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침습성 아스페르길루스증의 치료 목적으로 voriconazole을 단독으로 투여받는 폐이식 환자에서 voriconazole 약물혈중농도 모니터링의 유효성 검증

Validation of Voriconazole Therapeutic Drug Monitoring in Lung Transplant Recipients Receiving Voriconazole alone for Treatment of Invasive Aspergillosis

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Background: Invasive aspergillosis (IA) is associated with high morbidity and mortality, particularly among immunocompromised patients, such as lung transplant recipients. Voriconazole, the first-line therapy for IA, shows a non-linear pharmacokinetic profile and has a narrow therapeutic range. Careful and appropriate administration is necessary, primarily because it is used for critically ill patients; however, the clinical usefulness of therapeutic drug monitoring (TDM) has not been sufficiently verified. Therefore, in this study, we validated the safety and efficacy of voriconazole TDM in lung transplant recipients receiving only voriconazole for IA treatment. Methods: The electronic medical records of lung transplant recipients (≥19 years of age) administered only voriconazole for > 7 days for treatment of IA from June 1, 2013 to May 31, 2018 were analyzed retrospectively. Results: Among the 54 patients, 27 each were allocated to TDM and non-TDM groups, respectively. There were no significant differences in patient characteristics between the two groups except for ICU-hospitalization status. Of the TDM group patients, 81.5% needed adjustment of voriconazole dosage because the levels were out of target range. Comparison of two groups showed that treatment response was higher throughout treatment and switching rates of second-line agents were significantly lower in the TDM group, but it was insufficient to confirm safety improvements through voriconazole TDM. Conclusions: Considering that the treatment response tended to be higher and the rates of switching to second-line antifungal agents were lower in the TDM group, voriconazole TDM may increase the therapeutic effect on IA in lung transplant patients.

Abstract

Background: Invasive aspergillosis (IA) is associated with high morbidity and mortality, particularly among immunocompromised patients, such as lung transplant recipients. Voriconazole, the first-line therapy for IA, shows a non-linear pharmacokinetic profile and has a narrow therapeutic range. Careful and appropriate administration is necessary, primarily because it is used for critically ill patients; however, the clinical usefulness of therapeutic drug monitoring (TDM) has not been sufficiently verified. Therefore, in this study, we validated the safety and efficacy of voriconazole TDM in lung transplant recipients receiving only voriconazole for IA treatment. Methods: The electronic medical records of lung transplant recipients (≥19 years of age) administered only voriconazole for > 7 days for treatment of IA from June 1, 2013 to May 31, 2018 were analyzed retrospectively. Results: Among the 54 patients, 27 each were allocated to TDM and non-TDM groups, respectively. There were no significant differences in patient characteristics between the two groups except for ICU-hospitalization status. Of the TDM group patients, 81.5% needed adjustment of voriconazole dosage because the levels were out of target range. Comparison of two groups showed that treatment response was higher throughout treatment and switching rates of second-line agents were significantly lower in the TDM group, but it was insufficient to confirm safety improvements through voriconazole TDM. Conclusions: Considering that the treatment response tended to be higher and the rates of switching to second-line antifungal agents were lower in the TDM group, voriconazole TDM may increase the therapeutic effect on IA in lung transplant patients.

참고문헌 (26)

