Clinical treatment and management of invasive fungal disease in recipients of solid organ transplantation / 器官移植

With widespread application of solid organ transplantation (SOT), the incidence of postoperative invasive fungal disease (IFD) in SOT recipients has been increased year by year. In recent years, the awareness of preventive antifungal therapy for SOT recipients has been gradually strengthened. However, the problem of fungal resistance has also emerged, leading to unsatisfactory efficacy of original standardized antifungal regimens. Drug-drug interaction and hepatorenal toxicity induced by drugs are also challenges facing clinicians. In this article, the characteristics of drug-drug interaction and hepatorenal toxicity among triazole, echinocandin and polyene antifungal drugs and immunosuppressants were reviewed, and postoperative preventive strategies for IFD in different types of SOT recipients and treatment strategies for IFD caused by infection of different pathogens were summarized, aiming to provide reference for physicians in organ transplantation and related disciplines.

Comparison of different timing of empirical antifungal strategy in febrile neutropenic children with acute leukemia / 中国小儿急救医学

Objective:To compare the clinical value of early and deferred empirical antifungal strategies in febrile neutropenic children with acute leukemia.Methods:A total of 101 cases of febrile neutropenic children with acute leukemia hospitalized in Qilu Hospital of Shandong University from January 2019 to June 2021 were divided into two groups according to different empirical antifungal strategies.There were 41 cases in early group in which antifungal therapy was given within 4 days of fever, and 60 cases in deferred group in which antifungal therapy was not given within 4 days of fever.Outcomes such as time to stable defervescence, positive diagnosis rate of invasive fungal disease, incidence of severe pneumonia, rate of transference to PICU, exposure time and costs of antifungal agents, and infection-related hospitalization days were compared between two groups.Results:There were no significant differences in time to stable defervescence[5 (4, 7) days vs.5 (3, 7) days, P=0.986], positive diagnosis rate of invasive fungal disease[9.8%(4/41) vs.8.3%(5/60), P=1.000], incidence of severe pneumonia[19.5%(8/41) vs.10.0%(6/60), P=0.174], and rate of transference to PICU[2.4%(1/41)vs.0(0/60), P=0.406] between two groups.Exposure time of antifungal agents was longer in early group than that in deferred group[10 (6, 12)days vs.0 (0, 6)days, P<0.001]. Costs of antifungal agents were higher in early group than those in deferred group[0.78(0.51, 0.95)ten thousand yuan vs.0(0, 0.44)ten thousand yuan, P<0.001]. Infection-related hospitalization days were longer in early group than those in deferred group[16 (10, 21) days vs.9(6, 13)days, P<0.001]. Conclusion:For febrile neutropenic children with acute leukemia, clinical effect of early empirical antifungal strategy is not superior to that of deferred empirical antifungal strategy.Pediatricians should make reasonable antifungal decisions according to overall situation of patients.

Thymomodulin in association with antifungal drugs in the therapy of cats with disseminated cutaneous sporotrichosis: a prospective study / Associação de timomodulina na terapia de gatos com esporotricose cutânea disseminada: um estudo prospectivo

ABSTRACT: Feline sporotrichosis is a relevant mycose in veterinary medicine due to its severity and zoonotic potential and the fact that it can be difficult to treat. The immune status of the animal exerts influence on the prognosis of the disease and determines its clinical outcome. This study evaluated the efficacy of the immunomodulatory thymomodulin as an adjunct to antifungal therapy in cats with disseminated sporotrichosis; thymomodulin was used in association with itraconazole (ITL) and potassium iodide (KI) to treat this fungal disease in the feline patient. Thirty-one cats (n=31) diagnosed with disseminated cutaneous sporotrichosis were divided into two groups as follows: Group 1 (G1) (n=16), which included those animals that were treated with thymomodulin in association with ITL and KI, and Group 2 (G2) (n=15) which had pacientsthat received ITL and KI only. The response to different treatment modalities was assessed, considering the survival rate, time frame for the lesions to respond to therapy, and clinical improvement or deterioration according to a body condition score system. Animals from G1 had a survival rate of nearly 100% (93.6%) that was approximately twice higher than the survival rate of those animals from G2 (53%). Moreover, patients from G1 had a significantly better prognosis, improved body condition, and shorter time for remission of the extra cutaneous clinical signs (p<0.02). Our findings showed that the association of thymomodulin with ITL and KI improves the prognosis of cats with disseminated cutaneous sporotrichosis.

