Subcutaneous phaeohyphomycosis due to cladophialophora bantiana: a first case report in an immunocompetent patient in Latin America and a brief literature review

Abstract We report a rare case of subcutaneous phaeohyphomycosis caused by Cladophialophora bantiana in an immunocompetent patient in Amazonas, Brazil. This dematiaceous fungus has been mainly associated with life-threatening infections affecting the central nervous systems of immunosuppressed patients. We present the clinical, laboratory, and therapeutic aspects, and in vitro susceptibility test results for different antifungal drugs. A brief review of the cases reported in the literature over the past 20 years has also been discussed. According to the literature review, the present case is the first report of subcutaneous phaeohyphomycosis due to C. bantiana in an immunocompetent patient in Latin America.

Evaluación de la indicación, consumo y costos de antifúngicos en un hospital pediátrico de Chile / Evaluation of the prescription, consumption and costs of antifungal drugs in a pediatric hospital in Chile

Resumen Introducción: El incremento de la enfermedad fúngica invasora (EFI) en pacientes inmunocomprometidos ha conducido a la frecuente prescripción de fármacos altamente activos pero de elevado costo económico. Objetivo: Caracterizar el uso de antifúngicos, evaluar su indicación y determinar consumo y costos asociados. Métodos: Estudio descriptivo, retrospectivo, desde enero de 2015 a abril de 2016. Auditoría de prescripciones y revisión de fichas clínicas; cada prescripción se clasificó de acuerdo a si correspondía a una EFI posible, probable o probada. Se calcularon consumos y costos de tratamientos. Resultados: Se auditaron 152 prescripciones de antifúngicos en 79 pacientes. El costo total de los medicamentos antifúngicos fue de US$ 714.413. El 52,1% del gasto (US $ 372.319) correspondió a indicaciones en EFI probada, 10,7% (US $ 76.377) EFI probable, 0.8% (US $ 5.638) no-EFI, 12,2% (US $ 87.459) EFI posibles y 1,5% (US $ 10.896) EFI descartada y 22,6% (US$ 161.723) fue profilaxis. El mayor consumo fue en indicaciones relacionadas a EFI probada con un DOT probada de 10,54 días, siendo anfotericina B liposomal y voriconazol iv los fármacos con mayor consumo con un DOTprobada AnBL de 3,15 y DOT probada voriconazol iv de 3,01. Conclusiones: El consumo de medicamentos antifúngicos genera altos costos correspondiente al 12% del presupuesto total de farmacia de nuestra institución. El gasto se asoció principalmente a indicaciones en EFI probadas, voriconazol y anfotericina B liposomal los con mayor consumo, lo que sumado a su alto costo y días prolongados de terapia generan un gran impacto en el presupuesto.

Background: The increase of invasive fungal disease (IFD) in immunocompromised patients has led to the frequent prescription of highly active antifungal drugs but with a high economic cost. Aim: To characterize the use of antifungals drugs, evaluate its prescription and determine consumption and associated costs. Methods: Retrospective descriptive study from January 2015 to April 2016. Audit of prescriptions and review of clinical files. Each prescription was classified according to whether it corresponded to a possible, probable or proven invasive fungal disease (IFD). Consumptions and treatment costs were calculated. Results: 152 antifungal prescriptions were audited in 79 patients. The total cost of antifungal medications was US $ 714,413. 52.1% of the expenditure (US $ 372,319) corresponded to indications in proven IFD, 10.7% (US $ 76,377) probable IFD, 0.8% (US $ 5,638) non-IFI, 12.2% (US $ 87,459) IFD possible and 1.5% (US $ 10,896) non-IFD and 22.6% (US $ 161,723) was prophylaxis. The highest consumption was in indications related to IFD tested with a proven DOT of 10.54 days, with liposomal amphotericin B and iv voriconazole the drugs with the highest consumption with a DOT probable_AnBL of 3.15 and DOT proven voriconazole iv of 3.01. Conclusions: The consumption of antifungal drug medications generates high costs at 12% of the total pharmacy budget of our institution. The expense was associated mainly with the indications in IFI tested the voriconazole and amphotericin B liposomal with the highest consumption which added to its high cost and prolonged days of general therapy a big impact in the budget.

