Carbapenemase-producing Enterobacterales causing secondary infections during the COVID-19 crisis at a New York City hospital.

BACKGROUND: Patients with COVID-19 may be at increased risk for secondary bacterial infections with MDR pathogens, including carbapenemase-producing Enterobacterales (CPE). OBJECTIVES: We sought to rapidly investigate the clinical characteristics, population structure and mechanisms of resistance of CPE causing secondary infections in patients with COVID-19. METHODS: We retrospectively identified CPE clinical isolates collected from patients testing positive for SARS-CoV-2 between March and April 2020 at our medical centre in New York City. Available isolates underwent nanopore sequencing for rapid genotyping, antibiotic resistance gene detection and phylogenetic analysis. RESULTS: We identified 31 CPE isolates from 13 patients, including 27 Klebsiella pneumoniae and 4 Enterobacter cloacae complex isolates. Most patients (11/13) had a positive respiratory culture and 7/13 developed bacteraemia; treatment failure was common. Twenty isolates were available for WGS. Most K. pneumoniae (16/17) belonged to ST258 and encoded KPC (15 KPC-2; 1 KPC-3); one ST70 isolate encoded KPC-2. E. cloacae isolates belonged to ST270 and encoded NDM-1. Nanopore sequencing enabled identification of at least four distinct ST258 lineages in COVID-19 patients, which were validated by Illumina sequencing data. CONCLUSIONS: While CPE prevalence has declined substantially in New York City in recent years, increased detection in patients with COVID-19 may signal a re-emergence of these highly resistant pathogens in the wake of the global pandemic. Increased surveillance and antimicrobial stewardship efforts, as well as identification of optimal treatment approaches for CPE, will be needed to mitigate their future impact.

Escherichia coli Harboring mcr-1 in a Cluster of Liver Transplant Recipients: Detection through Active Surveillance and Whole-Genome Sequencing.

mcr-1, a plasmid-associated gene for colistin resistance, was first described in China in 2015, but its spread in the United States is unknown. We report detection of mcr-1-carrying Escherichia coli ST117 in a cluster of three liver transplant recipients.

Proton Pump Inhibitors Do Not Increase Risk for Clostridium difficile Infection in the Intensive Care Unit.

OBJECTIVES: Patients in the intensive care unit (ICU) frequently receive proton pump inhibitors (PPIs) and have high rates of Clostridium difficile infection (CDI). PPIs have been associated with CDI in hospitalized patients, but ICU patients differ fundamentally from non-ICU patients and few studies have focused on PPI use exclusively in the critical care setting. We performed a retrospective cohort study to determine the associations between PPIs and health-care facility-onset CDI in the ICU. METHODS: We analyzed data from all adult ICU patients at three affiliated hospitals (14 ICUs) between 2010 and 2013. Patients were excluded if they had recent CDI or an ICU stay of <3 days. We parsed electronic medical records for ICU exposures, focusing on PPIs and other potentially modifiable exposures that occurred during ICU stays. Health-care facility-onset CDI in the ICU was defined as a newly positive PCR for the C. difficile toxin B gene from an unformed stool, with subsequent receipt of anti-CDI therapy. We analyzed PPIs and other exposures as time-varying covariates and used Cox proportional hazards models to adjust for demographics, comorbidities, and other clinical factors. RESULTS: Of 18,134 patients who met the criteria for inclusion, 271 (1.5%) developed health-care facility-onset CDI in the ICU. Receipt of antibiotics was the strongest risk factor for CDI (adjusted HR (aHR) 2.79; 95% confidence interval (CI), 1.50-5.19). There was no significant increase in risk for CDI associated with PPIs in those who did not receive antibiotics (aHR 1.56; 95% CI, 0.72-3.35), and PPIs were actually associated with a decreased risk for CDI in those who received antibiotics (aHR 0.64; 95% CI, 0.48-0.83). There was also no evidence of increased risk for CDI in those who received higher doses of PPIs. CONCLUSIONS: Exposure to antibiotics was the most important risk factor for health-care facility-onset CDI in the ICU. PPIs did not increase risk for CDI in the ICU regardless of use of antibiotics.

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.

Challenges Associated With Using Large Data Sets for Quality Assessment and Research in Clinical Settings.