RESUMO: A esporotricose é uma das micoses de maior relevância na medicina veterinária, tanto pela sua gravidade, seu potencial zoonótico e seu difícil tratamento. Sabe-se que o aspecto imunológico do gato representa um fator prognóstico determinante. O objetivo desse trabalho foi avaliar a eficácia do imunomodulador timomodulina como adjuvante a terapia antifúngica, itraconazol (ITL) com iodeto de potássio (KI), em gatos com esporotricose disseminada. Trinta e um gatos (n=31) com esporotricose cutânea disseminada foram segregados em dois grupos, o grupo 1 (G1) (n=16) tratado com ITL, KI associada à timomodulina e o grupo 2 (G2) (n=15) apenas ITL e KI. Foi avaliada a resposta clínica aos diferentes tratamentos, levando em consideração a taxa de sobrevivência, tempo de resposta das lesões e progressão do escore de condição corporal. O G1 apresentou taxa de sobrevivência de quase 100% (93,6%), aproximadamente o dobro do encontrado no G2 (53%). Mais que isso, o G1 demonstrou significativamente melhor prognóstico, aprimoramento do escore de condição corporal e menor tempo para remissão dos sinais clínicos extracutâneos (p<0,02). Sendo assim, a associação da timomodulina ao ITL e KI melhora o prognóstico de gatos com esporotricose cutânea disseminada.

Synergic effect of simvastatin in combination with amphotericin B against environmental strains of Cryptococcus neoformans from northeastern Brazil: a prospective experimental study

BACKGROUND: Statins are used as cholesterol-lowering drugs and may also have direct antimicrobial effects. OBJECTIVE: To evaluate synergic interactions between simvastatin and both amphotericin B and fluconazole, against environmental strains of Cryptococcus neoformans isolated from captive birds' droppings. DESIGNAND SETTING: Experimental study conducted at Federal University of Piauí, Parnaíba, in collaboration with Federal University of Triângulo Mineiro, Uberaba, Brazil. METHODS: Statin susceptibility tests of Cryptococcus neoformans samples were performed as prescribed in standards. Interactions of simvastatin with amphotericin and fluconazole were evaluated using the checkerboard microdilution method. Presence of these interactions was quantitatively detected through determining the fractional inhibitory concentration index (FICI). RESULTS: Isolates of Cryptococcus neoformans were obtained from 30 of the 206 samples of dry bird excreta (14.5%) that were collected from pet shops and houses. Ten isolates were selected for susceptibility tests. All of them were susceptible to amphotericin and fluconazole. All presented minimum inhibitory concentration (MIC) > 128 µg/ml and, thus, were resistant in vitro to simvastatin. An in vitro synergic effect was shown through combined testing of amphotericin B and simvastatin, such that six isolates (60%) presented FICI < 0.500. Two isolates showed considerable reductions in MIC, from 1 µg/ml to 0.250 µg/ml. No synergic effect was observed through combining fluconazole and simvastatin. CONCLUSION: These results demonstrate that simvastatin should be considered to be a therapeutic alternative, capable of potentiating the action of amphotericin B. However, further studies are necessary to clarify the real effect of simvastatin as an antifungal agent.

Research progress on candidemia in patients with hematological malignancies / 中华临床感染病杂志

With the administration of antibacterial drugs , chemotherapy agents and corticosteroids , the incidence of candidemia in patients with hematological malignancies has been increased greatly in recent years.Due to the absence of typical symptoms , the high proportions of non-albicans candida, high antifungal resistance rate and high mortality, the candidemia in these patients remains a challenge in clinic practice.In this article we review the recent progress on the epidemiology , diagnosis and treatments , the antifungal resistance and its molecular basis of candidemia in patients with hematological malignancies .

Monetary costs and hospital burden associated with the management of invasive fungal infections in Mexico: a multicenter study

