Detection and Genetic Characterization of Community-Based SARS-CoV-2 Infections - New York City, March 2020.

To limit introduction of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), the United States restricted travel from China on February 2, 2020, and from Europe on March 13. To determine whether local transmission of SARS-CoV-2 could be detected, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) conducted deidentified sentinel surveillance at six NYC hospital emergency departments (EDs) during March 1-20. On March 8, while testing availability for SARS-CoV-2 was still limited, DOHMH announced sustained community transmission of SARS-CoV-2 (1). At this time, twenty-six NYC residents had confirmed COVID-19, and ED visits for influenza-like illness* increased, despite decreased influenza virus circulation.† The following week, on March 15, when only seven of the 56 (13%) patients with known exposure histories had exposure outside of NYC, the level of community SARS-CoV-2 transmission status was elevated from sustained community transmission to widespread community transmission (2). Through sentinel surveillance during March 1-20, DOHMH collected 544 specimens from patients with influenza-like symptoms (ILS)§ who had negative test results for influenza and, in some instances, other respiratory pathogens.¶ All 544 specimens were tested for SARS-CoV-2 at CDC; 36 (6.6%) tested positive. Using genetic sequencing, CDC determined that the sequences of most SARS-CoV-2-positive specimens resembled those circulating in Europe, suggesting probable introductions of SARS-CoV-2 from Europe, from other U.S. locations, and local introductions from within New York. These findings demonstrate that partnering with health care facilities and developing the systems needed for rapid implementation of sentinel surveillance, coupled with capacity for genetic sequencing before an outbreak, can help inform timely containment and mitigation strategies.

Quantitative Results of a National Intervention to Prevent Hospital-Onset Methicillin-Resistant Staphylococcus aureus Bloodstream Infection: A Pre-Post Observational Study.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the most common causes of health care-associated infection (HAI). Objective: To evaluate the effect of education and a tiered, evidence-based infection prevention strategy on rates of hospital-onset MRSA bloodstream infection (BSI). Design: Prospective, national, nonrandomized, interventional, 12-month, multiple cohort, pre-post observational quality improvement project. Setting: Acute care, long-term acute care, and critical access hospitals with a disproportionate burden of HAI. Patients: All patients admitted to participating facilities during the project period. Intervention: A multimodal infection prevention intervention consisting of recommendations and tools for prioritizing and implementing evidence-based infection prevention strategies, on-demand educational videos, Internet-based live educational presentations, and access to content experts. Measurements: Rates of hospital-onset MRSA BSI, overall and stratified by hospital type, during 12-month baseline and postintervention periods. Variation in outcomes across hospital types was examined. Results: Between November 2016 and May 2018, 387 hospitals in 23 states and the District of Columbia participated, 353 (91%) submitted MRSA data, and 172 (49%) indicated that MRSA prevention was a priority. Unadjusted overall rates of hospital-onset MRSA BSI were 0.075 (95% CI, 0.065 to 0.085) and 0.071 (CI, 0.063 to 0.080) per 1000 patient-days in the baseline and postintervention periods, respectively. Limitations: The intervention period was short. Participation and adherence to recommended interventions were not fully assessed. Baseline rates of hospital-onset MRSA BSI were relatively low. Prevention of MRSA was a priority in a minority of participating hospitals. Patient characteristics and other MRSA risk factors were not assessed. Conclusion: In hospitals with a disproportionate burden of HAIs, access to tools to assist with implementation of evidence-based prevention strategies and education resources alone may not be sufficient to prevent MRSA BSI. Primary Funding Source: Centers for Disease Control and Prevention.

Optimizing Contact Precautions to Curb the Spread of Antibiotic-resistant Bacteria in Hospitals: A Multicenter Cohort Study to Identify Patient Characteristics and Healthcare Personnel Interactions Associated With Transmission of Methicillin-resistant Staphylococcus aureus.

