registered with ClinicalTrials.gov, NCT03341273. FINDINGS: Between Dec 8, 2017, and March 9, 2020, 691 patients were assessed for eligibility and 499 were enrolled and randomly assigned to receive azithromycin (n=249) or placebo (n=250). Clinical improvement at day 5 was observed in 148 (63%, 95% CI 54 to 71) of 238 participants with full data in the placebo group and 155 (69%, 61 to 77) of 227 participants with full data in the azithromycin group in the intention-to-treat analysis (between-group difference -6%, 95% CI -15 to 2). The 95% CI for the difference did not meet the non-inferiority margin. Solicited adverse events and the severity of solicited adverse events were not significantly different between groups at day 5, except for increased abdominal pain associated with azithromycin (47 [23%, 95% CI 18 to 29] of 204 participants) compared with placebo (35 [16%, 12 to 21] of 221; between-group difference -7% [95% CI -15 to 0]; p=0·066). INTERPRETATION: Placebo was not non-inferior to azithromycin in terms of clinical improvement at day 5 in adults with lower respiratory tract infection and a low procalcitonin concentration. After accounting for both the rates of clinical improvement and solicited adverse events at day 5, it is unclear whether antibiotics are indicated for patients with lower respiratory tract infection and a low procalcitonin concentration. FUNDING: National Institute of Allergy and Infectious Diseases, bioMérieux.

Risk factors for meticillin-resistant Staphylococcus aureus (MRSA) carriage in MRSA-exposed household pets.

BACKGROUND: Household pets can carry meticillin-resistant Staphylococcus aureus (MRSA) introduced to the home by their human companions. Specific factors promoting pet carriage of this pathogen have not been fully elucidated. OBJECTIVE: This study evaluated MRSA cultured from pets and the home environment in households where a human infected with MRSA had been identified, and aimed to determine potential risk factors for pet MRSA carriage. MATERIALS AND METHODS: Humans diagnosed with community-associated MRSA (CA-MRSA) skin or soft-tissue infection (SSTI) in the mid-Atlantic United States were identified. One hundred forty-two dogs and cats from 57 affected households were identified of which 134 (94.4%) pets and the household environment were sampled for bacterial culture, PCR confirmation and spa-typing for MRSA strain determination. Samples were obtained 3 months later from 86 pets. RESULTS: At baseline, 12 (9.0%) pets carried MRSA. Potential risk factors associated with carriage included pet bed (environmental) MRSA contamination, flea infestation and prior antimicrobial use in the pet. Pets tended to carry human-adapted MRSA strains and spa-types of MRSA isolates cultured from pets were concordant with strains cultured from the home environment in seven of eight homes (87.5%) at baseline. CONCLUSIONS AND CLINICAL RELEVANCE: Results may inform risk-based veterinary clinical recommendations and provide evidence for selective pet testing as a possible alternative to early removal of pets from the homes of humans infected with MRSA. MRSA contamination of the home environment is likely an important risk factor for pet MRSA carriage, and household interventions should be considered to reduce risk of MRSA carriage in exposed pets.

Characterization of resistance to newer antimicrobials among carbapenem-resistant Klebsiella pneumoniae in the post-acute-care setting.

We assessed susceptibility patterns to newer antimicrobial agents among clinical carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from patients in long-term acute-care hospitals (LTACHs) from 2014 to 2015. Meropenem-vaborbactam and imipenem-relebactam nonsusceptibility were observed among 9.9% and 9.1% of isolates, respectively. Nonsusceptibility to ceftazidime-avibactam (1.1%) and plazomicin (0.8%) were uncommon.

Clinical Outcomes and Risk Factors for Carbapenem-resistant Enterobacterales Bloodstream Infection in Solid Organ Transplant Recipients.

