Quantitative Analysis of Tug Sign: An Endoscopic Finding of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disorder characterized by esophageal inflammation and dysfunction, with a rising incidence affecting approximately 1:1000 individuals worldwide.1,2 Chronic inflammation can lead to tissue remodeling in the esophagus with fibrosis in the lamina propria that is partially responsible for symptoms and complications of EoE.3,4 At times, a firmness to the esophagus can be appreciated with a noticeable force required to obtain biopsies from EoE. This sensation has been described as the "tug" or "pull" sign.5,6 Recently, with the advent of endoscopic functional luminal impedance, the fibroelastic properties of the esophagus, including diminished compliance and distensibility, have been described in patients with EoE.7 Quantification of these fibroelastic properties of the esophagus may aid in diagnosis and prognosis of EoE. To this date, a method to quantitatively measure the "tug sign" has not been developed. The primary objective of this study was to measure if a quantifiable difference in force is required to obtain endoscopic esophageal biopsies in patients with EoE compared with those without.

Preliminary Experience With the Human Acellular Vessel: A Descriptive Case Series Detailing Early Use of a Bioengineered Blood Vessel for Arterial Repair.

BACKGROUND: An infection-resistant, immediately available conduit for trauma and urgent vascular reconstruction remains a critical need for successful limb salvage. While autologous vein remains the gold standard, vein-limited patients and size mismatch are common issues. The Human Acellular Vessel (HAV) (Humacyte, Inc., Durham, NC) is a bioengineered conduit with off-the-shelf availability and resistance to infection, ideal characteristics for patients with challenging revascularization scenarios. This report describes HAV implantation in patients with complex limb-threatening ischemia and limited conduit options who may have otherwise faced limb loss. METHODS: The Food and Drug Administration (FDA) expanded-access program was used to allow urgent implantation of the HAV for arterial reconstruction. Electronic medical records were reviewed with extraction of relevant data including patient demographics, surgical implantation, patency, infectious complications, and mortality. RESULTS: The HAV was implanted in 8 patients requiring vascular reconstruction. Graft or soft tissue infection was present in 2 patients. One patient with severe penetrating pelvic injury had 4 HAV placed to repair bilateral external iliac artery and vein injuries. There was 1 technical failure due to poor outflow, 2 patients died unrelated to HAV use, and 5 lower extremity bypasses maintained patency at an average of 11.4 months (range: 4-20 months). No HAV infectious complications were identified. CONCLUSIONS: This report is the first United States series describing early outcomes using the HAV under the FDA expanded-access program for urgent vascular reconstruction. The HAV demonstrates resistance to infection, reliable patency, and offers surgeons an immediate option when confronted with complex revascularization scenarios. Assessment of long-term outcomes will be important for future studies.

Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Among Skilled Nursing Facility Residents and Staff Members-Los Angeles County, August-September 2020.

BACKGROUND: The prevalence of current or past coronavirus disease 2019 in skilled nursing facility (SNF) residents is unknown because of asymptomatic infection and constrained testing capacity early in the pandemic. We conducted a seroprevalence survey to determine a more comprehensive prevalence of past coronavirus disease 2019 in Los Angeles County SNF residents and staff members. METHODS: We recruited participants from 24 facilities; participants were requested to submit a nasopharyngeal swab sample for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing and a serum sample for detection of SARS-CoV-2 antibodies. All participants were cross-referenced with our surveillance database to identify persons with prior positive SARS-CoV-2 results. RESULTS: From 18 August to 24 September 2020, we enrolled 3305 participants (1340 residents and 1965 staff members). Among 856 residents providing serum samples, 362 (42%) had current or past SARS-CoV-2 infection. Of the 346 serology-positive residents, 199 (58%) did not have a documented prior positive SARS-CoV-2 PCR result. Among 1806 staff members providing serum, 454 (25%) had current or past SARS-CoV-2 infection. Of the 447 serology-positive staff members, 353 (79%) did not have a documented prior positive SARS-CoV-2 PCR result. CONCLUSIONS: Past testing practices and policies missed a substantial number of SARS-CoV-2 infections in SNF residents and staff members.

