Faculty Bibliography

e18681Background: Patients undergoing chemotherapy treatment are at risk for bacterial infection during their period of neutropenia. However, not all neutropenic patients are at high risk for developing infection. The purpose of this study was to evaluate the efficacy and safety of prophylactic oral levofloxacin in high, intermediate, and low infection risk patients with cancer in the ambulatory care setting. Methods: This was a retrospective chart review of 100 cancer patients with high, intermediate, and low overall infection risk who were prescribed outpatient oral levofloxacin prophylaxis between October 2019 and July 2020. This quality improvement project included adults with a history of malignancy and presence of neutropenia who have received chemotherapy treatment and oral levofloxacin therapy for overall infection prophylaxis. The primary efficacy outcome was the rate of hospital admission due to febrile neutropenia. The primary safety outcome was the occurrence of side effects of levofloxacin therapy. Secondary outcomes evaluated the duration of levofloxacin therapy, the rate of fluoroquinolone resistance in positive bacterial cultures, progression to sepsis in hospitalized patients and the rate of death due to mult-idrug resistance including fluoroquinolones. Results: Hospital admission due to febrile neutropenia after a chemotherapy cycle occurred in 18% of patients prescribed levofloxacin. Among hospitalized patients due to febrile neutropenia, 2% had low to intermediate overall infection risk and 16% had high overall infection risk. The primary safety outcome occurred in 25% of patients. The incidence of QTc prolongation occurred in 8% of patients; dermatologic side effects occurred in 9% of patients; the rate of Clostridioides difficile infection was 6%, and the rate of tendon rupture was 2%. Median duration of levofloxacin prophylaxis in the low overall infection risk group was 7 days, compared to the intermediate overall infection risk group (8.5 days) and the high overall infection risk group (14 days) with Kruskal-Wallis test p-value of 0.0009. The rate of fluoroquinolone resistance in positive bacterial cultures was 10%. Progression to sepsis in hospitalized patients occurred in 17% of patients. The rate of death due to multi-drug resistance including fluoroquinolone was 2%. Conclusions: Our findings signify preserved efficacy of levofloxacin prophylaxis in the ambulatory setting. Our findings should be considered to develop rational strategies to reduce fluoroquinolone overprescribing or limit duration of levofloxacin prophylaxis. If patients present with solid tumors and experience neutropenia, the use of antibacterial prophylaxis is not recommended because in general, patients recover from neutropenia quickly.

BACKGROUND:The 2021 International Society on Thrombosis and Haemostasis' (ISTH) recommends standard doses of apixaban and rivaroxaban regardless of high body mass index (BMI) and weight, but had not compare DOACs head-to-head in obesity or address underweight patients. METHODS:Our aim is to evaluate the safety and efficacy of DOACs in underweight and obese patients compared to warfarin. The primary endpoints include incidence of thromboembolic and bleeding events. Descriptive statistics was used for continuous variables. The Kruskal-Wallis test was used to compare the four-groups for continuous measures and the chi-square test or Fisher's exact test was used to analyze categorical data. The chi-square test or Fisher's exact test, was used for categorical variables, and the Mann-Whitney test (the non-parametric counterpart to the two-sample t-test) for continuous data. RESULTS:Of 2940 patients receiving anticoagulation for venous thromboembolism (VTE) treatment or atrial fibrillation (AF), 492 met eligibility criteria. Within each group, 248 patients received warfarin, 101 received apixaban, 100 received rivaroxaban and 43 received dabigatran. Patients were characterized in 4 body mass index (BMI) categories, in which 80 were underweight and 412 were obese. CONCLUSIONS:When each DOAC was compared to warfarin in rates of VTE, apixaban showed statistically significant lower rate of VTE (p = 0.0149). However, no statistical significance was identified in the rate of VTE between DOACs combined vs. warfarin (p = 0.1529). When each DOAC was compared to warfarin, apixaban showed the lowest rate of overall bleeding (p = 0.0194). However, no statistical difference in the rate of bleeding was observed between DOACs combined vs. warfarin (p = 0.3284). Patients with extreme body weights requiring anticoagulation for VTE and AF may safety benefit from DOAC therapy. This evaluation showed apixaban with the lowest rate of VTE and bleeding compared to warfarin, rivaroxaban, and dabigatran. These results provide experience for the clinician to use DOACs, particularly apixaban, in underweight and obese populations.

