SARS-CoV-2 Polymerase Chain Reaction Cycle Threshold Trends in Patients Who Are Immunocompromised and Implications for Isolation Precautions.

Among 495 patients who were immunocompromised and tested positive for SARS-CoV-2, polymerase chain reaction cycle thresholds remained <33 beyond 20 days more frequently in patients with hematologic malignancies, particularly those receiving B-cell-depleting or Bruton tyrosine kinase inhibitor therapy, as compared with those with solid organ malignancy (26% vs 5%).

Avian influenza viruses in wild birds in Canada following incursions of highly pathogenic H5N1 virus from Eurasia in 2021-2022.

Following the detection of novel highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b in Newfoundland, Canada, in late 2021, avian influenza virus (AIV) surveillance in wild birds was scaled up across Canada. Herein, we present the results of Canada's Interagency Surveillance Program for Avian Influenza in Wild Birds during the first year (November 2021-November 2022) following the incursions of HPAIV from Eurasia. The key objectives of the surveillance program were to (i) identify the presence, distribution, and spread of HPAIV and other AIVs; (ii) identify wild bird morbidity and mortality associated with HPAIV; (iii) identify the range of wild bird species infected by HPAIV; and (iv) genetically characterize detected AIV. A total of 6,246 sick and dead wild birds were tested, of which 27.4% were HPAIV positive across 12 taxonomic orders and 80 species. Geographically, HPAIV detections occurred in all Canadian provinces and territories, with the highest numbers in the Atlantic and Central Flyways. Temporally, peak detections differed across flyways, though the national peak occurred in April 2022. In an additional 11,295 asymptomatic harvested or live-captured wild birds, 5.2% were HPAIV positive across 3 taxonomic orders and 19 species. Whole-genome sequencing identified HPAIV of Eurasian origin as most prevalent in the Atlantic Flyway, along with multiple reassortants of mixed Eurasian and North American origins distributed across Canada, with moderate structuring at the flyway scale. Wild birds were victims and reservoirs of HPAIV H5N1 2.3.4.4b, underscoring the importance of surveillance encompassing samples from sick and dead, as well as live and harvested birds, to provide insights into the dynamics and potential impacts of the HPAIV H5N1 outbreak. This dramatic shift in the presence and distribution of HPAIV in wild birds in Canada highlights a need for sustained investment in wild bird surveillance and collaboration across interagency partners. IMPORTANCE: We present the results of Canada's Interagency Surveillance Program for Avian Influenza in Wild Birds in the year following the first detection of highly pathogenic avian influenza virus (HPAIV) H5N1 on the continent. The surveillance program tested over 17,000 wild birds, both sick and apparently healthy, which revealed spatiotemporal and taxonomic patterns in HPAIV prevalence and mortality across Canada. The significant shift in the presence and distribution of HPAIV in Canada's wild birds underscores the need for sustained investment in wild bird surveillance and collaboration across One Health partners.

Relationship between chlorhexidine gluconate concentration and microbial colonization of patients' skin.

OBJECTIVE: To characterize the relationship between chlorhexidine gluconate (CHG) skin concentration and skin microbial colonization. DESIGN: Serial cross-sectional study. SETTING/PARTICIPANTS: Adult patients in medical intensive care units (ICUs) from 7 hospitals; from 1 hospital, additional patients colonized with carbapenemase-producing Enterobacterales (CPE) from both ICU and non-ICU settings. All hospitals performed routine CHG bathing in the ICU. METHODS: Skin swab samples were collected from adjacent areas of the neck, axilla, and inguinal region for microbial culture and CHG skin concentration measurement using a semiquantitative colorimetric assay. We used linear mixed effects multilevel models to analyze the relationship between CHG concentration and microbial detection. We explored threshold effects using additional models. RESULTS: We collected samples from 736 of 759 (97%) eligible ICU patients and 68 patients colonized with CPE. On skin, gram-positive bacteria were cultured most frequently (93% of patients), followed by Candida species (26%) and gram-negative bacteria (20%). The adjusted odds of microbial recovery for every twofold increase in CHG skin concentration were 0.84 (95% CI, 0.80-0.87; P < .001) for gram-positive bacteria, 0.93 (95% CI, 0.89-0.98; P = .008) for Candida species, 0.96 (95% CI, 0.91-1.02; P = .17) for gram-negative bacteria, and 0.94 (95% CI, 0.84-1.06; P = .33) for CPE. A threshold CHG skin concentration for reduced microbial detection was not observed. CONCLUSIONS: On a cross-sectional basis, higher CHG skin concentrations were associated with less detection of gram-positive bacteria and Candida species on the skin, but not gram-negative bacteria, including CPE. For infection prevention, targeting higher CHG skin concentrations may improve control of certain pathogens.