The rapidly expanding use of electronic records in health-care settings is generating unprecedented quantities of data available for clinical, epidemiological, and cost-effectiveness research. Several challenges are associated with using these data for clinical research, including issues surrounding access and information security, poor data quality, inconsistency of data within and across institutions, and a paucity of staff with expertise to manage and manipulate large clinical data sets. In this article, we describe our experience with assembling a data-mart and conducting clinical research using electronic data from four facilities within a single hospital network in New York City. We culled data from several electronic sources, including the institution's admission-discharge-transfer system, cost accounting system, electronic health record, clinical data warehouse, and departmental records. The final data-mart contained information for more than 760,000 discharges occurring from 2006 through 2012. Using categories identified by the National Institutes of Health Big Data to Knowledge initiative as a framework, we outlined challenges encountered during the development and use of a domain-specific data-mart and recommend approaches to overcome these challenges.

Gender differences in risk of bloodstream and surgical site infections.

BACKGROUND: Identifying patients most at risk for hospital- and community-associated infections is one essential strategy for preventing infections. OBJECTIVE: To investigate whether rates of community- and healthcare-associated bloodstream and surgical site infections varied by patient gender in a large cohort after controlling for a wide variety of possible confounders. DESIGN: Retrospective cohort study. PARTICIPANTS: All patients discharged from January 1, 2006 through December 31, 2008 (133,756 adult discharges and 66,592 pediatric discharges) from a 650-bed tertiary care hospital, a 220-bed community hospital, and a 280-bed pediatric acute care hospital within a large, academic medical center in New York, NY. MAIN MEASURES: Data were collected retrospectively from various electronic sources shared by the hospitals and linked using patients' unique medical record numbers. Infections were identified using previously validated computerized algorithms. KEY RESULTS: Odds of community-associated bloodstream infections, healthcare-associated bloodstream infections, and surgical site infections were significantly lower for women than for men after controlling for present-on-admission patient characteristics and events during the hospital stay [odds ratios (95 % confidence intervals) were 0.85 (0.77-0.93), 0.82 (0.74-0.91), and 0.78 (0.68-0.91), respectively]. Gender differences were greatest for older adolescents (12-17 years) and adults 18-49 years and least for young children (<12 years) and older adults (≥ 70 years). CONCLUSIONS: In this cohort, men were at higher risk for bloodstream and surgical site infections, possibly due to differences in propensity for skin colonization or other anatomical differences.

Comparing the clinical severity of the first versus second wave of 2009 Influenza A (H1N1) in a New York City pediatric healthcare facility.

OBJECTIVE: We previously reported the epidemiology of 2009 Influenza A (H1N1) in our pediatric healthcare facility in New York City during the first wave of illness (May-July 2009). We hypothesized that compared with the first wave, the second wave would be characterized by increased severity of illness and mortality. DESIGN: : Case series conducted from May 2009 to April 2010. SETTING: Pediatric emergency departments and inpatient facilities of New York-Presbyterian Hospital. PATIENTS: All hospitalized patients ÷ 18 yrs of age with positive laboratory tests for influenza A. MEASUREMENTS AND MAIN RESULTS: We compared severity of illness during the first and second wave assessed by the number of hospitalized children, including those in the pediatric intensive care unit, bacterial superinfections, and mortality rate. Compared to the first wave, fewer children were hospitalized during the second wave (n = 115 vs. 76), but a comparable portion were admitted to the pediatric intensive care unit (30.4% vs. 19.7%; p = .10). Pediatric Risk of Mortality III scores, length of hospitalization in the pediatric intensive care unit, incidence of respiratory failure and pneumonia, and peak oxygenation indices were similar during both waves. Bacterial superinfections were comparable in the first vs. second wave (3.5% vs. 1.3%). During the first wave, no child received extracorporeal membrane oxygenation and one died, while during the second wave, one child received extracorporeal membrane oxygenation and there were no deaths. CONCLUSIONS: At our pediatric healthcare facility in New York City, fewer children were hospitalized with 2009 Influenza A (H1N1) during the second wave, but both waves had a similar spectrum of illness severity and low mortality rate.

Long-term survival and healthcare utilization outcomes attributable to sepsis and pneumonia.

