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.

Background The efficacy and safety of methylprednisolone in mechanically ventilated patients with acute respiratory distress syndrome due to coronavirus disease 2019 (COVID-19) are unclear. In this study, we evaluated the association between use of methylprednisolone and key clinical outcomes. Methods Clinical outcomes associated with the use of methylprednisolone were assessed in an unmatched, case-control study; a subset of patients also underwent propensity-score matching. Patients were admitted between March 1 and April 12, 2020. The primary outcome was ventilator-free days by 28 days after admission. Secondary outcomes included extubation, mortality, discharge, positive cultures, and hyperglycemia. Results A total of 117 patients met inclusion criteria. Propensity matching yielded a cohort of 42 well-matched pairs. Groups were similar except for hydroxychloroquine and azithromycin use, which were more common in patients who did not receive methylprednisolone. Mean ventilator free-days were significantly higher in patients treated with methylprednisolone (6.21±7.45 versus 3.14±6.22; P = 0.044). The probability of extubation was also increased in patients receiving methylprednisolone (45% versus 21%; P = 0.021), and there were no significant differences in mortality (19% versus 36%; P = 0.087). In a multivariable linear regression analysis, only methylprednisolone use was associated with higher number of ventilator-free days (P = 0.045). The incidence of positive cultures and hyperglycemia were similar between groups. Conclusions Methylprednisolone was associated with increased ventilator-free days and higher probability of extubation in a propensity-score matched cohort. Randomized, controlled studies are needed to further define methylprednisolone use in patients with COVID-19.

The role of procalcitonin in identifying community-associated bacterial infections among patients with coronavirus disease 2019 is not yet established. In 2443 patients with 148 bacterial co-infections, mean procalcitonin levels were significantly higher with any bacterial infection (13.16 ± 51.19 ng/mL, p=0.0091) and with bacteremia (34.25 ± 85.01 ng/mL, p=0.0125) than without infection (2.00 ±15.26 ng/mL). Procalcitonin (cutoff 0.25 or 0.50 ng/mL) did not reliably identify bacterial co-infections, but may be useful in excluding bacterial infection.

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.

ObjectiveTo characterise the long-term outcomes of patients with COVID-19 admitted to a large New York City medical centre at 3 and 6 months after hospitalisation and describe their healthcare usage, symptoms, morbidity and mortality.DesignRetrospective cohort through manual chart review of the electronic medical record.SettingNewYork-Presbyterian/Columbia University Irving Medical Center, a quaternary care academic medical centre in New York City.ParticipantsThe first 1190 consecutive patients with symptoms of COVID-19 who presented to the hospital for care between 1 March and 8 April 2020 and tested positive for SARS-CoV-2 on reverse transcriptase PCR assay.Main outcome measuresType and frequency of follow-up encounters, self-reported symptoms, morbidity and mortality at 3 and 6 months after presentation, respectively; patient disposition information prior to admission, at discharge, and at 3 and 6 months after hospital presentation.ResultsOf the 1190 reviewed patients, 929 survived their initial hospitalisation and 261 died. Among survivors, 570 had follow-up encounters (488 at 3 months and 364 at 6 months). An additional 33 patients died in the follow-up period. In the first 3 months after admission, most encounters were telehealth visits (59%). Cardiopulmonary symptoms (35.7% and 28%), especially dyspnoea (22.1% and 15.9%), were the most common reported symptoms at 3-month and 6-month encounters, respectively. Additionally, a large number of patients reported generalised (26.4%) or neuropsychiatric (24.2%) symptoms 6 months after hospitalisation. Patients with severe COVID-19 were more likely to have reduced mobility, reduced independence or a new dialysis requirement in the 6 months after hospitalisation.ConclusionsPatients hospitalised with SARS-CoV-2 infection reported persistent symptoms up to 6 months after diagnosis. These results highlight the long-term morbidity of COVID-19 and its burden on patients and healthcare resources.