A Trial of Automated Outbreak Detection to Reduce Hospital Pathogen Spread.

BACKGROUND: Detection and containment of hospital outbreaks currently depend on variable and personnel-intensive surveillance methods. Whether automated statistical surveillance for outbreaks of health care-associated pathogens allows earlier containment efforts that would reduce the size of outbreaks is unknown. METHODS: We conducted a cluster-randomized trial in 82 community hospitals within a larger health care system. All hospitals followed an outbreak response protocol when outbreaks were detected by their infection prevention programs. Half of the hospitals additionally used statistical surveillance of microbiology data, which alerted infection prevention programs to outbreaks. Statistical surveillance was also applied to microbiology data from control hospitals without alerting their infection prevention programs. The primary outcome was the number of additional cases occurring after outbreak detection. Analyses assessed differences between the intervention period (July 2019 to January 2022) versus baseline period (February 2017 to January 2019) between randomized groups. A post hoc analysis separately assessed pre-coronavirus disease 2019 (Covid-19) and Covid-19 pandemic intervention periods. RESULTS: Real-time alerts did not significantly reduce the number of additional outbreak cases (intervention period versus baseline: statistical surveillance relative rate [RR]=1.41, control RR=1.81; difference-in-differences, 0.78; 95% confidence interval [CI], 0.40 to 1.52; P=0.46). Comparing only the prepandemic intervention with baseline periods, the statistical outbreak surveillance group was associated with a 64.1% reduction in additional cases (statistical surveillance RR=0.78, control RR=2.19; difference-in-differences, 0.36; 95% CI, 0.13 to 0.99). There was no similarly observed association between the pandemic versus baseline periods (statistical surveillance RR=1.56, control RR=1.66; difference-in-differences, 0.94; 95% CI, 0.46 to 1.92). CONCLUSIONS: Automated detection of hospital outbreaks using statistical surveillance did not reduce overall outbreak size in the context of an ongoing pandemic. (Funded by the Centers for Disease Control and Prevention; ClinicalTrials.gov number, NCT04053075. Support for HCA Healthcare's participation in the study was provided in kind by HCA.).

Neuroinvasive Bacillus cereus Infection in Immunocompromised Hosts: Epidemiologic Investigation of 5 Patients With Acute Myeloid Leukemia.

Background: Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia. Methods: A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates. Results: Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year. Conclusions: B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen.

Impact of measurement and feedback on chlorhexidine gluconate bathing among intensive care unit patients: A multicenter study.

OBJECTIVE: To assess whether measurement and feedback of chlorhexidine gluconate (CHG) skin concentrations can improve CHG bathing practice across multiple intensive care units (ICUs). DESIGN: A before-and-after quality improvement study measuring patient CHG skin concentrations during 6 point-prevalence surveys (3 surveys each during baseline and intervention periods). SETTING: The study was conducted across 7 geographically diverse ICUs with routine CHG bathing. PARTICIPANTS: Adult patients in the medical ICU. METHODS: CHG skin concentrations were measured at the neck, axilla, and inguinal region using a semiquantitative colorimetric assay. Aggregate unit-level CHG skin concentration measurements from the baseline period and each intervention period survey were reported back to ICU leadership, which then used routine education and quality improvement activities to improve CHG bathing practice. We used multilevel linear models to assess the impact of intervention on CHG skin concentrations. RESULTS: We enrolled 681 (93%) of 736 eligible patients; 92% received a CHG bath prior to survey. At baseline, CHG skin concentrations were lowest on the neck, compared to axillary or inguinal regions (P < .001). CHG was not detected on 33% of necks, 19% of axillae, and 18% of inguinal regions (P < .001 for differences in body sites). During the intervention period, ICUs that used CHG-impregnated cloths had a 3-fold increase in patient CHG skin concentrations as compared to baseline (P < .001). CONCLUSIONS: Routine CHG bathing performance in the ICU varied across multiple hospitals. Measurement and feedback of CHG skin concentrations can be an important tool to improve CHG bathing practice.