Óleos essenciais e vegetais no controle in vitro de Colletotrichum gloeosporioides / Essential and vegetal oils in the in vitro control of Colletotrichum gloeosporioides

RESUMO O objetivo deste trabalho foi avaliar a atividade antifúngica de óleos essenciais e vegetais no controle in vitro de Colletotrichum gloeosporioides, agente causal da antracnose em pós-colheita de frutíferas. Treze óleos essenciais foram utilizados em concentrações de 0,00%, 0,40%, 0,80%, 1,70%, 3,20%, 6,25%, 12,50%, 25,00%, 50,00% e 100,00%, e uma linhagem padrão de Colletotrichum gloeosporioides. Foram avaliadas a concentração inibitória mínima e a concentração mínima fungicida a fim de caracterizar o potencial de cada um dos óleos essenciais avaliados. Verificou-se que os óleos utilizados apresentaram atividade fungicida em diferentes concentrações, as quais variaram de 0,80% (melaleuca), 3,20%, (eucalipto), 6,25% (limão, capim limão, cravo da índia, canela e nim), 12,5% (hortelã e citronela), 25% (copaíba), 50% (coco e gengibre) e 100% (manjericão). O óleo de nim apresentou maior redução da carga microbiana em função do tempo de exposição, sendo necessários 30 minutos para anulação da contagem microbiana. O efeito antifúngico dos óleos essenciais, para controle de Colletotrichum gloeosporioides, depende da planta e da concentração empregada.

ABSTRACT This study aimed to evaluate the antifungal effect of essential and vegetal oils in the in vitro control of Colletotrichum gloeosporioides, a causal agent of anthracnose in fruit postharvest. Thirteen essential oils were used at concentrations of 0.00%, 0.40%, 0.80%, 1.70%, 3.20%, 6.25%, 12.50%, 25.00%, 50.00%, and 100.00%, and also a standard strain of Colletotrichum gloeosporioides, The minimum inhibitory concentration and minimum fungicidal concentration were assessed to characterize the potential of each of the essential oils tested. We found that used oils showed fungicidal activity at different concentrations, which varied in 0.80% (Melaleuca alternifólia), 3.20%, (Eucalyptus globulus), 6.25% (Citrus limonium, Cymbopogon citratus, Syzygium aromaticum, Cinnamomum zeylanicum, and Azadirachta indica), 12.5% (Mentha piperita and Cymbopogon winterianus), 25% (Copaifera langsdorfii), 50% (Cocos nucifera and Zingiber officinale), and 100% (Ocimum basilicum). The Azadirachta indica oil showed greater reduction of microbial load because of the exposure time, and took 30 minutes for annulment of microbial count. The antifungal effect of essential oils to control Colletotrichum gloeosporioides depends on the plant and quantity of concentration.

Antifungal activity using medicinal plant extracts against pathogens of coffee tree / Atividade antifúngica utilizando extratos de plantas medicinais contra fitopatógenos do cafeeiro

Generally, the medicinal plants have antifungal substances that can be used for the plant protection against phytopathogens. The objective of this study was to know the efficiency of aqueous extracts from medicinal plants against the major etiological agents of coffee tree. The aqueous extracts used were extracted from bulbs of Allium sativum, leaves of Vernonia polysphaera, Cymbopogon citratus, Cymbopogon nardus, Cordia verbenacea, Eucalyptus citriodora, Ricinus communis, Azadirachta indica, Piper hispidinervum and flower buds of Syzygium aromaticum. The etiological agents considered for this study were Cercospora coffeicola, Colletotrichum gloeosporioides, Fusarium oxysporum, Phoma tarda, Rhizoctonia solani and Hemileia vastatrix. The screening for harmful extracts was done based on mycelial growth and conidial germination inhibition. All experiments performed were in vitro conditions. The inhibition of mycelial growth was performed mixing the extracts with the PDA. This mixture was poured in Petri dishes. On the center of the dishes was added one PDA disc with mycelium. It was incubated in a chamber set to 25ºC. The evaluation was done daily by measuring the mycelial growth. The germination assessment was also performed with Petri dishes containing agar-water medium at 2%. These were incubated at 25ºC for 24 hours. After this period the interruption of germination was performed using lactoglycerol. The experiments were conducted in a completely randomized design. The most effective plant extracts against the micelial growth and conidial germination were V. polysphaera, S. aromaticum and A. sativum.

