The purpose of this study was to determine the feasibility of facility-level wastewater surveillance in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in skilled nursing facility (SNF) wastewater using three concentration methods, as well as a proof-of-concept for antimicrobial resistance (AR) genes/organisms detection. Wastewater effluent samples were collected from an SNF over an 8-week period. Wastewater was concentrated using electronegative membrane filtration (enMF), polyethylene glycol precipitation, and Nanotrap(®) magnetic virus particles (NP). Quantification of the genome copy concentration from SARS-CoV-2 and bovine respiratory syncytial virus (BRSV), a SARS-CoV-2 surrogate spiked into all samples, was performed with droplet digital polymerase chain reaction (ddPCR). Wastewater sample aliquots were also enriched in microbiological culture media and screened for organisms with AR phenotypes on selective and differential agars. Multiplex real-time PCR was used to detect a broad array of carbapenem resistance genes. SARS-CoV-2 was detected and quantified from a single enMF-concentrated wastewater sample. The highest concentration of BRSV came from enMF-concentrated samples. Klebsiella, Enterobacter, Citrobacter, and Escherichia coli exhibiting AR phenotypes were successfully detected using culture-dependent approaches. Culture-independent, multiplex PCR indicated that bla(KPC) was the main carbapenemase gene detected in wastewater samples. Facility-level wastewater surveillance could be a useful strategy for SNFs.

In the United States, New Delhi metallo-beta-lactamase (NDM)-producing carbapenem-resistant Enterobacterales (CRE) are frequently associated with healthcare encounters. From September 2021 to September 2022, 21 patients with NDM-CRE identified from urine and without healthcare exposure were reported to the Centers for Disease Control and Prevention. Isolates were genetically similar to healthcare-associated strains.

IMPORTANCE: Antimicrobial resistance is a major public health problem in the US. Estimating national rates of antimicrobial-resistant infections commonly associated with health care can aid in targeted public health efforts. OBJECTIVE: To determine the national incidence rates of 6 pathogens over time: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp (VRE), extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella spp (excluding Klebsiella aerogenes) (ESCR-EK), carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Acinetobacter spp (CRAsp), and multidrug-resistant (MDR) Pseudomonas aeruginosa. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 2012 to 2022 on inpatient hospitalizations, clinical cultures, and facility-level characteristics. Hospital-months were included in the dynamic cohort if the hospital reported at least 1 culture with microbial growth accompanied by antimicrobial susceptibility testing (AST) results in the month. Data from the PINC-AI and Becton Dickinson Insights databases were used, and cases were defined as incident nonsurveillance cultures yielding an organism of interest with sufficient AST results for a phenotype of interest. Data were collected from January 2012 to December 2022 and analyzed from April 2023 to June 2024. EXPOSURE: Inpatient hospitalizations with a discharge date in an included hospital month. MAIN OUTCOMES AND MEASURES: National annual antimicrobial-resistant cases per 10 000 hospitalizations were obtained using weights based on facility-level characteristics. Cases were defined as community-onset if collected on or before day 3 of hospitalization and hospital-onset if obtained on day 4 or later. RESULTS: This study cohort included 332 to 606 hospitals per year between 2012 to 2022 and 7 158 139 cultures. Antimicrobial-resistant pathogens accounted for an estimated 569 749 (95% CI, 475 949-663 548) cases and 179.6 (95% CI, 163.1-196.1) cases per 10 000 hospitalizations in 2022. Of these cases, 77% (437 657; 95% CI, 364 529-510 785) were community-onset and 23% (132 092; 95% CI, 108 241-155 943) were hospital-onset. MRSA (44% [251 854; 95% CI, 209 558-294 150]) and ESCR-EK (35% [200 884; 95% CI, 163 692-238 077]) made up the largest proportions of total infections in 2022, respectively. Rates of hospital-onset MRSA, VRE, CRE, CRAsp, and MDR P aeruginosa had periods of decline from 2012 to 2019; however, all pathogens experienced an increase in hospital-onset rates in 2020 and 2021. Community-onset ESCR-EK rates increased from 2012 to 2022, while community-onset rates of MRSA, VRE, and MDR P aeruginosa declined. CONCLUSIONS AND RELEVANCE: While antimicrobial resistance rates have experienced uneven declines in the US from 2012 to 2022, the burden of resistance remains substantial. These findings suggest that more effective strategies to reduce antimicrobial resistance are needed.

