Faculty Bibliography

BACKGROUND:Although dalbavancin's (DBV's) long half-life and one-time dosing strategy confer ideal administration in the ambulatory setting, the optimal role of DBV in the management of acute bacterial skin and skin structure infections (ABSSSIs) remains to be elucidated. OBJECTIVES/OBJECTIVE:The primary objective of this study was to compare treatment outcomes of ABSSSI between patients who received DBV in the emergency department (ED) as part of standard care versus patients who received DBV as part of a telehealth program. METHODS:This was a retrospective cohort study evaluating patients who received DBV at 3 urban EDs. The primary end point was the incidence of ABSSSI recurrence. Secondary outcomes included need for hospital admission and ED length of stay (LOS; in hours). RESULTS:A total of 65 ABSSSI treatment courses were included; 42 were included in the telehealth criteria (TC) cohort and 23 in the initial criteria (IC) cohort. There were 14% (6/42) infection recurrences in the TC cohort and 22% (5/23) in the IC cohort, with median time to recurrence being 4 and 14 days, respectively. Median ED LOS was significantly shorter in the TC (5 vs 25 hours, P < 0.05). Numerically fewer individuals in the TC cohort required inpatient admission (0 vs n = 2, 9%). Conclusion and Relevance: Our results suggest that patients may be safely administered DBV in an ED setting, with telehealth follow-up. Providing structured patient selection criteria is an effective method of assisting ED providers in selecting appropriate DBV candidates to limit potential recurrences and readmissions.

Objective Patients with acute myelogenous leukemia or myelodysplastic syndrome undergoing induction chemotherapy are at increased risk of invasive fungal infection due to prolonged, severe neutropenia. Due to this risk, national guidelines recommend invasive fungal infection prophylaxis in this population until the resolution of neutropenia. Although posaconazole has demonstrated superiority over fluconazole and itraconazole, there is limited evidence for voriconazole for invasive fungal infection prophylaxis in this population. Even less data are available comparing posaconazole and voriconazole directly. The study objective was to investigate the efficacy and safety of delayed-release posaconazole tablets versus voriconazole for primary invasive fungal infection prophylaxis. The primary outcome was rate of discontinuation of either agent. Secondary outcomes included specific rates of discontinuation due to adverse events and drug-drug interactions, rates of breakthrough invasive fungal infection, and 30-day and 100-day mortality rates. Methods This was a retrospective cohort study of adult patients admitted to NYU Langone Health between 1 January 2014 and 31 August 2017 and initiated on invasive fungal infection prophylaxis during induction or reinduction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. Results In total, 77 patients were included in the study: 43 using posaconazole delayed-release tablets and 34 using oral voriconazole. In the posaconazole group, 30% of patients (n = 13) discontinued therapy for any reason compared with 35% (n = 12) of patients in the voriconazole group (p = 0.64). A higher percentage of patients in the voriconazole group discontinued due to adverse events (6 patients, 18% vs. 1 patient, 2%, p = 0.04). Mortality rates at 30 and 100 days were similar between both groups. No breakthrough invasive fungal infections was noted in either group. Conclusion Overall, discontinuations for any reason were similar in patients taking both posaconazole delayed-release and oral voriconazole. Both posaconazole delayed-release tablets and oral voriconazole appear to be effective at preventing invasive fungal infection in acute myelogenous leukemia and myelodysplastic syndrome patients undergoing induction chemotherapy, although posaconazole may be more tolerable.

Carfilzomib is a second-generation proteasome inhibitor that irreversibly inhibits chymotrypsin-like (CT-L) activities of the proteasome, and is indicated for relapsed or refractory multiple myeloma. Cardiotoxicity is a well-established adverse effect of carfilzomib. The extent of cardiac toxicity in the literature spans anywhere from palpitations to cardiac arrest, with the most commonly reported manifestation being new-onset or worsening heart failure. A pre-clinical study of the pharmacokinetics and pharmacodynamics of carfilzomib given via intravenous bolus or 30-minute infusion in rats showed that carfilzomib can strongly induce apoptosis and potently damage cardiac myocytes at clinically relevant concentrations. Moreover, the mortality rate with the bolus administration was 44% whereas the same dose administered as a 30-minute infusion did not result in mortality. There remains limited clinical data regarding the safety of carfilzomib at doses of 27-56 mg/m2 based on infusion times as these doses have not been well studied. This retrospective review was conducted to evaluate the safety of carfilzomib at doses >27 mg/m2 at all infusion times.