Macrophage activation syndrome is a life-threatening syndrome of uncontrolled immune activation with variable clinical presentation making early diagnosis difficult. It is often manifested by the development of multi-organ failure due to systemic inflammatory response. Patients with ulcerative colitis (UC) on purine antimetabolites are at high risk for severe myelosuppression due to the mechanism of thiopurine toxicity which potentially contributes to the development of macrophage activation syndrome. We present a case of a 39-year-old woman with a 2-year history of UC previously treated with 6-mercaptopurine (6-MP) and recent COVID-19 infection, who was admitted to our emergency department for C. difficile infection and subsequently developed macrophage activation syndrome. This case report also raises the question of whether abrupt discontinuation of 6-MP may have contributed to the worsening of the patient's symptoms of underlying hemophagocytic lymphohistiocytosis (HLH) and her rapid deterioration. Both macrophage activation syndrome and COVID-19 infection can produce a large number of pro-inflammatory cytokines termed "cytokine storm," but a pro-inflammatory cytokine panel breakdown helps to differentiate between the two. Our case report emphasizes the importance of close monitoring of patients on purine antimetabolite therapy who present with signs and symptoms of systemic toxicity.

Pharmacy residents undergo rigorous training to become skillful and knowledgeable independent practitioners. In addition to delivering direct clinical and operational pharmacy services, residents also participate in various administrative, educational, and scholarly activities as part of their residency experience. Throughout their training, residents may rely on individuals within their network for professional, personal, and emotional support, including residency program directors, preceptors, and co-residents from their respective institutions. Residents from nearby institutions can also serve as a vital resource. Throughout the nation, there are numerous pharmacy residency programs located within the same city or region. Fostering collaboration and relationships between residents from neighboring institutions may provide a support network to augment their training and cultivate an environment to promote work-life balance. We describe our 2-year experience in the formation of a citywide "Pharmacy Residents' Collaborative Committee."

Nitrofurantoin remains a key oral antibiotic stewardship program (ASP) option in the treatment of acute uncomplicated cystitis (AUC) due to multi-drug resistant (MDR) Gram negative bacilli (GNB). However, there have been concerns regarding decreased nitrofurantoin efficacy with renal insufficiency. In our experience over the past three decades, nitrofurantoin has been safe and effective in treating AUC in hospitalized adults with renal insufficiency. Accordingly, we retrospectively reviewed our recent experience treating AUC in hospitalized adults with decreased renal function (CrCl < 60 ml/min) with nitrofurantoin. Excluded were complicated urinary tract infections. Urinary isolated susceptibility testing was done by micro broth dilution (MBD). Treatment duration was 5-7 days. Cure was defined as eradication of the uropathogen and failure was defined as minimal/no decrease in urine colony counts. Of 26 evaluable patients with renal insufficiency (CrCl < 60 ml/min), nitrofurantoin eradicated the uropathogen in 18/26 (69%) of patients, and failed in 8/26 (31%). Of the eight failures, five were due to intrinsically resistant uropathogens, e.g., Proteus sp., and one failure was related to an alkaline urine. Of the treatment failures, only two were due to renal insufficiency, i.e., CrCl < 30 ml/min. Since there are few oral antibiotics available to treat AUC due to MDR GNB uropathogens, these results have important ASP implications. Currently, nitfurantoin is not recommended if CrCl < 60 ml/min. In our experience, used appropriately against susceptible uropathogens, nitrofurantoin was highly effective in nearly all patients with CrCl = 30-60 ml/min., and only failed in two patients due to renal insufficiency (CrCl < 30 ml/ml).

OBJECTIVES/OBJECTIVE:To investigate the associations between antibody responses to herpesviruses and the development of thalamic, total deep gray matter, cortical and central atrophy in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. METHODS:We analyzed volumetric brain outcomes in 193 CIS patients enrolled in a multi-center study of high-risk CIS. All patients had 2 or more MRI brain lesions and two or more oligoclonal bands in cerebrospinal fluid. Serum samples obtained at the screening visit prior to any treatment were analyzed for IgG antibodies against cytomegalovirus (anti-CMV) and Epstein-Barr virus (EBV) viral capsid antigen (VCA). All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months. RESULTS:Anti-EBV VCA highest quartile status was associated with regional atrophy measures for percent decrease in thalamus. Anti-CMV positivity was associated with greater total deep gray matter atrophy and whole brain atrophy. Anti-EBV VCA highest quartile status was associated as trends with greater whole brain, gray matter atrophy and central atrophy. The associations of anti-EBV VCA antibodies with thalamic atrophy were mediated by its associations with T2 lesions whereas the associations of anti-CMV positivity with deep gray matter atrophy were relatively independent of T2 lesions. CONCLUSIONS:Antibody responses to EBV and CMV are associated with global and regional brain atrophy in CIS patients treated with interferon-beta.