Recurring Trans-Atlantic Incursion of Clade 2.3.4.4b H5N1 Viruses by Long Distance Migratory Birds from Northern Europe to Canada in 2022/2023.

In December 2022 and January 2023, we isolated clade 2.3.4.4b H5N1 high-pathogenicity avian influenza (HPAI) viruses from six American crows (Corvus brachyrhynchos) from Prince Edward Island and a red fox (Vulpes vulpes) from Newfoundland, Canada. Using full-genome sequencing and phylogenetic analysis, these viruses were found to fall into two distinct phylogenetic clusters: one group containing H5N1 viruses that had been circulating in North and South America since late 2021, and the other one containing European H5N1 viruses reported in late 2022. The transatlantic re-introduction for the second time by pelagic/Icelandic bird migration via the same route used during the 2021 incursion of Eurasian origin H5N1 viruses into North America demonstrates that migratory birds continue to be the driving force for transcontinental dissemination of the virus. This new detection further demonstrates the continual long-term threat of H5N1 viruses for poultry and mammals and the subsequent impact on various wild bird populations wherever these viruses emerge. The continual emergence of clade 2.3.4.4b H5Nx viruses requires vigilant surveillance in wild birds, particularly in areas of the Americas, which lie within the migratory corridors for long-distance migratory birds originating from Europe and Asia. Although H5Nx viruses have been detected at higher rates in North America since 2021, a bidirectional flow of H5Nx genes of American origin viruses to Europe has never been reported. In the future, coordinated and systematic surveillance programs for HPAI viruses need to be launched between European and North American agencies.

Impact of SARS-CoV-2 Prevention Measures on Non-SARS-CoV-2 Hospital-Onset Respiratory Viral Infections: An Incidence Trend Analysis From 2015-2023.

We reviewed hospital-onset respiratory viral infections, 2015-2023, in one hospital to determine whether Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission prevention measures prevented non-SARS-CoV-2 respiratory viral infections. Masking, employee symptom attestations, and screening patients and visitors for symptoms were associated with a 44%-53% reduction in hospital-onset influenza and respiratory syncytial virus (RSV), accounting for changes in community incidence.

Mycobacterium abscessus Cluster in Cardiac Surgery Patients Potentially Attributable to a Commercial Water Purification System.

BACKGROUND: Nontuberculous mycobacteria are water-avid pathogens that are associated with nosocomial infections. OBJECTIVE: To describe the analysis and mitigation of a cluster of Mycobacterium abscessus infections in cardiac surgery patients. DESIGN: Descriptive study. SETTING: Brigham and Women's Hospital, Boston, Massachusetts. PARTICIPANTS: Four cardiac surgery patients. INTERVENTION: Commonalities among cases were sought, potential sources were cultured, patient and environmental specimens were sequenced, and possible sources were abated. MEASUREMENTS: Description of the cluster, investigation, and mitigation. RESULTS: Whole-genome sequencing confirmed homology among clinical isolates. Patients were admitted during different periods to different rooms but on the same floor. There were no common operating rooms, ventilators, heater-cooler devices, or dialysis machines. Environmental cultures were notable for heavy mycobacterial growth in ice and water machines on the cluster unit but little or no growth in ice and water machines in the hospital's other 2 inpatient towers or in shower and sink faucet water in any of the hospital's 3 inpatient towers. Whole-genome sequencing confirmed the presence of a genetically identical element in ice and water machine and patient specimens. Investigation of the plumbing system revealed a commercial water purifier with charcoal filters and an ultraviolet irradiation unit leading to the ice and water machines in the cluster tower but not the hospital's other inpatient towers. Chlorine was present at normal levels in municipal source water but was undetectable downstream from the purification unit. There were no further cases after high-risk patients were switched to sterile and distilled water, ice and water machine maintenance was intensified, and the commercial purification system was decommissioned. LIMITATION: Transmission pathways were not clearly characterized. CONCLUSION: Well-intentioned efforts to modify water management systems may inadvertently increase infection risk for vulnerable patients. PRIMARY FUNDING SOURCE: National Institutes of Health.

