Evidence of transmission of New Delhi metallo-ß-lactamase-producing Klebsiella pneumoniae through a gastrointestinal endoscope without an elevator channel.

OBJECTIVE: To investigate the source and transmission dynamics of an endoscope-associated New Delhi metallo-ß-lactamase-producing Klebsiella pneumonia (NDM-KP) outbreak. DESIGN: Epidemiological and genomic investigation. SETTING: Academic acute care hospital in New Jersey. PATIENTS: Five patients with active NDM-KP infection identified on clinical isolates, and four NDM-KP colonized patients identified via rectal swab screening. RESULTS: Over a twelve-month period, nine patients were identified with NDM-KP infection or colonization. Whole-genome sequencing (WGS) revealed that all of the identified cases were related by 25 mutational events or less. Seven of the cases were linked to gastrointestinal endoscopic procedures (four clinical cases and three positive screens among patients exposed to endoscopes suspected of transmission). Two cases demonstrated delayed transmission that occurred five months after the initial outbreak, likely through shared usage of a non-therapeutic gastroscope without an elevator channel. CONCLUSIONS: Although all endoscope cultures in our investigation were negative, the epidemiological link to gastrointestinal endoscopes, the high degree of relatedness via WGS, and the identification of asymptomatic NDM-KP colonization among patients exposed to shared endoscopes make the endoscopic mode of transmission most likely. This investigation highlights the probable transmission of NDM-KP via a gastroscope without an elevator channel, observed several months after an initial outbreak. We hypothesize that persistent mechanical defects may have contributed to the delayed device-related transmission of NDM-KP.

Sulbactam-durlobactam: a ß-lactam/ß-lactamase inhibitor combination targeting Acinetobacter baumannii.

Sulbactam-durlobactam is a pathogen-targeted ß-lactam/ß-lactamase inhibitor combination that has been approved by the US FDA for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex (ABC) in patients 18 years of age and older. Sulbactam is a penicillin derivative with antibacterial activity against Acinetobacter but is prone to hydrolysis by ß-lactamases encoded by contemporary isolates. Durlobactam is a diazabicyclooctane ß-lactamase inhibitor with activity against Ambler classes A, C and D serine ß-lactamases that restores sulbactam activity both in vitro and in vivo against multidrug-resistant ABC. Sulbactam-durlobactam is a promising alternative therapy for the treatment of serious Acinetobacter infections, which can have high rates of mortality.

Sulbactam­durlobactam: a drug for treating lung infections Acinetobacter is a type of bacteria. One type, called CRAB, causes serious infections and can be fatal. CRAB is very hard to treat because most drugs no longer work. Sulbactam­durlobactam (SUL-DUR) is a drug that can kill CRAB. The US FDA approved SUL-DUR in May of 2023 for treating lung infections (pneumonia) caused by CRAB. This article explains how SUL-DUR works. Use of SUL-DUR and other drugs to treat these types of infections are discussed. In conclusion, SUL-DUR is a promising therapy for serious infections caused by CRAB.

An Open-Label, Randomized Trial Comparing Fidaxomicin With Oral Vancomycin for the Treatment of Clostridioides difficile Infection in Hospitalized Patients Receiving Concomitant Antibiotics for Concurrent Infections.

BACKGROUND: Recurrent Clostridioides difficile infection (rCDI) occurs frequently, and concomitant antibiotic (CA) during the initial episode for treatment of non-CDI is a major risk factor. We sought to address the comparative efficacy of fidaxomicin versus vancomycin in the setting of CA during the initial CDI episode. METHODS: We conducted a randomized, controlled, open-label trial at 2 hospitals in Ann Arbor, Michigan. We consecutively consented and enrolled hospitalized patients ≥18 years old with diarrhea, a positive test for C. difficile, and ≥1 qualifying CA. Complicated CDI, CDI treatment for >24 hours prior to enrollment, and planned long-term (>12 weeks) CA use were notable exclusions. Clinical cure was defined as resolution of diarrhea for 2 consecutive days maintained until 2 days after therapy, and rCDI as recurrent diarrhea with positive testing ≤30 days after initial treatment. Patients were randomized to fidaxomicin or vancomycin. RESULTS: Baseline characteristics were similar in the 2 groups of 144 patients. Rates of clinical cure (73% vs 62.9%, P = .195) and rCDI (3.3% vs 4.0%; P > .99) were similar for fidaxomicin and vancomycin in the intention-to-treat and per-protocol cohorts, respectively. Only 4 patients developed rCDI. CONCLUSIONS: In this study of patients with CDI receiving CA, a numerically higher proportion were cured with fidaxomicin versus vancomycin, but this result did not reach statistical significance. Overall recurrence was lower than anticipated in both arms compared with previous studies that did not extend duration of CDI treatment during CA. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT02692651).

