scholarly journals 2106. Evaluation of Isavuconazole for the Prophylaxis and Treatment of Invasive Fungal Infections at a Large Academic Medical Center

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S712-S713
Author(s):  
Christine Vu ◽  
Meenakshi Rana ◽  
Patricia Saunders-Hao

Abstract Background Isavuconazole is an azole antifungal with in vitro activity against various fungi, including Candida spp, Aspergillus, and Mucormycetes. Currently, isavuconazole is FDA approved for the treatment of invasive aspergillosis and mucormycosis; however, there remains limited data to support prophylaxis use. Compared with other first-line azoles, isavuconazole’s broad spectrum of activity, favorable safety profile, and oral bioavailability makes it an attractive antifungal option. In July 2017, isavuconazole was added to our hospital formulary as a restricted antimicrobial. Since then, we have seen increased use for both prophylaxis and treatment of invasive fungal infections. Methods A single-center, retrospective chart review was conducted on adult patients who received at least 1 dose of isavuconazole at The Mount Sinai Hospital between July 1, 2017 and December 31, 2018. The electronic medical record was utilized to collect information on therapeutic indication, dosing, formulation, duration, reasons for switching to isavuconazole, prior antifungals, and proven or probable breakthrough invasive fungal infections (bIFIs) based on EORTG/MTG definitions. Results 54 patients received 61 courses of isavuconazole. Reasons for switching to isavuconazole are described in Table 1. Eleven patients received inappropriate intravenous formulations and 14% of orders were prescribed isavuconazole without a loading dose (Table 2). We identified 4 proven/probable bIFIs, representing 7.4% of patients and 6.6% of courses (Table 3). All patients died within 60 days of bIFI onset. Conclusion Since its addition to hospital formulary, we have observed varying isavuconazole prescribing practices, highlighting the need for improved antifungal stewardship. Rates of bIFIs on isavuconazole were lower than previously reported studies. Additional studies are needed to provide guidance on isavuconazole use and determine its role as prophylaxis therapy. Disclosures All authors: No reported disclosures.

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S87-S87
Author(s):  
Celestine Ishiekwene ◽  
Maxine Seales Kasangana ◽  
Monica Ghitan ◽  
Margaret Kuhn-Basti ◽  
Edward Chapnick ◽  
...  

Abstract Background Candida remains the most common cause of invasive fungal infections, with an attributable morality of 15–35%. Although five Candida species (C. albicans, C. tropicalis, C. parapsilosis, C. glabrata, and C. krusei) account for 92% of cases of candidemia, Candida albicans remains the most common cause of candidemia. However, recent studies report that the frequency of non albicans species are increasing globally and the distribution of Candida spp. varies significantly among different geographic regions and hospitals units. Objective We determine the distribution of Candida species causing candidemia at an adult level 1 Trauma Center in Brooklyn, New York and compared the trends of Candida species between 2005 and 2014. The results were compared with trends of US data collected in 2004 and 2012. Knowledge of the frequency of causative species would facilitate appropriate selection of empiric antifungal therapy. Methods We performed a retrospective chart review of patients with candidemia who were admitted in 2005 and 2014. We determined the frequency of Candida species and compared 2005 data with those in 2014. Results In total, 226 and 109 patients with candidemia were admitted to our hospital in 2005 and 2014, respectively. Although, C. albicans was the most common species (43% of candidemia in 2005), its frequency decreased to 33% in 2014. The frequencies of C. glabrata and C. parapsilosis increased in 2014 compared with those in 2005 (24% vs. 16% and 33% vs. 26%, respectively). Figure 1 compared the proportion of Candida species in Maimonides Medical Center to National data. Conclusion Our finding of an increase in non-albicans spp. causing candidemia is consistent with published reports. We saw more cases of C. parapsilosis compared with published data. Our results may be used to inform empiric antifungal therapy. Disclosures All authors: No reported disclosures.