BACKGROUND: The clinical outcomes associated with, and risk factors for, carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) in solid organ transplant (SOT) recipients remain ill-defined. METHODS: A multicenter retrospective cohort study was performed, including SOT recipients with an Enterobacterales BSI between 2005 and 2018. Exposed subjects were those with a CRE BSI. Unexposed subjects were those with a non-CRE BSI. A multivariable survival analysis was performed to determine the association between CRE BSI and risk of all-cause mortality within 60 d. Multivariable logistic regression analysis was performed to determine independent risk factors for CRE BSI. RESULTS: Of 897 cases of Enterobacterales BSI in SOT recipients, 70 (8%) were due to CRE. On multivariable analysis, CRE BSI was associated with a significantly increased hazard of all-cause mortality (adjusted hazard ratio, 2.85; 95% confidence interval [CI], 1.68-4.84; P < 0.001). Independent risk factors for CRE BSI included prior CRE colonization or infection (adjusted odds ratio [aOR] 9.86; 95% CI, 4.88-19.93; P < 0.001)' liver transplantation (aOR, 2.64; 95% CI, 1.23-5.65; P = 0.012)' lung transplantation (aOR, 3.76; 95% CI, 1.40-10.09; P = 0.009)' and exposure to a third-generation cephalosporin (aOR, 2.21; 95% CI, 1.17-4.17; P = 0.015) or carbapenem (aOR, 2.80; 95% CI, 1.54-5.10; P = 0.001) in the prior 6 months. CONCLUSIONS: CRE BSI is associated with significantly worse outcomes than more antibiotic-susceptible Enterobacterales BSI in SOT recipients.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) surface contamination in staff common areas and impact on healthcare worker infection: Prospective surveillance during the coronavirus disease 2019 (COVID-19) pandemic.

We prospectively surveyed SARS-CoV-2 RNA contamination in staff common areas within an acute-care hospital. An increasing prevalence of surface contamination was detected over time. Adjusting for patient census or community incidence of coronavirus disease 2019 (COVID-19), the proportion of contaminated surfaces did not predict healthcare worker COVID-19 infection on study units.

Transmission of Carbapenem-Resistant Klebsiella pneumoniae in US Hospitals.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKp) is the most prevalent carbapenem-resistant Enterobacterales in the United States. We evaluated CRKp clustering in patients in US hospitals. METHODS: From April 2016 to August 2017, 350 patients with clonal group 258 CRKp were enrolled in the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae, a prospective, multicenter, cohort study. A maximum likelihood tree was constructed using RAxML. Static clusters shared ≤21 single-nucleotide polymorphisms (SNP) and a most recent common ancestor. Dynamic clusters incorporated SNP distance, culture timing, and rates of SNP accumulation and transmission using the R program TransCluster. RESULTS: Most patients were admitted from home (n = 150, 43%) or long-term care facilities (n = 115, 33%). Urine (n = 149, 43%) was the most common isolation site. Overall, 55 static and 47 dynamics clusters were identified involving 210 of 350 (60%) and 194 of 350 (55%) patients, respectively. Approximately half of static clusters were identical to dynamic clusters. Static clusters consisted of 33 (60%) intrasystem and 22 (40%) intersystem clusters. Dynamic clusters consisted of 32 (68%) intrasystem and 15 (32%) intersystem clusters and had fewer SNP differences than static clusters (8 vs 9; P = .045; 95% confidence interval [CI]: -4 to 0). Dynamic intersystem clusters contained more patients than dynamic intrasystem clusters (median [interquartile range], 4 [2, 7] vs 2 [2, 2]; P = .007; 95% CI: -3 to 0). CONCLUSIONS: Widespread intrasystem and intersystem transmission of CRKp was identified in hospitalized US patients. Use of different methods for assessing genetic similarity resulted in only minor differences in interpretation.

Risk Factors for Colistin-Resistant Carbapenem-Resistant Klebsiella pneumoniae in the Postacute Care Setting.

We assessed risk factors for colistin resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) from 375 patients in long-term acute care hospitals. Recent colistin or polymyxin B exposure was associated with increased odds of colistin resistance (adjusted odds ratio = 1.11 per day of exposure, 95% confidence interval = 1.03-1.19, P = .007).

The Impact of Reported ß-Lactam Allergy on Clinical Outcomes and Antibiotic Use Among Solid Organ Transplant Recipients.

