Methicillin-resistant Staphylococcus aureus (MRSA) clusters in neonatal intensive care units (NICUs) and other neonatal units in New York State (NYS), 2001 to 2017.

BACKGROUND: New York State (NYS) mandates reporting of all hospital-associated communicable disease outbreaks. We describe trends in NYS surveillance for neonatal unit methicillin-resistant Staphylococcus aureus (MRSA) outbreaks, the evolution of national MRSA infection prevention and control (IPC) recommendations, and IPC measures taken by NYS neonatal units. METHODS: We evaluated trends of reported neonatal unit MRSA outbreaks by etiology from 2001 to 2017. We reviewed all reports and the use of IPC recommendations over time. RESULTS: From 2001 to 2017, 124 MRSA outbreaks were reported in 47 hospital neonatal units, with a total of 1,055 laboratory-confirmed infant cases, 18 infant deaths, and 52 laboratory-confirmed staff cases. The number of outbreaks increased with the level of care. During the study period, a higher proportion of hospitals reported implementing IPC measures, including reinforcing hand hygiene compliance (increased from 79.2% to 95.1%) and enhancing environmental cleaning and disinfection (increased from 4.2% to 78.0%) as well as performing active surveillance testing (AST) on exposed neonates (increased from 4.2% to 51.2%) and molecular testing on MRSA-positive isolates (increased from 5.3% to 18.9%). CONCLUSIONS: From 2001 to 2017, IPC measures in neonatal units increased in parallel with expanded national IPC recommendations. However, MRSA outbreaks in neonatal units continued to be frequent occurrences in NYS.

Phosphorylation of the aggregate-forming protein alpha-synuclein on serine-129 inhibits its DNA-bending properties.

Alpha-synuclein (aSyn) is a vertebrate protein, normally found within the presynaptic nerve terminal and nucleus, which is known to form somatic and neuritic aggregates in certain neurodegenerative diseases. Disease-associated aggregates of aSyn are heavily phosphorylated at serine-129 (pSyn), while normal aSyn protein is not. Within the nucleus, aSyn can directly bind DNA, but the mechanism of binding and the potential modulatory roles of phosphorylation are poorly understood. Here we demonstrate using a combination of electrophoretic mobility shift assay and atomic force microscopy approaches that both aSyn and pSyn can bind DNA within the major groove, in a DNA length-dependent manner and with little specificity for DNA sequence. Our data are consistent with a model in which multiple aSyn molecules bind a single 300 base pair (bp) DNA molecule in such a way that stabilizes the DNA in a bent conformation. We propose that serine-129 phosphorylation decreases the ability of aSyn to both bind and bend DNA, as aSyn binds 304 bp circular DNA forced into a bent shape, but pSyn does not. Two aSyn paralogs, beta- and gamma-synuclein, also interact with DNA differently than aSyn, and do not stabilize similar DNA conformations. Our work suggests that reductions in aSyn's ability to bind and bend DNA induced by serine-129 phosphorylation may be important for modulating aSyn's known roles in DNA metabolism, including the regulation of transcription and DNA repair.

Real-time virtual infection prevention and control assessments in skilled nursing homes, New York, March 2020-A pilot project.

OBJECTIVE: To describe a pilot project infection prevention and control (IPC) assessment conducted in skilled nursing facilities (SNFs) in New York State (NYS) during a pivotal 2-week period when the region became the nation's epicenter for coronavirus disease 2019 (COVID-19). DESIGN: A telephone and video assessment of IPC measures in SNFs at high risk or experiencing COVID-19 activity. PARTICIPANTS: SNFs in 14 New York counties, including New York City. INTERVENTION: A 3-component remote IPC assessment: (1) screening tool; (2) telephone IPC checklist; and (3) COVID-19 video IPC assessment (ie, "COVIDeo"). RESULTS: In total, 92 SNFs completed the IPC screening tool and checklist: 52 (57%) were conducted as part COVID-19 investigations, and 40 (43%) were proactive prevention-based assessments. Among the 40 proactive assessments, 14 (35%) identified suspected or confirmed COVID-19 cases. COVIDeo was performed in 26 (28%) of 92 assessments and provided observations that other tools would have missed: personal protective equipment (PPE) that was not easily accessible, redundant, or improperly donned, doffed, or stored and specific challenges implementing IPC in specialty populations. The IPC assessments took ∼1 hour each and reached an estimated 4 times as many SNFs as on-site visits in a similar time frame. CONCLUSIONS: Remote IPC assessments by telephone and video were timely and feasible methods of assessing the extent to which IPC interventions had been implemented in a vulnerable setting and to disseminate real-time recommendations. Remote assessments are now being implemented across New York State and in various healthcare facility types. Similar methods have been adapted nationally by the Centers for Disease Control and Prevention.

