Faculty Bibliography

Background/UNASSIGNED:The epidemiology of nosocomial bloodstream infections (NBSIs) in patients with coronavirus disease 2019 (COVID-19) is poorly understood, due in part to substantial disease heterogeneity resulting from multiple potential pathogens. Methods/UNASSIGNED:We identified risk factors for NBSIs and examined the association between NBSIs and mortality in a retrospective cohort of patients hospitalized with COVID-19 in 2 New York City hospitals during the height of the pandemic. We adjusted for the potential effects of factors likely to confound that association, including age, race, illness severity upon admission, and underlying health status. Results/UNASSIGNED:infections did not have an identifiable source and were not associated with common risk factors for infection by these organisms. Conclusions/UNASSIGNED:Pathogen species and mortality exhibited temporal differences. Early recognition of risk factors among COVID-19 patients could potentially decrease NBSI-associated mortality through early COVID-19 and antimicrobial treatment.

Nucleoside or nucleotide analogues (NAs) have the potential to cause lactic acidosis by inhibiting DNA polymerase-γ of human mitochondria and impairing aerobic metabolism. Patients may be asymptomatic, have mild non-specific symptoms, or present in multisystem organ failure. There is a paucity of data to guide management of life-threatening lactic acidosis due to NA therapy. Here we describe a case of a 60-year old critically ill male with decompensated cirrhosis secondary to hepatitis B virus (HBV) infection who developed severe lactic acidosis (13.8 mmol/L) 2 days after initiation of tenofovir alafenamide (TAF). All other possible etiologies for the elevated lactate were ruled out. Lactic acidosis resolved rapidly with TAF discontinuation and supplementation with cofactors supporting mitochondrial oxidative phosphorylation, including coenzyme Q10, levocarnitine, riboflavin, and thiamine. This case highlights the ability of TAF to cause lactic acidosis early after therapy initiation, especially in susceptible hosts, and reviews the potential role for cofactor supplementation for drug-induced mitochondrial injury.

BACKGROUND/UNASSIGNED:Corticosteroids and tocilizumab have been shown to improve survival in patients who require supplemental oxygen from coronavirus disease 2019 (COVID-19) pneumonia. The optimal dose of immunosuppression for the treatment of COVID-19 acute respiratory distress syndrome (ARDS) is still unknown. OBJECTIVE/UNASSIGNED:The objective of this study was to evaluate the effectiveness and safety of high- versus low-dose corticosteroids with or without tocilizumab for the treatment of COVID-19 ARDS. METHODS/UNASSIGNED:This was a retrospective study of patients admitted to the intensive care unit (ICU) requiring mechanical ventilation who received high- versus low-dose corticosteroids with or without tocilizumab. The primary outcome was survival to discharge. Safety outcomes included infections and incidence of hyperglycemia. RESULTS/UNASSIGNED:= 0.01). The highest rate of a bacterial pneumonia was in patients who received high-dose corticosteroids with tocilizumab. CONCLUSIONS/UNASSIGNED:In critically ill patients with COVID-19 ARDS requiring mechanical ventilation, we found no difference in high- versus low-dose corticosteroids with regard to survival to hospital discharge. However, patients receiving only low-dose corticosteroids without tocilizumab did worse than the other groups. Larger prospective studies are needed to determine the optimal immunosuppression dosing strategy in this patient population.

The use of acute mechanical circulatory support (MCS) has increased over the last decade. For patients with left-ventricular failure, an Impella^® (Abiomed, Danvers, MA) may be used to improve cardiac output. The purpose of this study is to describe Impella^® anticoagulation patterns and evaluate the safety and effectiveness of our protocol. This is a retrospective review of all adult patients who required at least 24 h of Impella^® support and received a heparin-based purge solution. In total, 109 patients were included in the final analysis. The most common indication for Impella^® device insertion was cardiogenic shock (76%) with the remaining patients receiving a device for a high-risk procedures; typically coronary artery bypass grafting or percutaneous coronary intervention. A total of 9 thrombotic events occurred among 8 (7%) patients and 50 bleeding events occurred among 43 (39%) patients, with the most common classification being BARC 3a (60%). A univariate analysis revealed that patients were more likely to bleed if they were less than 65 years old, had an indication of cardiogenic shock for Impella^®, inserted the device peripherally, were on dual antiplatelet therapy, or had an intra-aortic balloon pump prior to Impella^® insertion, the latter of which was confirmed with a multivariate analysis (OR 2.5 [1.072-5.830]; p = 0.034). For those monitored by anti-Xa, the presence of two or more values greater than 0.40 IU/mL was a risk factor for bleeding (p = 0.037). Our study identifies risk factors for bleeding in patients receiving temporary MCS with an Impella^®.