BACKGROUND: Hospital associated infections are major problems, which are increasing in incidence and very costly. However, most research has focused only on measuring consequences associated with the initial hospitalization. We explored the long-term consequences of infections in elderly Medicare patients admitted to an intensive care unit (ICU) and discharged alive, focusing on: sepsis, pneumonia, central-line-associated bloodstream infections (CLABSI), and ventilator-associated pneumonia (VAP); the relationships between the infections and long-term survival and resource utilization; and how resource utilization was related to impending death during the follow up period. METHODS: Clinical data and one year pre- and five years post-index hospitalization Medicare records were examined. Hazard ratios (HR) and healthcare utilization incidence ratios (IR) were estimated from state of the art econometric models. Patient demographics (i.e., age, gender, race and health status) and Medicaid status (i.e., dual eligibility) were controlled for in these models. RESULTS: In 17,537 patients, there were 1,062 sepsis, 1,802 pneumonia, 42 CLABSI and 52 VAP cases. These subjects accounted for 62,554 person-years post discharge. The sepsis and CLABSI cohorts were similar as were the pneumonia and VAP cohorts. Infection was associated with increased mortality (sepsis HR = 1.39, P < 0.01; and pneumonia HR = 1.58, P < 0.01) and the risk persisted throughout the follow-up period. Persons with sepsis and pneumonia experienced higher utilization than controls (e.g., IR for long-term care utilization for those with sepsis ranged from 2.67 to 1.93 in years 1 through 5); and, utilization was partially related to impending death. CONCLUSIONS: The infections had significant and lasting adverse consequences among the elderly. Yet, many of these infections may be preventable. Investments in infection prevention interventions are needed in both community and hospitals settings.

Outcomes among patients with Staphylococcus aureus bacteremia enrolled in a postdischarge outpatient parenteral antibiotic therapy program at an academic medical center.

We compared patients with Staphylococcus aureus bacteremia enrolled in outpatient parenteral antibiotic therapy monitoring program (OPAT-MP) upon hospital discharge with patients not enrolled. OPAT-MP patients were more likely to attend infectious diseases follow-up appointments. OPAT-related emergency room visits and/or readmissions were more common among non-OPAT-MP patients, but differences were not statistically significant.

Urinary catheter policies in home healthcare agencies and hospital transfers due to urinary tract infection.

BACKGROUND: Urinary tract infections (UTIs) are a frequent cause of hospital transfer for home healthcare (HHC) patients, particularly among patients with urinary catheters. METHODS: We conducted a cross-sectional, nationally representative HHC agency-level survey (2018-2019) and combined it with patient-level data from the Outcome and Assessment Information Set (OASIS) and Medicare inpatient data (2016-2018) to evaluate the association between HHC agencies' urinary catheter policies and hospital transfers due to UTI. Our sample included 28,205 patients with urinary catheters who received HHC from 473 Medicare-certified agencies between 2016-2018. Our survey assessed whether agencies had written policies in place for (1) replacement of indwelling catheters at fixed intervals, and (2) emptying the drainage bag. We used adjusted logistic regression to estimate the association of these policies with probability of hospital transfer due to UTI during a 60-day HHC episode. RESULTS: Probability of hospital transfer due to UTI during a HHC episode ranged from 5.62% among agencies with neither urinary catheter policy to 4.43% among agencies with both policies. Relative to agencies with neither policy, having both policies was associated with 21% lower probability of hospital transfer due to UTI (P < .05). CONCLUSION: Our findings suggest implementation of policies in HHC to promote best practices for care of patients with urinary catheters may be an effective strategy to prevent hospital transfers due to UTI.

Comparative effectiveness of aminoglycosides, polymyxin B, and tigecycline for clearance of carbapenem-resistant Klebsiella pneumoniae from urine.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an increasingly common cause of health care-associated urinary tract infections. Antimicrobials with in vitro activity against CRKP are typically limited to polymyxins, tigecycline, and often, aminoglycosides. We conducted a retrospective cohort study of cases of CRKP bacteriuria at New York-Presbyterian Hospital from January 2005 through June 2010 to compare microbiologic clearance rates based on the use of polymyxin B, tigecycline, or an aminoglycoside. We constructed three active antimicrobial cohorts based on the active agent used and an untreated cohort of cases that did not receive antimicrobial therapy with Gram-negative activity. Microbiologic clearance was defined as having a follow-up urine culture that did not yield CRKP. Cases without an appropriate follow-up culture or that received multiple active agents or less than 3 days of the active agent were excluded. Eighty-seven cases were included in the active antimicrobial cohorts, and 69 were included in the untreated cohort. The microbiologic clearance rate was 88% in the aminoglycoside cohort (n = 41), compared to 64% in the polymyxin B (P = 0.02; n = 25), 43% in the tigecycline (P < 0.001; n = 21), and 36% in the untreated (P < 0.001; n = 69) cohorts. Using multivariate analysis, the odds of clearance were lower for the polymyxin B (odds ratio [OR], 0.10; P = 0.003), tigecycline (OR, 0.08; P = 0.001), and untreated (OR, 0.14; P = 0.003) cohorts than for the aminoglycoside cohort. Treatment with an aminoglycoside, when active in vitro, was associated with a significantly higher rate of microbiologic clearance of CRKP bacteriuria than treatment with either polymyxin B or tigecycline.