ABSTRACT Background: Invasive fungal infections (IFIs) affect >1.5 million people per year. Nevertheless, IFIs are usually neglected and underdiagnosed. IFIs should be considered as a public-health problem and major actions should be taken to tackle them and their associated costs. Aim To report the incidence of IFIs in four Mexican hospitals, to describe the economic cost associated with IFIs therapy and the impact of adverse events such as acute kidney injury (AKI), liver damage (LD), and ICU stay. Methods: This was a retrospective, transversal study carried-out in four Mexican hospitals. All IFIs occurring during 2016 were included. Incidence rates and estimation of antifungal therapy's expenditure for one year were calculated. Adjustments for costs of AKI were done. An analysis of factors associated with death, AKI, and LD was performed. Results: Two-hundred thirty-eight cases were included. Among all cases, AKI was diagnosed in 16%, LD in 25%, 35% required ICU stay, with a 23% overall mortality rate. AKI and LD showed higher mortality rates (39% vs 9% and 44% vs 18%, respectively, p < 0.0001). The overall incidence of IFIs was 4.8 cases (95% CI = 0.72-8.92) per 1000 discharges and 0.7 cases (95% CI = 0.03-1.16) per 1000 patients-days. Invasive candidiasis showed the highest incidence rate (1.93 per 1000 discharges, 95% CI = −1.01 to 2.84), followed by endemic IFIs (1.53 per 1000 discharges 95% CI = −3.36 to 6.4) and IA (1.25 per 1000 discharges, 95% CI = −0.90 to 3.45). AKI increased the cost of antifungal therapy 4.3-fold. The total expenditure in antifungal therapy for all IFIs, adjusting for AKI, was $233,435,536 USD (95% CI $6,224,993 to $773,810,330). Conclusions: IFIs are as frequent as HIV asymptomatic infection and tuberculosis. Costs estimations allow to assess cost-avoidance strategies to increase targeted driven therapy and decrease adverse events and their costs.

Tratamiento exitoso de una fusariosis diseminada en un paciente neutropénico febril con terapia antifúngica combinada de voriconazol más anfotericina B deoxicolato / Successful treatment of disseminated fusariosis in a febrile neutropenic patient with combined antifungal therapy of voriconazol plus amphotericin B deoxycholate

Resumen Presentamos el caso clínico de un paciente con una leucemia linfoblástica aguda (LLA) que desarrolló una fusariosis diseminada por Fusarium verticillioides durante un episodio prolongado de neutropenia febril post quimioterapia. Fue exitosamente tratado cuando se usó terapia combinada de voriconazol más anfotericina B deoxicolato.

We report a case of a patient with acute lymphoblastic leukemia (ALL), who developed a disseminated infection by Fusarium verticillioides during chemotherapy-induced neutropenia. He was successfully treated only after combination therapy with voriconazole plus amphotericin B deoxycolate was used, but not when these compounds were used in an isolated form.

Actualización en el diagnóstico y manejo de aspergilosis invasora en pacientes adultos / Update in the diagnostic and therapeutic approach of invasive aspergillosis in adult population

Resumen La enfermedad fúngica invasora producida por Aspergillus spp., es la infección por hongos filamentosos más frecuentemente reportada en individuos inmunocomprometidos y responsable de una muy alta mortalidad en este grupo de pacientes. En los últimos años se han logrado importantes avances, tanto en su diagnóstico como terapéuticos. Al momento actual se ha identificado una serie de factores de riesgo asociados a su desarrollo, permitiendo la categorización de pacientes en condición de alto, intermedio y bajo riesgo de aspergilosis invasora (AI); y también se han establecido criterios diagnósticos que consideran factores del hospedero, laboratorio micológico tradicional, biomarcadores como galactomanano y 1→3-β-d-glucano, junto a la mejor comprensión e interpretación de las imágenes tomográficas que han permitido consensuar las categorías diagnósticas. Esto, sumado a la incorporación de nuevos antifúngicos y estrategias terapéuticas en diferentes escenarios, ha permitido lograr una disminución de la mortalidad asociada. En este artículo se realiza una puesta al día de los aspectos epidemiológicos, los factores de riesgo, el diagnóstico, la prevención y profilaxis además del enfrentamiento terapéutico, incluyendo las estrategias de uso de terapia antifúngica empírica, precoz y dirigida, así como los aspectos más relevantes de los antifúngicos de primera elección y alternativos para el manejo actualizado de AI.

The invasive fungal disease produced by Aspergillus spp., is the infection by filamentous fungi most frequently reported among immunocompromised individuals and responsible for a very high mortality in this group of patients. In recent years, important advances have been made both from the diagnostic and therapeutic point of view. At present, a series of risk factors associated with its development have been identified, allowing the categorization of patients in high, intermediate and low risk of invasive aspergillosis (IA); and diagnostic criteria have also been established that consider factors of the host, traditional mycological laboratory, biomarkers such as galactomannan and 1→3-β-d-glucan, together with the better understanding and interpretation of the tomographic images that have allowed to reach a consensus on the diagnostic categories. This added to the incorporation of new antifungals and therapeutic strategies in different scenarios, have allowed decreasing the associated mortality. In this review, are updated the epidemiological aspects, the risk factors, the diagnosis, prevention and prophylaxis as well as the therapeutic confrontation, including strategies for the use of empirical, precocious and directed antifungal therapy, as well as the most relevant aspects of the first-choice and alternative antifungals for the IA management.

