Plerixafor for the Treatment of WHIM Syndrome.

WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis), a primary immunodeficiency disorder involving panleukopenia, is caused by autosomal dominant gain-of-function mutations in CXC chemokine receptor 4 (CXCR4). Myelokathexis is neutropenia caused by neutrophil retention in bone marrow. Patients with WHIM syndrome are often treated with granulocyte colony-stimulating factor (G-CSF), which can increase neutrophil counts but does not affect cytopenias other than neutropenia. In this investigator-initiated, open-label study, three severely affected patients with WHIM syndrome who could not receive G-CSF were treated with low-dose plerixafor, a CXCR4 antagonist, for 19 to 52 months. Myelofibrosis, panleukopenia, anemia, and thrombocytopenia were ameliorated, the wart burden and frequency of infection declined, human papillomavirus-associated oropharyngeal squamous-cell carcinoma stabilized, and quality of life improved markedly. Adverse events were mainly infections attributable to the underlying immunodeficiency. One patient died from complications of elective reconstructive surgery. (Funded by the National Institutes of Health.).

Multiple Variants of SARS-CoV-2 in a University Outbreak After Spring Break - Chicago, Illinois, March-May 2021.

To prevent transmission of SARS-CoV-2, the virus that causes COVID-19, colleges and universities have implemented multiple strategies including testing, isolation, quarantine, contact tracing, masking, and vaccination. In April 2021, the Chicago Department of Public Health (CDPH) was notified of a large cluster of students with COVID-19 at an urban university after spring break. A total of 158 cases of COVID-19 were diagnosed among undergraduate students during March 15-May 3, 2021; the majority (114; 72.2%) lived in on-campus dormitories. CDPH evaluated the role of travel and social connections, as well as the potential impact of SARS-CoV-2 variants, on transmission. Among 140 infected students who were interviewed, 89 (63.6%) reported recent travel outside Chicago during spring break, and 57 (40.7%) reported indoor social exposures. At the time of the outbreak, undergraduate-aged persons were largely ineligible for vaccination in Chicago; only three of the students with COVID-19 (1.9%) were fully vaccinated. Whole genome sequencing (WGS) of 104 specimens revealed multiple distinct SARS-CoV-2 lineages, suggesting several nearly simultaneous introductions. Most specimens (66; 63.5%) were B.1.1.222, a lineage not widely detected in Chicago before or after this outbreak. These results demonstrate the potential for COVID-19 outbreaks on university campuses after widespread student travel during breaks, at the beginning of new school terms, and when students participate in indoor social gatherings. To prevent SARS-CoV-2 transmission, colleges and universities should encourage COVID-19 vaccination; discourage unvaccinated students from travel, including during university breaks; implement serial COVID-19 screening among unvaccinated persons after university breaks; encourage masking; and implement universal serial testing for students based on community transmission levels.

Universal molecular Clostridioides difficile screening and overtreatment in solid organ transplant recipients.

BACKGROUND: Screening for Clostridioides difficile (CD) colonization can be performed using molecular testing to identify the presence of microbial DNA of the toxin gene. Colonization rates for hospitalized patients are as high as 20% and may be considerably higher in solid organ transplant (SOT) recipients. Treatment for CD should be based on clinical disease and not colonization, yet clinicians may misinterpret a positive CD screen resulting in overtreatment. OBJECTIVES: The objective of this analysis is to determine how often positive CD screens resulted in inappropriate treatment with oral vancomycin. METHODS: Clostridioides difficile screens were performed using the Xpert C difficile assay (Cepheid), a nucleic acid amplification testing method utilizing polymerase chain reaction (PCR), on peri-rectal swabs for newly admitted patients. This was a single-center cohort study of adult patients with CD screens hospitalized between July 2015 and November 2018. The primary outcome was the rate of inappropriate oral vancomycin treatment in all patients and in SOT recipients, defined as therapy in the absence of diarrhea. RESULTS: Of the 47 076 total CD screens reviewed, 1,921 were positive. In the SOT cohort, 58 of 329 screens were positive (4.1% vs 17.9%, P < .01). Of all patients with a positive CD screen, 20.1% (386/1921) were treated with oral vancomycin within 48 hours of swab collection. In the SOT cohort, 39.6% (23/58) with positive CD screens were treated with oral vancomycin within 48 hours. Of the SOT patients who received oral vancomycin, 39% (9/23) did not have true CD infection. CONCLUSION: Solid organ transplant recipients were more likely to have CD colonization detected by peri-rectal screening than the general inpatient population. SOT and non-SOT patients were treated with oral vancomycin at similar rates in response to the positive screen. Nearly half of the oral vancomycin use in SOT recipients was likely overtreatment, but this finding is limited by the low number of patients in this cohort.

Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012-2013.

Background: Influenza vaccination aims to prevent infection by influenza virus and reduce associated morbidity and mortality; however, vaccine effectiveness (VE) can be modest, especially for subtype A(H3N2). Low VE has been attributed to mismatches between the vaccine and circulating influenza strains and to the vaccine's elicitation of protective immunity in only a subset of the population. The low H3N2 VE in the 2012-2013 season was attributed to egg-adaptive mutations that created antigenic mismatch between the actual vaccine strain (IVR-165) and both the intended vaccine strain (A/Victoria/361/2011) and the predominant circulating strains (clades 3C.2 and 3C.3). Methods: We investigated the basis of low VE in 2012-2013 by determining whether vaccinated and unvaccinated individuals were infected by different viral strains and by assessing the serologic responses to IVR-165, A/Victoria/361/2011, and 3C.2 and 3C.3 strains in an adult cohort before and after vaccination. Results: We found no significant genetic differences between the strains that infected vaccinated and unvaccinated individuals. Vaccination increased titers to A/Victoria/361/2011 and 3C.2 and 3C.3 representative strains as much as to IVR-165. These results are consistent with the hypothesis that vaccination boosted cross-reactive immune responses instead of specific responses against unique vaccine epitopes. Only approximately one-third of the cohort achieved a ≥4-fold increase in titer. Conclusions: In contrast to analyses based on ferret studies, low H3N2 VE in 2012-2013 in adults does not appear to be due to egg adaptation of the vaccine strain. Instead, low VE might have been caused by low vaccine immunogenicity in a subset of the population.

Understanding the Experiences of Obstetrics and Gynaecology Residents Who Take Parental Leave During Training in Canada: A Needs Assessment.

OBJECTIVE: This study sought to identify and understand the barriers and supports associated with taking parental leave during obstetrics and gynaecology residency training in Canada, with the aim of helping to direct parental leave policies. METHODS: Participants were recruited by social media, program directors, and through the SOGC. The study included a short demographic questionnaire and a semistructured qualitative interview in person, by either telephone or videoconference. The interviews were recorded, transcribed, and anonymized. Descriptive thematic analysis using the constant comparative method of grounded theory was performed on each transcript by two independent investigators. Codes were applied to each sentence of the transcript to identify the main idea in the text segment. Once coding was complete the investigators looked for relationships among codes to define themes. Data collection continued until a saturation of themes was reached. RESULTS: Fifteen participants from across Canada completed the study. The most significant challenges surrounding parental leave during residency included breastfeeding, difficulty on return to work (skill loss, time management, examination preparation), and work-life balance. The major supports noted included family, colleagues and mentors, adequate childcare, and program flexibility surrounding the leave. Participants' suggestions for alleviating the stressors included a gradual return to work and careful planning surrounding returning rotation. CONCLUSION: Trainees identified formal program supports, non-surgical or core initial rotation back, and a gradual return to work as important areas to address in policies surrounding resident parental leave during Canadian obstetrics and gynaecology training.

An Apple a Day.

In this narrative medicine essay, an infectious diseases physician compares her past near bucolic experience in the emergency department when treated for anaphylaxis with the now perpetually chaotic and crowded scene ushered in by COVID-19.

Risk of infection transmission in curvilinear array echoendoscopes: results of a prospective reprocessing and culture registry.