BACKGROUND: Healthcare personnel (HCP) acquire antibiotic-resistant bacteria on their gloves and gowns when caring for intensive care unit (ICU) patients. Yet, contact precautions for patients with methicillin-resistant Staphylococcus aureus (MRSA) remains controversial despite existing guidelines. We sought to understand which patients are more likely to transfer MRSA to HCP and to identify which HCP interactions are more likely to lead to glove or gown contamination. METHODS: This was a prospective, multicenter cohort study of cultured HCP gloves and gowns for MRSA. Samples were obtained from patients' anterior nares, perianal area, and skin of the chest and arm to assess bacterial burden. RESULTS: Among 402 MRSA-colonized patients with 3982 interactions, we found that HCP gloves and gowns were contaminated with MRSA 14.3% and 5.9% of the time, respectively. Contamination of either gloves or gowns occurred in 16.2% of interactions. Contamination was highest among occupational/physical therapists (odds ratio [OR], 6.96; 95% confidence interval [CI], 3.51, 13.79), respiratory therapists (OR, 5.34; 95% CI, 3.04, 9.39), and when any HCP touched the patient (OR, 2.59; 95% CI, 1.04, 6.51). Touching the endotracheal tube (OR, 1.75; 95% CI, 1.38, 2.19), bedding (OR, 1.43; 95% CI, 1.20, 1.70), and bathing (OR, 1.32; 95% CI, 1.01, 1.75) increased the odds of contamination. We found an association between increasing bacterial burden on the patient and HCP glove or gown contamination. CONCLUSIONS: Gloves and gowns are frequently contaminated with MRSA in the ICU. Hospitals may consider using fewer precautions for low-risk interactions and more for high-risk interactions and personnel.

Cost-effectiveness of ceftazidime-avibactam for treatment of carbapenem-resistant Enterobacteriaceae bacteremia and pneumonia.

Background: Ceftazidime/avibactam (CAZ-AVI) may improve outcomes among patients with carbapenem-resistant Enterobacteriaceae (CRE) infections compared to conventional therapies. However, CAZ-AVI's cost-effectiveness is unknown.Methods: We used a decision analytic model to estimate the health and economic consequences of CAZ-AVI-based therapy compared to colistin-based therapy (COL) for a hypothetical cohort of patients with CRE pneumonia or bacteremia over a 5-year horizon. Model inputs were from published sources and included CRE mortality with COL (41%), CAZ-AVI's absolute risk reduction in CRE mortality (23%), daily cost of CAZ-AVI ($926), risk of nephrotoxicity with COL (42%) and probability of discharge to long-term care (LTC) following CRE infection (56%). Outcomes included quality adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICER; $/QALY). 1-way and probabilistic sensitivity analyses were performed and ICERs were compared to willingness to pay standards of $100,000/QALY and $150,000/QALY.Results: In the base case, CAZ-AVI had an ICER of $95,000/QALY. At a $100,000/QALY threshold, results were sensitive to a number of variables including: the probability and cost of LTC, quality of life following CRE infection, CAZ-AVI's absolute risk reduction in mortality, all-cause mortality, daily cost of CAZ-AVI, and healthcare costs after CRE infection. The ICER did not exceed $150,000/QALY after varying all model inputs across a wide range of plausible values. In probabilistic sensitivity analysis, CAZ-AVI was the optimal strategy in 59% and 99% of simulations at $100,000/QALY and $150,000/QALY threshold, respectively.Conclusion: CAZ-AVI is a cost-effective treatment for CRE bacteremia and pneumonia based on accepted willingness to pay standards in the US.

The Expanding Role of Antimicrobial Stewardship Programs in Hospitals in the United States: Lessons Learned from a Multisite Qualitative Study.

BACKGROUND: Misuse of antibiotics can lead to the development of antibiotic resistance, which adversely affects morbidity, mortality, length of stay, and cost. To combat the threat of antimicrobial resistance, The Joint Commission and the Centers for Medicare & Medicaid Services have initiated or proposed requirements for hospitals to have antimicrobial stewardship programs (ASPs), but implementation remains challenging. A key-informant interview study was conducted to describe the characteristics and innovative strategies of leading ASPs. METHODS: Semistructured interviews were conducted with 12 program leaders at four ASPs in the United States, chosen by purposive sampling on the basis of national reputation, scholarship, and geography. Questions focused on ASP implementation, program structure, strengths, weaknesses, lessons learned, and future directions. Content analysis was used to identify dominant themes. RESULTS: Three major themes were identified. The first was evolution of ASPs from a top-down structure to a more diffuse approach involving unit-based pharmacists, multidisciplinary staff, and shared responsibility for antimicrobial prescribing under the ASPs' leadership. The second theme was integration of information technology (IT) systems, which enabled real-time interventions to optimize antimicrobial therapy and patient management. The third was barriers to technology integration, including limited resources for data analysis and poor interoperability between software systems. CONCLUSION: The study provides valuable insights on program implementation at a sample of leading ASPs across the United States. These ASPs used expansion of personnel to amplify the ASP's impact and integrated IT resources into daily work flow to improve efficiency. These findings can be used to guide implementation at other hospitals and aid in future policy development.

