Background Voriconazole is the therapy of choice for aspergillosis and a new treatment option for candidiasis. Liver disease, age, genetic polymorphism of the cytochrome CYP2C19, and comedications influence voriconazole metabolism. Large variations in voriconazole pharmacokinetics may be associated with decreased efficacy or with toxicity. Methods This study was conducted to assess the utility of measuring voriconazole blood levels with individualized dose adjustments. Results A total of 181 measurements with high-pressure liquid chromatography were performed during 2388 treatment days in 52 patients. A large variability in voriconazole trough blood levels was observed, ranging from 5.5 mg/L (a level possibly associated with toxicity) in 31% of cases. Lack of response to therapy was more frequent in patients with voriconazole levels 1 mg/L (15 [12%] of 39 patients; P=.02). Blood levels >1 mg/L were reached after increasing the voriconazole dosage, with complete resolution of infection in all 6 cases. Among 16 patients with voriconazole trough blood levels >5.5 mg/L, 5 patients (31%) presented with an encephalopathy, including 4 patients who were treated intravenously with a median voriconazole dosage of 8 mg/kg per day, whereas none of the patients with levels Conclusions Voriconazole therapeutic drug monitoring improves the efficacy and safety of therapy in severely ill patients with invasive mycoses.

Voriconazole Therapeutic Drug Monitoring in Patients with Invasive Mycoses Improves Efficacy and Safety Outcomes

Summary: Candida parapsilosis is an emerging major human pathogen that has dramatically increased in significance and prevalence over the past 2 decades, such that C. parapsilosis is now one of the leading causes of invasive candidal disease. Individuals at the highest risk for severe infection include neonates and patients in intensive care units. C. parapsilosis infections are especially associated with hyperalimentation solutions, prosthetic devices, and indwelling catheters, as well as the nosocomial spread of disease through the hands of health care workers. Factors involved in disease pathogenesis include the secretion of hydrolytic enzymes, adhesion to prosthetics, and biofilm formation. New molecular genetic tools are providing additional and much-needed information regarding C. parapsilosis virulence. The emerging information will provide a deeper understanding of C. parapsilosis pathogenesis and facilitate the development of new therapeutic approaches for treating C. parapsilosis infections.

Candida parapsilosis, an Emerging Fungal Pathogen

https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(15)30057-4/pdf

Infections due to emerging and uncommon medically important fungal pathogens.

Background: Nail invasion by nondermatophytic molds (NDM) is considered uncommon with prevalence rates ranging from 1.45% to 17.6%. Objective: We report the clinical features and response to treatment of onychomycosis caused by these molds. Methods: From 1995 through 1998 we performed a mycologic study on 1548 patients affected by nail disorders, and we diagnosed 431 cases of onychomycosis including 59 cases of onychomycosis caused by molds. These include 17 patients with onychomycosis caused by Scopulariopsis brevicaulis , 26 patients with onychomycosis caused by Fusarium sp, 9 patients with onychomycosis caused by Acremonium sp, and 7 patients with onychomycosis caused by Aspergillus sp. Results: Onychomycosis caused by S brevicaulis , Fusarium sp, and Aspergillus sp may often be suspected by clinical examination. In fact 38 of 50 patients with onychomycosis resulting from these molds were affected by proximal subungual onychomycosis associated with inflammation of the proximal nailfold. In our experience mold onychomycosis is not significantly associated with systemic diseases or immunodepression. NDM are difficult to eradicate; by using and combining different treatments (systemic itraconazole, systemic terbinafine, topical terbinafine after nail plate avulsion, and ciclopirox nail lacquer) we were able to cure only 69.2% of patients with S brevicaulis onychomycosis, 71.4% of patients with Acremonium onychomycosis, and 40% of patients with Fusarium onychomycosis. Aspergillus onychomycosis, on the other hand, responded very well to therapy and all our patients were cured after systemic or topical treatment. Eradication of the mold produced a complete cure of the nail abnormalities in all the patients who responded to treatment. Conclusion: Clinical examination usually suggests diagnosis of onychomycosis resulting from NDM. Topical treatment can be more successful than systemic therapy to cure onychomycosis caused by S brevicaulis , Fusarium sp, and Acremonium sp. (J Am Acad Dermatol 2000;42:217-24.)

