Faculty Bibliography

BACKGROUND/UNASSIGNED:Patients with cardiogenic shock after percutaneous coronary intervention (PCI) may require mechanical circulatory support (MCS). The combination of dual antiplatelet therapy with cangrelor and continuous anticoagulation required for MCS may increase the risk of bleeding. OBJECTIVE/UNASSIGNED:The objective of the study is to describe the complications and outcomes of patients who received cangrelor during MCS following PCI. METHODS/UNASSIGNED:This is a single-center, retrospective, observational case series of 17 patients who received cangrelor while on MCS from June 2017 to September 2019. RESULTS/UNASSIGNED:In a case series of 17 patients, 8 patients (47%) were supported with an Impella device and 4 patients (24%) with venoarterial (VA) extracorporeal membrane oxygenation (ECMO); 5 required (29%) concomitant VA ECMO and Impella support in the setting of cardiogenic shock. All patients received triple antithrombotic therapy with aspirin, heparin, and cangrelor. Cangrelor was commonly initiated at a median dose of 0.75 (range 0.5-4) µg/kg/min. Cangrelor dose adjustments included changes in increments up to 0.25 µg/kg/min with review of P2Y12 levels. A total of 10 patients (59%) experienced a bleeding event, most commonly located at the peripheral cannulation site (40%) and in the gastrointestinal tract (30%). Seven (70%) and 3 (30%) of the bleeding complications were classified as major and minor, respectively. No patient developed in-stent thrombosis during the hospitalization; 14 (82%) patients survived their MCS course. CONCLUSION AND RELEVANCE/UNASSIGNED:This case series suggests that cangrelor doses less than 0.75 µg/kg/min may be beneficial. Larger studies should evaluate alternative dosing regimens.

Introduction/UNASSIGNED:Warfarin remains the preferred oral anticoagulant for the treatment of venous thromboembolism (VTE) in patients with advanced chronic kidney disease (CKD). Although the direct oral anticoagulants (DOACs) have become preferred for treatment of VTE in the general population, patients with advanced CKD were excluded from the landmark trials. Postmarketing, safety data have demonstrated oral factor Xa inhibitors (OFXais) such as apixaban and rivaroxaban to be alternatives to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation. However, it remains unknown if these safety data can be extrapolated to the treatment of VTE and CKD. Methods/UNASSIGNED:A retrospective cohort study from January 2013 to October 2019 was performed at NYU Langone Health. All adult patients with CKD stage 4 or greater, treated with anticoagulation for VTE, were screened. The primary outcome was tolerability of anticoagulant therapy at 3 months, defined as a composite of bleeding, thromboembolic events, and/or discontinuation rates. The secondary outcomes included bleeding, discontinuations, and recurrent thromboembolism. Results/UNASSIGNED:. OFXais were better tolerated compared to warfarin for the treatment of VTE in CKD, with lower rates of bleeding, discontinuations, and recurrent thromboembolism in a small cohort. Future prospective studies are necessary to confirm these findings.

Background/UNASSIGNED:Ceftriaxone (CTX) and penicillin G (PCN G) are considered reasonable treatment options for viridans group streptococci (VGS) bloodstream infections, but comparisons between these agents are limited. We evaluated clinical outcomes among patients treated with these agents for complicated VGS bacteremia. Methods/UNASSIGNED:infections, treatment modification or discontinuation due to AEs from therapy, and development of extended-spectrum beta-lactamase resistance. Secondary outcomes included individual safety end points, VGS bacteremia recurrence, hospital readmission, and all-cause mortality. Results/UNASSIGNED: = .139). The driver of the composite outcome was hospital readmission due to VGS bacteremia or therapy complications. No secondary end points differed significantly between groups. On multivariate analysis, source removal was a protective factor of the primary composite safety outcome. Conclusions/UNASSIGNED:Despite potential safety concerns with the prolonged use of CTX in complicated VGS bacteremia, this study did not demonstrate higher rates of treatment failure, adverse events, or resistance.

Bleeding following cardiac surgery that warrants transfusion of blood products is associated with significant complications, including increased mortality at 1 year following surgery. Factor concentrates, such as prothrombin complex concentrate (PCC), or recombinant activated factor VII (rFVIIa) have been used off-label for bleeding in cardiac surgery that is refractory to conventional therapy. The objective of this retrospective study is to assess the hemostatic effectiveness of 4-factor PCC or rFVIIa for bleeding after a broad range of cardiac surgeries. Patients were included if they were at least 18 years of age and had undergone cardiac surgery with bleeding requiring intervention with 4-factor PCC or rFVIIa. There were no differences observed in the number of packed red blood cells (4-factor PCC: 2 units vs. rFVIIa: 2 units), fresh frozen plasma (0 units vs. 1 unit) or platelet (2 units vs. 2 units) transfusions following the administration of 4-factor PCC or rFVIIa. The patients in the rFVIIa group, required more cryoprecipitate than those in the 4-factor PCC group (4-factor PCC: 2 units (range 0-6) vs. rFVIIa: 2 units (range 0-8), p = 0.03). There were no differences in secondary outcomes of chest tube output at 2, 6, 12 and 24 hours, nor was there a difference in reexploration rates or the median length of stay in the intensive care unit. Thromboembolic complications at 30 days were similar between the two groups (4-factor PCC: 13% vs. rFVIIa 26%, p = 0.08). The total median dose requirement for 4-factor PCC was 1000 units (15 units/kg) and 2 mg (20 mcg/kg) for rFVIIa. The results demonstrate feasibility of utilizing the minimum amount of drug in order to achieve a desired effect. Both 4-factor PCC and rFVIIa appear to be safe and effective options for the management of bleeding associated with cardiac surgery.