Case of an atypical pituitary abscess.

A pituitary abscess is a rare intrasellar infection. Correct identification can be challenging preoperatively given its non-specific symptoms and imaging findings. We report a case of a young woman presenting with secondary amenorrhea, visual field deficits and a 2.6 cm pituitary lesion diagnosed to be a craniopharyngioma. A concomitant unexpected pituitary abscess was diagnosed intraoperatively without associated meningeal symptoms.

Coronavirus Disease 2019 (COVID-19) Infections Among Healthcare Workers, Los Angeles County, February-May 2020.

Across the world, healthcare workers (HCW) are at a greater risk of infection by coronavirus disease 2019 (COVID-19) due to the nature of their work. The Los Angeles County Department of Public Health (LAC DPH) set out to understand the impact of COVID-19 on healthcare facilities and HCWs by tracking and analyzing data from case-patient interviews of HCWs. As of 31 May, over 3 months into the pandemic, nearly 5500 positive HCWs were reported to LAC DPH, representing 9.6% of all cases. Cases reported working in 27 different setting types, including outpatient medical offices, correctional facilities, emergency medical services, and so forth, with the highest proportion from long-term care facilities (46.6%) and hospitals (27.7%). Case patients included both clinical and nonclinical roles, with nearly half (49.4%) of positive HCWs being nurses. Over two-thirds of HCWs (68.6%) worked at some point during their infectious period, and nearly half (47.9%) reported a known exposure to a positive patient and/or coworker within their facility. Overall, compared to all LAC cases, HCWs reported lower rates of hospitalization (5.3% vs 12.2%) and death (0.7% vs 4.3%) from COVID-19. There are many factors that increase HCWs risk of infection, including high-risk work environment, limited supply of personal protective equipment, and even pressure to help and work during a pandemic. In response to these data, LAC DPH created resources and provided guidance for healthcare facilities to best protect their patients and staff during the COVID-19 pandemic.

Effect of Contact Precautions on Staphylococcus aureus and Clinical Outcomes of Colonized Patients in the Neonatal Intensive Care Unit.

BACKGROUND: Staphylococcus aureus is a common pathogen in neonatal intensive care units (NICUs), yet little is known about the effect of contact precautions and clinical outcomes of colonized patients. METHODS: Retrospective cohort study of all neonates from August 2014 to November 2018 colonized with either methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA) and select noncolonized patients at two neonatal intensive care units at the University of California, Los Angeles. Outcomes during two time periods (during and after the use of contact precautions) were assessed. RESULTS: A total of 234 patients were included in the study: 83 colonized and 151 noncolonized patients. There was a fourfold higher incidence of MSSA colonization versus MRSA (P < 0.001). There was a higher incidence of positive surveillance cultures after contact precautions were discontinued (P = 0.01), but this did not correlate with a higher incidence of invasive cultures (P = 0.475). There were twice as many MSSA invasive cultures than MRSA, but a higher rate of invasion with MRSA (P < 0.05). Colonized patients were more likely to develop an invasive infection than noncolonized (P = 0.003 MRSA; P = 0.004 MSSA). When controlling for gestational age and surgical interventions, colonization was more likely to be associated with skin and soft tissue infections (P < 0.001) and a longer length of stay by a mean of 27.8 days (P < 0.0001). CONCLUSIONS: Contact precautions resulted in a lower incidence of colonization without a difference in invasive cultures in our NICUs. Those colonized with S. aureus had a higher incidence of skin and soft tissue infections and a longer NICU length of stay.

Outbreak Investigations: A Brief Primer for Gastroenterologists.