BACKGROUND AND AIMS: The complex design of the elevator mechanism in duodenoscopes has been recognized as a challenge for disinfection and recently implicated as a potential source of persistent bacterial contamination. Curvilinear array (CLA) echoendoscopes also have an elevator mechanism; however, there are no recommendations or data regarding the risk of persistent bacterial contamination of echoendoscopes. Here we hoped to determine the yield of microbial growth with routine bacterial surveillance cultures of reprocessed CLA echoendoscopes. METHODS: Beginning in February 2015 to February 2016, CLA echoendoscopes at a single tertiary care center underwent prospective bacterial surveillance cultures after reprocessing. Any growth of gram-negative bacilli was considered to be critical. Echoendoscopes with a positive result underwent quarantine followed by repeat disinfection and culture. RESULTS: During the study period, 540 cultures were obtained; 521 (96.5%) were primary cultures obtained from 18 CLA echoendoscopes. Twenty-two primary cultures (4.2%) were positive for gram-negative bacilli after high-level disinfection reprocessing. Eleven different bacteria were isolated: Klebsiella pneumoniae, Citrobacter freundii, Escherichia coli, Pseudomonas aeruginosa, Klebsiella oxytoca, Sphingomonas paucimobilis, Acinetobacter baumanii, Enterobacter cloacae, Hafnia alvei, Pseudomonas putida, and Stenotrophomonas maltophilia. Antibiotic sensitivity data on 19 of 24 bacteria (79.2%) isolated from positive primary cultures revealed no documented cases of carbapenem-resistant enterobacteriaceae, cephalosporin-resistant-Klebsiella, or multidrug-resistant Acinetobacter. There have been no documented cases of patient-to-patient transmission. CONCLUSIONS: After following standard high-level disinfection and reprocessing, CLA echoendoscopes can remain culture positive for high-concern organisms. Recommendations regarding infection risk should take into consideration elevator-containing echoendoscopes in addition to duodenoscopes to ensure patient safety and endoscope reprocessing efficacy.

Impact of Pharmacy Practice Model Expansion on Pharmacokinetic Services: Optimization of Vancomycin Dosing and Improved Patient Safety.

Background: The impact of pharmacy interventions on optimizing vancomycin therapy has been described, however interventions vary among studies and the most optimal pharmacy practice model (PPM) for pharmacokinetic (PK) services has not been established. Objective: The purpose of this study is to demonstrate the value of 24 hours a day, 7 days a week (24/7) PK services. Methods: New PK services were implemented in 2 phases with institutional PPM expansion. Phase 1 included universal monitoring by pharmacists with recommendations made to prescribers during business hours. Phase 2 expanded clinical pharmacists' coverage to 24/7 and provided an optional 24/7 pharmacist-managed PK consult service. We compared vancomycin therapeutic trough attainment, dosing, and clinical and safety outcomes between phases 1 and 2 in adult inpatients receiving therapeutic intravenous vancomycin. Results. One hundred and fifty patients were included in each phase. Phase 2 had a greater proportion of vancomycin courses with therapeutic initial trough concentrations (27.5% vs 46.1%; p = 0.002), higher initial trough concentrations (10.9 mcg/mL vs 16.4 mcg/mL; p < 0.001), and optimized initial vancomycin dosing (13.5 mg/kg vs 16.2 mg/kg; p < 0.001). Phase 2 also saw significant reduction in the incidence of vancomycin-associated nephrotoxicity (21.1% vs 11.7%; p = 0.038). Dose optimization and improvement in initial target trough attainment were most notable among intensive care unit (ICU) patients. Conclusions. Our study demonstrated that 24/7 PK services implemented with institutional PPM expansion optimized vancomycin target trough attainment and improved patient safety.

Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus - United States, May 2013-August 2016.

Candida auris, an emerging fungus that can cause invasive infections, is associated with high mortality and is often resistant to multiple antifungal drugs. C. auris was first described in 2009 after being isolated from external ear canal discharge of a patient in Japan (1). Since then, reports of C. auris infections, including bloodstream infections, have been published from several countries, including Colombia, India, Israel, Kenya, Kuwait, Pakistan, South Africa, South Korea, Venezuela, and the United Kingdom (2-7). To determine whether C. auris is present in the United States and to prepare for the possibility of transmission, CDC issued a clinical alert in June 2016 informing clinicians, laboratorians, infection control practitioners, and public health authorities about C. auris and requesting that C. auris cases be reported to state and local health departments and CDC (8). This report describes the first seven U.S. cases of C. auris infection reported to CDC as of August 31, 2016. Data from these cases suggest that transmission of C. auris might have occurred in U.S. health care facilities and demonstrate the need for attention to infection control measures to control the spread of this pathogen.

