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Antimicrobial Stewardship Strategies in Hematologic Malignancies

Explore effective antimicrobial management in patients with hematologic malignancies, focusing on treatment and prophylactic strategies in this vulnerable population. Understand the impact of interventions on patient care and outcomes.

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Antimicrobial Stewardship Strategies in Hematologic Malignancies

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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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