Olivier Lortholary

Increasing Incidence of Zygomycosis (Mucormycosis), France, 1997–2006

Results were derived from a population-based study using hospital discharge data.

Results Obtained with Various Antifungal Susceptibility Testing Methods Do Not Predict Early Clinical Outcome in Patients with Cryptococcosis

ABSTRACT The in vitro susceptibilities of Cryptococcus neoformans isolates from consecutive human immunodeficiency virus-positive and -negative patients to the antifungal agents fluconazole, amphotericin B, and flucytosine were determined by different techniques, including the CLSI method, Etest, and broth microdilution in yeast nitrogen base (YNB) medium, during a multicenter prospective study in France. The relationship between the in vitro data and the clinical outcome 2 weeks after the initiation of antifungal therapy was assessed. In addition, the correlation between the strain serotype and the in vitro activities of the antifungals was determined, and the susceptibility results obtained with the different techniques were also compared. Thirty-seven patients received a combination of amphotericin B with flucytosine as first-line therapy, 22 were treated with amphotericin B alone, and 15 received fluconazole alone. Whatever the antifungal tested, there was no trend toward higher MICs for strains isolated from patients who failed to respond to a given therapy compared to those from patients who did not with either the CLSI method, Etest, or broth microdilution in YNB medium. The MICs obtained by the CLSI or Etest method were significantly lower for serotype D strains than for serotype A strains for both fluconazole and amphotericin B, while flucytosine MICs were not different according to serotype. These findings suggest that the in vitro antifungal susceptibility of C. neoformans, as determined with the techniques used, is not able to predict the early clinical outcome in patients with cryptococcosis.

Comparative In Vitro Activities of Caspofungin and Micafungin, Determined Using the Method of the European Committee on Antimicrobial Susceptibility Testing, against Yeast Isolates Obtained in France in 2005-2006

ABSTRACT The in vitro activities of caspofungin and micafungin against 1,038 yeast isolates have been determined. The caspofungin and micafungin MICs were lower for Candida albicans, Candida glabrata, and Candida tropicalis than for Candida parapsilosis, Candida guilliermondii, and Candida krusei. A clear correlation was seen between the MICs for the two drugs.

Clinical potential of midostaurin in advanced systemic mastocytosis

Advanced (Ad) systemic mastocytoses (SM) include aggressive SM (ASM) and mast cell leukemia (MCL) with or without an associated clonal hematological non-mast cell lineage disease (AHNMD). They are rare (<15%) but are associated with a poor prognosis due to rapid organ dysfunction. To date, responses to high-dose chemotherapy, cladribine, and imatinib were revealed to be suboptimal with a median survival time of 24 months. Midostaurin is a potent multikinase inhibitor including the most frequent KIT D816V mutation (>80%). We herein present a review of the most recent data of the use of midostaurin in AdSM. First, a multicenter Phase II study (CPKC412D2213) revealed an unprecedented overall response rate (ORR) of 69% regardless of KIT mutational status, with 38% of major response (MR) among 26 AdSM patients treated with midostaurin alone 200 mg daily. Second, a sponsor-initiated, multicenter, single-arm open Phase II study (CPKC412D2201) confirmed a high and durable ORR of 60% including 45% of MR among 89 AdSM patients. Finally, a French compassionate use program managed by the French Reference Centre for Mastocytosis allowed the treatment of almost a hundred AdSM patients to date in France since the CPKC412D2201 study closure. The outcome of the first 28 treated patients under cover of this on-going procedure revealed an ORR of 71% including 57% of MR. Most importantly, survival analysis revealed in comparison to a historical control cohort of AdSM patients who did not receive midostaurin a twofold lower risk of death (p=0.02) in midostaurin-treated patients. Side effects revealed were acceptable and manageable (mostly digestive). Midostaurin appears to be an effective and safe treatment of AdSM. However, its effect on the course of the AHNMD is less clear. For the future, combined therapy (hypomethylating agents, cladribine, mammalian target of rapamycin inhibitors, chemotherapy, and allogeneic bone marrow transplantation) may further improve long-term survival, particularly that of MCL and AdSM patients with AHNMD.

COL6-01 Thème : Infections nosocomiales et fongiques Augmentation de l’incidence des zygomycoses en France métropolitaine, 1997 - 2006

Introduction La frequence des zygomycoses semble augmenter, notamment parmi les personnes immunodeprimees. Nous voulions estimer l’incidence des zygomycoses dans la population francaise en decrivant les caracteristiques cliniques et epidemiologiques de cette infection fongique grave. Methodes Les nouvelles admissions liees a une zygomycose en France metropolitaine entre 1997 et 2006, extraites de la base de donnees anonymisee du PMSI, ont ete analysees selon l’annee d’hospitalisation, l’âge, le sexe, le departement de residence des patients, les formes cliniques de la maladie et les pathologies associees. Resultats 547 cas de zygomycoses (289 hommes et 258 femmes) etaient identifies. L’âge moyen etait de 54,8 ans (0 a 96 ans). Le taux d’incidence annuel moyen atteignait 0,9 cas par million de personnes et augmentait avec l’âge : 0,2/10 6 chez les moins de 15 ans vs 2,5/10 6 chez les 65 ans et plus. L’incidence annuelle augmentait au cours du temps : de 0,7 cas/10 6 en 1997 a 1,2 cas/10 6 en 2006. Les formes invasives (pulmonaires, rhinocerebrales ou disseminees) etaient les plus frequemment rapportees (37 %), suivies des formes cutanees ou gastro-intestinales (34 %). La localisation n’etait pas precisee pour 29 % des cas. Les pathologies associees incluaient notamment une immunosuppression (20 %) ou un diabete (19 %). Conclusion Les donnees de surveillance passive a travers le PMSI permettent de mieux documenter les tendances. Elles montrent une augmentation reguliere de l’incidence des zygomycoses en France. Toutefois les caracteristiques clinico-epidemiologiques, mycologiques et therapeutiques de la maladie necessitent des analyses complementaires. Une etude retrospective plus approfondie va etre menee dans ce but, a partir des dossiers medicaux des patients identifies par le PMSI et le CNRMA.

Infections émergentes : focus sur les zygomycoses

Auteur(s) : Alienor Xhaard1, Fanny Lanternier1, Olivier Lortholary1,2 1Universite Paris-Descartes, Service des maladies infectieuses et tropicales, Centre d’infectiologie Necker-Pasteur, Hopital Necker-Enfants Malades, Paris 2Centre National de reference mycologie et antifongiques, CNRS URA3012, Unite de mycologie moleculaire, Institut Pasteur, Paris Les zygomycetes sont des champignons filamenteux, ubiquitaires, cosmopolites et saprophytes. Ils sont presents dans le sol et les vegetaux [...]