Transmission of pathogens during endoscopy and subsequent outbreak investigations generated by potential nosocomial transmissions have become a major concern for gastroenterologists. These investigations have resulted in significant media coverage for individual institutions and can cause massive disruption to the institution if not handled well. Gastroenterologists should have a central role in investigation of these outbreaks and management of the communications and patient notification that is required. This article summarizes important aspects of outbreak investigations for physicians who do not frequently manage these investigations and gives practical advice for how gastroenterologists can help identify outbreaks and manage these investigations successfully.

Seafood graded oral food challenge outcomes in a pediatric tertiary care center.

BACKGROUND: There are sparse data regarding the predictors of positive oral food challenges and reaction severity for seafood in children. OBJECTIVE: Identify clinical characteristics in children with seafood allergy who were most likely to experience a negative oral food challenge (OFC). METHODS: A retrospective chart review was performed for children who had a graded OFC to seafood at a pediatric tertiary care center from 2008 through 2019. RESULTS: Sixty-three (60% male; average age 8 years; range 1-21 years) OFCs were performed, of which 21 were fish and 42 were shellfish. There were 10 (16%) positive OFCs and positive OFC rate was similar between fish (19%) and shellfish (14%). Forty-three children who underwent OFC had a reported history of IgE-mediated symptoms. Five of six children who had a history of anaphylaxis had a negative OFC. There was no difference in positive OFCs due to age, history of atopy, or initial allergic reaction history. The clinical characteristics of the positive OFCs were similar between fish and shellfish. A positive skin prick test to fish or shellfish did not increase the risk of a positive OFC. While the positive OFC rate did not differ for the shellfish food-specific IgE (FSIgE) level, there was a significant difference for fish (median <0.34 kUA/L vs. 1.63 kUA/L for pass and fail, respectively; P = 0.023). CONCLUSION: A retrospective study of OFCs to seafood showed that the rate of a positive OFC was low. While seafood allergy is thought to be rarely outgrown, children who have a low FsIgE and/or skin testing can successfully tolerate seafood.

Evaluation of the National Healthcare Safety Network standardized infection ratio risk adjustment for healthcare-facility-onset Clostridioides difficile infection in intensive care, oncology, and hematopoietic cell transplant units in general acute-care hospitals.

OBJECTIVE: To evaluate the National Health Safety Network (NHSN) hospital-onset Clostridioides difficile infection (HO-CDI) standardized infection ratio (SIR) risk adjustment for general acute-care hospitals with large numbers of intensive care unit (ICU), oncology unit, and hematopoietic cell transplant (HCT) patients. DESIGN: Retrospective cohort study. SETTING: Eight tertiary-care referral general hospitals in California. METHODS: We used FY 2016 data and the published 2015 rebaseline NHSN HO-CDI SIR. We compared facility-wide inpatient HO-CDI events and SIRs, with and without ICU data, oncology and/or HCT unit data, and ICU bed adjustment. RESULTS: For these hospitals, the median unmodified HO-CDI SIR was 1.24 (interquartile range [IQR], 1.15-1.34); 7 hospitals qualified for the highest ICU bed adjustment; 1 hospital received the second highest ICU bed adjustment; and all had oncology-HCT units with no additional adjustment per the NHSN. Removal of ICU data and the ICU bed adjustment decreased HO-CDI events (median, -25%; IQR, -20% to -29%) but increased the SIR at all hospitals (median, 104%; IQR, 90%-105%). Removal of oncology-HCT unit data decreased HO-CDI events (median, -15%; IQR, -14% to -21%) and decreased the SIR at all hospitals (median, -8%; IQR, -4% to -11%). CONCLUSIONS: For tertiary-care referral hospitals with specialized ICUs and a large number of ICU beds, the ICU bed adjustor functions as a global adjustment in the SIR calculation, accounting for the increased complexity of patients in ICUs and non-ICUs at these facilities. However, the SIR decrease with removal of oncology and HCT unit data, even with the ICU bed adjustment, suggests that an additional adjustment should be considered for oncology and HCT units within general hospitals, perhaps similar to what is done for ICU beds in the current SIR.

Minimizing central line-associated bloodstream infections in a high-acuity liver transplant intensive care unit.