Evaluación de la terapia empírica antifúngica en pacientes con riesgo para candidemia en la unidad de cuidados intensivos / Evaluation of antifungal empirical therapy in patients with candidemia risk in the intensive care unit

La candidemia es una importante causa de evolución deletérea de los pacientes críticamente enfermos en las unidades de cuidados intensivos. A pesar de la importancia del diagnóstico temprano, en la mayor parte de los casos éste se hace de manera presuntiva. Dada la importancia que representa para la vida del paciente y la dificultad en el diagnóstico, se debe considerar el inicio de su tratamiento en la mayoría de los casos de manera empírica basado en factores de riesgo. Se evaluó la terapia empírica antifúngica en pacientes con factores de riesgo para candidemia ingresados en la Unidad de Cuidados Intensivos de la ciudad hospitalaria “Dr. Enrique Tejera” Enero-Junio 2014. Es un estudio de tipo prospectivo, observacional y de corte transversal, la muestra estuvo constituida por 79 pacientes ingresados en la Unidad de cuidados Intensivos de la ciudad hospitalaria “Dr. Enrique Tejera”, en el periodo Enero-Junio 2014, se excluyó a los pacientes neutropénicos y con patologías hematoncológicas. Los pacientes registraron una edad promedio de 32 años, el 60,8% del sexo masculino, el factor de riesgo para candidemia más común fue el uso de catéteres venosos, 35 recibieron terapia empírica antifúngica y de estos, 14 evolucionaron satisfactoriamente. Un total de 27 pacientes (34,1%) tenían Candida Score >3 puntos, 6 de ellos mejoró posterior a la indicación de terapia empírica. La mayoría de los pacientes presentó más de un factor de riesgo para candidemia, los pacientes presentaron en general respuesta óptima a la terapia empírica, el Candida Score no fue un predictor para el éxito de la terapia empírica.

Candidemia is an important cause of deleterious changes in critically ill patients in intensive care units. Despite the importance of early diagnosis, in most cases a presumptive diagnosis is made. Given the risk it represents for the life of the patient and the difficulty in diagnosing it, in most cases candidemia treatment should be started empirically based on risk factors. Empirical anti-fungal therapy was assessed in patients with risk factors for candidemia admitted to the Intensive Care Unit of the “Dr. Enrique Tejera Hospital” between January and June 2014. In this prospective, observational, cross-sectional study, the sample consisted of 79 patients admitted to the intensive care unit. Neutropenic and oncology patients were excluded. Patients reported an average age of 32 years, 60.8% male. The most common risk factor for candidemia was use of central vein catheters. 35 received empirical antifungal therapy and of these 14 progressed satisfactorily. A total of 27 patients had Candida score >3 points. Most patients had more than one risk factor for candidemia; patients had an overall optimal response to empirical therapy. Candida Score was not a predictor of the success of empirical therapy.

The treatment f coccidioidomycosis / Tratamento da coccidioidomicose

SUMMARYTherapy of coccidioidomycosis continues to evolve. For primary pulmonary disease, antifungal therapy is frequently not required while prolonged courses of antifungals are generally needed for those in whom extrathoracic disseminated has occurred. Intravenous amphotericin B should be reserved for those with severe disease. Oral triazole antifungals have had a great impact on the management of coccidioidomycosis. Both fluconazole and itraconazole at 400 mg daily have been effective for various forms of coccidioidomycosis, including meningitis, although relapse after therapy is discontinued is a problem. Individuals with suppressed cellular immunity are at increased risk for symptomatic coccidioidomycosis and they include those with HIV infection, those on immunosuppressive medications, and those who have received a solid organ transplant. Pregnant women and African-American men have been identified as two other groups who are at an increased risk for symptomatic and severe infection.