Parent-reported social-communication changes in children diagnosed with autism spectrum disorder during the COVID-19 pandemic in the UK.

Introduction: The coronavirus pandemic has swept across the United Kingdom (UK). Given the ever-evolving situation, little is known about the repercussions of coronavirus and the subsequent lockdowns for children diagnosed with Autism Spectrum Disorder (ASD). Therefore, this study explores the social-communicative impact of the first lockdown (March 2020 - July 2020) in the UK and the return to school period (September 2020 - October 2020), following prolonged disruption to routine, in children diagnosed with ASD. Methods : Parents of autistic children completed 2 separate online surveys following the first lockdown in the UK (n = 176) and also when children returned to school following the summer break (n = 54). Results : The results suggested that self-regulation skills (p < .05) and co-operation skills (p < .05) were most affected over the course of the lockdown. Children's physical activity levels were perceived to significantly increase during the return to school (p < .0001), which was associated with better social-communication outcomes (p < .05). Conclusion : Future work is needed to confirm and explore the findings. Such work could be implemented to protect and improve the social-communicative outcomes of autistic children.

Epidemiology of resistant gram-negative bacteria in nursing homes.

BACKGROUND: Resistant gram-negative bacteria (R-GNB) colonization in nursing home patients can cause clinical infection and intrafacility transmission. Limited data exist on the roles of age and function on R-GNB colonization. METHODS: A secondary data analysis was performed from a cohort study of 896 patients admitted to 6 Michigan nursing homes between November 2013 and May 2018. Swabs obtained upon enrollment, weekly for 1 month, then monthly until nursing home discharge from 5 anatomical sites were cultured for GNB. R-GNB were defined as resistant to ciprofloxacin, ceftazidime, or imipenem. Patients with growth of the same R-GNB as the initial positive visit, from any anatomical site at any subsequent visit, were considered persistently colonized. Demographic data, antibiotic use, device use, and physical self-maintenance scales (PSMSs) were obtained upon enrollment. Characteristics were compared between patients with R-GNB colonization versus those without, and those with persistent R-GNB colonization versus those with spontaneous decolonization. RESULTS: Of 169 patients with a positive R-GNB culture and ≥2 subsequent study visits, 89 (53%) were transiently colonized and 80 (47%) were persistently colonized. Compared to uncolonized patients, persistent and transient R-GNB colonization were associated with higher PSMS score: 1.14 (95% confidence interval or CI, 1.05-1.23; P = .002) and 1.10 (95% CI, 1.01-1.19; P = .023), respectively. Persistent colonization was independently associated with longer duration of nursing home stay (1.02; 95% CI, 1.01-1.02; P < .001). Higher readmission rate among persistently colonized patients was observed on unadjusted analysis. CONCLUSIONS: Persistent R-GNB colonization is associated with younger age, functional disability, and prolonged length of nursing home stay. In-depth longitudinal studies to understand new acquisition and transmission dynamics of R-GNB in nursing homes are needed.

Dancing out for a voice; a narrative review of the literature exploring autism, physical activity, and dance.

Autism Spectrum Disorder is characterised by profound challenges with social communication and social interaction. Currently, there are few therapeutic interventions that successfully target some of the functionally impairing traits associated with autism. Furthermore, many of these interventions comprise a variety of limitations; including, limited accessibility, extensive durations, or the requirement of a trained professional to deliver the intervention. New research suggests that instead of targeting all traits associated with Autism Spectrum Disorder with a single solution, scientific research should focus on providing therapeutic tools that alleviate functionally impairing facets specific to the individual. Owing to the nature of physical activity, sports, and dance (coordinated movement) these activities could provide opportunities to enhance communication skills and social development in autistic children. Therefore, this paper gives a narrative overview of the literature surrounding communication and coordinated movement; outlining what is meant by communication challenges, exploring the benefits of coordinated movement for traits associated with Autism Spectrum Disorder, and delineating how coordinated movement elicits positive outcomes for autistic children.