BACKGROUND: Increases in liver transplant patient perioperative acuity have resulted in frail immunosuppressed patients at elevated risk for nosocomial infections. Avoiding central line-associated bloodstream infections (CLABSIs) is paramount to facilitate transplantation and post-transplant recovery. In 2015, our liver transplant intensive care unit (ICU) CLABSIs accounted for more than 25% of all CLABSI at our institution. We therefore undertook a multidisciplinary collaborative among clinical epidemiology, nursing, transplant surgery, and critical care to eliminate CLABSI events. METHODS: From 2014-2016, using Lean methodology and plan-do-study-act (PDSA) cycles, 14 interventions were implemented in the liver transplant ICU. Interventions were aimed at infection prevention, care standardization, and team-based monitoring. Implementation used quality improvement methodology including audit and feedback, education, standardization, multidisciplinary stakeholder involvement, and PDSA cycles. Process measures were monitored and audited. CLABSI rates per 1,000 central venous catheter (CVC) days were tracked by clinical epidemiology. RESULTS: During the intervention, 901 CVC catheter audits were completed. Improvements were seen on all process measures, and complete compliance increased from 25%-67%. CLABSI infection rates dropped from 4.2 to 1.8 in 1,000 CVC days, with an average of less than 1 CLABSI per month. This marked a 61.2% annual reduction, which correlated with an estimated $935,000 annual savings. CONCLUSION: Concerted ongoing multidisciplinary collaboratives are essential to minimize CLABSI and optimize value and quality in a challenging, high-acuity patient population.

Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial.

Importance: The appropriate duration of antibiotics for staphylococcal bacteremia is unknown. Objective: To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events. Design, Setting, and Participants: A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization. Interventions: Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care. Main Outcomes and Measures: Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia. Results: Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, -6.2% to ∞]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, -3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, -1.8 days [95% CI, -3.1 to -0.6]). Conclusions and Relevance: Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm. Trial Registration: ClinicalTrials.gov Identifier: NCT01191840.

Practical methods for effective vancomycin-resistant enterococci (VRE) surveillance: experience in a liver transplant surgical intensive care unit.

OBJECTIVE: We evaluated the utility of vancomycin-resistant Enterococcus (VRE) surveillance by varying 2 parameters: admission versus weekly surveillance and perirectal swabbing versus stool sampling. DESIGN: Prospective, patient-level surveillance program of incident VRE colonization. SETTING: Liver transplant surgical intensive care unit (SICU) of a tertiary-care referral medical center with a high prevalence of VRE.PatientsAll patients admitted to the SICU from June to August 2015. METHODS: We conducted a point-prevalence estimate followed by admission and weekly surveillance by perirectal swabbing and/or stool sampling. Incident colonization was defined as a negative screen followed by positive surveillance. VRE was detected by culture on Remel Spectra VRE chromogenic agar. Microbiologically-confirmed VRE bloodstream infections (BSIs) were tracked for 2 months. Statistical analyses were calculated using the McNemar test, the Fisher exact test, the t test, and the χ2 test. RESULTS: In total, 91 patients underwent VRE surveillance testing. The point prevalence of VRE colonization was 60.9%; VRE prevalence on admission was 30.1%. Weekly surveillance identified an additional 7 of 28 patients (25.0%) with incident colonization. VRE BSIs were more common in VRE-colonized patients than in noncolonized patients (8 of 43 vs 2 of 48; P=.028). In a direct comparison, perirectal swabs were more sensitive than stool samples in detecting VRE (64 of 67 vs 56 of 67; P=.023). Compliance with perirectal swabbing was 89% (201 of 226) compared to 56% (127 of 226) for stool collection (P≤0.001). CONCLUSIONS: We recommend weekly VRE surveillance over admission-only screening in high-burden units such as liver transplant SICUs. Perirectal swabs had greater collection compliance and sensitivity than stool samples, making them the preferred methodology. Further work may have implications for antimicrobial stewardship and infection control.