WHAT IS KNOWN AND OBJECTIVE/OBJECTIVE:Nationwide shortages of small-volume parenteral solutions (SVPS) compelled hospitals to develop strategies including the use of intravenous push (IVP) administration of antibiotics to reserve SVPS for absolute necessities. It is unknown if administration of beta-lactam antibiotics (BL) via IVP results in worse clinical outcomes compared to intravenous piggyback (IVPB) due to the potential inability to achieve pharmacodynamic targets. METHODS:Our health-system implemented a mandatory IVP action plan for BL from October 2017 to September 2018. This was a retrospective study of adult patients with GNB who received empiric therapy with IVPB (30 minutes) or IVP (5 minutes) cefepime (FEP) or meropenem (MEM) for at least 2 days. Endpoints included clinical response, microbiological clearance and mortality. All data are presented as n (%) or median (interquartile range). RESULTS:The final cohort included 213 patients (IVPB n = 105, IVP n = 108). The primary source of bacteremia was urinary, with Escherichia coli being the primary pathogen. Escalation of therapy was similar between groups (15 [14%] vs 11 [10%], P = .36) at a median of 3 days (P = .68). No significant differences were observed in any secondary endpoints including microbiological clearance, bacteremia recurrence, time to defervescence, WBC normalization, vasopressor duration or in-hospital mortality. WHAT IS NEW AND CONCLUSION/CONCLUSIONS:Our findings suggest no differences in clinical response with the use of IVP compared to IVPB FEP and MEM for treatment of GNB. This form of administration may be considered as a fluid conservation strategy in times of shortage.

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.

PURPOSE:To describe our medical center's pharmacy services preparedness process and offer guidance to assist other institutions in preparing for surges of critically ill patients such as those experienced during the coronavirus disease 2019 (COVID-19) pandemic. SUMMARY:The leadership of a department of pharmacy at an urban medical center in the US epicenter of the COVID-19 pandemic proactively created a pharmacy action plan in anticipation of a surge in admissions of critically ill patients with COVID-19. It was essential to create guidance documents outlining workflow, provide comprehensive staff education, and repurpose non-intensive care unit (ICU)-trained clinical pharmacotherapy specialists to work in ICUs. Teamwork was crucial to ensure staff safety, develop complete scheduling, maintain adequate drug inventory and sterile compounding, optimize the electronic health record and automated dispensing cabinets to help ensure appropriate prescribing and effective management of medication supplies, and streamline the pharmacy workflow to ensure that all patients received pharmacotherapeutic regimens in a timely fashion. CONCLUSION:Each hospital should view the COVID-19 crisis as an opportunity to internally review and enhance workflow processes, initiatives that can continue even after the resolution of the COVID-19 pandemic.

PURPOSE:To describe our hospital pharmacy department's preparation for an influx of critically ill patients during the coronavirus disease 2019 (COVID-19) pandemic and offer guidance on clinical pharmacy services preparedness for similar crisis situations. SUMMARY:Personnel within the department of pharmacy at a medical center at the US epicenter of the COVID-19 pandemic proactively prepared a staffing and pharmacotherapeutic action plan in anticipation of an expected surge in admissions of critically ill patients with COVID-19 and expansion of acute care and intensive care unit (ICU) capacity. Guidance documents focusing on supportive care and pharmacotherapeutic treatment options were developed. Repurposing of non-ICU-trained clinical pharmacotherapy specialists to work collaboratively with clinician teams in ICUs was quickly implemented; staff were prepared for these duties through use of shared tools to facilitate education and practice standardization. CONCLUSION:As challenges were encountered at the initial peak of the pandemic, interdisciplinary collaboration and teamwork was crucial to ensure that all patients were proactively assessed and that their respective pharmacotherapeutic regimens were optimized.

Background: Viridans group streptococci (VGS) is an infrequent yet significant cause of bloodstream infections, and complicated cases may require prolonged antibiotic therapy. Ceftriaxone (CTX) and penicillin G (PCN G) are both considered first line options for VGS infections, but comparisons between these agents are limited. We evaluated the clinical outcomes amongst patients treated with CTX and PCN G for complicated VGS bacteremia.
Method(s): This was a single-center, retrospective study of adult patients with >=1 positive VGS blood culture who were treated with either CTX or PCN G/ampicillin (both included in PCN G arm) between January 2013 and June 2019. The primary outcome was a composite of safety endpoints, including hospital readmission due to VGS or an adverse event (AE) from therapy, Clostridioides difficile infections, treatment modification or discontinuation due to an antibiotic-related AE, and development of extended-spectrum beta lactamase resistance. Secondary outcomes included the individual safety endpoints, VGS bacteremia recurrence, hospital readmission, and all-cause mortality.
Result(s): Of 328 patients screened for inclusion, 94 patients met eligibility criteria (CTX n= 64, PCN G n=34). Median age was 68 years (IQR 56-81) and 68% were male. Study patients did not present with critical illness, as reflected by a median Pitt bacteremia score of 0 in the CTX and 1 in the PCN G arms, P=0.764. Streptococcus mitis was the most common VGS isolate and infective endocarditis (IE) was the predominant source of infection. CTX was not significantly associated with increased risk of the primary outcome (14% vs. 27%; P= 0.139). The driver of the composite outcome was hospital readmission due to VGS bacteremia or therapy complications. Results were similar in the subgroup of patients with IE (12.5% vs. 23.5%). No secondary endpoints differed significantly between groups. On multivariate analysis, source removal was a protective factor of the primary outcome (OR 0.1; 95% CI 0.020-0.6771; P= 0.017).
Conclusion(s): Despite potential safety concerns with the prolonged use of CTX in complicated VGS bacteremia, this study did not demonstrate a higher rate of treatment failure, adverse events, or resistance. These findings warrant further exploration