Vasilios Athans

A pharmacist-driven antimicrobial stewardship intervention targeting cytomegalovirus viremia in ambulatory solid organ transplant recipients

There is a growing need for robust antimicrobial stewardship interventions in both ambulatory and solid organ transplant (SOT) populations.

Trowels and Tribulations: Review of Antimicrobial‐Impregnated Bone Cements in Prosthetic Joint Surgery

Antimicrobial‐impregnated bone cement (AIBC) is a staple of contemporary orthopedic surgery and has been used to either treat or prevent prosthetic joint infection. Applied intraoperatively during primary arthroplasty or prosthetic joint exchange, this drug‐delivery vehicle has become a popular means of maximizing drug concentrations within a joint space while minimizing systemic exposure. Antimicrobial characteristics conducive to cement loading include availability of a crystalline powder formulation, molecular characteristics, minimal impact on cement integrity, and other variables promoting drug elution. Antimicrobials most commonly incorporated into cements are vancomycin and aminoglycosides, usually in combination due to synergistic antibacterial activity and enhanced cement elution. Other classes include the β‐lactams, lipopeptides, oxazolidinones, and antifungals. With the exception of several commercially available AIBCs, most products are compounded extemporaneously without a formal safety or efficacy assessment. Few randomized controlled trials have been conducted to assess the benefit or optimal use of these cement preparations, and variable methodology renders cross‐study comparison challenging. Given the lack of standardization and multidisciplinary oversight often seen with practical AIBC use, additional data are needed. This review presents information intended to guide AIBC preparation, selection, dosing, and safe use. In addition, opportunities for best practice development, antimicrobial stewardship, and future research are discussed.

Pharmacoepidemiology of Antibiotic Prescribing Among 135,000 Adult Outpatient Encounters in Northeast Ohio

Abstract Background Nearly 154 million ambulatory visits in the United States result in an outpatient antibiotic prescription (OAP) annually, 30% of which are unnecessary. Remaining prescriptions may benefit from improved antibiotic selection. At our institution, a quarterly OAP report associated with 4 common encounter diagnoses was developed. The objectives of this study were to assess OAP rate for each diagnosis, and to assess the rate of guideline-concordant selection when an OAP was issued. Methods OAP report from January 2016 – March 2017 was queried to conduct a retrospective pharmacoepidemiology study including data from 106 outpatient sites, 33 care institutes, and 1400 providers in Northeast Ohio. The report aggregated OAPs for all office and telephone encounters with a diagnosis code for otitis media, pharyngitis, sinusitis, or urinary tract infection. For each diagnosis, encounters that resulted in an OAP were then categorized as guideline-concordant or -discordant based on the antibiotic selected and includes consideration of labeled penicillin allergy and consensus guideline recommendations (Figure 1). All data were filterable to the practice site, care institute, or prescriber level. Results A total of 135,177 patient encounters were captured during the study period (9766 otitis media, 39570 pharyngitis, 60940 sinusitis, 24901 urinary tract infection). Mean patient age was 50 (±15) years. At least 1 OAP was issued in 8444 (86%) otitis media, 16143 (41%) pharyngitis, 46343 (76%) sinusitis, and 15464 (62%) urinary tract infection encounters. For encounters in which an OAP was issued, the rate of guideline-concordant antibiotic selection by diagnosis was 46% for otitis media, 58% for pharyngitis, 64% for sinusitis, and 50% for urinary tract infection. Antibiotic selection for pharyngitis and sinusitis during Q1 2017 are detailed in Figures 2 and 3, respectively. Conclusion Audit of outpatient prescribing data revealed a high rate of OAP issuance for these four common diagnoses. The use of guideline-discordant antibiotics was also prevalent and commonly consisted of macrolides, fluoroquinolones, tetracyclines, and cephalosporins. These data provide an important baseline that underscores the need for outpatient stewardship and facilitates targeted prospective interventions. Disclosures All authors: No reported disclosures.

Real-World Use – Isavuconazole at a Large Academic Medical Center

Abstract Background Invasive fungal infections cause significant mortality and morbidity. Isavuconazole (ISV) is a new triazole approved for treatment of mucormycosis and aspergillosis. Data on its effectiveness outside clinical trials and in patients receiving prior triazole prophylaxis are lacking. Methods We conducted a retrospective cohort study on all patients at the Cleveland Clinic 6/1/2015–1/31/2017 who received ISV to determine 6-week response in a population with varying underlying diseases, and previous triazole prophylaxis or treatment. Descriptive statistics and univariate associations were calculated. Results Thirty-three patients were identified including organ transplant recipients (5), hematopoietic cell transplant recipients (7), and acute leukemia (18). Twenty-five had lung involvement while 13 had rhino-orbital-cerebral disease. In 13 cases, a fungal pathogen was identified: Mucorales (7) and Aspergillus (6). Fifteen received triazole prophylaxis prior to initiating ISV. Twenty-four received antifungal therapy immediately prior to switching to ISV: amphotericin B (1), fluconazole (1), voriconazole (16), posaconazole (4), and micafungin (2). Switching was often to broaden empiric coverage (18). Six-week response according to subgroups is presented in Figure 1 patients had therapeutic drug monitoring (TDM). Median level (IQR) was 6.75 (5.6–7.0) g/ml. Patients given ISV following triazole prophylaxis, those undergoing TDM, and those with an identified fungal pathogen had increased odds of complete or partial response, but this did not reach statistical significance (Figure 2). At 6 weeks mortality was 36%; complete or partial response observed in 45%. No ISV-related adverse effects reported. Conclusion To our knowledge, this is the first study to assess a real-world setting and a heterogeneous population with previous triazole prophylaxis or treatment. Our 6-week response (45%) compares favorably to published trials (35% Aspergillus; 11% Mucorales). Mortality in our study (36%) is similarly comparable to trial results (19% Aspergillus; 35% Mucorales). No major safety signal was observed. Larger cohorts are needed to describe additional real-world ISV use and determine associations with patient outcomes. Disclosures All authors No reported disclosures.

Internally-Developed Antimicrobial Use Benchmarking at a Large Academic Medical Center and Integrated Health System

Vasilios Athans, PharmD, BCPS1, Elizabeth Neuner, PharmD, BCPS (AQ-ID)1, Andrea Pallotta, PharmD, BCPS (AQ-ID), AAHIVP1, Jeffrey Chalmers, PharmD1, Eric Vogan, BSPS, MS1, Xin Jiang, MS1, Thomas Fraser, MD, FSHEA2, Steven Gordon, MD, FIDSA, FSHEA2 1Department of Pharmacy, Cleveland Clinic 2 Department of Infectious Diseases, Cleveland Clinic Contact information: Vasilios Athans, PharmD, BCPS 9500 Euclid Ave. Cleveland, OH, 44195 E-mail: athansv@ccf.org