The backbone induction therapy for primary central nervous system lymphoma (PCNSL) is high dose methotrexate (HD-MTX) and rituximab, which can be combined with other chemotherapeutic agents. The optimal dose of HD-MTX remains unclear, as doses between 3 and 8 g/m² have been shown to be effective. In this retrospective study, HD-MTX dosed at 3-5 g/m² demonstrated an overall response of 81.8%, with 11 (50%) complete responses. The median overall survival was not met at 29 months and median progression free survival was 12.5 months.There were two discontinuations due to nephrotoxicity. The most common adverse event was hepatotoxicity (18.5%), with no treatment-related mortality events observed.Overall, HD-MTX dosed at 3-5 g/m² demonstrated similar efficacy and lower toxicity compared to higher doses in PCNSL patients. Reducing the initial HD-MTX dose may help ensure tolerability and completion of induction therapy, especially in patients with co-morbidities or older age who have poorer outcomes.

Background/UNASSIGNED:Limited data support use of pneumococcal urinary antigen testing (PUAT) for patients with community-acquired pneumonia (CAP) as an antimicrobial stewardship tool. At our institution, CAP guidelines and admission order set were standardized to include universal PUAT. Methods/UNASSIGNED:This was a retrospective study of adults hospitalized in 2019 who had PUAT performed. We compared incidence and timing of de-escalation in PUAT- positive vs -negative groups and described patients' outcomes. Results/UNASSIGNED:, in-hospital mortality, or 30-day infection-related readmission. Conclusions/UNASSIGNED:We observed earlier de-escalation in the PUAT-positive group. This seems to be due to discontinuation of atypical rather than anti-MRSA or antipseudomonal coverage. Further antimicrobial stewardship interventions are warranted.

Cardiac arrest has many implications for morbidity and mortality. Few interventions have been shown to improve return of spontaneous circulation (ROSC) and long-term outcomes after cardiac arrest. Ischemic-reperfusion injury upon achieving ROSC creates an imbalance between oxygen supply and demand. Multiple events occur in the postcardiac arrest period, including excitotoxicity, mitochondrial dysfunction, and oxidative stress and inflammation, all of which contribute to ongoing brain injury and cellular death. Given that complex pathophysiology underlies global brain hypoxic ischemia, neuroprotective strategies targeting multiple stages of the neuropathologic cascade should be considered as a means of mitigating secondary neuronal injury and improving neurologic outcomes and survival in cardiac arrest victims. In this review article, we discuss a number of different pharmacologic agents that may have a potential role in targeting these injurious pathways following cardiac arrest. Pharmacologic therapies most relevant for discussion currently include memantine, perampanel, magnesium, propofol, thiamine, methylene blue, vitamin C, vitamin E, coenzyme Q₁₀ , minocycline, steroids, and aspirin.

BACKGROUND AND OBJECTIVE/UNASSIGNED:With the coronavirus disease 2019 (COVID-19) pandemic, rates of in-hospital antimicrobial use increased due to perceived bacterial and fungal coinfections along with COVID-19. We describe the incidence of these coinfections and antimicrobial use in patients hospitalized with COVID-19 to help guide effective antimicrobial use in this population. SETTING/UNASSIGNED:This study was conducted in 3 tertiary-care referral university teaching hospitals in New York City. METHODS/UNASSIGNED:This multicenter retrospective observational cohort study involved all patients admitted with COVID-19 from January 1, 2020, to February 1, 2021. Variables of interest were extracted from a de-identified data set of all COVID-19 infections across the health system. Population statistics are presented as median with interquartile range (IQR) or proportions with 95% confidence intervals (CIs) as indicated. RESULTS/UNASSIGNED:Among 7,209 of patients admitted with COVID-19, 663 (9.2%) had a positive culture from the respiratory tract or blood sometime during their initial hospital admission. Positive respiratory cultures occurred found in 449 (6.2%) patients, and 20% were collected within 48 hours of admission. Blood culture positivity occurred in 334 patients (4.6%), with 33.5% identified within 48 hours of admission. A higher proportion of patients received antimicrobials in the first wave than in the later pandemic period (82.4% vs 52.0%). Antimicrobials were prescribed to 70.1% of inpatients, with a median of 6 antimicrobial days per patient. Infection-free survival decreased over the course of hospitalization. CONCLUSIONS/UNASSIGNED:We detected a very low incidence of coinfection with COVID-19 at admission. A longer duration of hospitalization was associated with an increased risk of coinfection. Antimicrobial use far exceeded the true incidence and detection of coinfections in these patients.

Prescribing patterns for oral anticoagulants in patients with nonvalvular atrial fibrillation and venous thromboembolism is shifting from vitamin K antagonists, such as warfarin to the direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, and apixaban. Although many hospital systems have implemented clinical decision support or enhanced monitoring for patients prescribed warfarin, there is limited evidence to suggest similar levels of enhanced monitoring for DOACs. The antithrombotic stewardship team at our institution developed guidelines and implemented computerized clinical decision support (CCDS) tools to enhance medication and patient safety related to the DOACs. We sought to assess the safety and effectiveness of these CCDS tools available to clinicians upon DOAC prescription in hospitalized patients. We performed a retrospective review of 121 patients who received at least two doses of a DOAC from January 2013 to July 2014. We assessed dosing of the DOAC according to the CCDS provided upon order entry. Adherence to CCDS was 80% (n = 24), 75% (n = 46), and 87% (n = 27) in the dabigatran, apixaban, and rivaroxaban group, respectively. Our data demonstrate that implementing CCDS for DOACs into the electronic medical record may ensure safe prescribing of high-risk medications.