International Journal of Clinical Pharmacy

, Volume 38, Issue 6, pp 1398–1406 | Cite as

Drug utilization study of systemic antifungal agents in a Brazilian tertiary care hospital

  • Maria Clara Padovani de Souza
  • Andrezza Gouvêa dos Santos
  • Adriano Max Moreira ReisEmail author
Research Article


Background The inappropriate use of systemic antifungal agents can result in unnecessary exposure, adverse events, increased microbial resistance and increased costs. Aim This study analysed the use of systemic antifungal agents and adherence to treatment guidelines for fungal infections. Setting A Brazilian tertiary hospital. Methods This cross-sectional study investigated 183 patients who were treated with systemic antifungals. Antifungal drugs were classified according to the fourth level of the Anatomical Therapeutic Chemical classification system. The appropriateness of treatments was analysed with respect to the indication, dose and potential drug–drug interactions. Descriptive and univariate statistical analyses were performed. The main outcome measure was the frequency of adherence to treatment guidelines for fungal infections. Results The number of established treatments was 320, with 163 (50.9 %) pre-emptive, 63 (19.7 %) targeted, 56 (17.5 %) empirical and 38 (11.9 %) prophylactic treatments. The overall adherence to the treatment guidelines was 29.4 %. The proportion of appropriate treatment considering indication, dosage and drug–drug interactions was 84.1, 67.8 and 47.2 %, respectively. The most commonly prescribed systemic antifungal agents were fluconazole in 170 (53.1 %), voriconazole in 43 (13.4 %) and amphotericin B deoxycholate in 36 (11.3 %) cases. Conclusion The study showed a low proportion of appropriate antifungal drug use; the dosage and drug–drug interactions criteria were the determining factors for the high percentage of non-adherence to treatment guidelines in the hospital. The profile of antifungal agents used showed the predominance of fluconazole as well as the use of new antifungal drugs.


Drug interactions Drug therapy Invasive fungal infection Systemic antifungal 



The authors would like to acknowledge the Pró-Reitoria de Pesquisa da Universidade Federal de Minas Gerais for supporting this publication through the Qualitative Improvement Program of Scientific Production and Fundação de Apoio a Pesquisa de Minas Gerais-FAPEMIG for providing a scientific initiation scholarship.


There was no specific funding source for this study.

Conflicts of interest

The authors declare no conflicts of interest.