A description of the first Candida auris-colonized individuals in New York State, 2016-2017.

Candida auris (C. auris) is a globally emerging multidrug-resistant yeast. New York State (NYS) first detected C. auris in July 2016 and is the state most affected. This brief report describes characteristics of the first 114 individuals colonized with C. auris identified through active surveillance/screening by NYS Department of Health. "Colonized/screened" individuals were old (median age, 74 year), had extensive health care exposures and underlying conditions (multiple health care facility admissions in the 90 days prior with more than 80% requiring mechanical ventilation), and had 30- and 90-day mortality rates of 17.5% and 37.7%, respectively (with approximately 60% expired in the 2-year follow-up period). This description is helpful to inform additional prevention measures and add to the collective understanding of C. auris in the United States.

Congenital Measles in a Premature 25-week Gestation Infant.

We describe a premature infant with congenital measles. Laboratory testing confirmed measles in the mother (polymerase chain reaction- and IgM-positive) and congenital measles in the infant (polymerase chain reaction-positive, culture-positive and IgM-positive). The infant never developed a rash, pneumonia, or neurologic complications. This case supports using compatible laboratory findings to diagnose congenital measles in infants without clinical manifestations of measles.

Candida auris Colonization After Discharge to a Community Setting: New York City, 2017-2019.

BACKGROUND: Patients colonized with multidrug-resistant Candida auris and discharged to a community setting can subsequently seek care in a different healthcare facility and might be a source of nosocomial transmission of C auris. METHODS: We designed a case management pilot program for a cohort of New York City residents who had a history of positive C auris culture identified during clinical or screening activities in healthcare settings and discharged to a community setting during 2017-2019. Approximately every 3 months, case managers coordinated C auris colonization assessments, which included swabs of groin, axilla, and body sites yielding C auris previously. Patients eligible to become serially negative were those with ≥2 C auris colonization assessments after initial C auris identification. Clinical characteristics of serially negative and positive patients were compared. RESULTS: The cohort included 75 patients. Overall, 45 patients were eligible to become serially negative and had 552 person-months of follow-up. Of these 45 patients, 28 patients were serially negative (62%; rate 5.1/100 person-months), 8 were serially positive, and 9 could not be classified as either. There were no clinical characteristics that were significantly different between serially negative and positive patients. The median time from initial C auris identification to being serially negative at assessments was 8.6 months (interquartile range, 5.7-10.8 months). CONCLUSIONS: A majority of patients, assessed at least twice after C auris identification, no longer had C auris detectable on serial colonization assessments.

Factors Associated With Candida auris Colonization and Transmission in Skilled Nursing Facilities With Ventilator Units, New York, 2016-2018.

BACKGROUND: Candida auris is an emerging, multidrug-resistant yeast that spreads in healthcare settings. People colonized with C. auris can transmit this pathogen and are at risk for invasive infections. New York State (NYS) has the largest US burden (>500 colonized and infected people); many colonized individuals are mechanically ventilated or have tracheostomy, and are residents of ventilator-capable skilled nursing facilities (vSNF). We evaluated the factors associated with C. auris colonization among vSNF residents to inform prevention interventions. METHODS: During 2016-2018, the NYS Department of Health conducted point prevalence surveys (PPS) to detect C. auris colonization among residents of vSNFs. In a case-control investigation, we defined a case as C. auris colonization in a resident, and identified up to 4 residents with negative swabs during the same PPS as controls. We abstracted data from medical records on patient facility transfers, antimicrobial use, and medical history. RESULTS: We included 60 cases and 218 controls identified from 6 vSNFs. After controlling for potential confounders, the following characteristics were associated with C. auris colonization: being on a ventilator (adjusted odds ratio [aOR], 5.9; 95% confidence interval [CI], 2.3-15.4), receiving carbapenem antibiotics in the prior 90 days (aOR, 3.5; 95% CI, 1.6-7.6), having ≥1 acute care hospital visit in the prior 6 months (aOR, 4.2; 95% CI, 1.9-9.6), and receiving systemic fluconazole in the prior 90 days (aOR, 6.0; 95% CI, 1.6-22.6). CONCLUSIONS: Targeted screening of patients in vSNFs with the above risk factors for C. auris can help identify colonized patients and facilitate the implementation of infection control measures. Antimicrobial stewardship may be an important factor in the prevention of C. auris colonization.