Impact of Early Detection of Respiratory Viruses by Multiplex PCR Assay on Clinical Outcomes in Adult Patients.

Rapid and definitive diagnosis of viral respiratory infections is imperative in patient triage and management. We compared the outcomes for adult patients with positive tests for respiratory viruses at a tertiary care center across two consecutive influenza seasons (winters of 2010-2011 and 2012). Infections were diagnosed by conventional methods in the first season and by multiplex PCR (FilmArray) in the second season. FilmArray decreased the time to diagnosis of influenza compared to conventional methods (median turnaround times of 1.7 h versus 7.7 h, respectively; P = 0.015); FilmArray also decreased the time to diagnosis of non-influenza viruses (1.5 h versus 13.5 h, respectively; P < 0.0001). Multivariate logistic regression found that a diagnosis of influenza by FilmArray was associated with significantly lower odds ratios (ORs) for admission (P = 0.046), length of stay (P = 0.040), duration of antimicrobial use (P = 0.032), and number of chest radiographs (P = 0.005), when controlling for potential confounders. We conclude that the rapid turnaround time, multiplex nature of the test (allowing simultaneous detection of an array of viruses), and superior sensitivity of FilmArray may improve the evaluation and management of patients suspected of having respiratory virus infections.

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

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

Clinical outcomes associated with polymyxin B dose in patients with bloodstream infections due to carbapenem-resistant Gram-negative rods.

There is significant variation in the use of polymyxin B (PMB), and optimal dosing has not been defined. The purpose of this retrospective study was to evaluate the relationship between PMB dose and clinical outcomes. We included patients with bloodstream infections (BSIs) due to carbapenem-resistant Gram-negative rods who received ≥48 h of intravenous PMB. The objective was to evaluate the association between PMB dose and 30-day mortality, clinical cure at day 7, and development of acute kidney injury (AKI). A total of 151 BSIs were included. The overall 30-day mortality was 37.8% (54 of 151), and the median PMB dosage was 1.3 mg/kg (of total body weight)/day. Receipt of PMB dosages of <1.3 mg/kg/day was significantly associated with 30-day mortality (46.5% versus 26.3%; P = 0.02), and this association persisted in multivariable analysis (odds ratio [OR] = 1.58; 95% confidence interval [CI] = 1.05 to 1.81; P = 0.04). Eighty-two percent of patients who received PMB dosages of <1.3 mg/kg/day had baseline renal impairment. Clinical cure at day 7 was not significantly different between dosing groups. AKI was more common in patients receiving PMB dosages of ≥250 mg/day (66.7% versus 32.0%; P = 0.03), and this association persisted in multivariable analysis (OR = 4.32; 95% CI = 1.15 to 16.25; P = 0.03). PMB dosages of <1.3 mg/kg/day were administered primarily to patients with renal impairment, and this dosing was independently associated with 30-day mortality. However, dosages of ≥250 mg/day were independently associated with AKI. These data support the use of PMB without dose reduction in the setting of renal impairment.

Crisis in hospital-acquired, healthcare-associated infections.

Healthcare-associated infections (HAIs) cause significant morbidity and mortality. Recognition of the burden, cost, and preventability of HAIs has resulted in new initiatives to encourage adherence to recommended infection prevention practices and new research to better understand the pathogenesis of HAIs and to develop novel approaches to prevention. Although substantial progress in HAI prevention has been made over the past decade, many opportunities for improvement remain and new challenges continue to arise. Optimal protection of patients from the harms associated with HAIs will require not only allocation of adequate financial resources and additional scientific research, but also a strong commitment to excellence among all healthcare providers, including consistent use of proven prevention practices and appropriate use of antimicrobial agents. Although it is a daunting task, there has never been a better opportunity for the healthcare system to make the changes necessary to achieve the goal of elimination of HAIs.

Cost-effectiveness of blood donor screening for Babesia microti in endemic regions of the United States.