  1. 1.
    Nivoix Y, Launoy A, Lutun P, Moulin JC, Phai Pang KA, Fornecker LM, et al. Adherence to recommendations for the use of antifungal agents in a tertiary care hospital. J Antimicrob Chemother. 2012;67:2506–13.PubMedCrossRefGoogle Scholar
  2. 2.
    Metzke B, Neubauer WC, Hieke S, Jung M, Wäsch R, Engelhardt M. Use of systemic antifungals in daily clinical practice in the haematology and oncology setting: results of a prospective observational analysis. Pharmacoepidemiol Drug Saf. 2012;21:953–63.PubMedCrossRefGoogle Scholar
  3. 3.
    Ramírez E, García-Rodríguez J, Borobia A, Ortega JM, Lei S, Barrios-Fernández A, et al. Use of antifungal agents in a pediatric and adult high-risk areas. Eur J Clin Microbiol Infect Dis. 2012;31:337–47.PubMedCrossRefGoogle Scholar
  4. 4.
    Gross BN, Steib-Bauert M, Kern WV, Knoth H, Borde JP, Krebs S, et al. Hospital use of systemic antifungal drugs: a multi-center surveillance update from Germany. Infection. 2015;43:423–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Muñoz P, Rojas L, Cervera C, Garrido G, Fariñas MC, Valerio M, et al. Poor compliance with antifungal drug use guidelines by transplant physicians: a framework for educational guidelines and an international consensus on patient safety. Clin Transplant. 2012;26:87–96.PubMedCrossRefGoogle Scholar
  6. 6.
    Pfaller MA, Pappas PG, Wingard JR. Invasive fungal pathogens: current epidemiological trends. Clin Infect Dis. 2006;43:S3–14.CrossRefGoogle Scholar
  7. 7.
    Zarb P, Amadeo B, Muller A, Drapier N, Vankerckhoven V, Davey P, et al. Antifungal therapy in European hospitals: data from the ESAC point-prevalence surveys 2008 and 2009. Clin Microbiol Infect. 2012;18:E389–95.PubMedCrossRefGoogle Scholar
  8. 8.
    Valerio M, Muñoz P, Rodríguez CG, Caliz B, Padilla B, Fernández-Cruz A, et al. Antifungal stewardship in a tertiary-care institution: a bedside intervention. Clin Microbiol Infect. 2015;21:492.e1–9.CrossRefGoogle Scholar
  9. 9.
    López-Medrano F, San Juan R, Lizasoain M, Catalán M, Ferrari JM, Chaves F, et al. A non-compulsory stewardship programme for the management of antifungals in a university-affiliated hospital. Clin Microbiol Infect. 2013;19:56–61.PubMedCrossRefGoogle Scholar
  10. 10.
    Mondain V, Lieutier F, Hasseine L, Gari-Toussaint M, Poiree M, Lions C, et al. A 6-year antifungal stewardship programme in a teaching hospital. Infection. 2013;41:621–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Colombo AL, Guimarães T, Camargo LF, Richtmann R, Queiroz-Telles F, et al. Brazilian guidelines for the management of candidiasis—a joint meeting report of three medical societies: Sociedade Brasileira de Infectologia, Sociedade Paulista de Infectologia and Sociedade Brasileira de Medicina Tropical. Braz J Infect Dis. 2013;17:283–312.PubMedCrossRefGoogle Scholar
  12. 12.
    Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;48:503–35.PubMedCrossRefGoogle Scholar
  13. 13.
    Sutepvarnon A, Apisarnthanarak A, Camins B, Mondy K, Fraser VJ. Inappropriate use of antifungal medications in a tertiary care center in Thailand: a prospective study. Infect Control Hosp Epidemiol. 2008;29:370–3.PubMedCrossRefGoogle Scholar
  14. 14.
    Garey KW, Pai MP, Suda KJ, Turpin RS, Rege MD, Mingo DE, et al. Inadequacy of fluconazole dosing in patients with candidemia based on Infectious Diseases Society of America (IDSA) guidelines. Pharmacoepidemiol Drug Saf. 2007;16:919–27.PubMedCrossRefGoogle Scholar
  15. 15.
    Salci TP, Gimenes M, dos Santos CA, Svidzinski TI, Caparroz-Assef SM. Utilization of fluconazole in an intensive care unit at a university hospital in Brazil. Int J Clin Pharm. 2013;35:176–80.PubMedCrossRefGoogle Scholar
  16. 16.
    World Health Organization (WHO). ATC/DDD Index 2015. WHO Collaborating Centre for Drug Statistics Methodology. Norwegian Institute of Public Health. 2015. Accessed 10 Feb 2015.
  17. 17.