Investigation of Presumptive HIV Transmission Associated with Hospitalization Using Nucleotide Sequence Analysis - New York, 2017.

Since implementation of Standard Precautions* for the prevention of bloodborne pathogen transmission in 1985, health care-associated transmission of human immunodeficiency virus (HIV) in the United States has been rare (1). In October 2017, the New York City Department of Health and Mental Hygiene (NYCDOHMH) and the New York State Department of Health (NYSDOH) were notified by a clinician of a diagnosis of acute HIV infection in a young adult male (patient A) without recognized risk factors (i.e., he was monogamous, had an HIV-negative partner, and had no injection drug use) who had recently been hospitalized for a chronic medical condition. The low risk coupled with the recent hospitalization and medical procedures prompted NYSDOH, NYCDOHMH, and CDC to investigate this case as possible health care-associated transmission of HIV. Among persons with known HIV infection who had hospitalization dates overlapping those of patient A, one person (patient B) had an HIV strain highly similar to patient A's strain by nucleotide sequence analysis. The sequence relatedness, combined with other investigation findings, indicated a likely health care-associated transmission. Nucleotide sequence analysis, which is increasingly used for detecting HIV clusters (i.e., persons with closely related HIV strains) and to inform public health response (2,3), might also be used to identify possible health care-associated transmission of HIV to someone with health care exposure and no known HIV risk factors (4).

Candida auris Isolates Resistant to Three Classes of Antifungal Medications - New York, 2019.

Candida auris is a globally emerging yeast that causes outbreaks in health care settings and is often resistant to one or more classes of antifungal medications (1). Cases of C. auris with resistance to all three classes of commonly prescribed antifungal drugs (pan-resistance) have been reported in multiple countries (1). C. auris has been identified in the United States since 2016; the largest number (427 of 911 [47%]) of confirmed clinical cases reported as of October 31, 2019, have been reported in New York, where C. auris was first detected in July 2016 (1,2). As of June 28, 2019, a total of 801 patients with C. auris were identified in New York, based on clinical cultures or swabs of skin or nares obtained to detect asymptomatic colonization (3). Among these patients, three were found to have pan-resistant C. auris that developed after receipt of antifungal medications, including echinocandins, a class of drugs that targets the fungal cell wall. All three patients had multiple comorbidities and no known recent domestic or foreign travel. Although extensive investigations failed to document transmission of pan-resistant isolates from the three patients to other patients or the environment, the emergence of pan-resistance is concerning. The occurrence of these cases underscores the public health importance of surveillance for C. auris, the need for prudent antifungal prescribing, and the importance of conducting susceptibility testing on all clinical isolates, including serial isolates from individual patients, especially those treated with echinocandin medications. This report summarizes investigations related to the three New York patients with pan-resistant infections and the subsequent actions conducted by the New York State Department of Health and hospital and long-term care facility partners.

Laboratory Analysis of an Outbreak of Candida auris in New York from 2016 to 2018: Impact and Lessons Learned.

Candida auris is a multidrug-resistant yeast which has emerged in health care facilities worldwide; however, little is known about identification methods, patient colonization, environmental survival, spread, and drug resistance. Colonization on both biotic (patients) and abiotic (health care objects) surfaces, along with travel, appear to be the major factors for the spread of this pathogen across the globe. In this investigation, we present laboratory findings from an ongoing C. auris outbreak in New York (NY) from August 2016 through 2018. A total of 540 clinical isolates, 11,035 patient surveillance specimens, and 3,672 environmental surveillance samples were analyzed. Laboratory methods included matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for yeast isolate identification, real-time PCR for rapid surveillance sample screening, culture on selective/nonselective media for recovery of C. auris and other yeasts from surveillance samples, antifungal susceptibility testing to determine the C. auris resistance profile, and Sanger sequencing of the internal transcribed spacer (ITS) and D1/D2 regions of the ribosomal gene for C. auris genotyping. Results included (a) identification and confirmation of C. auris in 413 clinical isolates and 931 patient surveillance isolates as well as identification of 277 clinical cases and 350 colonized cases from 151 health care facilities, including 59 hospitals, 92 nursing homes, 1 long-term acute care hospital (LTACH), and 2 hospices, (b) successful utilization of an in-house developed C. auris real-time PCR assay for the rapid screening of patient and environmental surveillance samples, (c) demonstration of relatively heavier colonization of C. auris in nares than in the axilla/groin, and (d) predominance of the South Asia clade I with intrinsic resistance to fluconazole and elevated MIC to voriconazole (81%), amphotericin B (61%), flucytosine (5FC) (3%), and echinocandins (1%). These findings reflect greater regional prevalence and incidence of C. auris and the deployment of better detection tools in an unprecedented outbreak.