  1. Badiee P, "Opportunistic invasive fungal infections: diagnosis & clinical management", Indian J Med Res, 139(2), pp.195~204 (2014)
  2. Maschmeyer G, "Invasive aspergillosis:epidemiology, diagnosis and management in immunocompromised patients", Drugs, 67(11), pp.1567~1601 (2007)
  3. Gavalda J, "Invasive fungal infections in solid organ transplant recipients", Clin Microbiol Infect, 20(Suppl 7), pp.27~48 (2014)
  4. Mitsani D, "Prospective, observational study of voriconazole therapeutic drug monitoring among lung transplant recipients receiving prophylaxis: factors impacting levels of and associations between serum troughs, efficacy, and toxicity", Antimicrob Agents Chemother, 56(5), pp.2371~2377 (2012)
  5. Morgan J, "Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program", Med Mycol, 43(Suppl 1), pp.S49~S58 (2005)
  6. Lin SJ, "Aspergillosis case-fatality rate:systematic review of the literature", Clin Infect Dis, 32(3), pp.358~366 (2001)
  7. Patterson TF, "Practice Guidelines for the Diagnosis and Management of Aspergillosis:2016 Update by the Infectious Diseases Society of America", Clin Infect Dis, 63(4), pp.e1~e60 (2016)
  8. Ullmann AJ, "Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline", Clin Microbiol Infect, 24(Suppl 1), pp.e1~e38 (2018)
  9. Herbrecht R, "Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis", N Engl J Med, 347(6), pp.408~415 (2002)
  10. Lat A, "Update on the optimal use of voriconazole for invasive fungal infections", Infect Drug Resist, 4, pp.43~53 (2011)
  11. 김상일, "새로운 항진균제의 국내 사용 및 전망", Infection and Chemotherapy, 42(4), pp.209~215 (2010), 대한감염학회
  12. Theuretzbacher U, "Pharmacokinetic", pharmacodynamic profile of voriconazole, 2006, pp.45(7), 649~663
  13. Andes D, "Antifungal therapeutic drug monitoring: established and emerging indications", Antimicrob Agents Chemother, 53(1), pp.24~34 (2009)
  14. Hashemizadeh Z, "Observational Study of Associations between Voriconazole Therapeutic Drug Monitoring, Toxicity, and Outcome in Liver Transplant Patients", Antimicrob Agents Chemother, 61(12) (2017)
  15. Park WB, "The effect of therapeutic drug monitoring on safety and efficacy of voriconazole in invasive fungal infections: a randomized controlled trial", Clin Infect Dis, 55(8), pp.1080~1087 (2012)
  16. Denning DW, "Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis", Clin Infect Dis, 34(5), pp.563~571 (2002)
  17. Chu HY, "Voriconazole therapeutic drug monitoring: retrospective cohort study of the relationship to clinical outcomes and adverse events", BMC Infectious Diseases, 13(1), pp.105~ (2013)
  18. Pascual A, "Challenging recommended oral and intravenous voriconazole doses for improved efficacy and safety: population pharmacokinetics-based analysis of adult patients with invasive fungal infections", Clin Infect Dis, 55(3), pp.381~390 (2012)
  19. Han K, "Bioavailability and population pharmacokinetics of voriconazole in lung transplant recipients", Antimicrob Agents Chemother, 54(10), pp.4424~4431 (2010)
  20. De Pauw B, "Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer", Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC, Clin Infect Dis, pp.2008, 46(12)[DOI]
  21. Hamada Y, "Practice guidelines for therapeutic drug monitoring of voriconazole: a consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring", J Infect Chemother, 19(3), pp.381~392 (2013)
  22. Dou YH, "The role of procalcitonin in the identification of invasive fungal infection-a systemic review and meta-analysis", Diagn Microbiol Infect Dis, 76(4), pp.464~469 (2013)
  23. Zhou W, "Diagnostic Value of Galactomannan Antigen Test in Serum and Bronchoalveolar Lavage Fluid Samples from Patients with Nonneutropenic Invasive Pulmonary Aspergillosis", J Clin Microbiol, 55(7), pp.2153~2161 (2017)
  24. Segal BH, "Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria", Clin Infect Dis, 47(5), pp.674~683 (2008)
  25. Snyder LD, "Immune mechanisms of lung allograft rejection", Semin Respir Crit Care Med, 27(5), pp.534~543 (2006)
  26. Cornely OA, "EQUAL Aspergillosis Score 2018: An ECMM score derived from current guidelines to measure QUALity of the clinical management of invasive pulmonary aspergillosis", Mycoses, 61(11), pp.833~836 (2018)

관련 논문AI추천

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