title: Breakthrough invasive fungal disease in patients receiving posaconazole primary prophylaxis: a 4-year study.
abstract: Posaconazole (PSC) is currently recommended as primary prophylaxis in neutropenic patients with acute myeloid leukaemia (AML) and in allogenic haematopoietic stem cell transplantation (AHSCT) recipients with graft-versus-host disease (GVHD). Studies focusing on breakthrough invasive fungal disease (IFD) upon PSC prophylaxis show disparate results. In order to evaluate the incidence of IFD in patients on PSC prophylaxis and identify IFD risk factors, we carried out a retrospective study of all consecutive patients on PP from January 2007 to December 2010 in our hospital. Breakthrough IFDs were identified from the database of the central pharmacy and the French administrative database (PMSI), registering final medical diagnoses of hospitalized patients. Medical data were reviewed to study proven or probable IFD, according to EORTC/MSG definition. PSC plasma concentrations (PPC) were also retrieved. Poisson models were used for statistical analysis. Two hundred and seventy-nine patients received PSC prophylaxis for a median duration of 1.4 months (range 0.2-17.9). Proven (n=6) or probable (n=3) IFDs were diagnosed in nine cases (3.2%). IFD incidence rate per 100 person-month was 1.65 (95% CI, 0.79-2.97). IFDs were candidaemia (Candida glabrata, n=2), pulmonary invasive aspergillosis (n=3), disseminated fusariosis (n=2) and pulmonary mucormycosis (n=2). Seven deaths were reported, directly related to IFD in three patients (33.3%). First dosage of PPC under 0.3 mg/L was the single significant risk factor for IFD (RR, 7.77; 95% CI, 1.30-46.5; p 0.025). Breakthrough IFD in patients receiving PSC prophylaxis is rare but associated with a poor outcome. Low PSC plasma concentrations are associated with an increased risk of IFD.
authors.affiliation: Infectious Diseases Intervention Unit, Hôpital Saint-Louis, APHP, University of Paris Diderot Paris 7, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Lerolle
authors.forename: E
authors.initials: E
authors.lastname: Raffoux
authors.forename: G
authors.initials: G
authors.lastname: Socie
authors.forename: S
authors.initials: S
authors.lastname: Touratier
authors.forename: H
authors.initials: H
authors.lastname: Sauvageon
authors.forename: R
authors.initials: R
authors.lastname: Porcher
authors.forename: S
authors.initials: S
authors.lastname: Bretagne
authors.forename: A
authors.initials: A
authors.lastname: Bergeron
authors.forename: E
authors.initials: E
authors.lastname: Azoulay
authors.forename: J-M
authors.initials: JM
authors.lastname: Molina
authors.forename: M
authors.initials: M
authors.lastname: Lafaurie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods*; D025141:Drug Resistance, Fungal; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D016867:Immunocompromised Host; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000453:epidemiology* / Q000382:microbiology; D012189:Retrospective Studies; D014230:Triazoles / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole
keywords: Antifungal prophylaxis; candidaemia; fusariosis; invasive aspergillosis; invasive fungal disease; mucormycosis; posaconazole; therapeutic drug monitoring