Antimicrobial resistance (AMR) is an urgent threat to public health, but gaps in surveillance limit the detection of emergent novel threats and knowledge about the global distribution of AMR genes. International travelers frequently acquire AMR organisms, and thus may provide a window into AMR dynamics in otherwise poorly monitored regions and environments. To assess the utility of travelers as global AMR sentinels, we collected pre- and post-travel stool samples from 608 travelers, which were screened for the presence of extended-spectrum beta-lactamase producing Enterobacterales, carbapenem-resistant Enterobacterales, and mcr-mediated colistin-resistant Enterobacterales. A total of 307 distinct AMR organisms were sequenced in order to determine genotypic patterns and their association with travel region and behavior. Travel-associated AMR organisms were overwhelmingly E. coli, which exhibited considerable phylogenetic diversity regardless of travel region. However, the prevalence of resistance genes varied by region, with bla (CTX-M-55) and bla (CTX-M-27) significantly more common in travelers returning from South America and South-Eastern Asia, respectively. Hybrid assembly and plasmid reconstruction revealed the genomic neighborhood of bla (CTX-M-55) frequently matched a motif previously linked to animal populations. Contact with animals was also associated with virulence factors in acquired AMR organisms, including carriage of the ColV plasmid, a driver of avian pathogenic E. coli. We identified novel variants of the mcr-1 gene in strains acquired from Western Africa, highlighting the potential for traveler surveillance to detect emerging clinical threats. Ongoing efforts to track travel-acquired organisms could complement existing global AMR surveillance frameworks.

Vancomycin-resistant Staphylococcus aureus (VRSA) is a rare but serious public health concern. We describe a VRSA case in North Carolina, USA. The isolate from the case belonged to the USA600 lineage and clonal complex 45. No transmission was identified. Confirmed VRSA cases should include a thorough investigation and public health response.

BACKGROUND: Outbreaks of emerging multidrug-resistant organisms (eMDROs), including carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter baumannii, and Candida auris, have been reported among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. We describe eMDRO clusters in SARS-CoV-2 units and associated infection control (IC) practices early in the SARS-CoV-2 pandemic. METHODS: We conducted a retrospective survey of a convenience sample of health departments in 11 states to describe clusters of eMDROs that began before November 1, 2020 and involved SARS-CoV-2 units. Cluster characteristics and IC practices during the cluster period were assessed using a standardized outbreak report form, and descriptive analyses were performed. RESULTS: Overall, 18 eMDRO clusters (10 carbapenem-resistant Enterobacterales, 6 C auris, 1 carbapenem-resistant Pseudomonas aeruginosa, and 1 carbapenem-resistant A baumannii) in 18 health care facilities involving 397 patients were reported from 10 states. During the cluster period, 60% of facilities reported a shortage of isolation gowns, 69% extended use of gowns, and 67% reported difficulty obtaining preferred disinfectants. Reduced frequency of hand hygiene audits was reported in 85% of acute care hospitals during the cluster period compared with before the pandemic. CONCLUSIONS: Changes in IC practices and supply shortages were identified in facilities with eMDRO outbreaks during the SARS-CoV-2 pandemic and might have contributed to eMDRO transmission.

Firearm-related deaths and injuries have increased in recent years. Comprehensive and timely information on firearm injuries and the communities and geographic locations most affected by firearm violence is crucial for guiding prevention activities. However, traditional surveillance systems for firearm injury, which are mostly based on hospital encounters and mortality-related data, often lack information on the location where the shooting occurred. This study examined annual and monthly rates of emergency medical services (EMS) encounters for firearm injury per 100,000 total EMS encounters during January 2019-September 2023 in 858 counties in 27 states, by patient characteristics and characteristics of the counties where the injuries occurred. Overall, annual rates of firearm injury EMS encounters per 100,000 total EMS encounters ranged from 222.7 in 2019 to 294.9 in 2020; rates remained above prepandemic levels through 2023. Rates were consistently higher among males than females. Rates stratified by race and ethnicity were highest among non-Hispanic Black or African American persons; rates stratified by age group were highest among persons aged 15-24 years. The greatest percentage increases in annual rates occurred in urban counties and in counties with higher prevalence of severe housing problems, higher income inequality ratios, and higher rates of unemployment. States and communities can use the timely and location-specific data in EMS records to develop and implement comprehensive firearm injury prevention strategies to address the economic, social, and physical conditions that contribute to the risk for violence, including improvements to physical environments, secure firearm storage, and strengthened social and economic supports.