2003 ◽  
Vol 37 (1) ◽  
pp. 90-98 ◽  
Author(s):  
Staci A Pacetti ◽  
Steven P Gelone

OBJECTIVE To briefly discuss the changing epidemiology of fungal infections and review currently available agents; provide a review of caspofungin; and discuss its pharmacology, pharmacokinetics, dosing guidelines, safety and efficacy, and role in the treatment of invasive fungal infections as it relates to current antifungal therapy. DATA SOURCES A MEDLINE (1966 to August 2002) database search using key words caspofungin, echino candins, fungal infections, and invasive aspergillosis, was completed to identify relevant articles including reviews, recent studies, treatment guidelines, and data from Merck and Company. STUDY SELECTION In vitro studies and all clinical trials were evaluated to summarize the clinical efficacy and safety of caspofungin. DATA SYNTHESIS The incidence of fungal infections is increasing as the population at risk expands. Cost, resistance, and morbidity and mortality are key issues. Adding to the antifungal armamentarium is necessary to address these therapeutic dilemmas. Caspofungin is the first member of a new class of antifungal agents, the echinocandins, to be approved for clinical use. Caspofungin is classified as a glucan synthase inhibitor and represents a class of agents with a novel mechanism of action. Unlike currently available agents (polyenes, pyrimidines, azoles) that exert their effect on the fungal cell membrane, the echinocandins are the first agents to inhibit fungal cell wall synthesis. Caspofungin exhibits activity against Aspergillus spp. and Candida spp., including non-albicans species. Data from clinical trials demonstrate that caspofungin is effective in patients with invasive aspergillosis as well as candida esophagitis. Its Food and Drug Administration–approved indication is limited to invasive aspergillosis refractory to or intolerant of current therapy. CONCLUSIONS Caspofungin has activity against Aspergillus spp. as well as a variety of Candida spp. Clinical data support its usefulness in the treatment of invasive aspergillosis and select candida infections. As additional clinical data become available, it seems likely that the therapeutic role of caspofungin will expand. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-03-001-H01


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S360-S360
Author(s):  
Abigail Servais ◽  
John Schoen ◽  
Trevor C Van Schooneveld ◽  
Erica J Stohs ◽  
Scott Bergman

Abstract Background Isavuconazonium is an appealing anti-fungal due to its broad spectrum of activity, predictable pharmacokinetics, oral bioavailability, and lack of QTc prolongation, but real-world experience with it is limited. At our academic medical center, isavuconazonium is restricted to the infectious diseases (ID) service for treatment of invasive fungal infections, including endemic mycoses due to high prevalence, and is recommended for patients intolerant of first-line agents. The purpose of this study was to describe isavuconazonium use at our institution and assess adherence to its formulary guidelines. Methods Inpatients with an order for isavuconazonium between June 2016 and November 2018 were analyzed via retrospective chart review. Prescribing team, indication, and rationale for use were evaluated. Results There were 97 inpatient encounters with an isavuconazonium order among 57 patients. Of those, 30 were solid-organ transplants and 9 had bone marrow transplants. Indications for isavuconazonium were: histoplasmosis 25%, high-risk fungal prophylaxis 21%, invasive aspergillosis 9%, candidiasis 2%, and other 44% (Table 1). Preceding anti-fungal therapy included: voriconazole 49%, posaconazole 12%, fluconazole 9%, micafungin 7%, amphotericin B 5%, itraconazole 4%, and none 35%. The rationale for the use of isavuconazonium is described in Table 2. ID consultation occurred in 79% of patients. Those without a consult had an indication of prophylaxis or were continuation of therapy started outpatient or at an outside hospital (OSH). Conclusion Histoplasmosis was the most common infection treated with isavuconazonium, despite limited data for that indication. Further investigation of the clinical course for these patients is warranted. Reasons for use most commonly centered on concern for QTc prolongation, clinical failure, and drug interactions. Over one-third of patients received no anti-fungal therapy prior to initiation. Adherence to required ID consultation was high. Patients on isavuconazonium for prophylaxis or as continuation therapy without a consult may still benefit from ID review to assess the appropriateness of therapy. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 7 (1) ◽  
pp. 17
Author(s):  
Frederic Lamoth ◽  
Russell E. Lewis ◽  
Dimitrios P. Kontoyiannis