Survey of coronavirus disease 2019 (COVID-19) infection control policies at leading US academic hospitals in the context of the initial pandemic surge of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) omicron variant.

OBJECTIVE: To assess coronavirus disease 2019 (COVID-19) infection policies at leading US medical centers in the context of the initial wave of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) omicron variant. DESIGN: Electronic survey study eliciting hospital policies on masking, personal protective equipment, cohorting, airborne-infection isolation rooms (AIIRs), portable HEPA filters, and patient and employee testing. SETTING AND PARTICIPANTS: "Hospital epidemiologists from U.S. News top 20 hospitals and 10 hospitals in the CDC Prevention Epicenters program."  As it is currently written, it implies all 30 hospitals are from the CDC Prevention Epicenters program, but that only applies to 10 hospitals.  Alternatively, we could just say "Hospital epidemiologists from 30 leading US hospitals." METHODS: Survey results were reported using descriptive statistics. RESULTS: Of 30 hospital epidemiologists surveyed, 23 (77%) completed the survey between February 15 and March 3, 2022. Among the responding hospitals, 18 (78%) used medical masks for universal masking and 5 (22%) used N95 respirators. 16 hospitals (70%) required universal eye protection. 22 hospitals (96%) used N95s for routine COVID-19 care and 1 (4%) reserved N95s for aerosol-generating procedures. 2 responding hospitals (9%) utilized dedicated COVID-19 wards; 8 (35%) used mixed COVID-19 and non-COVID-19 units; and 13 (57%) used both dedicated and mixed units. 4 hospitals (17%) used AIIRs for all COVID-19 patients, 10 (43%) prioritized AIIRs for aerosol-generating procedures, 3 (13%) used alternate risk-stratification criteria (not based on aerosol-generating procedures), and 6 (26%) did not routinely use AIIRs. 9 hospitals (39%) did not use portable HEPA filters, but 14 (61%) used them for various indications, most commonly as substitutes for AIIRs when unavailable or for specific high-risk areas or situations. 21 hospitals (91%) tested asymptomatic patients on admission, but postadmission testing strategies and preferred specimen sites varied substantially. 5 hospitals (22%) required regular testing of unvaccinated employees and 1 hospital (4%) reported mandatory weekly testing even for vaccinated employees during the SARS-CoV-2 omicron surge. CONCLUSIONS: COVID-19 infection control practices in leading hospitals vary substantially. Clearer public health guidance and transparency around hospital policies may facilitate more consistent national standards.

Prevention of SARS-CoV-2 and respiratory viral infections in healthcare settings: current and emerging concepts.

PURPOSE OF REVIEW: COVID-19 has catalyzed a wealth of new data on the science of respiratory pathogen transmission and revealed opportunities to enhance infection prevention practices in healthcare settings. RECENT FINDINGS: New data refute the traditional division between droplet vs airborne transmission and clarify the central role of aerosols in spreading all respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), even in the absence of so-called 'aerosol-generating procedures' (AGPs). Indeed, most AGPs generate fewer aerosols than talking, labored breathing, or coughing. Risk factors for transmission include high viral loads, symptoms, proximity, prolonged exposure, lack of masking, and poor ventilation. Testing all patients on admission and thereafter can identify early occult infections and prevent hospital-based clusters. Additional prevention strategies include universal masking, encouraging universal vaccination, preferential use of N95 respirators when community rates are high, improving native ventilation, utilizing portable high-efficiency particulate air filters when ventilation is limited, and minimizing room sharing when possible. SUMMARY: Multifaceted infection prevention programs that include universal testing, masking, vaccination, and enhanced ventilation can minimize nosocomial SARS-CoV-2 infections in patients and workplace infections in healthcare personnel. Extending these insights to other respiratory viruses may further increase the safety of healthcare and ready hospitals for novel respiratory viruses that may emerge in the future.