BACKGROUND: Understanding the epidemiology of carbapenem-resistant A. baumannii complex (CRAB) and the patients impacted is an important step towards informing better infection prevention and control practices and improving public health response. METHODS: Active, population-based surveillance was conducted for CRAB in 9 U.S. sites from January 1-December 31, 2019. Medical records were reviewed, isolates were collected and characterized including antimicrobial susceptibility testing and whole genome sequencing. RESULTS: Among 136 incident cases in 2019, 66 isolates were collected and characterized; 56.5% were from cases who were male, 54.5% were from persons of Black or African American race with non-Hispanic ethnicity, and the median age was 63.5 years. Most isolates, 77.2%, were isolated from urine, and 50.0% were collected in the outpatient setting; 72.7% of isolates harbored an acquired carbapenemase gene (aCP), predominantly bla(OXA-23) or bla(OXA-24/40); however, an isolate with bla(NDM) was identified. The antimicrobial agent with the most in vitro activity was cefiderocol (96.9% of isolates were susceptible). CONCLUSIONS: Our surveillance found that CRAB isolates in the U.S. commonly harbor an aCP, have an antimicrobial susceptibility profile that is defined as difficult-to-treat resistance, and epidemiologically are similar regardless of the presence of an aCP.

School-based outbreaks often precede increased incidence of acute respiratory infections in the greater community. We conducted acute respiratory infection surveillance among children to elucidate commonly detected pathogens in school settings and their unique characteristics and epidemiological patterns. The ORegon CHild Absenteeism due to Respiratory Disease Study (ORCHARDS) is a longitudinal, laboratory-supported, school-based, acute respiratory illness (ARI) surveillance study designed to evaluate the utility of cause-specific student absenteeism monitoring for early detection of increased activity of influenza and other respiratory viruses in schools from kindergarten through 12th grade. Eligible participants with ARIs provided demographic, epidemiologic, and symptom data, along with a nasal swab or oropharyngeal specimen. Multipathogen testing using reverse-transcription polymerase chain reaction (RT-PCR) was performed on all specimens for 18 respiratory viruses and 2 atypical bacterial pathogens (Chlamydia pneumoniae and Mycoplasma pneumoniae). Between 5 January 2015 and 9 June 2023, 3498 children participated. Pathogens were detected in 2455 of 3498 (70%) specimens. Rhinovirus/enteroviruses (36%) and influenza viruses A/B (35%) were most commonly identified in positive specimens. Rhinovirus/enteroviruses and parainfluenza viruses occurred early in the academic year, followed by seasonal coronaviruses, RSV, influenza viruses A/B, and human metapneumovirus. Since its emergence in 2020, SARS-CoV-2 was detected year-round and had a higher median age than the other pathogens. A better understanding of the etiologies, presentations, and patterns of pediatric acute respiratory infections can help inform medical and public health system responses.

Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses. For comparison, we have included transcriptomics datasets from cells treated with type I and type II human interferon. Raw multi-omics data and metadata were deposited in public repositories, and we provide a central location linking the raw data with experimental metadata and ready-to-use, quality-controlled, statistically processed multi-omics datasets not previously available in any public repository. This compendium of infection-induced host response data for reuse will be useful for those endeavouring to understand viral disease pathophysiology and network biology.

BACKGROUND: Carbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) are extensively drug resistant bacteria. We investigated the source of a multistate CP-CRPA outbreak. METHODS: Cases were defined as a U.S. patient's first isolation of P. aeruginosa sequence type 1203 with the carbapenemase gene blaVIM-80 and cephalosporinase gene blaGES-9 from any specimen source collected and reported to CDC between January 1, 2022-May 15, 2023. We conducted a 1:1 matched case-control study at the post-acute care facility with the most cases, assessed exposures associated with case status for all case-patients, and tested products for bacterial contamination. RESULTS: We identified 81 case-patients from 18 states, 27 of whom were identified through surveillance cultures. Four (7%) of 54 case-patients with clinical cultures died within 30 days of culture collection, and four (22%) of 18 with eye infections underwent enucleation. In the case-control study, case-patients had increased odds of receiving artificial tears compared to controls (crude matched OR: 5.0, 95% CI: 1.1, 22.8). Overall, artificial tears use was reported by 61 (87%) of 70 case-patients with information; 43 (77%) of 56 case-patients with brand information reported use of Brand A, an imported, preservative-free, over-the-counter (OTC) product. Bacteria isolated from opened and unopened bottles of Brand A were genetically related to patient isolates. FDA inspection of the manufacturing plant identified likely sources of contamination. CONCLUSIONS: A manufactured medical product serving as the vehicle for carbapenemase-producing organisms is unprecedented in the U.S. The clinical impacts from this outbreak underscore the need for improved requirements for U.S. OTC product importers.