BACKGROUND: Babesia microti is the leading reported cause of red blood cell (RBC) transfusion-transmitted infection in the United States. Donor screening assays are in development. STUDY DESIGN AND METHODS: A decision analytic model estimated the cost-effectiveness of screening strategies for preventing transfusion-transmitted babesiosis (TTB) in a hypothetical cohort of transfusion recipients in Babesia-endemic areas of the United States. Strategies included: 1) no screening; 2) Uniform Donor Health History Questionnaire (UDHQ), "status quo"; 3) recipient risk targeting using donor antibody and polymerase chain reaction (PCR) screening; 4) universal endemic donor antibody screening; and 5) universal endemic donor antibody and PCR screening. Outcome measures were TTB cases averted, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs; $/QALY). We assumed a societal willingness to pay of $1 million/QALY based on screening for other transfusion-transmitted infections. RESULTS: Compared to no screening, the UDHQ avoids 0.02 TTB cases per 100,000 RBC transfusions at an ICER of $160,000/QALY whereas recipient risk-targeted strategy using antibody/PCR avoids 1.62 TTB cases per 100,000 RBC transfusions at an ICER of $713,000/QALY compared to the UDHQ. Universal endemic antibody screening avoids 3.39 cases at an ICER of $760,000/QALY compared to the recipient risk-targeted strategy. Universal endemic antibody/PCR screening avoids 3.60 cases and has an ICER of $8.8 million/QALY compared to universal endemic antibody screening. Results are sensitive to blood donor Babesia prevalence, TTB transmission probability, screening test costs, risk and severity of TTB complications, and impact of babesiosis diagnosis on donor quality of life. CONCLUSION: Antibody screening for Babesia in endemic regions is appropriate from an economic perspective based on the societal willingness to pay for preventing infectious threats to blood safety.

High touch surface bioburden associated with the use of disinfectants with and without continuously active disinfection in ambulatory care settings.

A quaternary ammonium and alcohol-based disinfectant with reported continuous activity demonstrated reduced microbial buildup on surfaces over time compared to routine disinfectants without continuous activity in in vitro and hospital studies. We compared these disinfectants in ambulatory settings and found no difference in bioburden on high-touch surfaces over time.

Healthcare personnel opinions regarding the feasibility of a risk-tailored approach to contact precautions for methicillin-resistant Staphylococcus aureus in the acute care setting.

"All or none" approaches to the use of contact precautions for methicillin-resistant Staphylococcus aureus (MRSA) both fail to recognize that transmission risk varies. This qualitative study assessed healthcare personnel perspectives regarding the feasibility of a risk-tailored approach to use contact precautions for MRSA more strategically in the acute care setting.

Multidrug-resistant organisms in dialysis patients.

Multidrug-resistant organisms (MDROs) have emerged as important causes of healthcare-associated infections (HAIs), and these infections are associated with significant morbidity and mortality. Dialysis patients have been particularly affected by these pathogens, with colonization and infection rates often exceeding those seen in persons with other types of healthcare exposure. The infection control practices that are currently recommended for use in dialysis facilities and other healthcare settings have the potential to eliminate, or at least substantially reduce transmission of and infection with MDROs. Unfortunately, recent data suggest that these recommended practices are not consistently implemented. Additional efforts and research are needed to increase healthcare workers' awareness of and adherence to infection prevention measures, to develop new and more effective prevention strategies, and to determine cost-effective approaches to MDRO prevention to optimize the safety and quality of care provided to dialysis patients.

Universal glove and gown use and acquisition of antibiotic-resistant bacteria in the ICU: a randomized trial.