Onychomycosis caused by nondermatophytic molds: Clinical features and response to treatment of 59 cases

Human fusariosis

A retrospective study was conducted in France to investigate Fusarium infections which are now recognized as emerging opportunistic infections. The clinical and mycological findings for 31 cases diagnosed between 1984 and 1993 by members of the French Groupe d'Etudes des Mycoses Opportunistes were analysed. All suffered from haematological disease, most often acute leucaemia (n = 19). Twenty-two had received cytostatic chemotherapy and ten had undergone bone marrow transplantation. Prolonged aplasia and pancytopenia were present in 18 and 11 patients, respectively. Skin (61%) and blood (42%) were the sites most frequently involved. Fusarium solani (n = 7), Fusarium oxysporum (n = 7), Fusarium verticilloides (n = 7) were the species most frequently isolated. Nine antifungal treatments were used, associated with colony-stimulating factors in five cases. None was unambiguously superior to all the others. The overall mortality was 51·6% with a specific mortality ≥ 25·8%. The disseminated form of the infection...

Invasive Fusarium infections: a retrospective survey of 31 cases

In vitro susceptibility testing of Candida and Aspergillus spp. to voriconazole and other antifungal agents using Etest: results of a French multicentre study.

Objectifs. L'aspergillose invasive est une cause importante de morbidite et de mortalite chez les patients immuno-deprimes. En France, l'absence de donnees epidemiologiques concernant cette affection a suscite la creation d'un reseau de surveillance dans les villes francaises de province, parallelement a celui de l'Assistance Publique de Paris, dans le but de connaitre la distribution temporo-spatiale de cette affection, de mieux apprehender les facteurs de risque et enfin de situer le profil clinique et evolutif actuel de l'aspergillose invasive. Methode. L'enquete que nous rapportons ici s'est deroulee en 1990 et 1991 et elle recense tous les cas d'aspergillose invasive diagnostiques dans Il villes (19 hopitaux, 36 services), grâce a la collaboration des biologistes mycologues appartenant au Groupe d'Etude des Mycoses Opportunistes (GEMO). Cent trente-six dossiers ont ete retenus (81 en 1990, et 55 en 1991), et analyses. Resultats. Les aspergilloses invasives surviennent essentiellement en hematologie (65 %), ou en reanimation (22 %). Vingt-deux patients sur 136 ont subi une transplantation (6 transplantations d'organe, 16 greffes de moelle osseuse). Deux facteurs favorisants sont significativement plus frequents chez les patients d'oncohematologie par rapport aux autres patients: l'agranulocytose et la chimiotherapie. Si l'on compare les patients transplantes aux non transplantes, seul le traitement immunosuppresseur est significativement plus frequent. Dans 64 % des cas, il existe une notion de travaux d'amenagement ou de construction dans l'etablissement ou dans son voisinage, avec une legere predominance hivernale mais statistiquement non significative. L'infection fongique est suspectee cliniquement dans 80 % des cas avec un delai de 20 jours en mediane, entre l'admission et la suspicion clinique. La localisation initiale est essentiellement pulmonaire (93 %), avec un tableau clinique associant: fievre (72 %), dyspnee (57 %), toux (45 %), image radiologique evocatrice (73 %) et plus rarement, hemoptysie (15 %) et douleurs thoraciques (10 %). Aspergillus fumigatus est isole dans 78 % des cas, associe a une autre espece dans 8 % des cas. Le diagnostic d'aspergillose invasive est prouve histologiquement dans 41 % des cas, hautement probable et probable dans respectivement 30 et 29 % des cas. L'amphotericine B i.v. reste la prescription de premiere intention (83 %). L'itraconazole est utilise soit en monotherapie (13/44), soit associe a l'amphotericine B i.v. (19/44), ou encore en relais de celle-ci (12/44). Le taux global de mortalite est de 71,5 %. Conclusion. Cette etude, bien qu'imparfaite et non exhaustive, apporte les premieres donnees chiffrees sur l'importance de l'aspergillose invasive en France (hopitaux de l'Assistance Publique de Paris exclus).

Profil actuel de l'aspergillose invasive en France : Enquête du Groupe d'Etude des Mycoses Opportunistes (GEMO) dans 19 centres hospitaliers (11 villes

Détection d'antigène circulant de Candida par un test au latex

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Invasive Fusarium infections: a retrospective survey of 31 cases

In vitro susceptibility testing of Candida and Aspergillus spp. to voriconazole and other antifungal agents using Etest: results of a French multicentre study.

Profil actuel de l'aspergillose invasive en France : Enquête du Groupe d'Etude des Mycoses Opportunistes (GEMO) dans 19 centres hospitaliers (11 villes

Détection d'antigène circulant de Candida par un test au latex