Chicago Ebola Response Network (CERN): A Citywide Cross-hospital Collaborative for Infectious Disease Preparedness.

The 2014-2015 Ebola virus disease (EVD) epidemic and international public health emergency has been referred to as a "black swan" event, or an event that is unlikely, hard to predict, and highly impactful once it occurs. The Chicago Ebola Response Network (CERN) was formed in response to EVD and is capable of receiving and managing new cases of EVD, while also laying the foundation for a public health network that can anticipate, manage, and prevent the next black swan public health event. By sharing expertise, risk, and resources among 4 major academic centers, Chicago created a sustainable network to respond to the latest in a series of public health emergencies. In this respect, CERN is a roadmap for how a region can prepare to respond to public health emergencies, thereby preventing negative impacts through planning and implementation.

Influenza among afebrile and vaccinated healthcare workers.

BACKGROUND: To prevent transmission of influenza from healthcare workers (HCWs) to patients, many hospitals exclude febrile HCWs from working, but allow afebrile HCWs with respiratory symptoms to have contact with patients. During the 2013-2014 influenza season at our hospital, an influenza-positive HCW with respiratory symptoms but no fever was linked to a case of possible healthcare-associated influenza in a patient. Therefore, we implemented a temporary policy of mandatory influenza testing for HCWs with respiratory symptoms. METHODS: From 3 January through 28 February 2014, we tested HCWs with respiratory symptoms for influenza and other respiratory pathogens by polymerase chain reaction of flocked nasopharyngeal swabs. HCWs also reported symptoms and influenza vaccination status, and underwent temperature measurement. We calculated the proportion of influenza-positive HCWs with fever and prior influenza vaccination. RESULTS: Of 449 HCWs, 243 (54%) had a positive test for any respiratory pathogen; 34 (7.6%) HCWs tested positive for influenza. An additional 7 HCWs were diagnosed with influenza by outside physicians. Twenty-one (51.2%) employees with influenza had fever. Among influenza-infected HCWs, 20 had previously received influenza vaccination, 18 had declined the vaccine, and 3 had unknown vaccination status. There was no significant difference in febrile disease among influenza-infected employees who had received the influenza vaccine and those who had not received the vaccine (45% vs 61%; P = .32). CONCLUSIONS: Nearly half of HCWs with influenza were afebrile prior to their diagnosis. HCWs with respiratory symptoms but no fever may pose a risk of influenza transmission to patients and coworkers.

Native Aortic Valve Endocarditis Caused by Scopulariopsis Species: Case Report, Considerations for Management, and Review of Literature.

We present the first case of native aortic valve endocarditis caused by Scopulariopsis. Intraoperative images and videos from valve replacement surgery illustrate the severity of fungal endocarditis. This case demonstrates the aggressive presentation of left-sided fungal endocarditis, highlights challenges with treating highly resistant fungi, and considers the potential utility of olorofim.

Clostridioides difficile colonization and the frequency of subsequent treatment for C. difficile infection in critically ill patients.

OBJECTIVE: To determine risk factors for Clostridioides difficile colonization and C. difficile infection (CDI) among patients admitted to the intensive care unit (ICU). DESIGN: Retrospective observational cohort study. SETTING: Tertiary-care facility. PATIENTS: All adult patients admitted to an ICU from July 1, 2015, to November 6, 2019, who were tested for C. difficile colonization. Patients with CDI were excluded. METHODS: Information was collected on patient demographics, comorbidities, laboratory results, and prescriptions. We defined C. difficile colonization as a positive nucleic acid amplification test for C. difficile up to 48 hours before or 24 hours after intensive care unit (ICU) admission without evidence of active infection. We defined active infection as the receipt of an antibiotic whose only indication is the treatment of CDI. The primary outcome measure was the development of CDI up to 30 days after ICU admission. Logistic regression was used to model associations between clinical variables and the development of CDI. RESULTS: The overall C. difficile colonization rate was 4% and the overall CDI rate was 2%. Risk factors for the development of CDI included C. difficile colonization (aOR, 13.3; 95% CI, 8.3-21.3; P < .0001), increased ICU length of stay (aOR, 1.04; 95% CI, 1.03-1.05; P < .0001), and a history of inflammatory bowel disease (aOR, 3.8; 95% CI, 1.3-11.1; P = .02). Receipt of any antibiotic during the ICU stay was associated with a borderline increased odds of CDI (aOR, 1.9; 95% CI, 1.0-3.4; P = .05). CONCLUSION: C. difficile colonization is associated with the development of CDI among ICU patients.