Ralstonia pickettii and Pseudomonas aeruginosa Bloodstream Infections Associated With Contaminated Extracorporeal Membrane Oxygenation Water Heater Devices.

We report on probable factory-based contamination of portable water heaters with waterborne pathogens and 2 bloodstream infections potentially attributable to off-label use of these water heaters to warm extracorporeal membrane oxygenation circuits. Great caution is warranted when using water-based devices to care for critically ill patients.

Concise syntheses of GB22, GB13, and himgaline by cross-coupling and complete reduction.

Neuroactive metabolites from the bark of Galbulimima belgraveana occur in variable distributions among trees and are not easily accessible through chemical synthesis because of elaborate bond networks and dense stereochemistry. Previous syntheses of complex congeners such as himgaline have relied on iterative, stepwise installation of multiple methine stereocenters. We decreased the synthetic burden of himgaline chemical space to nearly one-third of the prior best (7 to 9 versus 19 to 31 steps) by cross-coupling high fraction aromatic building blocks (high Fsp2) followed by complete, stereoselective reduction to high fraction sp3 products (high Fsp3). This short entry into Galbulimima alkaloid space should facilitate extensive chemical exploration and biological interrogation.

Cluster of Burkholderia cepacia Complex Infections Associated With Extracorporeal Membrane Oxygenation Water Heater Devices.

BACKGROUND: Burkholderia cepacia complex is a group of potential nosocomial pathogens often linked to contaminated water. We report on a cluster of 8 B. cepacia complex infections in cardiothoracic intensive care unit patients, which were attributed to contaminated extracorporeal membrane oxygenation (ECMO) water heaters. METHODS: In December 2020, we identified an increase in B. cepacia complex infections in the cardiothoracic intensive care unit at Brigham and Women's Hospital. We sought commonalities, sequenced isolates, obtained environmental specimens, and enacted mitigation measures. RESULTS: Whole-genome sequencing of 13 B. cepacia complex clinical specimens between November 2020 and February 2021 identified 6 clonally related isolates, speciated as Burkholderia contaminans. All 6 occurred in patients on ECMO. Microbiology review identified 2 additional B. contaminans cases from June 2020 that may have also been cluster related, including 1 in a patient receiving ECMO. All 8 definite or probable cluster cases required treatment; 3 patients died, and 3 experienced recurrent infections. After ECMO was identified as the major commonality, all 9 of the hospital's ECMO water heaters were cultured, and B. contaminans grew in all cultures. Cultures from air sampled adjacent to the water heaters were negative. Water heater touch screens were culture positive for B. contaminans, and the sink drain in the ECMO heater reprocessing room also grew clonal B. contaminans. Observations of reprocessing revealed opportunities for cross-contamination between devices through splashing from the contaminated sink. The cluster was aborted by removing all water heaters from clinical service. CONCLUSIONS: We identified a cluster of 8 B. cepacia complex infections associated with contaminated ECMO water heaters. This cluster underscores the potential risks associated with water-based ECMO heaters and, more broadly, water-based care for vulnerable patients.

Rapid Control of Hospital-Based Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Clusters Through Daily Testing and Universal Use of N95 Respirators.

The highly contagious severe acute respiratory syndrome coronavirus 2 Omicron variant increases risk for nosocomial transmission despite universal masking, admission testing, and symptom screening. We report large increases in hospital-onset infections and 2 unit-based clusters. The clusters rapidly abated after instituting universal N95 respirators and daily testing. Broader use of these strategies may prevent nosocomial transmissions.