IMPORTANCE: Antibiotic-resistant bacteria are associated with increased patient morbidity and mortality. It is unknown whether wearing gloves and gowns for all patient contact in the intensive care unit (ICU) decreases acquisition of antibiotic-resistant bacteria. OBJECTIVE: To assess whether wearing gloves and gowns for all patient contact in the ICU decreases acquisition of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) compared with usual care. DESIGN, SETTING, AND PARTICIPANTS: Cluster-randomized trial in 20 medical and surgical ICUs in 20 US hospitals from January 4, 2012, to October 4, 2012. INTERVENTIONS: In the intervention ICUs, all health care workers were required to wear gloves and gowns for all patient contact and when entering any patient room. MAIN OUTCOMES AND MEASURES: The primary outcome was acquisition of MRSA or VRE based on surveillance cultures collected on admission and discharge from the ICU. Secondary outcomes included individual VRE acquisition, MRSA acquisition, frequency of health care worker visits, hand hygiene compliance, health care­associated infections, and adverse events. RESULTS: From the 26,180 patients included, 92,241 swabs were collected for the primary outcome. Intervention ICUs had a decrease in the primary outcome of MRSA or VRE from 21.35 acquisitions per 1000 patient-days (95% CI, 17.57 to 25.94) in the baseline period to 16.91 acquisitions per 1000 patient-days (95% CI, 14.09 to 20.28) in the study period, whereas control ICUs had a decrease in MRSA or VRE from 19.02 acquisitions per 1000 patient-days (95% CI, 14.20 to 25.49) in the baseline period to 16.29 acquisitions per 1000 patient-days (95% CI, 13.48 to 19.68) in the study period, a difference in changes that was not statistically significant (difference, −1.71 acquisitions per 1000 person-days, 95% CI, −6.15 to 2.73; P = .57). For key secondary outcomes, there was no difference in VRE acquisition with the intervention (difference, 0.89 acquisitions per 1000 person-days; 95% CI, −4.27 to 6.04, P = .70), whereas for MRSA, there were fewer acquisitions with the intervention (difference, −2.98 acquisitions per 1000 person-days; 95% CI, −5.58 to −0.38; P = .046). Universal glove and gown use also decreased health care worker room entry (4.28 vs 5.24 entries per hour, difference, −0.96; 95% CI, −1.71 to −0.21, P = .02), increased room-exit hand hygiene compliance (78.3% vs 62.9%, difference, 15.4%; 95% CI, 8.99% to 21.8%; P = .02) and had no statistically significant effect on rates of adverse events (58.7 events per 1000 patient days vs 74.4 events per 1000 patient days; difference, −15.7; 95% CI, −40.7 to 9.2, P = .24). CONCLUSIONS AND RELEVANCE: The use of gloves and gowns for all patient contact compared with usual care among patients in medical and surgical ICUs did not result in a difference in the primary outcome of acquisition of MRSA or VRE. Although there was a lower risk of MRSA acquisition alone and no difference in adverse events, these secondary outcomes require replication before reaching definitive conclusions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT0131821.

Clinical and Bacterial Characteristics Associated with Glove and Gown Contamination by Carbapenem-Resistant Klebsiella pneumoniae in the Health Care Setting.

Carbapenem-resistant Klebsiella pneumoniae (CRKp) is a pathogen of significant concern to public health, as it has become increasingly associated with difficult-to-treat community-acquired and hospital-associated infections. Transmission of K. pneumoniae between patients through interactions with shared health care personnel (HCP) has been described as a source of infection in health care settings. However, it is not known whether specific lineages or isolates of K. pneumoniae are associated with increased transmission. Thus, we used whole-genome sequencing to analyze the genetic diversity of 166 carbapenem-resistant K. pneumoniae isolates from five U.S. hospitals in four states as part of a multicenter study examining risk factors for glove and gown contamination by carbapenem-resistant Enterobacterales (CRE). The CRKp isolates exhibited considerable genomic diversity with 58 multilocus sequence types (STs), including four newly designated STs. ST258 was the most prevalent ST, representing 31% (52/166) of the CRKp isolates, but was similarly prevalent among patients who had high, intermediate, and low CRKp transmission. Increased transmission was associated with clinical characteristics including a nasogastric (NG) tube or an endotracheal tube or tracheostomy (ETT/Trach). Overall, our findings provide important insight into the diversity of CRKp associated with transmission from patients to the gloves and gowns of HCP. These findings suggest that certain clinical characteristics and the presence of CRKp in the respiratory tract, rather than specific lineages or genetic content, are more often associated with increased transmission of CRKp from patients to HCP. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae (CRKp) is a significant public health concern that has contributed to the spread of carbapenem resistance and has been linked to high morbidity and mortality. Transmission of K. pneumoniae among patients through interactions with shared health care personnel (HCP) has been described as a source of infection in health care settings; however, it remains unknown whether particular bacterial characteristics are associated with increased CRKp transmission. Using comparative genomics, we demonstrate that CRKp isolates associated with high or intermediate transmission exhibit considerable genomic diversity, and there were no K. pneumoniae lineages or genes that were universally predictive of increased transmission. Our findings suggest that certain clinical characteristics and the presence of CRKp, rather than specific lineages or genetic content of CRKp, are more often associated with increased transmission of CRKp from patients to HCP.