OBJECTIVE: We investigated concurrent outbreaks of Pseudomonas aeruginosa carrying bla(VIM) (VIM-CRPA) and Enterobacterales carrying bla(KPC) (KPC-CRE) at a long-term acute-care hospital (LTACH A). METHODS: We defined an incident case as the first detection of bla(KPC) or bla(VIM) from a patient's clinical cultures or colonization screening test. We reviewed medical records and performed infection control assessments, colonization screening, environmental sampling, and molecular characterization of carbapenemase-producing organisms from clinical and environmental sources by pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing. RESULTS: From July 2017 to December 2018, 76 incident cases were identified from 69 case patients: 51 had bla(KPC,) 11 had bla(VIM,) and 7 had bla(VIM) and bla(KPC). Also, bla(KPC) were identified from 7 Enterobacterales, and all bla(VIM) were P. aeruginosa. We observed gaps in hand hygiene, and we recovered KPC-CRE and VIM-CRPA from drains and toilets. We identified 4 KPC alleles and 2 VIM alleles; 2 KPC alleles were located on plasmids that were identified across multiple Enterobacterales and in both clinical and environmental isolates. CONCLUSIONS: Our response to a single patient colonized with VIM-CRPA and KPC-CRE identified concurrent CPO outbreaks at LTACH A. Epidemiologic and genomic investigations indicated that the observed diversity was due to a combination of multiple introductions of VIM-CRPA and KPC-CRE and to the transfer of carbapenemase genes across different bacteria species and strains. Improved infection control, including interventions that minimized potential spread from wastewater premise plumbing, stopped transmission.

The cognitive and performance benefits of group work in undergraduate courses depend on understanding how to structure groups to promote communication and comfort while also promoting diversity and reducing conflict. The current study utilized social network analysis combined with self-reported survey data from 555 students in 155 groups to understand how students identified group members whom they wished to work with. Students' willingness to work with their peers was positively associated with behavioral traits pertaining to attention, participation, and preparedness in class. We tested whether preventing students from choosing their group members until completing a multiweek period of random assignment to different groups each week influenced group selection criteria, and we found little effect. Students continued to depend on demographic similarities such as gender and ethnicity when selecting groupmates and enforcing random interactions before the group formation did not influence group satisfaction and/or grades. Random interactions before group formation did influence the willingness of students to continue working with peers who were persistently poorly rated based on behavioral attributes and contribution to the group work. Thus, the effort of random assignment could be beneficial to identify struggling students and improve collaboration.

BACKGROUND: Nursing home residents are at high risk for infection, hospitalization, and colonization with multidrug-resistant organisms. METHODS: We performed a cluster-randomized trial of universal decolonization as compared with routine-care bathing in nursing homes. The trial included an 18-month baseline period and an 18-month intervention period. Decolonization entailed the use of chlorhexidine for all routine bathing and showering and administration of nasal povidone-iodine twice daily for the first 5 days after admission and then twice daily for 5 days every other week. The primary outcome was transfer to a hospital due to infection. The secondary outcome was transfer to a hospital for any reason. An intention-to-treat (as-assigned) difference-in-differences analysis was performed for each outcome with the use of generalized linear mixed models to compare the intervention period with the baseline period across trial groups. RESULTS: Data were obtained from 28 nursing homes with a total of 28,956 residents. Among the transfers to a hospital in the routine-care group, 62.2% (the mean across facilities) were due to infection during the baseline period and 62.6% were due to infection during the intervention period (risk ratio, 1.00; 95% confidence interval [CI], 0.96 to 1.04). The corresponding values in the decolonization group were 62.9% and 52.2% (risk ratio, 0.83; 95% CI, 0.79 to 0.88), for a difference in risk ratio, as compared with routine care, of 16.6% (95% CI, 11.0 to 21.8; P<0.001). Among the discharges from the nursing home in the routine-care group, transfer to a hospital for any reason accounted for 36.6% during the baseline period and for 39.2% during the intervention period (risk ratio, 1.08; 95% CI, 1.04 to 1.12). The corresponding values in the decolonization group were 35.5% and 32.4% (risk ratio, 0.92; 95% CI, 0.88 to 0.96), for a difference in risk ratio, as compared with routine care, of 14.6% (95% CI, 9.7 to 19.2). The number needed to treat was 9.7 to prevent one infection-related hospitalization and 8.9 to prevent one hospitalization for any reason. CONCLUSIONS: In nursing homes, universal decolonization with chlorhexidine and nasal iodophor led to a significantly lower risk of transfer to a hospital due to infection than routine care. (Funded by the Agency for Healthcare Research and Quality; Protect ClinicalTrials.gov number, NCT03118232.).