Invasive fungal infections (IFIs) are associated with high mortality rates and timely appropriate antifungal therapy is essential for good outcomes. Emerging antifungal resistance among Candida and Aspergillus spp., the major causes of IFI, is concerning and has led to the increasing incorporation of in vitro antifungal susceptibility testing (AST) to guide clinical decisions. However, the interpretation of AST results and their contribution to management of IFIs remains a matter of debate. Specifically, the utility of AST is limited by the delay in obtaining results and the lack of pharmacodynamic correlation between minimal inhibitory concentration (MIC) values and clinical outcome, particularly for molds. Clinical breakpoints for Candida spp. have been substantially revised over time and appear to be reliable for the detection of azole and echinocandin resistance and for outcome prediction, especially for non-neutropenic patients with candidemia. However, data are lacking for neutropenic patients with invasive candidiasis and some non-albicans Candida spp. (notably emerging Candida auris). For Aspergillus spp., AST is not routinely performed, but may be indicated according to the epidemiological context in the setting of emerging azole resistance among A. fumigatus. For non-Aspergillus molds (e.g., Mucorales, Fusarium or Scedosporium spp.), AST is not routinely recommended as interpretive criteria are lacking and many confounders, mainly host factors, seem to play a predominant role in responses to antifungal therapy. This review provides an overview of the pre-clinical and clinical pharmacodynamic data, which constitute the rationale for the use and interpretation of AST testing of yeasts and molds in clinical practice.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S667-S668
Author(s):  
Ann-Marie Idusuyi ◽  
Maureen Campion ◽  
Kathleen Belusko

Abstract Background The new ASHP/IDSA consensus guidelines recommend area under the curve (AUC) monitoring to optimize vancomycin therapy. Little is known about the ability to implement this recommendation in a real-world setting. At UMass Memorial Medical Center (UMMMC), an AUC pharmacy to dose protocol was created to manage infectious diseases (ID) consult patients on vancomycin. The service was piloted by the pharmacy residents and 2 clinical pharmacists. The purpose of this study was to determine if a pharmacy to dose AUC protocol can safely and effectively be implemented. Methods A first-order kinetics calculator was built into the electronic medical record and live education was provided to pharmacists. Pharmacists ordered levels, wrote progress notes, and communicated to teams regarding dose adjustments. Patients were included based upon ID consult and need for vancomycin. After a 3-month implementation period, a retrospective chart review was completed. Patients in the pre-implementation group were admitted 3 months prior to AUC pharmacy to dose, had an ID consult and were monitored by trough (TR) levels. The AUC group was monitored with a steady state peak and trough level to calculate AUC. The primary outcome evaluated time to goal AUC vs. time to goal TR. Secondary outcomes included number of dose adjustments made, total daily dose of vancomycin, and incidence of nephrotoxicity. Results A total of 64 patients met inclusion criteria, with 37 patients monitored by TR and 27 patients monitored by AUC. Baseline characteristics were similar except for weight in kilograms (TR 80.0 ±25.4 vs AUC 92.0 ±26.7; p=0.049). The average time to goal AUC was 4.13 (±2.08) days, and the average time to goal TR was 4.19 (±2.30) days (p=0.982). More dose adjustments occurred in the TR group compared to the AUC (1 vs 2; p=0.037). There was no difference between the two groups in dosing (TR 15.8 mg/kg vs AUC 16.4 mg/kg; p=0.788). Acute kidney injury occurred in 5 patients in the AUC group and 11 patients in the TR group (p=0.765). Conclusion Fewer dose adjustments and less nephrotoxicity was seen utilizing an AUC based protocol. Our small pilot has shown that AUC pharmacy to dose can be safely implemented. Larger studies are needed to evaluate reduction in time to therapeutic goals. Disclosures All Authors: No reported disclosures