Impact of the ventilator bundle on ventilator-associated pneumonia in intensive care unit.

OBJECTIVE: The ventilator bundle is being promoted to prevent adverse events in ventilated patients including ventilator-associated pneumonia (VAP). We aimed to: (i) examine adoption of the ventilator bundle elements; (ii) determine effectiveness of individual elements and setting characteristics in reducing VAP; (iii) determine effectiveness of two infection-specific elements on reducing VAP; and, (iv) assess crossover effects of complying with VAP elements on central line-associated bloodstream infections. DESIGN: Cross-sectional survey. SETTING: Four hundred and fifteen ICUs from 250 US hospitals. PARTICIPANTS: Managers/directors of infection prevention and control departments. INTERVENTIONS: Adoption and compliance with ventilator bundle elements. MAIN OUTCOME MEASURES: VAP rates. RESULTS: The mean VAP rate was 2.7/1000 ventilator days. Two-thirds (n = 284) reported presence of the full ventilator bundle policy. However, only 66% (n = 188/284) monitored implementation; of those, 39% (n = 73/188) reported high compliance. Only when an intensive care unit (ICU) had a policy, monitored compliance and achieved high compliance were VAP rates lower. Compliance with individual elements or just one of two infection-related element had no impact on VAP (ß = -0.79, P= 0.15). There was an association between complying with two infection elements and lower rates (ß = -1.81, P< 0.01). There were no crossover effects. Presence of a full-time hospital epidemiologist (HE) was significantly associated with lower VAP rates (ß = -3.62, P< 0.01). CONCLUSIONS: The ventilator bundle was frequently present but not well implemented. Individual elements did not appear effective; strict compliance with infection elements was needed. Efforts to prevent VAP may be successful in settings of high levels of compliance with all infection-specific elements and in settings with full-time HEs.

Quantitative characterization of high-touch surfaces in emergency departments and hemodialysis facilities.

An observational study was conducted to characterize high-touch surfaces in emergency departments and hemodialysis facilities. Certain surfaces were touched with much greater frequency than others. A small number of surfaces accounted for the majority of touch episodes. Prioritizing disinfection of these surfaces may reduce pathogen transmission within healthcare environments.

Association of Infection-Related Hospitalization With Cognitive Impairment Among Nursing Home Residents.

Importance: Hospitalizations for infections among nursing home (NH) residents remain common despite national initiatives to reduce them. Cognitive impairment, which markedly affects quality of life and caregiving needs, has been associated with hospitalizations, but the association between infection-related hospitalizations and long-term cognitive function among NH residents is unknown. Objective: To examine whether there are changes in cognitive function before vs after infection-related hospitalizations among NH residents. Design, Setting, and Participants: This cohort study used data from the Minimum Data Set 3.0 linked to Medicare hospitalization data from 2011 to 2017 for US nursing home residents aged 65 years or older who had experienced an infection-related hospitalization and had at least 2 quarterly Minimum Data Set assessments before and 4 or more after the infection-related hospitalization. Analyses were performed from September 1, 2019, to December 21, 2020. Exposure: Infection-related hospitalization lasting 1 to 14 days. Main Outcomes and Measures: Using an event study approach, associations between infection-related hospitalizations and quarterly changes in cognitive function among NH residents were examined overall and by sex, age, Alzheimer disease and related dementias (ADRD) diagnosis, and sepsis vs other infection-related diagnoses. Resident-level cognitive function was measured using the Cognitive Function Scale (CFS), with scores ranging from 1 (intact) to 4 (severe cognitive impairment). Results: Of the sample of 20 698 NH residents, 71.0% were women and 82.6% were non-Hispanic White individuals; the mean (SD) age at the time of transfer to the hospital was 82 (8.5) years. The mean CFS score was 2.17, and the prevalence of severe cognitive impairment (CFS score, 4) was 9.0%. During the first quarter after an infection-related hospitalization, residents experienced a mean increase of 0.06 points in CFS score (95% CI, 0.05-0.07 points; P < .001), or 3%. The increase in scores was greatest among residents aged 85 years or older vs younger residents by approximately 0.022 CFS points (95% CI, 0.004-0.040 points; P < .05). The prevalence of severe cognitive impairment increased by 1.6 percentage points (95% CI, 1.2-2.0 percentage points; P < .001), or 18%; the increases were observed among individuals with ADRD but not among those without it. After an infection-related hospitalization, cognition among residents who had experienced sepsis declined more than for residents who had not by about 0.02 CFS points (95% CI, 0.00-0.04 points; P < .05). All observed differences persisted without an accelerated rate of decline for at least 6 quarters after infection-related hospitalization. No differences were observed by sex. Conclusions and Relevance: In this cohort study, infection-related hospitalization was associated with immediate and persistent cognitive decline among nursing home residents, with the largest increase in CFS scores among older residents, those with ADRD, and those who had experienced sepsis. Identification of NH residents at risk of worsened cognition after an infection-related hospitalization may help to ensure that their care needs are addressed to prevent further cognitive decline.