Association of Exposure to High-risk Antibiotics in Acute Care Hospitals With Multidrug-Resistant Organism Burden in Nursing Homes.

Importance: Little is known about the contribution of hospital antibiotic prescribing to multidrug-resistant organism (MDRO) burden in nursing homes (NHs). Objectives: To characterize antibiotic exposures across the NH patient's health care continuum (preceding health care exposure and NH stay) and to investigate whether recent antibiotic exposure is associated with MDRO colonization and room environment contamination at NH study enrollment. Design, Setting, and Participants: This is a secondary analysis of a prospective cohort study (conducted from 2013-2016) that enrolled NH patients and followed them up for as long as 6 months. The study was conducted in 6 NHs in Michigan among NH patients who were enrolled within 14 days of admission. Clinical metadata abstraction, multi-anatomical site screening, and room environment surveillance for MDROs were conducted at each study visit. Data were analyzed between May 2019 and November 2021. Exposures: Antibiotic data were abstracted from NH electronic medical records by trained research staff and characterized by class, route, indication, location of therapy initiation, risk for Clostridioides difficile infection (C diffogenic agents), and 2019 World Health Organization Access, Watch, and Reserve (AWARE) antibiotic stewardship framework categories. Main Outcomes and Measures: The primary outcomes were MDRO colonization and MDRO room environment contamination at NH study enrollment, measured using standard microbiology methods. Multivariable logistic regression was used to identify whether antibiotic exposure within 60 days was associated with MDRO burden at NH study enrollment. Additionally, antibiotic exposure data were characterized using descriptive statistics. Results: A total of 642 patients were included (mean [SD] age, 74.7 [12.2] years; 369 [57.5%] women; 402 [62.6%] White; median [IQR] NH days to enrollment, 6.0 [3.0-7.0]). Of these, 422 (65.7%) received 1191 antibiotic exposures: 368 (57.3%) received 971 hospital-associated prescriptions, and 119 (18.5%) received 198 NH-associated prescriptions. Overall, 283 patients (44.1%) received at least 1 C diffogenic agent, and 322 (50.2%) received at least 1 high-risk WHO AWARE antibiotic (watch or reserve agent). More than half of NH patients (364 [56.7%]) and room environments (437 [68.1%]) had MDRO-positive results at enrollment. In multivariable analysis, recent antibiotic exposure was positively associated with baseline MDRO colonization (odds ratio [OR], 1.70; 95% CI, 1.22-2.38) and MDRO environmental contamination (OR, 1.67; 95% CI, 1.17-2.39). Exploratory stratification by C diffogenic agent exposure increased the effect size (MDRO colonization: OR, 1.99; 95% CI, 1.33-2.96; MDRO environmental contamination: OR, 1.86; 95% CI, 1.24-2.79). Likewise, exploratory stratification by exposure to high-risk WHO AWARE antibiotics increased the effect size (MDRO colonization: OR, 2.32; 95% CI, 1.61-3.36; MDRO environmental contamination: OR, 1.86; 95% CI, 1.26-2.75). Conclusions and Relevance: The findings of this study suggest that high-risk, hospital-based antibiotics are a potentially high-value target to reduce MDROs in postacute care NHs. This study underscores the potential utility of integrated hospital and NH stewardship programming on regional MDRO epidemiology.

Environmental contamination with SARS-CoV-2 in nursing homes.