Background. Oral treatment strategies for Enterobacteriaceae bacteremia (EB) are controversial, with both beta-lactams (BL) and fluoroquinolones (FQ) used in clinical practice. FQ may be preferred for their high bioavailability, but other oral antibiotics are needed due to concerns of resistance and adverse effects. As an effort to facilitate antibiotic stewardship, BL should be explored as an additional oral option for EB treatment. Methods. This retrospective study compared clinical characteristics and outcomes in patients with EB treated with BL vs. FQ as definitive oral therapy between January 2013 and July 2017. Adult patients diagnosed with their first incidence of EB and transitioned from IV antibiotics to either study antibiotic class were included. Primary and secondary outcomes assessed recurrence, collateral damage, readmission, and all-cause mortality. Results. A total of 173 patients were included (BL n = 59, FQ n = 114). Median age was 70 years, Pitt bacteremia score was 2 (range 0-7), and Charlson Comorbidity Index was 5 (0-12); all were comparable between groups. Urinary source of infection was most common (57%). The majority of oral BL courses used cefpodoxime (63%). More patients in FQ vs. BL had a prior transplant (9% vs. 0%, P = 0.05), presence of abscess (11% vs. 0%, P = 0.01), and Infectious Diseases consultation (63% vs. 34%, P = 0.0001). Onset of EB in an intensive care unit was more common in BL vs. FQ (24% vs. 10%, P = 0.01). Median duration of IV and oral therapy was 5 vs. 4 days, P = 0.22 and 11 vs. 12 days, P = 0.17 in BL and FQ, respectively. Recurrence within 90 days was 7% in BL and 4% in FQ, P = 0.49 (adjusted OR 1.44, 95% CI 0.31-6.66; P = 0.64). Multivariate analysis identified liver cirrhosis (OR 16.89, 95% CI 1.06-268.32; P = 0.05) as an independent predictor of recurrence within 90 days. All secondary outcomes were similar between BL vs. FQ: superinfection within 90 days (10% vs. 9%, P = 0.76), C. difficile infection within 90 days (3% vs. 1%, P = 0.27), 30-day readmission (15% vs. 20%, P = 0.43), all-cause 30-day mortality (0% vs. 3%, P = 0.55). Conclusion. In our cohort of patients with EB, clinical outcomes were similar between those treated with oral BL compared with FQ. Oral BL may be considered for definitive treatment of EB, although further investigation in larger studies is needed

Limited evidence is available to guide periprocedural management of oral anticoagulants in the setting of interventional radiology (IR) procedures. For direct oral anticoagulants, therapy interruption (TI) is based on medication half-life and procedural bleeding risk. Periprocedural management of warfarin includes INR monitoring, and possible bridging with parenteral anticoagulants. It is unknown if these recommendations apply to IR procedures. To evaluate bleeding complications and thromboembolic events following periprocedural management of the factor Xa (FXa) inhibitors or warfarin in patients undergoing IR procedures. We performed a retrospective, observational study at NYU Langone Health (NYULH) of all adult patients who underwent an IR procedure from January 2015 to July 2017 and were receiving apixaban, rivaroxaban, or warfarin. Patients who were pregnant or who had a mechanical heart valve were excluded. At NYULH, TI is not required for FXa inhibitors, and an INR < 3 is recommended for patients on warfarin undergoing low risk procedures. For moderate/high risk procedures, TI for 48 h or 72 h with reduced renal function, is recommended for FXa inhibitors, and an INR < 1.5 is recommended for patients on warfarin. We evaluated 350 IR procedures, with a total of 174 low bleeding risk and 176 moderate/high bleeding risk. The 30-day major bleeding rate was 0.9%, clinically relevant non-major bleeding rate was 3%, minor bleeding rate was 1% and thromboembolic event rate was 1%. The periprocedural oral anticoagulation management strategy at NYULH appears safe given the low 30-day incidence of bleeding and thromboembolic events.