BACKGROUND: Culture-based studies have shown that acquisition of extended-spectrum β-lactamase-producing Enterobacterales is common during international travel; however, little is known about the role of the gut microbiome before and during travel, nor about acquisition of other antimicrobial-resistant organisms. We aimed to identify (1) whether the gut microbiome provided colonisation resistance against antimicrobial-resistant organism acquisition, (2) the effect of travel and travel behaviours on the gut microbiome, and (3) the scale and global heterogeneity of antimicrobial-resistant organism acquisition. METHODS: In this metagenomic analysis, participants were recruited at three US travel clinics (Boston, MA; New York, NY; and Salt Lake City, UT) before international travel. Participants had to travel internationally between Dec 8, 2017, and April 30, 2019, and have DNA extractions for stool samples both before and after travel for inclusion. Participants were excluded if they had at least one low coverage sample (<1 million read pairs). Stool samples were collected at home before and after travel, sent to a clinical microbiology laboratory to be screened for three target antimicrobial-resistant organisms (extended-spectrum β-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, and mcr-mediated colistin-resistant Enterobacterales), and underwent DNA extraction and shotgun metagenomic sequencing. We profiled metagenomes for taxonomic composition, antibiotic-resistant gene content, and characterised the Escherichia coli population at the strain level. We analysed pre-travel samples to identify the gut microbiome risk factors associated with acquisition of the three targeted antimicrobial resistant organisms. Pre-travel and post-travel samples were compared to identify microbiome and resistome perturbation and E coli strain acquisition associated with travel. FINDINGS: A total of 368 individuals travelled between the required dates, and 296 had DNA extractions available for both before and after travel. 29 travellers were excluded as they had at least one low coverage sample, leaving a final group of 267 participants. We observed a perturbation of the gut microbiota, characterised by a significant depletion of microbial diversity and enrichment of the Enterobacteriaceae family. Metagenomic strain tracking confirmed that 67% of travellers acquired new strains of E coli during travel that were phylogenetically distinct from their pre-travel strains. We observed widespread enrichment of antibiotic-resistant genes in the gut, with a median 15% (95% CI 10-20, p<1 × 10(-10)) increase in burden (reads per kilobase per million reads). This increase included antibiotic-resistant genes previously classified as threats to public health, which were 56% (95% CI 36-91, p=2 × 10(-11)) higher in abundance after travel than before. Fluoroquinolone antibiotic-resistant genes were aquired by 97 (54%) of 181 travellers with no detected pre-travel carriage. Although we found that visiting friends or relatives, travel to south Asia, and eating uncooked vegetables were risk factors for acquisition of the three targeted antimicrobial resistant organisms, we did not observe an association between the pre-travel microbiome structure and travel-related antimicrobial-resistant organism acquisition. INTERPRETATION: This work highlights a scale of E coli and antimicrobial-resistant organism acquisition by US travellers not apparent from previous culture-based studies, and suggests that strategies to control antimicrobial-resistant organisms addressing international traveller behaviour, rather than modulating the gut microbiome, could be worthwhile. FUNDING: US Centers for Disease Control and Prevention and National Institute of Allergy and Infectious Diseases.

Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

BACKGROUND: Contaminated healthcare facility wastewater plumbing is recognized as a source of carbapenemase-producing organism transmission. In August 2019, the Tennessee Department of Health (TDH) identified a patient colonized with Verona integron-encoded metallo-beta-lactamase-producing carbapenem-resistant Pseudomonas aeruginosa (VIM-CRPA). A record review revealed that 33% (4 of 12) of all reported patients in Tennessee with VIM had history of prior admission to acute care hospital (ACH) A intensive care unit (ICU) Room X, prompting further investigation. METHODS: A case was defined as polymerase chain reaction detection of bla(VIM) in a patient with prior admission to ACH A from November 2017 to November 2020. The TDH performed point prevalence surveys, discharge screening, onsite observations, and environmental testing at ACH A. The VIM-CRPA isolates underwent whole-genome sequencing (WGS). RESULTS: In a screening of 44% (n = 11) of 25 patients admitted to Room X between January and June 2020, we identified 36% (n = 4) colonized with VIM-CRPA, resulting in 8 cases associated with Room X from March 2018 to June 2020. No additional cases were identified in 2 point-prevalence surveys of the ACH A ICU. Samples from the bathroom and handwashing sink drains in Room X grew VIM-CRPA; all available case and environmental isolates were found to be ST253 harboring bla(VIM-1) and to be closely related by WGS. Transmission ended after implementation of intensive water management and infection control interventions. CONCLUSIONS: A single ICU room's contaminated drains were associated with 8 VIM-CRPA cases over a 2-year period. This outbreak highlights the need to include wastewater plumbing in hospital water management plans to mitigate the risk of transmission of antibiotic-resistant organisms to patients.