Primary Prevention of Clostridium difficile-Associated Diarrhea: Current Controversies and Future Tools.

PURPOSE OF REVIEW: Clostridium difficile infection (CDI) is a major cause of morbidity and mortality in hospitalized patients and rates in most places have not decreased significantly despite broad efforts by both hospitals and public health entities. This review aims to provide readers with a better understanding of the limitations of current prevention strategies. We also review potential future tools that may be available for the primary prevention of CDI in the next decade. RECENT FINDINGS: Research over the last decade has expanded our appreciation of the role of asymptomatic shedding in the healthcare setting and in the community. This review demonstrates that poor quality data underlies even well-established guidance from national authorities on basic topics such as contact precautions, avoidance of alcohol-based hand hygiene products, CDI testing, supplemental cleaning modalities, and the use of bleach solutions. Additionally, we review research on novel preventative interventions such as identification of asymptomatic carriers, supplemental environmental cleaning technologies, vaccines, and the manipulation of the intestinal microbiome. While there is preliminary data that supports further research in all of these areas, the research is not yet robust enough on which to base local or national policy recommendations, though late-phase human clinical trials of CDI vaccine trials are ongoing. Over the last decade, researchers have begun to reassess the traditional infection prevention model for CDI. Data suggesting a greater role for asymptomatic shedders has increased our understanding of current vertical prevention techniques and is forcing researchers to look more at new processes and technologies to decrease disease incidence.

Safely reprocessing duodenoscopes: current evidence and future directions.

Highly publicised outbreaks of various infections related to the use of duodenoscopes have increased public awareness of the once arcane and largely ignored subject of endoscope reprocessing. Since 2015, national professional societies, multiple federal agencies, and even the US Senate have written reports and guidelines on duodenoscope reprocessing. However, their recommendations are sometimes contradictory and difficult to implement, and new research on the topic is published regularly which further complicates the situation. With this flood of new and sometimes contradictory information, clinicians can feel confused about how to assure the safety of their patients undergoing duodenosocopy. This Review summarises the most salient current research on duodenoscope-associated outbreaks and reprocessing, and aims to provide clinicians with practical information applicable to their practice.

Noninfectious Hospital Adverse Events Decline After Elimination of Contact Precautions for MRSA and VRE.

OBJECTIVETo evaluate the impact of discontinuing routine contact precautions (CP) for endemic methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) on hospital adverse events.DESIGNRetrospective, nonrandomized, observational, quasi-experimental study.SETTINGAcademic medical center with single-occupancy rooms.PARTICIPANTSInpatients.METHODSWe compared hospital reportable adverse events 1 year before and 1 year after discontinuation of routine CP for endemic MRSA and VRE (preintervention and postintervention periods, respectively). Throughout the preintervention period, daily chlorhexidine gluconate bathing was expanded to nearly all inpatients. Chart reviews were performed to identify which patients and events were associated with CP for MRSA/VRE in the preintervention period as well as the patients that would have met prior criteria for MRSA/VRE CP but were not isolated in the postintervention period. Adverse events during the 2 periods were compared using segmented and mixed-effects Poisson regression models.RESULTSThere were 24,732 admissions in the preintervention period and 25,536 in the postintervention period. Noninfectious adverse events (ie, postoperative respiratory failure, hemorrhage/hematoma, thrombosis, wound dehiscence, pressure ulcers, and falls or trauma) decreased by 19% (12.3 to 10.0 per 1,000 admissions, P=.022) from the preintervention to the postintervention period. There was no significant difference in the rate of infectious adverse events after CP discontinuation (20.7 to 19.4 per 1,000 admissions, P=.33). Patients with MRSA/VRE showed the largest reduction in noninfectious adverse events after CP discontinuation, with a 72% reduction (21.4 to 6.08 per 1,000 MRSA/VRE admissions; P<.001).CONCLUSIONAfter discontinuing routine CP for endemic MRSA/VRE, the rate of noninfectious adverse events declined, especially in patients who no longer required isolation. This suggests that elimination of CP may substantially reduce noninfectious adverse events.Infect Control Hosp Epidemiol 2018;788-796.