RESUMOA terapia da coccidioidomicose continua a evoluir. Para a doença pulmonar primária, o tratamento antifúngico frequentemente não é necessário, enquanto períodos prolongados de tratamento antifúngico são geralmente necessários para aqueles nos quais houve disseminação extratorácica. A anfotericina B intravenosa deve ser reservada para pacientes com doença grave. Antifúngicos triazólicos orais têm tido um grande impacto no manejo da coccidioidomicose. Tanto fluconazol quanto itraconazol em doses diárias de 400 mg foram eficazes contra várias formas de coccidioidomicose, incluindo a meníngea, embora recaídas após a interrupção da terapia ainda constituam um problema. Indivíduos com supressão da imunidade celular apresentam risco aumentado para a coccidioidomicose sintomática, incluindo pacientes infectados pelo HIV, em uso de medicações imunossupressoras, e os que receberam transplantes de órgãos sólidos. Mulheres grávidas e homens afro-americanos foram identificados como dois outros grupos que apresentam risco aumentado de infecção sintomática e grave.

Report of 27 culture-positive fungal endophthalmitis / 中国感染与化疗杂志

Objective To report the clinical features and treatment outcomes of 27 patients with fungal endophthalmitis (27 eyes)over a five year period.Methods The authors retrospectively reviewed the etiology,direct smear examination,fungal cul-ture and treatments of 27 patients with culture-proven fungal endophthalmitis at the affiliated Hospital of Medical College Qing-dao University from 2007 to 2012.Results Exogenous infection was defined in 21 patients (77.8%),including 20 associated with penetrating wound,and 1 following cataract surgery.Endogenous infection was found in 6 patients (22.2%),including 3 associated with recent use of high-dose steroids,1 after abortion,1 following pelvic fracture,and 1 with long-term use of im-munosuppressive agents.Fungal hyphae were found in 17 smears of 27 samples (63.0%)by direct microscopic examination. The fungal strains cultured from 27 samples belonged to 8 genus and 12 species.The most common isolates were Aspergillus , Fusarium and Candida species.A.flavus (22.2%)and A.fumigatus (18.5%)were the predominant Aspergillus species. F .moniliforme (14.8%)and F .oxysporum (11 .1 %)were the most predominant Fusarium species.Two eyes were eviscer-ated immediately due to the serious condition.Among the other 25 eyes,22 (88.0%)got improvement after at least one of such treatments as intravitreal injection of antifungal agent,vitrectomy or penetrating keratoplasty (PK).Conclusions Exoge-nous fungal endophthalmitis is the most common type of fungal endophthalmitis in this hospital.Penetrating wound is the main cause of such infections.Microscopic examination of hyphae and fungal culture were effective for the diagnosis of fungal endophthalmitis.Aspergillus is the predominant pathogens, followed by Fusarium.Intravitreal injection of antifungal a-gent combined with vitrectomy is an effective treatment of fungal endophthalmitis.

Clinical Outcomes and Prognostic Factors of Empirical Antifungal Therapy with Itraconazole in the Patients with Hematological Malignancies: A Prospective Multicenter Observational Study in Korea

PURPOSE: To identify prognostic factors for the outcomes of empirical antifungal therapy, we performed a multicenter, prospective, observational study in immunocompromised patients with hematological malignancies. MATERIALS AND METHODS: Three hundred seventy-six patients (median age of 48) who had neutropenic fever and who received intravenous (IV) itraconazole as an empirical antifungal therapy for 3 or more days were analyzed. The patients with possible or probable categories of invasive fungal disease (IFD) were enrolled. RESULTS: The overall success rate was 51.3% (196/376). Age >50 years, underlying lung disease (co-morbidity), poor performance status [Eastern Cooperative Oncology Group (ECOG) > or =2], radiologic evidence of IFD, longer duration of baseline neutropenic fever (> or =4 days), no antifungal prophylaxis or prophylactic use of antifungal agents other than itraconazole, and high tumor burden were associated with decreased success rate in univariate analysis. In multivariate analysis, age >50 years (p=0.009) and poor ECOG performance status (p=0.005) were significantly associated with poor outcomes of empirical antifungal therapy. Twenty-two patients (5.9%) discontinued itraconazole therapy due to toxicity. CONCLUSION: We concluded that empirical antifungal therapy with IV itraconazole in immunocompromised patients is effective and safe. Additionally, age over 50 years and poor performance status were poor prognostic factors for the outcomes of empirical antifungal therapy with IV itraconazole.

Success Rate and Risk Factors for Failure of Empirical Antifungal Therapy with Itraconazole in Patients with Hematological Malignancies: A Multicenter, Prospective, Open-Label, Observational Study in Korea

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462)

Candida albicans biofilm inhibition by synergistic action of terpenes and fluconazole.

