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Antimicrobial Stewardship Strategies in Patients with Hematologic Malignancies Carley Buchanan, PharmD Infectious Diseases Clinical Pharmacist Western Pennsylvania Hospital March 9, 2019. Disclosure. I have no actual or potential conflict of interest in relation to this presentation.

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  1. Antimicrobial Stewardship Strategies in Patients with Hematologic Malignancies Carley Buchanan, PharmDInfectious Diseases Clinical PharmacistWestern Pennsylvania Hospital March 9, 2019

  2. Disclosure • I have no actual or potential conflict of interest in relation to this presentation.

  3. Objective • Discuss strategies to manage antimicrobial treatment and prophylaxis in patients with hematologic malignancies.

  4. Patients with Hematologic Malignancies • Often severely immunocompromised • Chemotherapy, HSCT • Neutropenic for extended duration of time • Frequent inpatient admissions • Exposed to a multitude of antimicrobials • Prophylaxis, treatment of infections HSCT: hematopoietic stem cell transplant

  5. IDSA Recommendations • “We suggest ASPs develop facility-specific guidelines for fever and neutropenia (F&N) management in hematology-oncology patients over no such approach.” • “We suggest implementation of ASP interventions to improve the appropriate prescribing of antifungal treatment in immunocompromised patients.” • Implementation of stewardship intervention should be done in collaboration with the hematology-oncology team ASPs: antibioticstewardship programs Clin Infect Dis. 2016;62(10):e51-77.

  6. Febrile Neutropenia (FN) • Fever occurs in >80% of hematology patients who are neutropenic following chemotherapy • Where can ASPs impact patient care? • Empiric treatment choice and dosing • Role of antifungals • De-escalation • Duration of therapy • Allergy assessment Clin Infect Dis. 2004;39 Suppl 1:S32-7.

  7. Empiric Treatment of FN • Empiric treatment choice • Anti-pseudomonal beta-lactam +/- anti-MRSA agent • Algorithm based approach • Febrile Neutropenia Algorithm • Antimicrobial dosing strategies • Extended infusion • Site-specific microbiology data, education • Other alternatives

  8. Alternative Cefepime Dosing Lodise TP et al. Pharmacotherapy. 2006;26:1320–1332

  9. Alternative Cefepime Dosing • Retrospective chart review of 150 patients at WPH • June 2015 – September 2017 • Control: cefepime 2g q8h • Intervention: cefepime 1g q6h • Inclusion criteria • Patients >18 years of age hospitalized with FN • Absolute neutrophil count <500 cells/uL • Documented temperature of >38.3 °C or 38.0 °C sustained over 1 hour • Primary outcome • Time to defervescence WPH: West Penn Hospital Moffa, M et al. Poster #1594. Presented at ID WeekOct 2018.

  10. Baseline Characteristics *Variables presented as median (interquartile range) SAPS II: simplified acute physiology score ANC: absolute neutrophil count Moffa, M et al. Poster #1594. Presented at ID WeekOct 2018.

  11. Outcomes *Variables presented as median (interquartile range) Moffa, M et al. Poster #1594. Presented at ID WeekOct 2018.

  12. Moffa, M et al. Poster #1594. Presented at ID WeekOct 2018.

  13. Conclusion • No significant difference in time to defervescence or mortality at 30 days between patients who received cefepime 2g q8h compared to 1g q6h for the treatment of FN • This alternative dosing strategy results in less cefepime drug exposure and less potential risk for drug toxicities • Limitations: • Small number of patients with gram negative infection • Cefepime related toxicity not evaluated • Power Moffa, M et al. Poster #1594. Presented at ID WeekOct 2018.

  14. Additional Findings • Time to anti-pseudomonal beta-lactam administration • Increased mortality with Pseudomonas aeruginosa infections • Anti-pseudmonal beta-lactam administration within 60 mins ADC: automateddispensing cabinet Moffa, M et al. Poster #1594. Presented at ID WeekOct 2018.

  15. Febrile Neutropenia Treatment Duration • Variety of recommendations IDSA: Infectious Diseases Society of America NCCN: National Comprehensive Cancer Network ESMO: European Society for Medical Oncology ECIL: European Conference on Infections in Leukemia Clin Infect Dis. 2011;52(4):427-31. Baden LR et al. NCCN Guideline Version 1.2018. Ann Oncol. 2016;27(suppl 5):v111-v118. Haematologica. 2013;98(12):1826-35.

  16. How Long Study Aguilar-Guisado et al. • Open label, randomized, controlled phase 4 trial • Inclusion criteria: • >18 years of age, admitted to hematology ward, receiving treatment for hematologic malignancy or undergoing HSCT, with high-risk for FN, with no microbiological diagnosis Lancet Haematol. 2017 Dec;4(12):e573-e583

  17. How Long Study Aguilar-Guisado et al. • Conclusion • “In high-risk patients with hematologic malignancies and febrile neutropenia empiric therapy can be discontinued after 72h of apyrexia and clinical recovery irrespective of neutrophil count.” Data expressed as mean (SD) EAT: empirical antimicrobial therapy Lancet Haematol. 2017 Dec;4(12):e573-e583

  18. Fluoroquinolone (FQ) Prophylaxis • Recommended for use in high-risk patients • Reductions in mortality and febrile episodes • Risks of fluoroquinolones • Increased resistance • Clostridium difficile infection • Adverse reactions • Extensive warnings • Tendon rupture, CNS effects, aortic ruptures/tears • Levofloxacin prophylaxis and ESBL bacteremia J Clin Oncol. 2018;:JCO1800374. Clin Infect Dis. 2018;67(11):1720-1728.

  19. Fluoroquinolone Prophylaxis Alternatives • Withhold FQ and replace with conditional order for anti-pseudomonal beta-lactam while admitted • PRN order entered in place of FQ prophylaxis for neutropenic patients undergoing acute myeloid leukemia (AML) induction • Cefepime stocked in automated dispensing cabinet • FQ prophylaxis algorithm

  20. Fluoroquinolone Prophylaxis Alternatives *Patients may have experienced more than one episode of bacteremia GNR: gram negative rod

  21. Preliminary Conclusions • Similar rates of: • Mortality • ICU admission • Febrile neutropenia • Improved resistance patterns • Increased GNR bacteremia

  22. Summary • Multiple roles for ASPs in hematologic malignancies • Areas for intervention • Algorithms • Febrile neutropenia, anti-fungal • Alternative dosing strategies • Duration • Limiting empiric therapy when no source identified • Decreasing exposure to fluoroquinolone prophylaxis

  23. Assessment Question • During the empiric treatment of febrile neutropenia which class of medication should be administered first? a. Anti-MRSA agent b. Antifungal c. Anti-pseudomonal beta-lactam d. Antiviral

  24. Questions?

  25. Antimicrobial Stewardship Strategies in Patients with Hematologic Malignancies Carley Buchanan, PharmDInfectious Diseases Clinical PharmacistWestern Pennsylvania Hospital March 9, 2019

  26. Alternative Cefepime Dosing: Exclusion Criteria • Age < 18 or > 89 years of age • CrCl< 30 mL/min or on dialysis • Subjective fevers only • Admission from outside hospital • Received other empiric antimicrobial prior to cefepime • Change in dosing scheme after initial 36 hours therapy • Change in antibiotic due to allergy, adverse drug event, or targeted therapy based on cultures/susceptibilities • Pregnancy • Residence at correctional facility

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