2020 ◽  
Vol 41 (S1) ◽  
pp. s258-s258
Author(s):  
Madhuri Tirumandas ◽  
Theresa Madaline ◽  
Gregory David Weston ◽  
Ruchika Jain ◽  
Jamie Figueredo

Background: Although central-line–associated bloodstream infections (CLABSI) in US hospitals have improved in the last decade, ~30,100 CLABSIs occur annually.1,2 Central venous catheters (CVC) carry a high risk of infections and should be limited to appropriate clinical indications.6,7 Montefiore Medical Center, a large, urban, academic medical center in the Bronx, serves a high-risk population with multiple comobidities.8–11 Despite this, the critical care medicine (CCM) team is often consulted to place a CVC when a peripheral intravenous line (PIV) cannot be obtained by nurses or primary providers. We evaluated the volume of CCM consultation requests for avoidable CVCs and related CLABSIs. Methods: Retrospective chart review was performed for patients with CCM consultation requests for CVC placement between July and October 2019. The indication for CVC, type of catheter inserted or recommended, and NHSN data were used to identify CLABSIs. CVCs were considered avoidable if a PIV was used for the stated indication and duration of therapy, with no anatomical contraindications to PIV in nonemergencies, according to the Michigan Appropriateness Guide for Intravenous Catheters (MAGIC).6Results: Of 229 total CCM consults, 4 (18%) requests were for CVC placement; 21 consultations (9%) were requested for avoidable CVCs. Of 40 CVC requests, 18 (45%) resulted in CVC placement by the CCM team, 4 (10%) were deferred for nonurgent PICC by interventional radiology, and 18 (45%) were deferred in favor of PIV or no IV. Indications for CVC insertion included emergent chemotherapy (n = 8, 44%) and dialysis (n = 3, 16%), vasopressors (n = 3, 16%), antibiotics (n = 2, 11%) and blood transfusion (n = 2, 11%). Of 18 CVCs, 9 (50%) were potentially avoidable: 2 short-term antibiotics and rest for nonemergent indications; 2 blood transfusions, 1 dialysis, 2 chemotherapy and 2 vasopressors. Between July and October 2019, 6 CLABSIs occurred in CVCs placed by the CCM team; in 3 of 6 CLABSI events (50%), the CVC was avoidable. Conclusions: More than half of consultation requests to the CCM team for CVCs are avoidable, and they disproportionately contribute to CLABSI events. Alternatives for intravenous access could potentially avoid 9% of CCM consultations and 50% of CLABSIs in CCM-inserted CVCs on medical-surgical wards.Funding: NoneDisclosures: None


2021 ◽  
pp. 019459982110129
Author(s):  
Randall S. Ruffner ◽  
Jessica W. Scordino

Objectives During septoplasty, normal cartilage and bone are often sent for pathologic examination despite benign appearance. We explored pathology results following septoplasty from April 2016 to April 2018, examining clinical value and relevance, implications, and cost analysis. Study Design Retrospective chart review. Setting Single-institution academic medical center. Methods A retrospective chart review was compiled by using Current Procedural Terminology code 30520 for septoplasty for indication of nasal obstruction, deviated septum, and nasal deformity. Results A total of 236 consecutive cases were identified spanning a 2-year period. Septoplasty specimens were sent for pathology evaluation in 76 (31%). The decision to send a specimen for histopathology was largely physician dependent. No cases yielded unexpected or significant pathology that changed management. The average total charges for septoplasty were $10,200 at our institution, with 2.2% of procedural charges accounting for pathology preparation and review, averaging $225. Nationally, this results in an estimated charged cost of $58.5 million. The Centers for Medicare and Medicaid Services (CMS) reimbursement for septoplasty pathology charges was $46 in 2018, accounting for 1.3% of hospital-based reimbursements and 2.2% of ambulatory center reimbursements. With CMS as a national model for reimbursement, $11.8 million is spent yearly for septoplasty histopathology. Given that CMS reimbursement is significantly lower than private insurers, national total reimbursement is likely considerably higher. Conclusion Routine pathology review of routine septoplasty specimens is unnecessary, unremarkable, and wasteful. Correlation of the patient’s presentation and intraoperative findings should justify the need for pathology evaluation. This value-based approach can offer significant direct and indirect cost savings. Level of evidence 4.