BACKGROUND: Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres. METHODS: For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model's generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings. FINDINGS: Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms. INTERPRETATION: We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance. FUNDING: WHO, US National Institutes of Health.

Cronobacter sakazakii, a species of gram-negative bacteria belonging to the Enterobacteriaceae family, is known to cause severe and often fatal meningitis and sepsis in young infants. C. sakazakii is ubiquitous in the environment, and most reported infant cases have been attributed to contaminated powdered infant formula (powdered formula) or breast milk that was expressed using contaminated breast pump equipment (1-3). Previous investigations of cases and outbreaks have identified C. sakazakii in opened powdered formula, breast pump parts, environmental surfaces in the home, and, rarely, in unopened powdered formula and formula manufacturing facilities (2,4-6). This report describes two infants with C. sakazakii meningitis reported to CDC in September 2021 and February 2022. CDC used whole genome sequencing (WGS) analysis to link one case to contaminated opened powdered formula from the patient's home and the other to contaminated breast pump equipment. These cases highlight the importance of expanding awareness about C. sakazakii infections in infants, safe preparation and storage of powdered formula, proper cleaning and sanitizing of breast pump equipment, and using WGS as a tool for C. sakazakii investigations.

After more than 3 years without a documented cholera case, the Republic of Haiti reported its first resurgent case on 30 September 2022 (1–3). As of 18 February 2023, more than 27,000 cholera cases have been hospitalized and 594 deaths confirmed from all 10 departments (4). Here, we describe Vibrio cholerae isolates first characterized by the Laboratoire National de Santé Publique (LNSP) and include both genotypic and phenotypic antimicrobial resistance profiles. Whole-genome sequencing (WGS) analysis was compared with recently circulating cholera toxin-producing V. cholerae O1 in a maximum likelihood phylogeny.

Risk for transmission of monkeypox virus (MPXV) (clade IIb) to healthcare workers (HCWs) is low. Although many cases have been reported among HCW, only a few have been occupationally acquired. We report a case of non-needle stick MPXV transmission to an HCW in the United States.

During June 2017-November 2019, a total 36 patients with carbapenem-resistant Pseudomonas aeruginosa harboring Verona-integron-encoded metallo-β-lactamase were identified in a city in western Texas, USA. A faucet contaminated with the organism, identified through environmental sampling, in a specialty care room was the likely source for infection in a subset of patients.

The CDC's Emerging Infections Program (EIP) conducted population- and laboratory-based surveillance of US carbapenem-resistant Pseudomonas aeruginosa (CRPA) from 2016 through 2018. To characterize the pathotype, 1,019 isolates collected through this project underwent antimicrobial susceptibility testing and whole-genome sequencing. Sequenced genomes were classified using the seven-gene multilocus sequence typing (MLST) scheme and a core genome (cg)MLST scheme was used to determine phylogeny. Both chromosomal and horizontally transmitted mechanisms of carbapenem resistance were assessed. There were 336 sequence types (STs) among the 1,019 sequenced genomes, and the genomes varied by an average of 84.7% of the cgMLST alleles used. Mutations associated with dysfunction of the porin OprD were found in 888 (87.1%) of the genomes and were correlated with carbapenem resistance, and a machine learning model incorporating hundreds of genetic variations among the chromosomal mechanisms of resistance was able to classify resistant genomes. While only 7 (0.1%) isolates harbored carbapenemase genes, 66 (6.5%) had acquired non-carbapenemase β-lactamase genes, and these were more likely to have OprD dysfunction and be resistant to all carbapenems tested. The genetic diversity demonstrates that the pathotype includes a variety of strains, and clones previously identified as high-risk make up only a minority of CRPA strains in the United States. The increased carbapenem resistance in isolates with acquired non-carbapenemase β-lactamase genes suggests that horizontally transmitted mechanisms aside from carbapenemases themselves may be important drivers of the spread of carbapenem resistance in P. aeruginosa.