Brucella Exposure Risk Events in 10 Clinical Laboratories, New York City, USA, 2015 to 2017.

From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 Brucella exposure risk events (Brucella events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with Brucella was suspected. In 3 Brucella events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 Brucella events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 Brucella events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Brucella Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the Brucella events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.

Hepatitis B Virus Mutant Infections in Hemodialysis Patients: A Case Series.

RATIONALE & OBJECTIVE: Hepatitis B virus (HBV) transmission in hemodialysis units has become a rare event since implementation of hemodialysis-specific infection control guidelines: performing hemodialysis for hepatitis B surface antigen (HBsAg)-positive patients in an HBV isolation room, vaccinating HBV-susceptible (HBV surface antibody and HBsAg negative) patients, and monthly HBsAg testing in HBV-susceptible patients. Mutations in HBsAg can result in false-negative HBsAg results, leading to failure to identify HBsAg seroconversion from negative to positive. We describe 4 unique cases of HBsAg seroconversion caused by mutant HBV infection or reactivation in hemodialysis patients. STUDY DESIGN: Following identification of a possible HBsAg seroconversion and mutant HBV infection, public health investigations were launched to conduct further HBV testing of case patients and potentially exposed patients. A case patient was defined as a hemodialysis patient with suspected mutant HBV infection because of false-negative HBsAg testing results. Confirmed case patients had HBV DNA sequences demonstrating S-gene mutations. SETTING & PARTICIPANTS: Case patients and patients potentially exposed to the case patient in the respective hemodialysis units in multiple US states. RESULTS: 4 cases of mutant HBV infection in hemodialysis patients were identified; 3 cases were confirmed using molecular sequencing. Failure of some HBsAg testing platforms to detect HBV mutations led to delays in applying HBV isolation procedures. Testing of potentially exposed patients did not identify secondary transmissions. LIMITATIONS: Lack of access to information on past HBsAg testing platforms and results led to challenges in ascertaining when HBsAg seroconversion occurred and identifying and testing all potentially exposed patients. CONCLUSIONS: Mutant HBV infections should be suspected in patients who test HBsAg negative and concurrently test positive for HBV DNA at high levels. Dialysis providers should consider using HBsAg assays that can also detect mutant HBV strains for routine HBV testing.

Multistate Outbreak of Burkholderia cepacia Complex Bloodstream Infections After Exposure to Contaminated Saline Flush Syringes: United States, 2016-2017.

BACKGROUND: Burkholderia cepacia complex (Bcc) has caused healthcare-associated outbreaks, often in association with contaminated products. The identification of 4 Bcc bloodstream infections in patients residing at a single skilled nursing facility (SNF) within 1 week led to an epidemiological investigation to identify additional cases and the outbreak source. METHODS: A case was initially defined via a blood culture yielding Bcc in a SNF resident receiving intravenous therapy after 1 August 2016. Multistate notifications were issued to identify additional cases. Public health authorities performed site visits at facilities with cases to conduct chart reviews and identify possible sources. Pulsed-field gel electrophoresis (PFGE) was performed on isolates from cases and suspect products. Facilities involved in manufacturing suspect products were inspected to assess possible root causes. RESULTS: An outbreak of 162 Bcc bloodstream infections across 59 nursing facilities in 5 states occurred during September 2016-January 2017. Isolates from patients and pre-filled saline flush syringes were closely related by PFGE, identifying contaminated flushes as the outbreak source and prompting a nationwide recall. Inspections of facilities at the saline flush manufacturer identified deficiencies that might have led to the failure to sterilize a specific case containing a partial lot of the product. CONCLUSIONS: Communication and coordination among key stakeholders, including healthcare facilities, public health authorities, and state and federal agencies, led to the rapid identification of an outbreak source and likely prevented many additional infections. Effective processes to ensure the sterilization of injectable products are essential to prevent similar outbreaks in the future.