BACKGROUND: SARS-CoV-2 outbreaks in nursing homes (NHs) have been devastating and have led to the creation of coronavirus disease 2019 (COVID-19) units within NHs to care for affected patients. Frequency and persistence of SARS-CoV-2 environmental contamination in these units have not been studied. METHODS: A prospective cohort study was conducted between October 2020 and January 2021 in four Michigan NHs. Swabs from high-touch surfaces in COVID-19-infected patient rooms were obtained at enrollment and follow-up. Demographic and clinical data were collected from clinical records. Primary outcome of interest was the probability of SARS-CoV-2 RNA detection from specific environmental surfaces in COVID-19 patient rooms. We used multivariable logistic regression to assess patient risk factors for SARS-CoV-2 contamination. Pairwise Phi coefficients were calculated to measure correlation of site-specific environmental detection upon enrollment and during follow-up. RESULTS: One hundred and four patients with COVID-19 were enrolled (61.5% >80 years; 67.3% female; 89.4% non-Hispanic White; 51% short stay) and followed up for 241 visits. The study population had significant disabilities in activities of daily living (ADL; 81.7% dependent in four or more ADLs) and comorbidities, including dementia (55.8%), diabetes (40.4%), and heart failure (32.7%). Over the 3-month study period, 2087 swab specimens were collected (1896 COVID-19 patient rooms, 191 common areas). SARS-CoV-2 positivity was 28.4% (538/1896 swabs) on patient room surfaces and 3.7% (7/191 swabs) on common area surfaces. Nearly 90% (93/104) of patients had SARS-CoV-2 contamination in their room at least once. Environmental contamination upon enrollment correlated with contamination of the same site during follow-up. Functional independence increased the odds of proximate contamination. CONCLUSIONS: Environmental detection of viral RNA from surfaces in the rooms of COVID-19 patients is nearly universal and persistent; more investigation is needed to determine the implications of this for infectiousness. Patients with greater independence are more likely than fully dependent patients to contaminate their immediate environment.

Multidrug-Resistant Gram-Negative Bacteria: Infection Prevention and Control Update.

Multidrug-resistant gram-negative bacteria (MDR-GNB) pose one of the greatest challenges to health care today because of their propensity for human-to-human transmission and lack of therapeutic options. Containing the spread of MDR-GNB is challenging, and the application of multifaceted infection control bundles during an evolving outbreak makes it difficult to measure the relative impact of each measure. This article will review the utility of various infection control measures in containing the spread of various MDR-GNB and will provide the supporting evidence for these interventions.

Risk Factors for and Mechanisms of COlistin Resistance Among Enterobacterales: Getting at the CORE of the Issue.

BACKGROUND: Despite the recent emergence of plasmid-mediated colistin resistance, the epidemiology and mechanisms of colistin-resistant Enterobacterales (CORE) infections remain poorly understood. METHODS: A case-case-control study was conducted utilizing routine clinical isolates obtained at a single tertiary health system in Ann Arbor, Michigan. Patients with CORE isolates from January 1, 2016, to March 31, 2017, were matched 1:1 with patients with colistin-susceptible Enterobacterales (COSE) and uninfected controls. Multivariable logistic regression was used to compare clinical and microbiologic features of patients with CORE and COSE to controls. A subset of available CORE isolates underwent whole-genome sequencing to identify putative colistin resistance genes. RESULTS: Of 16 373 tested clinical isolates, 166 (0.99%) were colistin-resistant, representing 103 unique patients. Among 103 CORE isolates, 103 COSE isolates, and 102 uninfected controls, antibiotic exposure in the antecedent 90 days and age >55 years were predictors of both CORE and COSE. Of 33 isolates that underwent whole-genome sequencing, a large variety of mutations associated with colistin resistance were identified, including 4 mcr-1/mcr-1.1 genes and 4 pmrA/B mutations among 9 Escherichia coli isolates and 5 mgrB and 3 PmrA mutations among 8 Klebsiella pneumoniae isolates. Genetic mutations found in Enterobacter species were not associated with known phenotypic colistin resistance. CONCLUSIONS: Increased age and prior antibiotic receipt were associated with increased risk for patients with CORE and for patients with COSE. Mcr-1, pmrA/B, and mgrB were the predominant colistin resistance-associated mutations identified among E. coli and K. pneumoniae, respectively. Mechanisms of colistin resistance among Enterobacter species could not be determined.

When planning meets reality: COVID-19 interpandemic survey of Michigan Nursing Homes.