SHEA/IDSA/APIC Practice Recommendation: Strategies to prevent healthcare-associated infections through hand hygiene: 2022 Update.

The purpose of this document is to highlight practical recommendations to assist acute-care hospitals in prioritization and implementation of strategies to prevent healthcare-associated infections through hand hygiene. This document updates the Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals through Hand Hygiene, published in 2014. This expert guidance document is sponsored by the Society for Healthcare Epidemiology (SHEA). It is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America, the Association for Professionals in Infection Control and Epidemiology, the American Hospital Association, and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise.

Introduction to A Compendium of Strategies to Prevent Healthcare-Associated Infections In Acute-Care Hospitals: 2022 Updates.

Since the initial publication of A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals in 2008, the prevention of healthcare-associated infections (HAIs) has continued to be a national priority. Progress in healthcare epidemiology, infection prevention, antimicrobial stewardship, and implementation science research has led to improvements in our understanding of effective strategies for HAI prevention. Despite these advances, HAIs continue to affect ∼1 of every 31 hospitalized patients, leading to substantial morbidity, mortality, and excess healthcare expenditures, and persistent gaps remain between what is recommended and what is practiced.The widespread impact of the coronavirus disease 2019 (COVID-19) pandemic on HAI outcomes in acute-care hospitals has further highlighted the essential role of infection prevention programs and the critical importance of prioritizing efforts that can be sustained even in the face of resource requirements from COVID-19 and future infectious diseases crises.The Compendium: 2022 Updates document provides acute-care hospitals with up-to-date, practical expert guidance to assist in prioritizing and implementing HAI prevention efforts. It is the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Disease Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, with major contributions from representatives of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Pediatric Infectious Disease Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), the Surgical Infection Society (SIS), and others.

Universal screening for Clostridioides difficile at an urban academic medical center.

We implemented universal inpatient Clostridioides difficile screening at an 800-bed hospital. Over 3 years, 2,010 of 47,048 screening tests (4.2%) were positive, with significantly higher rates of C. difficile colonization on transplant units than medical-surgical units: 5.4% (152 of 2,801) versus 4.3% (880 of 20,564), respectively (P = .005). Compliance with screening ranged from 79% to 96%.

High consequence infectious diseases training using interprofessional simulation and TeamSTEPPS.

BACKGROUND: The comfort level of health care workers to respond to an infectious disease outbreak or epidemic is likely directly related to the amount of education, training, and experience they have in responding to these events. METHODS: A quasi-experimental study evaluated health care workers' state anxiety, self-efficacy, and interprofessional teamwork when working with patients simulated to have a potentially high consequence infectious disease. RESULTS: Pretest-posttest 1 scores revealed a significant decrease in state anxiety (P < .0001) and an increase in self-efficacy (P < .0001). Overall state anxiety preintervention (pretest) to postintervention (posttest 3) significantly decreased (P = .0265). Overall TeamSTEPPS knowledge significantly increased (P < .0001) from baseline. CONCLUSIONS: Simulation exercises are an effective strategy to increase self-efficacy and decrease state anxiety for health care workers. Positive teamwork scores indicate that the subjects value interprofessional teamwork.

Clinical Sensitivity of Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid Amplification Tests for Diagnosing Coronavirus Disease 2019.

Utilizing 34 348 severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) nucleic acid amplification test (NAAT) results from 2 health systems, we estimated the clinical sensitivity of a single SARS-CoV-2 NAAT. We found that SARS-CoV-2 NAAT has 82%-97% sensitivity for diagnosing coronavirus disease 2019 among symptomatic patients.

Three-Tiered COVID-19 Cohorting Strategy and Implications for Memory-Care.

An outbreak of SARS-CoV-2 in a skilled nursing facility (SNF) can be devastating for residents and staff. Difficulty identifying asymptomatic and presymptomatic cases and lack of vaccination or treatment options make management challenging. We created, implemented, and now present a guide to rapidly deploy point-prevalence testing and 3-tiered cohorting in an SNF to mitigate an outbreak. We outline key challenges to SNF cohorting.