Candida auris in Healthcare Facilities, New York, USA, 2013-2017.

Candida auris is an emerging yeast that causes healthcare-associated infections. It can be misidentified by laboratories and often is resistant to antifungal medications. We describe an outbreak of C. auris infections in healthcare facilities in New York City, New York, USA. The investigation included laboratory surveillance, record reviews, site visits, contact tracing with cultures, and environmental sampling. We identified 51 clinical case-patients and 61 screening case-patients. Epidemiologic links indicated a large, interconnected web of affected healthcare facilities throughout New York City. Of the 51 clinical case-patients, 23 (45%) died within 90 days and isolates were resistant to fluconazole for 50 (98%). Of screening cultures performed for 572 persons (1,136 total cultures), results were C. auris positive for 61 (11%) persons. Environmental cultures were positive for samples from 15 of 20 facilities. Colonization was frequently identified during contact investigations; environmental contamination was also common.

The ubiquitin-proteasome system as a transcriptional regulator of plant immunity.

The ubiquitin-proteasome system (UPS) has been shown to play vital roles in diverse plant developmental and stress responses. The UPS post-translationally modifies cellular proteins with the small molecule ubiquitin, resulting in their regulated degradation by the proteasome. Of particular importance is the role of the UPS in regulating hormone-responsive gene expression profiles, including those triggered by the immune hormone salicylic acid (SA). SA utilizes components of the UPS pathway to reprogram the transcriptome for establishment of local and systemic immunity. Emerging evidence has shown that SA induces the activity of Cullin-RING ligases (CRLs) that fuse chains of ubiquitin to downstream transcriptional regulators and consequently target them for degradation by the proteasome. Here we review how CRL-mediated degradation of transcriptional regulators may control SA-responsive immune gene expression programmes and discuss how the UPS can be modulated by both endogenous and foreign exogenous signals. The highlighted research findings paint a clear picture of the UPS as a central hub for immune activation as well as a battle ground for hijacking by pathogens.

Molecular typing and whole genome next generation sequencing of human adenovirus 8 strains recovered from four 2012 outbreaks of keratoconjunctivitis in New York State.

Ocular infections caused by human adenovirus (HAdV) are highly contagious. The most severe are usually caused by members of species HAdV-D (types HAdV8, 19, 37, 53, 54, and 56) and can manifest as epidemic keratoconjunctivitis (EKC), often resulting in prolonged impairment of vision. During the early months of 2012, EKC outbreaks occurred in neonatal intensive care units (NICUs) in 3 hospitals in New York State (New York and Suffolk Counties). A total of 32 neonates were affected. For 14 of them, HAdV8 was laboratory-confirmed as the causative agent. Nine healthcare workers were also affected with 3 laboratory-confirmed, HAdV-positive EKC. A fourth EKC outbreak was documented among patients attending a private ophthalmology practice in Ulster County involving a total of 35 cases. Epidemiological linkage between the neonatal intensive care unit outbreaks was demonstrated by molecular typing of virus isolates with restriction enzyme analysis and next generation whole genome sequencing. The strain isolated from the ophthalmology clinic was easily distinguishable from the others by restriction enzyme analysis.

Two Imported Cases of Congenital Rubella Syndrome and Infection-Control Challenges in New York State, 2013-2015.

Rubella was declared eliminated in the United States in 2004. During 2013-2015, 2 infants with congenital rubella syndrome (CRS) were born in New York State. Both mothers were foreign born and traveled to Yemen during their pregnancy. Delayed consideration of CRS led to preventable exposures and a substantial public health response.

A Case of Adult Intestinal Toxemia Botulism During Prolonged Hospitalization in an Allogeneic Hematopoietic Cell Transplant Recipient.

We report a laboratory-confirmed case of adult intestinal toxemia botulism in an allogeneic hematopoietic stem cell transplantation (allo-HCT) recipient. Onset of symptoms occurred within the hospitalized setting, making this case particularly unique. Botulism may have arisen because of significant intestinal disruption and compromise, and not directly from immune compromise.