Background: Reported ß-lactam allergies (BLAs) are common and frequently inaccurate, but there are limited data on the clinical implications of BLA among solid organ transplant (SOT) recipients. We examined the impact of BLA on clinical outcomes and antibiotic use among SOT recipients. Methods: This retrospective cohort study included adult patients undergoing single-organ heart, kidney, liver, lung, or pancreas transplant at a United States academic medical center from 1 April 2017 to 31 December 2020. Demographic and clinical data were collected from the electronic health record. Multivariate median regression was performed to evaluate the association between BLA and days alive and out of the hospital in the first 180 days posttransplant (DAOH180). Multivariate logistic regression was performed to evaluate the association between BLA and antibiotic use. Results: Among 1700 SOT recipients, 285 (16.8%) had a BLA at the time of transplant. BLA was not associated with DAOH180 (adjusted median difference, -0.8 days [95% confidence interval {CI}, -2.7 to 1.2]; P = .43). Patients with BLA were more likely to receive intravenous vancomycin (adjusted odds ratio [aOR], 1.8 [95% CI, 1.3-2.6]; P < .001), clindamycin (aOR, 9.9 [95% CI, 5.1-18.9]; P < .001), aztreonam (aOR, 19.6 [95% CI, 5.9-64.4]; P < .001), fluoroquinolones (aOR, 3.8 [95% CI, 2.8-5.0]; P < .001), or aminoglycosides (aOR, 3.9 [95% CI, 2.5-6.2]; P < .001). Conclusions: BLA was associated with use of ß-lactam alternative antibiotics but not DAOH180 among SOT recipients.

Impact of deceased organ donor injection drug use on donor culture positivity and recipient outcomes.

BACKGROUND: Due to the ongoing opioid epidemic in the United States, deceased organ donors increasingly have a history of injection drug use (IDU), raising concerns about infectious risks to solid organ transplant (SOT) recipients. We sought to determine how recent IDU among deceased organ donors impacted donor culture results and recipient outcomes. METHODS: A retrospective cohort study was performed at three transplant centers. Exposed donors were those with "recent IDU" (in the prior 12 months). Primary outcomes included (1) positive donor cultures for bacteria or Candida species, (2) recipient bacterial or Candida infection within 3 months posttransplant, and (3) recipient graft failure or death within 12 months posttransplant. Mixed effects multivariable regression models were used to evaluate the relationship between recent donor IDU and each outcome. RESULTS: A total of 658 SOT recipients who received organs from 394 donors were included. Sixty-six (17%) donors had a history of recent IDU. Recent IDU in donors was associated with a significantly increased odds of donor culture positivity (aOR 3.65, 95% CI 1.06-12.60, p = .04) but was not associated with SOT recipient infection (aHR 0.98, 95% CI 0.71-1.36, p = .92) or graft failure or death (aHR 0.67, 95% CI 0.29-1.51, p = .33). CONCLUSION: Donors with recent IDU are more likely to have positive cultures, but their recipients' outcomes are unaffected, suggesting organs from donors with recent IDU may be safely utilized.

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.

Comparability of clinical trials and spontaneous reporting data regarding COVID-19 vaccine safety.

Severe adverse events (AEs) after COVID-19 vaccination are not well studied in randomized controlled trials (RCTs) due to rarity and short follow-up. To monitor the safety of COVID-19 vaccines ("Pfizer" vaccine dose 1 and 2, "Moderna" vaccine dose 1 and 2, and "Janssen" vaccine single dose) in the U.S., especially regarding severe AEs, we compare the relative rankings of these vaccines using both RCT and the Vaccine Adverse Event Reporting System (VAERS) data. The risks of local and systemic AEs were assessed from the three pivotal COVID-19 vaccine trials and also calculated in the VAERS cohort consisting of 559,717 reports between December 14, 2020 and September 17, 2021. AE rankings of the five vaccine groups calculated separately by RCT and VAERS were consistent, especially for systemic AEs. For severe AEs reported in VAERS, the reported risks of thrombosis and GBS after Janssen vaccine were highest. The reported risk of shingles after the first dose of Moderna vaccine was highest, followed by the second dose of the Moderna vaccine. The reported risk of myocarditis was higher after the second dose of Pfizer and Moderna vaccines. The reported risk of anaphylaxis was higher after the first dose of Pfizer vaccine. Limitations of this study are the inherent biases of the spontaneous reporting system data, and only including three pivotal RCTs and no comparison with other active vaccine safety surveillance systems.