Author(s):  
Pavani Rangachari ◽  
Jie Chen ◽  
Nishtha Ahuja ◽  
Anjeli Patel ◽  
Renuka Mehta

This retrospective study examines demographic and risk factor differences between children who visited the emergency department (ED) for asthma once (“one-time”) and more than once (“repeat”) over an 18-month period at an academic medical center. The purpose is to contribute to the literature on ED utilization for asthma and provide a foundation for future primary research on self-management effectiveness (SME) of childhood asthma. For the first round of analysis, an 18-month retrospective chart review was conducted on 252 children (0–17 years) who visited the ED for asthma in 2019–2020, to obtain data on demographics, risk factors, and ED visits for each child. Of these, 160 (63%) were “one-time” and 92 (37%) were “repeat” ED patients. Demographic and risk factor differences between “one-time” and “repeat” ED patients were assessed using contingency table and logistic regression analyses. A second round of analysis was conducted on patients in the age-group 8–17 years to match another retrospective asthma study recently completed in the outpatient clinics at the same (study) institution. The first-round analysis indicated that except age, none of the individual demographic or risk factors were statistically significant in predicting of “repeat” ED visits. More unequivocally, the second-round analysis revealed that none of the individual factors examined (including age, race, gender, insurance, and asthma severity, among others) were statistically significant in predicting “repeat” ED visits for childhood asthma. A key implication of the results therefore is that something other than the factors examined is driving “repeat” ED visits in children with asthma. In addition to contributing to the ED utilization literature, the results serve to corroborate findings from the recent outpatient study and bolster the impetus for future primary research on SME of childhood asthma.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Michael Ashamalla ◽  
Justin Pieper ◽  
Daniel Sedhom ◽  
Neil Yager ◽  
Mikhail Torosoff

Background: There is conflicting evidence concerning the obesity paradox in stroke patients. We sought to examine the relationship between gender, BMI, and prevalence of comorbidities in patients with non-hemorrhagic stroke. Materials and Methods: Retrospective chart review was performed in 996 consecutive patients treated for non-hemorrhagic stroke at a single academic medical center. Patients were divided according to gender and specific BMI groups according to the National Institute of Health. This study was approved by the institutional IRB. Results: Patients with BMI from 0-18.5 and 18.5-24.9 were more likely to be female (63.2% and 58.4% p<.05). Whereas patients with BMI over 25-30 and 30-35 were more likely to be male (60.82% and 59.2% p<.05). Morbidly obese patients (BMI>35) were equally likely to be men or women. In men higher BMI correlated with presentation at younger age. Diabetes was most prevalent in patients with BMI over 35 (40% males, 44% females, p<.05). In females, HTN was associated with BMI 30-34.5 and 35+ (80.5% and 73.3%, P<.05). Males showed a similar though non-significant trend. The prevalence of end stage renal disease, systemic atherosclerosis, and PVD was not significantly correlated with BMI in either gender. Conclusion: Gender and BMI significantly affect associated comorbidities in patients with non-hemorrhagic stroke, possibly suggestive of unique gender specific disease mechanisms. Additional studies investigating the effect of gender and BMI on diagnostic evaluation and treatment of patients with non-hemorrhagic stroke are warranted.


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