Background Patients with COVID-19 may be at increased risk for secondary bacterial infections. At our quaternary care hospital in New York City, the rapid escalation of COVID-19 cases was accompanied by a massive surge in the need for hospital and critical care capacity. During this time, we noted a increase in infections caused by carbapenemase-producing Enterobacterales (CPE). Methods We retrospectively assessed microbiology data to identify patients with positive testing for SARS-CoV-2 who had clinical cultures with meropenem-resistant and/or carbapenemase gene-positive Enterobacterales. We obtained microbiological and clinical data by manual chart review. Available clinical isolates underwent long-range genomic sequencing using the MinION (Oxford) for rapid genotyping, resistance gene detection, and phylogenetic analysis. Results From March 1 to May 18, we identified 33 CPE isolates from 13 patients, including 29 Klebsiella pneumonia and four Enterobacter cloacae. Most patients (11/13) had a positive respiratory culture, and 7/13 developed bacteremia. All patients had prolonged, complex hospitalizations with extensive antibiotic exposure. We performed long-range sequencing on 19 isolates from 12 patients. 15/16 K. pneumoniae isolates belonged to sequence type (ST) 258 encoding KPC (14 KPC-2; 1 KPC-3); one ST70 isolate encoded KPC-2. All four E. cloacae isolates belonged to ST270 and encoded NDM-1. Phylogenetic analysis of ST258 isolates including historical isolates from our hospital revealed a distinct lineage of isolates from COVID-19 patients (72% bootstrap support), with expected clustering of isolates from the same patient and patients that were cohorted together. Conclusion While CPE have declined substantially in New York City in recent years, increased detection in patients with COVID-19 may signal a reemergence of these highly resistant pathogens in the wake of the global pandemic. System-level factors, such as the rapid scale-up of critical care capacity, while clearly needed to address the unprecedented reach of COVID-19, may have contributed to isolate clustering in these patients. Increased surveillance and antimicrobial stewardship efforts will be needed to mitigate the impact of CPE in the future. Disclosures All Authors: No reported disclosures

Background: The progression of clinical manifestations in patients with coronavirus disease 2019 (COVID-19) highlights the need to account for symptom duration at the time of hospital presentation in decision-making algorithms. Methods: We performed a nested case–control analysis of 4103 adult patients with COVID-19 and at least 28 days of follow-up who presented to a New York City medical center. Multivariable logistic regression and classification and regression tree (CART) analysis were used to identify predictors of poor outcome. Results: Patients presenting to the hospital earlier in their disease course were older, had more comorbidities, and a greater proportion decompensated (<4 days, 41%; 4–8 days, 31%; >8 days, 26%). The first recorded oxygen delivery method was the most important predictor of decompensation overall in CART analysis. In patients with symptoms for <4, 4–8, and >8 days, requiring at least non-rebreather, age ≥ 63 years, and neutrophil/lymphocyte ratio ≥ 5.1; requiring at least non-rebreather, IL-6 ≥ 24.7 pg/mL, and D-dimer ≥ 2.4 µg/mL; and IL-6 ≥ 64.3 pg/mL, requiring non-rebreather, and CRP ≥ 152.5 mg/mL in predictive models were independently associated with poor outcome, respectively. Conclusion: Symptom duration in tandem with initial clinical and laboratory markers can be used to identify patients with COVID-19 at increased risk for poor outcomes.

Background The opioid epidemic has resulted in a dramatic resurgence of bacterial infections, most notably those due to Staphylococcus aureus (SA). We compared the demographic, clinical, and molecular factors of injection drug users (IDUs) and non-IDUs with SA bacteremia. Methods Patients with SA bacteremia were identified through a query of the electronic medical record EMR from January 2018 to December 2019 at a New York City medical center. All cases of community-associated (CA) SA bacteremia among adults with a history of active injection drug use were evaluated. Patients with positive SA blood cultures ≤ 72 hours of admission were considered CA. IDUs were identified with keyword searches and were deemed active if they had a history of use in the 12 months prior to admission. A randomly selected group of non-IDUs with CA SA bacteremia was used for comparison at a 4:1 ratio. Available SA isolates underwent Illumina whole genome sequencing (WGS). Using SRST2 multilocus sequence types (MLST), antimicrobial resistance genes and putative virulence factors were extracted. Results From January 2018 to December 2019, 669 patients with SA bacteremia were identified. 29 patients were active IDUs. Compared to 112 randomly selected non-IDUs, IDUs were significantly younger and more likely to be unstably housed (Table 1). Rates of MRSA were similar in IDUs (31%) and non-IDUs (32.1%). Endocarditis (44.8% vs 11.6%) and abscesses (27.6% vs 8.9%) were diagnosed more frequently in IDUs than non-IDUs. A positive hepatitis C antibody was strongly associated with SA bacteremia in IDUs (62.1% vs 6.3%, p&lt; 0.001). WGS demonstrated comparable proportions of sequence types across IDUs and non-IDUs. ST8 accounted for the majority of infections in both groups (Table 2). MRSA bacteremia due to ST8 occurred in a higher proportion of IDUs (7/29, 24.1%) than non-IDUs (14/112, 12.5%). Conclusion IDUs with CA SA bacteremia have unique demographic and clinical features that differentiate them from non-IDUs. Endocarditis rates in IDUs are of particular concern. Use of these risk factors could allow hospitals to rapidly identify IDUs and offer them necessary medical and social services. WGS revealed a majority of MRSA bacteremia was due to one sequence type in IDUs (ST8). Further analysis of virulence genes in this cohort are ongoing. Disclosures Franklin D. Lowy, MD, GlaxoSmithKline (Advisor or Review Panel member)UpToDate (Other Financial or Material Support, Topic Writer and Editor) Anne-Catrin Uhlemann, MD, PhD, Merck (Grant/Research Support)