Antimicrobial stewardship perspectives from a New York City hospital during the COVID-19 pandemic: Challenges and opportunities.

PURPOSE: To share challenges and opportunities for antimicrobial stewardship programs based on one center's experience during the early weeks of the coronavirus disease 2019 (COVID-19) pandemic. SUMMARY: In the spring of 2020, New York City quickly became a hotspot for the COVID-19 pandemic in the United States, putting a strain on local healthcare systems. Antimicrobial stewardship programs faced diagnostic and therapeutic uncertainties as well as healthcare resource challenges. With the lack of effective antivirals, antibiotic use in critically ill patients was difficult to avoid. Uncertainty drove antimicrobial use and thus antimicrobial stewardship principles were paramount. The dramatic influx of patients, drug and equipment shortages, and the need for prescribers to practice in alternative roles only compounded the situation. Establishing enhanced communication, education, and inventory control while leveraging the capabilities of the electronic medical record were some of the tools used to optimize existing resources. CONCLUSION: New York City was a unique and challenging environment during the initial peak of the COVID-19 pandemic. Antimicrobial stewardship programs can learn from each other by sharing lessons learned and practice opportunities to better prepare other programs facing COVID-19 case surges.

Cycle Thresholds Among Solid Organ Transplant Recipients Testing Positive for SARS-CoV-2.

BACKGROUND: The optimal duration of transmission-based precautions among immunocompromised patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. METHODS: Retrospective review of patients with solid organ transplant with positive SARS-CoV-2 polymerase chain reaction result from nasopharyngeal specimens admitted to the hospital between March 13, 2020 and May 15, 2020. RESULTS: Twenty-one percent of solid organ transplant recipients with positive SARS-CoV-2 polymerase chain reaction detected ≥20 d after symptom onset (or after first positive test among asymptomatic individuals) had a low cycle threshold (ie, high viral load). The majority of these patients were asymptomatic or symptomatically improved. CONCLUSIONS: Solid organ transplant recipients may have prolonged high viral burden of SARS-CoV-2. Further data are needed to understand whether cycle threshold data can help inform strategies for prevention of healthcare-associated transmission of SARS-CoV-2 and for appropriate discontinuation of transmission-based precautions.

Invasive aspergillosis after pandemic (H1N1) 2009.

We report 2 patients with invasive aspergillosis after infection with pandemic (H1N1) 2009. Influenza viruses are known to cause immunologic defects and impair ciliary clearance. These defects, combined with high-dose corticosteroids prescribed during influenza-associated adult respiratory distress syndrome, may be novel risk factors predisposing otherwise immunocompetent patients to invasive aspergillosis.

A comparison of the incidence of midline catheter-associated bloodstream infections to that of central line-associated bloodstream infections in 5 acute care hospitals.

In a retrospective study conducted over 12 months in a multi-hospital system, the incidence of bloodstream infections associated with midline catheters was not significantly lower than that associated with central venous catheters (0.88 vs 1.10 infections per 1,000 catheter-days). Additional research is needed to further characterize the infectious risks of midline catheters and to determine optimal strategies to minimize these risks.

Antimicrobial-resistant bacteria in the community setting.

Over the past decade, antimicrobial resistance has emerged as a major public-health crisis. Common bacterial pathogens in the community such as Streptococcus pneumoniae have become progressively more resistant to traditional antibiotics. Salmonella strains are beginning to show resistance to crucial fluoroquinolone drugs. Community outbreaks caused by a resistant form of Staphylococcus aureus, known as community-associated meticillin (formerly methicillin)-resistant Staphylococcus aureus, have caused serious morbidity and even deaths in previously healthy children and adults. To decrease the spread of such antimicrobial-resistant pathogens in the community, a greater understanding of their means of emergence and survival is needed.