Distributed learning for heterogeneous clinical data with application to integrating COVID-19 data across 230 sites.

Integrating real-world data (RWD) from several clinical sites offers great opportunities to improve estimation with a more general population compared to analyses based on a single clinical site. However, sharing patient-level data across sites is practically challenging due to concerns about maintaining patient privacy. We develop a distributed algorithm to integrate heterogeneous RWD from multiple clinical sites without sharing patient-level data. The proposed distributed conditional logistic regression (dCLR) algorithm can effectively account for between-site heterogeneity and requires only one round of communication. Our simulation study and data application with the data of 14,215 COVID-19 patients from 230 clinical sites in the UnitedHealth Group Clinical Research Database demonstrate that the proposed distributed algorithm provides an estimator that is robust to heterogeneity in event rates when efficiently integrating data from multiple clinical sites. Our algorithm is therefore a practical alternative to both meta-analysis and existing distributed algorithms for modeling heterogeneous multi-site binary outcomes.

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.

Persisting uropathogenic Escherichia coli lineages show signatures of niche-specific within-host adaptation mediated by mobile genetic elements.

Large-scale genomic studies have identified within-host adaptation as a hallmark of bacterial infections. However, the impact of physiological, metabolic, and immunological differences between distinct niches on the pathoadaptation of opportunistic pathogens remains elusive. Here, we profile the within-host adaptation and evolutionary trajectories of 976 isolates representing 119 lineages of uropathogenic Escherichia coli (UPEC) sampled longitudinally from both the gastrointestinal and urinary tracts of 123 patients with urinary tract infections. We show that lineages persisting in both niches within a patient exhibit increased allelic diversity. Habitat-specific selection results in niche-specific adaptive mutations and genes, putatively mediating fitness in either environment. Within-lineage inter-habitat genomic plasticity mediated by mobile genetic elements (MGEs) provides the opportunistic pathogen with a mechanism to adapt to the physiological conditions of either habitat, and reduced MGE richness is associated with recurrence in gut-adapted UPEC lineages. Collectively, our results establish niche-specific adaptation as a driver of UPEC within-host evolution.

Risk factors for antimicrobial resistance among Staphylococcus isolated from pets living with a patient diagnosed with methicillin-resistant Staphylococcus aureus infection.

It has been suggested that pets play a critical role in the maintenance of methicillin-resistant (MR) and multidrug-resistant (MDR) Staphylococcus spp. in the household. We examined risk factors for carriage of antimicrobial-resistant coagulase-positive staphylococci, with particular attention to Staphylococcus aureus and Staphylococcus pseudintermedius isolated from pets living in households of people diagnosed with methicillin-resistant S. aureus (MRSA) skin or soft-tissue infection. We analyzed data collected cross-sectionally from a study conducted in 2012 that evaluated the transmission of MRSA and other staphylococci from humans, their pets and the environment (Pets and Environmental Transmission of Staphylococci [PETS] study). We used unadjusted and adjusted stratified logistic regression analyses with household-clustered standard errors to evaluate the association between demographic, healthcare-related, contact-related and environmental risk factors and MDR Staphylococcus spp. isolated from dogs and cats. Staphylococcal isolates obtained from dogs (n = 63) and cats (n = 47) were included in these analyses. The use of oral or injectable antimicrobials by the pets during the prior year was the main risk factor of interest. Based on our results, 50% (12/24) of S. aureus, 3.3% (1/30) of S. pseudintermedius and 25% (14/56) of other coagulase-positive staphylococci (CPS) were determined to be MDR. S. aureus isolates were more likely to be MDR compared with S. pseudintermedius. We did not find a significant statistical association between the use of oral or injectable antimicrobials in the prior year and the presence of MDR bacteria. The results suggest that drivers of antimicrobial resistance in household staphylococci may vary by bacterial species, which could have implications for one health intervention strategies for staphylococci and inform the investigation of other reverse zoonoses, such as COVID-19.