Marcio Nucci1, Jeffrey Jenks2, George R Thompson3, Martin Hoenigl2,4, Marielle Camargo Dos Santos5, Fabio Forghieri6, Juan Carlos Rico7, Valentina Bonuomo8, Leyre López-Soria9, Cornelia Lass-Flörl10, Anna Candoni11, Carolina Garcia-Vidal12, Chiara Cattaneo13, Jochem Buil14, Ricardo Rabagliati15, Maria Pia Roiz16, Carlota Gudiol17, Nicola Fracchiolla18, Maria Isolina Campos-Herrero19, Mario Delia20, Francesca Farina21, Jesus Fortun22, Gianpaolo Nadali8, Enric Sastre17, Arnaldo L Colombo5, Elena Pérez Nadales23, Ana Alastruey-Izquierdo24, Livio Pagano25. 1. University Hospital, Universidade Federal do Rio de Janeiro - Rua Prof Rodolpho Paulo Rocco 255, 21941-913 Rio de Janeiro, Brazil. 2. Division of Infectious Diseases and Global Public Health, University of California, San Diego - 9500 Gilman Drive MC 0507 La Jolla, CA, USA. 3. Department of Internal Medicine, Division of Infectious Diseases and Department of Medical Microbiology and Immunology, University of California-Davis - 3146 Tupper Hall, 1 Shields Ave., Davis, CA, USA. 4. Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz - Auenbruggerpl. 2, 8036 Graz, Austria. 5. Division of Infectious Diseases, Escola Paulista de Medicina, Universidade Federal de São Paulo - Rua Botucatu, 740, 04023-062 - São Paulo, Brazil. 6. Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia - Via Università, 4, 41121 Modena, Italy. 7. Division of Infectious Diseases, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock - 4301 W Markham St, Little Rock, AR 72205, USA. 8. Hematology Unit, Azienda Ospedaliera Universitaria Integrata di Verona - Piazzale Aristide Stefani, 1, 37126 Verona, Italy. 9. Servicio de Microbiología, Hospital Universitario Cruces, Barakaldo - Cruces Plaza, S/N, 48903 Barakaldo, Bizkaia, Spain. 10. Division of Hygiene and Medical Microbiology, Medical University of Innsbruck - Christoph-Probst-Platz 1, Innrain 52, A - 6020 Innsbruck, Austria. 11. Division of Haematology, Santa Maria Della Misericordia University Hospital of Udine - Piazzale Santa Maria Della Misericordia, 15, 33100 Udine, Italy. 12. Infectious Diseases Department, Hospital Clinic of Barcelona-IDIBAPS, University of Barcelona - C. de Villarroel, 170, 08036 Barcelona, Spain. 13. Haematology Unit, Spedali Civili di Brescia, Via del Medolo, 2, 25123 Brescia, Italy. 14. Center of Expertise in Mycology Radboud University Medical Center/Canisius-Wilhelmina Hospital - Weg door Jonkerbos 100, 6532 SZ Nijmegen, The Netherlands. 15. Department of Infectious Diseases, Faculty of Medicine, Pontificia Universidad Católica de Chile - Av Libertador Bernardo O'Higgins 340, Santiago, Región Metropolitana, Chile. 16. Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla - Av. de Valdecilla, 25, 39008 Santander, Cantabria, Spain. 17. Department of Infectious Diseases, Bellvitge University Hospital - Carrer de la Feixa Llarga, s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain. 18. Unità di Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Via della Commenda, 10, 20122, Milano, Italy. 19. Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria - Calle Plaza Barranco de la Ballena, s/n, 35010 Las Palmas de Gran Canaria, Las Palmas, Spain. 20. Sezione di Ematologia, Dipartimento dell'Emergenza e dei Trapianti d'Organo, Università di Bari - Piazza Umberto I, 1, 70121, Bari, Italy. 21. Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute - Via Olgettina, 60, 20132, Milano, Italy. 22. Infectious Diseases Department, Hospital Universitario Ramón y Cajal - M-607, km. 9, 100, 28034, Madrid, Spain. 23. Hospital Universitario Reina Sofia, Universidad de Córdoba - Av. Menendez Pidal, s/n, 14004 Córdoba, Spain. 24. Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III - Ctra. de Pozuelo, 28, 28222 Majadahonda, Madrid, Spain. 25. Istituto di Ematologia, Fondazione Policlinico Universitario A. Gemelli-IRCCS-Università Cattolica del Sacro Cuore - Largo Francesco Vito, 1, 00168 Roma RM, Italy.
Abstract
BACKGROUND: Invasive fusariosis (IF) affects mostly severely immunocompromised hosts and is associated with poor outcome. Since Fusarium species exhibit high MICs for most antifungal agents, this could explain the poor prognosis. However, a clear-cut correlation between MIC and outcome has not been established. OBJECTIVE: To evaluate the correlation between MIC and outcome (6 week death rate) in patients with IF. METHODS: We performed a multicentre retrospective study of patients with IF who received treatment and had MIC levels determined by EUCAST or CLSI for the drug(s) used during treatment. We compared the MIC50 and MIC distribution among survivors and patients who died within 6 weeks from the diagnosis of IF. RESULTS: Among 88 patients with IF, 74 had haematological diseases. Primary treatment was monotherapy in 52 patients (voriconazole in 27) and combination therapy in 36 patients (liposomal amphotericin B + voriconazole in 23). The MIC50 and range for the five most frequent agents tested were: voriconazole 8 mg/L (range 0.5-64), amphotericin B 2 mg/L (range 0.25-64), posaconazole 16 mg/L (range 0.5-64), itraconazole 32 mg/L (range 4-64), and isavuconazole 32 mg/L (range 8-64). There was no difference in MIC50 and MIC distribution among survivors and patients who died. By contrast, persistent neutropenia and receipt of corticosteroids were strong predictors of 6 week mortality. CONCLUSIONS: Our study did not show any correlation between MIC and mortality at 6 weeks in patients with IF.
BACKGROUND: Invasive fusariosis (IF) affects mostly severely immunocompromised hosts and is associated with poor outcome. Since Fusarium species exhibit high MICs for most antifungal agents, this could explain the poor prognosis. However, a clear-cut correlation between MIC and outcome has not been established. OBJECTIVE: To evaluate the correlation between MIC and outcome (6 week death rate) in patients with IF. METHODS: We performed a multicentre retrospective study of patients with IF who received treatment and had MIC levels determined by EUCAST or CLSI for the drug(s) used during treatment. We compared the MIC50 and MIC distribution among survivors and patients who died within 6 weeks from the diagnosis of IF. RESULTS: Among 88 patients with IF, 74 had haematological diseases. Primary treatment was monotherapy in 52 patients (voriconazole in 27) and combination therapy in 36 patients (liposomal amphotericin B + voriconazole in 23). The MIC50 and range for the five most frequent agents tested were: voriconazole 8 mg/L (range 0.5-64), amphotericin B 2 mg/L (range 0.25-64), posaconazole 16 mg/L (range 0.5-64), itraconazole 32 mg/L (range 4-64), and isavuconazole 32 mg/L (range 8-64). There was no difference in MIC50 and MIC distribution among survivors and patients who died. By contrast, persistent neutropenia and receipt of corticosteroids were strong predictors of 6 week mortality. CONCLUSIONS: Our study did not show any correlation between MIC and mortality at 6 weeks in patients with IF.