The number of nonfatal opioid-involved overdoses treated by health care providers has risen in the United States; the median number of emergency department (ED) visits for these overdoses was significantly higher during 2020 than during 2019 (1). ED visit data can underestimate nonfatal opioid-involved overdose incidence because, increasingly, persons experiencing a nonfatal opioid overdose are refusing transport to EDs by emergency medical services (EMS) (2). A study in Kentucky found that during a 6-month period, 19.8% of persons treated by EMS for an opioid overdose refused transport to an ED (2). Thus, EMS encounter data involving suspected nonfatal opioid-involved overdoses complement ED data and also allow for near real-time analysis (3). This report describes trends in rates of EMS encounters for nonfatal opioid-involved overdoses per 10,000 total EMS encounters (rates) by selected patient- and county-level characteristics during January 2018–March 2022 in 491 counties from 21 states using data from biospatial, Inc.* During this period, the nonfatal opioid-involved overdose rate increased, on average, 4.0% quarterly. Rates increased for both sexes and for most age groups. Rates were highest among non-Hispanic White (White) and non-Hispanic Native Hawaiian or other Pacific Islander (NH/OPI) persons, and increases were largest among non-Hispanic Black (Black), followed by Hispanic or Latino (Hispanic) persons. Rates increased in both urban and rural counties and for all quartiles of county-level characteristics (i.e., unemployment, education, and uninsured), except in counties with the lowest percentage of uninsured persons. Rates were highest and rate increases were largest in urban counties and counties with higher unemployment rates. This analysis of nonfatal opioid-involved overdose trends in EMS data highlights the utility of these data and the importance of addressing inequities that contribute to disproportionate overdose risk, such as through focused outreach to racial and ethnic minority groups, who disproportionately experience these inequities, and communities with higher levels of unemployment. EMS providers are in a unique position to engage in postoverdose response protocols and promote evidence-based overdose education and facilitate linkage to care and harm reduction services.†,§

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are usually healthcare-associated but are also emerging in the community. METHODS: Active, population-based surveillance was conducted to identify case-patients with cultures positive for Enterobacterales not susceptible to a carbapenem (excluding ertapenem) and resistant to all third-generation cephalosporins tested at 8 US sites from January 2012 to December 2015. Medical records were used to classify cases as health care-associated, or as community-associated (CA) if a patient had no known health care risk factors and a culture was collected <3 days after hospital admission. Enterobacterales isolates from selected cases were submitted to CDC for whole genome sequencing. RESULTS: We identified 1499 CRE cases in 1194 case-patients; 149 cases (10%) in 139 case-patients were CA. The incidence of CRE cases per 100,000 population was 2.96 (95% CI: 2.81, 3.11) overall and 0.29 (95% CI: 0.25, 0.35) for CA-CRE. Most CA-CRE cases were in White persons (73%), females (84%) and identified from urine cultures (98%). Among the 12 sequenced CA-CRE isolates, 5 (42%) harbored a carbapenemase gene. CONCLUSIONS: Ten percent of CRE cases were CA; some isolates from CA-CRE cases harbored carbapenemase genes. Continued CRE surveillance in the community is critical to monitor emergence outside of traditional health care settings.

BACKGROUND: Nursing homes (NHs) provide care in a congregate setting for residents at high risk of severe outcomes from SARS-CoV-2 infection. In spring 2020, NHs were implementing new guidance to minimize SARS-CoV-2 spread among residents and staff. OBJECTIVE: To assess whether telephone and video-based infection control assessment and response (TeleICAR) strategies could efficiently assess NH preparedness and help resolve gaps. DESIGN: We incorporated Centers for Disease Control and Prevention COVID-19 guidance for NH into an assessment tool covering 6 domains: visitor restrictions; health care personnel COVID-19 training; resident education, monitoring, screening, and cohorting; personal protective equipment supply; core infection prevention and control (IPC); and communication to public health. We performed TeleICAR consultations on behalf of health departments. Adherence to each element was documented and recommendations provided to the facility. SETTING AND PARTICIPANTS: Health department-referred NHs that agreed to TeleICAR consultation. METHODS: We assessed overall numbers and proportions of NH that had not implemented each infection control element (gap) and proportion of NH that reported making ≥1 change in practice following the assessment. RESULTS: During April 13 to June 12, 2020, we completed TeleICAR consultations in 629 NHs across 19 states. Overall, 524 (83%) had ≥1 implementation gaps identified; the median number of gaps was 2 (interquartile range: 1-4). The domains with the greatest number of facilities with gaps were core IPC practices (428/625; 68%) and COVID-19 education, monitoring, screening, and cohorting of residents (291/620; 47%). CONCLUSIONS AND IMPLICATIONS: TeleICAR was an alternative to onsite infection control assessments that enabled public health to efficiently reach NHs across the United States early in the COVID-19 pandemic. Assessments identified widespread gaps in core IPC practices that put residents and staff at risk of infection. TeleICAR is an important strategy that leverages infection control expertise and can be useful in future efforts to improve NH IPC.