BACKGROUND:Parameters within reconstitution, storage, stability, and administration may be optimized according to the unique pharmacokinetics of each antibiotic to ensure a successful desensitization. OBJECTIVE:The study aims to evaluate the successfulness and safety of antibiotic desensitization protocols developed by the pharmacy department at our institution. METHODS:A retrospective study was conducted at an 800-bed, urban, tertiary care, academic medical center. A total of 36 patients 18 years of age or older, admitted to our intensive care units between March 2013 and July 2017, who underwent antibiotic desensitization utilizing our pharmacy developed protocols were included. RESULTS:In 36 patients, 61 desensitization cases were identified and included; 17 (47%) were male, 27 (75%) were Caucasian, and the median age was 55 years (range 19-94). In all, 15 different antibiotics were administered for desensitization, with meropenem (n = 12, 20%), ampicillin (n = 7, 11%), piperacillin/tazobactam (n = 7, 11%), and penicillin (n = 7, 11%) being the most common; 59 (97%) of 61 desensitizations were completed successfully with or without experiencing reactions, and 53 (89%) of the successful desensitization cases were completed without reactions. Two cases were categorized as anaphylaxis, which was severe enough to terminate the desensitization process. Of the 59 cases successfully completed, the 6 (10%) cases that experienced reactions were managed successfully during desensitization with completion of the process. Conclusion and Relevance: The findings suggest that our pharmacy-developed antibiotic desensitization protocols are successful and safe and may be adapted by other institutions.

Inotropes are an integral component of the early stabilization of the patient presenting with cardiogenic shock. Despite years of clinical experience with the 2 most commonly used inotropes, dobutamine and milrinone, there remains limited data comparing outcomes between the two. We conducted a retrospective review to compare the effectiveness and safety of milrinone or dobutamine for the initial management of cardiogenic shock. Adult patients with cardiogenic shock regardless of etiology who received initial inotrope therapy with either milrinone (n = 50) or dobutamine (n = 50) and did not receive mechanical circulatory support were included. The primary end point was the time to resolution of cardiogenic shock. Changes in hemodynamic parameters from baseline and adverse events were also assessed. Resolution of shock was achieved in similar numbers in both the groups (milrinone 76% vs dobutamine 70%, P = .50). The median time to resolution of shock was 24 hours in both groups ( P = .75). There were no differences in hemodynamic changes during inotrope therapy, although dobutamine trended toward a greater increase in cardiac index. Arrhythmias were more common in patients treated with dobutamine than milrinone, respectively (62.9% vs 32.8%, P < .01), whereas hypotension occurred to a similar extent in both groups (milrinone 49.2% vs dobutamine 40.3%, P = .32). The use of concomitant vasoactive medications, dosage required, and duration of therapy did not differ between groups. There was no difference in the overall rate of discontinuation due to adverse event; however, milrinone was more commonly discontinued due to hypotension (13.1% vs 0%, P < .01) and dobutamine was more commonly discontinued due to arrhythmia (0% vs 11.3%, P < .01). Milrinone and dobutamine demonstrated similar effectiveness and safety profiles but with differences in adverse events. The choice of milrinone or dobutamine as initial inotrope therapy for cardiogenic shock may depend more on tolerability of adverse events.

Our goal was to provide comprehensive data on the effectiveness of ketamine in refractory status epilepticus (RSE) and to describe the potential consequences of long-term ketamine infusion. Ketamine, an N-methyl D-aspartate (NMDA) receptor antagonist, blocks excitatory pathways contributing to ongoing seizure. While ketamine use is standard in anaesthetic induction, no definitive protocol exists for its use in RSE, and little is known about its adverse effects in long-term, high-dose administration. We present two cases of RSE that responded rapidly to ketamine infusion, both with fatal outcomes secondary to metabolic acidosis and cardiovascular collapse. We performed a systematic review of the application and consequences of ketamine use in RSE. PubMed, Ovid, MEDLINE and PMC were searched for articles describing ketamine treatment for RSE according to a predetermined search strategy and inclusion criteria. The systematic review revealed wide discrepancies in ketamine dosing (infusion maintenance dose range 0.0075-10.5 mg/kg/hour), but good outcomes in medically managed RSE (75% of studies reported moderate or complete seizure control in adults, 62.5% in paediatrics). Additionally, literature review elucidated a potentially causal relationship between prolonged ketamine infusion and both cardiovascular and metabolic dysregulation. Ketamine is effective in RSE by antagonising excitotoxic NMDA receptors. However, there is high variability in ketamine dosing and scarce data on its safety in long-term infusion. Metabolic acidosis and haemodynamic instability associated with the use of long-term, high-dose ketamine infusions must be of concern to clinicians administering ketamine to critically ill patients.