BACKGROUND: Nursing home (NH) populations have borne the brunt of morbidity and mortality of COVID-19. We surveyed Michigan NHs to evaluate preparedness, staffing, testing, and adaptations to these challenges. METHODS: Interpandemic survey responses were collected May 1-12, 2020. We used Pearson's Chi-squared test, Fisher's exact test, and logistic regression to evaluate relationships. RESULTS: Of 452 Michigan NHs contacted via e-mail, 145 (32.1%) opened the survey and of these, 143 (98.6%) responded. Sixty-eight percent of respondents indicated their response plan addressed most issues. NHs reported receiving rapidly changing guidance from many sources. Two-thirds reported shortages of personal protective equipment and other supplies. Half (50%) lacked sufficient testing resources with only 36% able to test residents and staff with suspected COVID-19. A majority (55%) experienced staffing shortages. Sixty-three percent experienced resignations, with front-line clinical staff more likely to resign, particularly in facilities caring for COVID-19 patients (P < .001). Facilities adapted quickly, creating COVID-19 units (78%) to care for patients on site. To reduce isolation, NHs facilitated communication via phone calls (98%), videoconferencing (96%), and window visits (81%). A majority continued to provide requisite therapies (90%). CONCLUSIONS: NHs experienced shortages of resources, testing supplies, and staffing challenges. COVID-19 in the facility was a key predictor of staff resignations. Facilities relied on rapidly changing, often conflicting advice from multiple sources, suggesting high-yield areas of improvement.

Doping practices in international weightlifting: analysis of sanctioned athletes/support personnel from 2008 to 2019 and retesting of samples from the 2008 and 2012 Olympic Games.

BACKGROUND: The pervasiveness of doping and findings of anti-doping corruption threaten weightlifting's position at the 2024 Olympic Games. Analysing the practices of doping in weightlifters could identify patterns in doping that assist in future detection. METHODS: We analysed publicly available data on sanctioned athletes/support personnel from the International Weightlifting Federation between 2008 and 2019 and announced retrospective Anti-Doping Rule Violations (ADRVs) from the 2008 and 2012 Olympic Games. RESULTS: There were 565 sanctions between 2008 and 2019 of which 82% related to the detection of exogenous Anabolic Androgenic Steroid (AAS) metabolites and markers indicating endogenous AAS usage. The detection of exogenous AAS metabolites, markers of endogenous AAS usage and other substance metabolites varied by IWF Continental Federation (p ≤ 0.05) with Europe (74%, 11%, 15%) and Asia (70%, 15%, 15%) showing a higher detection of exogenous AAS compared to Pan America (37%, 30%, 33%) and Africa (50%, 17%, 33%). When looking at the 10 most detected substances, the nations with the highest number of sanctions (range 17-35) all had at least one overrepresented substance that accounted for 38-60% of all detected substances. The targeted re-analysis of samples from the 2008 and 2012 Olympic Games due to the discovery of long-term metabolites for exogenous AAS resulted in 61 weightlifters producing retrospective ADRVs. This includes 34 original medallists (9 gold, 10 silver and 15 bronze), the highest of any sport identified by Olympic Games sample re-testing. The exogenous AAS dehydrochloromethyltestosterone and stanozolol accounted for 83% of detected substances and were present in 95% of these samples. CONCLUSION: Based on these findings of regional differences in doping practices, weightlifting would benefit from the targeted testing of certain regions and continuing investment in long-term sample storage as the sensitivity and specificity of detection continues to improve.

Partnering with Local Hospitals and Public Health to Manage COVID-19 Outbreaks in Nursing Homes.