In February 2020, during the early days of the COVID-19 pandemic, 232 evacuees from Wuhan, China, were placed under federal 14-day quarantine upon arrival at a US military base in San Diego, California. We describe the monitoring of evacuees and responders for symptoms of COVID-19, case and contact investigations, infection control procedures, and lessons learned to inform future quarantine protocols for evacuated people from a hot spot resulting from a novel pathogen. Thirteen (5.6%) evacuees had COVID-19compatible symptoms and 2 (0.9%) had laboratory-confirmed SARS-CoV-2. Two case investigations identified 43 contacts; 3 (7.0%) contacts had symptoms but tested negative for SARS-CoV-2 infection. Daily symptom and temperature screening of evacuees and enacted infection control procedures resulted in rapid case identification and isolation and no detected secondary transmission among evacuees or responders. Lessons learned highlight the challenges associated with public health response to a novel pathogen and the evolution of mitigation strategies as knowledge of the pathogen evolves.

Carbapenem-resistant Enterobacterales (CRE) are a growing public health concern due to resistance to multiple antibiotics and potential to cause health care-associated infections with high mortality. Carbapenemase-producing CRE are of particular concern given that carbapenemase-encoding genes often are located on mobile genetic elements that may spread between different organisms and species. In this study, we performed phenotypic and genotypic characterization of CRE collected at eight U.S. sites participating in active population- and laboratory-based surveillance of carbapenem-resistant organisms. Among 421 CRE tested, the majority were isolated from urine (n = 349, 83%). Klebsiella pneumoniae was the most common organism (n = 265, 63%), followed by Enterobacter cloacae complex (n = 77, 18%) and Escherichia coli (n = 50, 12%). Of 419 isolates analyzed by whole genome sequencing, 307 (73%) harbored a carbapenemase gene; variants of bla(KPC) predominated (n = 299, 97%). The occurrence of carbapenemase-producing K. pneumoniae, E. cloacae complex, and E. coli varied by region; the predominant sequence type within each genus was ST258, ST171, and ST131, respectively. None of the carbapenemase-producing CRE isolates displayed resistance to all antimicrobials tested; susceptibility to amikacin and tigecycline was generally retained.

We reviewed trimethoprim-sulfamethoxazole antibiotic susceptibility testing data among Staphylococcus aureus using 3 national inpatient databases. In all 3 databases, we observed an increases in the percentage of methicillin-resistant Staphylococcus aureus that were not susceptible to trimethoprim-sulfamethoxazole. Providers should select antibiotic regimens based on local resistance patterns and should report changes to the public health department.

BACKGROUND: Passive reporting to the Centers for Disease Control and Prevention has identified carbapenemase-producing organisms (CPOs) among solid organ transplant (SOT) recipients, potentially representing an emerging source of spread. We analyzed CPO prevalence in wards where SOT recipients receive inpatient care to inform public health action to prevent transmission. METHODS: From September 2019 to June 2020, five U.S. hospitals conducted consecutive point prevalence surveys (PPS) of all consenting patients admitted to transplant units, regardless of transplant status. We used the Cepheid Xpert® Carba-R assay to identify carbapenemase genes (bla(KPC) , bla(NDM) , bla(VIM) , bla(IMP) , bla(OXA-48) ) from rectal swabs. Laboratory-developed molecular tests were used to retrospectively test for a wider range of bla(IMP) and bla(OXA) variants. RESULTS: In total, 154 patients were screened and 92 (60%) were SOT recipients. CPOs were detected among 7 (8%) SOT recipients, from two of five screened hospitals: 4 bla(KPC) , 1 bla(NDM) , 2 blaOXA(-23) . CPOs were detected in 2 (3%) of 62 non-transplant patients. In three of five participating hospitals, CPOs were not identified among any patients admitted to transplant units. CONCLUSIONS: Longitudinal surveillance in transplant units, as well as PPS in areas with diverse CPO epidemiology, may inform the utility of routine screening in SOT units to prevent the spread of CPOs. This article is protected by copyright. All rights reserved.