Geralmente, as plantas medicinais têm substâncias antifúngicas que podem ser utilizadas para a proteção das plantas contra fitopatógenos. O objetivo deste estudo foi conhecer a eficiência de extratos aquosos de plantas medicinais contra os principais agentes etiológicos do cafeeiro. Os extratos aquosos utilizados foram extraídos de bulbos de Allium sativum, folhas de Vernonia polysphaera, Cymbopogon citratus, Cymbopogon nardus, Cordia verbenacea, Eucalyptus citriodora, Ricinus communis, Azadirachta indica, Piper hispidinervum e botões florais de Syzygium aromaticum. Os agentes etiológicos considerados neste estudo foram Cercospora coffeicola, Colletotrichum gloeosporioides, Fusarium oxysporum, Phoma tarda, Rhizoctonia solani e Hemileia vastatrix. A triagem dos extratos foi realizada com base no crescimento micelial e na inibição da germinação de conídios. Todos os experimentos foram realizados em condições in vitro. A inibição do crescimento micelial foi realizada misturando-se os extratos com PDA. Esta mistura foi vertida em placas de Petri. No centro das placas foi adicionado um disco de PDA com micélio. Incubou-se em câmara programada para 25°C. A avaliação foi feita diariamente através da medição do crescimento micelial. O experimento sobre a germinação também foi realizado com placas com meio ágar-água a 2%. Estas foram incubadas durante 24 horas. Após este período, a interrupção da germinação foi realizada utilizando lactoglicerol. Os experimentos foram conduzidos em delineamento inteiramente casualizado. Os extratos de plantas mais eficazes contra o crescimento micelial e germinação de conídios foram V. polysphaera, S. aromaticum e A. sativum.

Antifúngicos de uso clínico, análisis de un laboratorio de micología / Antifungal therapy for clinical use, analysis of a mycology laboratory

Se hace una revisión exhaustiva desde un punto de vista del laboratorio de micología al uso de los antifúngicos clásicos tanto de uso clínico como tópico para el uso en humano como el uso en animales además se describen los nuevos antifúngicos que han aparecido en el mercado como el Voriconazol, Terbinafina y las Equinocandinas, cuyo futuro es promisorio tanto en infecciones superficiales y sistémicas.

Changing strategies for treatment of systemic mycoses

There have been a number of changes in strategies in antifungal therapy in the past few years. AIDS related mycoses hade decreased, and the increse of fluconazole resistant Candida albicans may be slowing because fewer severely immune depressed patients require constant fluconazole suppression. Candida species continue to be relatively commun blood culture isolates. About half of these are C.albicans and half non-albicans species. In recent years, we have moved from the use of amphotericin B to fluconazole for initial treatment of candidemia. We have seen fluconazole resistent isolates emerge, primarily C.glabrata and a few C.krusei, but also C.albicans. It is unclear whether the increasing use of fluconazole in intensive care units will worsen this problem. There appears to be no advantage for the lipid formulations of amphotericin B, though they are useful to reduce or prevent renal toxicity. In the United States and Europe, prevention and treatment of aspergillosis have become increasingly important. There are increasing data suggesting that lipid formulations are more effective for both treatment and prevention of invasive disease in the most vulnerable patients with this infection. Renal toxicity is reduced but not avoided by use of the lipid formulations of amphotericin B. For those patients with less acutely progressing disease, the triazoles may be effective options. It is unclear at present whether itraconazole, voriconazole, or posaconazole will be the most favored drug. One promising new class, now in clinical trials, is the echinocandin group. Other agents, such as the sordarins, the chitin synthase inhibitors, and topoisomerase inhibitors, have promise but are much earlier in development. Unfortunately, we still have >50 (percent) treatment failure with acute invasive aspergillosis, and 20 (percent)-30 (percent) failures with candidemia. Now that we have multiple classes of antifungal drugs available, and others in preclinical trials, it would be advantageous to begin more active exploration of conbination therapy with antifungals and with combined immune modulators and antifungals.