Multidrug Resistant Acinetobacter baumanii: A 15-Year Trend Analysis.

From 2000 to 2009, rates of multidrug-resistant Acinetobacter baumanii increased 10-fold to 0.2 per 1,000 patient days. From 2010 to 2015, however, rates markedly declined and have stayed below 0.05 per 1,000 patient days. Herein, we present a 15-year trend analysis and discuss interventions that may have led to the decline.Infect Control Hosp Epidemiol 2018;39:608-611.

Prevalence and Outcomes of Primary Immunodeficiency in Hospitalized Children in the United States.

BACKGROUND: Primary immunodeficiency diseases (PIDDs) are rare yet life-threatening chronic conditions in children. The prevalence and outcomes of PIDDs in the pediatric population in the United States are not well understood. OBJECTIVE: The objectives of this study were to (1) determine the epidemiology of children hospitalized with PIDD in the United States and (2) characterize the clinical outcomes of hospitalized children with PIDDs. METHODS: Retrospective cohort analysis of the 2003-2012 Kids' Inpatient Database of children aged 2-18 years admitted with a primary or secondary diagnosis code of PIDD was performed. Secondary immunodeficiency diseases were excluded. RESULTS: There were 26,794 pediatric patients hospitalized with a diagnosis of a PIDD from 2003 to 2012. The national prevalence of all PIDDs per 100,000 was 66.6, 82.2, 97.4, and 126.8 in 2003, 2006, 2009, and 2012, respectively. The highest prevalence was in children 0-5 years of age (15,105 hospitalizations; 56%). There was no difference in prevalence between B-cell defects and T-cell defects. PIDDs affected all ethnic populations equally. Respiratory-related diagnoses were the most common comorbidity by an organ system. Overall mortality was 1.99%. Age was inversely correlated with clinical outcome. Children 0-5 years had higher mortality (424 deaths, 79.85%), mean hospital charges ($35,480), and length of stay (LOS) (5.6 days) compared with older age cohorts. CONCLUSIONS: The prevalence of PIDDs in the hospitalized pediatric population in the United States may have increased over time. Younger age is associated with higher mortality, hospital costs, and LOS. Further study is needed to determine cost-effective management strategies to improve outcomes in infants and young children with PIDD.

Evolution and Transmission of Carbapenem-Resistant Klebsiella pneumoniae Expressing the blaOXA-232 Gene During an Institutional Outbreak Associated With Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND: Whole-genome sequencing (WGS) is an emerging and powerful technique by which to perform epidemiological studies in outbreak situations. METHODS: WGS was used to identify and evaluate an outbreak of OXA-232-expressing carbapenem-resistant Klebsiella pneumoniae (CRKP) transmitted to 16 patients over the course of 40 weeks via endoscopic retrograde cholangiopancreatography procedures at a single institution. WGS was performed on 32 OXA-232 CRKP isolates (1-7 per patient) and single-nucleotide variants (SNVs) were analyzed, with reference to the index patient's isolate. RESULTS: Interhost genetic diversity of isolates was between 0 and 15 SNVs during the outbreak; molecular clock calculations estimated 12.31 substitutions per genome per year (95% credibility interval, 7.81-17.05). Both intra- and interpatient diversification at the plasmid and transposon level was observed, significantly impacting the antibiogram of outbreak isolates. The majority of isolates evaluated (n = 27) harbored a blaCTX-M-15 gene, but some (n = 5) lacked the transposon carrying this gene, which resulted in susceptibility to aztreonam and third- and fourth-generation cephalosporins. Similarly, an isolate from a colonized patient lacked the transposon carrying rmtF and aac(6')lb genes, resulting in susceptibility to aminoglycosides. CONCLUSIONS: This study broadens the understanding of how bacteria diversify at the genomic level over the course of a defined outbreak and provides reference for future outbreak investigations.