    Maertens J, Marchetti O, Herbrecht R, Cornely OA, Flückiger U, Frêre P, et al. European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3-2009 update. Bone Marrow Transplant. 2011;46:709–18.PubMedCrossRefGoogle Scholar
  18. 18.
    Drugdex® System: DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Accessed 20 Apr 2015.
  19. 19.
    Drug-reax® System: DRUG-REAX® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Accessed 20 Apr 2015.
  20. 20.
    Micallef C, Aliyu SH, Santos R, Brown NM, Rosembert D, Enoch DA. Introduction of an antifungal stewardship programme targeting high-cost antifungals at a tertiary hospital in Cambridge, England. J Antimicrob Chemother. 2015;70:1908–11.PubMedGoogle Scholar
  21. 21.
    Enoch DA, Idris SF, Aliyu SH, Micallef C, Sule O, Karas JA. Micafungin for the treatment of invasive aspergillosis. J Infect. 2014;68:507–26.PubMedCrossRefGoogle Scholar
  22. 22.
    Cornely OA, Meems L, Herbrecht R, Viscoli C, van Amsterdam RG, Ruhnke M. Randomised, multicentre trial of micafungin vs. an institutional standard regimen for salvage treatment of invasive aspergillosis. Mycoses. 2015;58:58–64.PubMedCrossRefGoogle Scholar
  23. 23.
    Garey KW, Neuhauser MM, Bearden DT, Cannon JP, Lewis RE, Gentry LO, et al. Evaluation of antifungals in the surgical intensive care unit: a multi-institutional study. Mycoses. 2006;49:226–31.PubMedCrossRefGoogle Scholar
  24. 24.
    Trevisan DD, Silva JB, Oliveira HC, Secoli SR, Lima MH. Prevalence and clinical significance of potential drug–drug interaction in hematopoietic stem cell transplantation. Cancer Chemother Pharmacol. 2015;75:393–400.PubMedCrossRefGoogle Scholar
  25. 25.
    Andes D, Pascual A, Marchetti O. Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother. 2009;53:24–34.PubMedCrossRefGoogle Scholar
  26. 26.
    Brüggemann RJ, Alffenaar JW, Blijlevens NM, Billaud EM, Kosterink JG, Verweij PE, et al. Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents. Clin Infect Dis. 2009;48:1441–58.PubMedCrossRefGoogle Scholar
  27. 27.
    Tay KY, Ewald MB, Bourgeois FT. Use of QT-prolonging medications in US emergency departments, 1995–2009. Pharmacoepidemiol Drug Saf. 2014;23:9–17.PubMedCrossRefGoogle Scholar
  28. 28.
    Lin YL, Hsiao CL, Wu YC, Kung MF. Electrophysiologic, pharmacokinetic, and pharmacodynamic values indicating a higher risk of torsades de pointes. J Clin Pharmacol. 2011;51:819–29.PubMedCrossRefGoogle Scholar
  29. 29.
    Lin YL, Kung MF. Magnitude of QT prolongation associated with a higher risk of torsades de pointes. Pharmacoepidemiol Drug Saf. 2009;18:235–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Jardin CG, Putney D, Michaud S. Assessment of drug-induced torsade de pointes risk for hospitalized high-risk patients receiving QT-prolonging agents. Ann Pharmacother. 2014;48:196–202.PubMedCrossRefGoogle Scholar
  31. 31.
    Azcert. 2013. Accessed 3 Jan 2015.
  32. 32.
    Woosley RL, Romero K. Assessing cardiovascular drug safety for clinical decision-making. Nat Rev Cardiol. 2013;10:330–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Walsh T, Anaissie E, Denning D, Herbrecht R, Kontoyiannis D, Marr K, Morrison V, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327–60.PubMedCrossRefGoogle Scholar
  34. 34.
    Ostrosky-Zeichner L. Invasive mycoses: diagnostic challenges. Am J Med. 2012;125:S14–24.PubMedCrossRefGoogle Scholar
  35. 35.
    Schneider T, Halter J, Heim D, Passweg J, Stern M, Tichelli A, et al. Pre-emptive diagnosis and treatment of fungal infections—evaluation of a single-centre policy. Clin Microbiol Infect. 2012;18:189–94.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Maria Clara Padovani de Souza
    • 1
  • Andrezza Gouvêa dos Santos
    • 2
  • Adriano Max Moreira Reis
    • 2
    Email author
  1. 1.Hospital das ClínicasUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  2. 2.Faculdade de FarmáciaUniversidade Federal de Minas GeraisBelo HorizonteBrazil

Personalised recommendations