BACKGROUND/OBJECTIVES: Almost half of deaths related to COVID-19 in the United States are linked to nursing homes (NHs). We describe among short-term and long-term residents at three NHs in Michigan the outbreak identification process, universal testing, point prevalence of COVID-19, and subsequent containment efforts, outcomes, and challenges. DESIGN: Outbreak investigation. SETTING: Three NHs in southeast Michigan. PARTICIPANTS: All residents (N = 215) at three NHs (total beds = 356) affiliated with a large academic healthcare system. METHODS: Upon detection of confirmed cases within the facility, each NH in collaboration and consultation with local hospital, public health officials, and parent corporation implemented immediate facility-wide testing and the following intervention measures: cohorting of COVID-19 positive residents; communication regarding testing and results with residents, healthcare professionals, and families; personal protective equipment reeducation and use throughout facilities; and dedicated staffing for infected patients cohorted in a dedicated COVID-19 wing. We collected patient data regarding demographics, symptoms, comorbidities, hospitalization, and 14-day outcomes. RESULTS: A total of 29 cases of COVID-19 were identified at three participating NHs. Nineteen cases of COVID-19 were identified through symptom-triggered testing from March 23 to April 23, 2020; 10 (4.7%) additional cases were identified through universal testing of 215 residents conducted from April 7 to 15, 2020. The hospitalization rate was 37.9%. The case fatality rate was 20.7% (6/29); these patients had multiple comorbidities. No residents who tested positive through the point-prevalence survey required hospitalization, and five were discharged home within 14 days. CONCLUSION: Proactive and coordinated steps between NH medical directors and administrators, referral hospitals including their laboratories, and local public health officials are necessary to rapidly respond to an outbreak and limit the transmission of COVID-19. This coordinated public health approach may save lives, minimize the burden to the healthcare system, and reduce healthcare costs.

Clinical and Molecular Epidemiology of Extended-Spectrum Beta-Lactamase-Producing Escherichia Coli Infections in Metro Detroit: Early Dominance of the ST-131 Clone.

INTRODUCTION: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli infections have become endemic worldwide. We aimed to describe the molecular and clinical epidemiology of ESBL-producing E. coli infections during a period of rising global prevalence. METHODS: Three hundred sixty-nine consecutive ESBL-producing E. coli infections in Detroit from 2010-2011 were analyzed. Sequence typing (ST) and CH typing were performed. Clinical characteristics and outcomes were compared between patients infected with ST131 and non-ST131 isolates. RESULTS: Ninety-six percent of isolates were ST 131, and 78.6% of ST 131 isolates produced blaCTX-M-15. Median time to effective therapy was 48 h vs. 35 h (P = 0.38) in the ST131 vs. non-ST131 groups. Ninety-day mortality rates (8% vs. 8%, P = 1.0) were similar between the two groups. CONCLUSION: blaCTX-M-15 ST131 E. coli predominated in Detroit during an early period of global ST131 dissemination. Patients with ST131 E. coli infections had similar clinical outcomes to those with non-ST131 E. coli infections.

Incorporating preauthorization into antimicrobial stewardship pharmacist workflow reduces Clostridioides difficile and gastrointestinal panel testing.

OBJECTIVE: To evaluate whether incorporating mandatory prior authorization for Clostridioides difficile testing into antimicrobial stewardship pharmacist workflow could reduce testing in patients with alternative etiologies for diarrhea. DESIGN: Single center, quasi-experimental before-and-after study. SETTING: Tertiary-care, academic medical center in Ann Arbor, Michigan. PATIENTS: Adult and pediatric patients admitted between September 11, 2019 and December 10, 2019 were included if they had an order placed for 1 of the following: (1) C. difficile enzyme immunoassay (EIA) in patients hospitalized >72 hours and received laxatives, oral contrast, or initiated tube feeds within the prior 48 hours, (2) repeat molecular multiplex gastrointestinal pathogen panel (GIPAN) testing, or (3) GIPAN testing in patients hospitalized >72 hours. INTERVENTION: A best-practice alert prompting prior authorization by the antimicrobial stewardship program (ASP) for EIA or GIPAN testing was implemented. Approval required the provider to page the ASP pharmacist and discuss rationale for testing. The provider could not proceed with the order if ASP approval was not obtained. RESULTS: An average of 2.5 requests per day were received over the 3-month intervention period. The weekly rate of EIA and GIPAN orders per 1,000 patient days decreased significantly from 6.05 ± 0.94 to 4.87 ± 0.78 (IRR, 0.72; 95% CI, 0.56-0.93; P = .010) and from 1.72 ± 0.37 to 0.89 ± 0.29 (IRR, 0.53; 95% CI, 0.37-0.77; P = .001), respectively. CONCLUSIONS: We identified an efficient, effective C. difficile and GIPAN diagnostic stewardship approval model.