The current treatment options for Candida albicans biofilm-device related infections are very scarce due to their intrinsic increased tolerance to antimycotics. The aim of this work was to study synergistic action of terpenes (eugenol, menthol and thymol) with fluconazole (FLA) on C. albicans biofilm inhibition. The minimum inhibitory concentration (MIC) assayed using CLSI M27-A3 broth micro-dilution method showed antifungal activity against C. albicans MTCC 227 at a concentration of 0.12 % (v/v) for both thymol and eugenol as compared to 0.25 % (v/v) for menthol. FLA was taken as positive control. The effect of these terpenes on metabolic activity of preformed C. albicans biofilm cells was evaluated using 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay in 96-well polystyrene microtiter plate. Thymol and eugenol were more effective at lower concentrations of ≥ 1.0 % (v/v) than menthol. Synergistic studies using checkerboard micro-dilution assay showed fractional inhibitory concentration index (Σ FIC=0.31) between thymol/FLA followed by eugenol/FLA (Σ FIC=0.37) and menthol/FLA (Σ FIC<0.5) against pre-formed C. albicans biofilms. Thymol with fluconazole showed highest synergy in reduction of biofilm formation than eugenol and menthol which was not observed when their activities were observed independently. Adherence assay showed 30% viability of C. albicans cells after 2 h of treatment with 0.05 % (v/v) thymol/FLA. Effect of thymol/FLA on C. albicans adhesion visualized by SEM micrographs showed disruption in number of candidal cells and alteration in structural design of C. albicans. Thus, the study demonstrated synergistic effect of terpenes with fluconazole on C. albicans biofilm, which could be future medications for biofilm infections.

Risk Factors for Mortality in Patients with Candidemia and the Usefulness of a Candida Score / 대한의진균학회지

BACKGROUND: Although effective antifungal agents for the treatment of candidemia have recently been introduced, the mortality rate attributed to candidemia remains high (19~49%). OBJECTIVE: This study aimed at evaluating the risk factors for mortality in patients with candidemia and at assessing the usefulness of a Candida Score in these patients. METHODS: A cohort of patients with positive blood cultures for Candida species was retrospectively analyzed at Soonchunhyang University Hospital, a 750-bed teaching hospital, from May 2003 to February 2012. The Candida Score was calculated by assigning 1 point to any of total parenteral nutrition (TPN), surgery, or multifocal Candida species colonization, and 2 points to severe sepsis. RESULTS: Sixty patients (68.3% men; mean age (standard deviation [SD]), 61.8 [18.9] years) with blood cultures positive for Candida species were identified. Most patients had been admitted to an intensive care unit (48 [80%]), were receiving broad-spectrum antibiotics (37 [61.7%]), had TPN (29 [48.3%]), had diabetes mellitus (23 [38.3%]), and were receiving hemodialysis (10 [16.7%]). The mean (SD) Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 19.60 (8.8). Twenty-three patients (38.3%) had a Candida Score >2.5. The Candida species causing infection included C. albicans (41 [68.3%]), C. tropicalis (7 [11.7%]), C. parapsilosis (4 [6.7%]), C. krusei (3 [5%]), C. glabrata (3 [5%]), C. guilliermondii (1 [1.7%]), and C. catenulata (1 [1.7%]). Only 32 patients (53.3%) received adequate antifungal treatment. The candidemia-related mortality rate was 61.7% (n = 37 patients). Multivariate logistic regression analysis demonstrated that a high APACHE II score (adjusted odds ratio [aOR], 1.2; 95% confidence interval [95% CI], 1.0~1.3; p = 0.01), presence of a malignancy (aOR, 14.8; 95% CI, 2.5~88.0; p = 0.003), and treatment with an antifungal agent (aOR, 0.2; 95% CI, 0.0~1.0; p = 0.048) were associated with disease-related mortality. CONCLUSION: The risk factors for mortality in patients with candidemia are a high APACHE II scores and presence of a malignancy. However, the sensitivity of the Candida Score was not high (38.3%). New methods to rapidly identify candidemia and avoid delays in treatment with appropriate antifungal therapy are needed.

Efficacy of Autologous Tragal Perichondrium Graft after Proper Antifungal Treatment in Fungal Necrotizing Scleritis

PURPOSE: To compare the efficacy of an autologous tragal perichondrium graft after proper antifungal treatment between 2 cases of fungal necrotizing scleritis. CASE SUMMARY: A 58-year-old female was referred to our clinic with fungal necrotizing scleritis of the left eye which had occurred after pterygium removal. Scleral melting around calcification was observed. After proper treatment with antifungal agents, the authors performed autologous tragal perichondrium graft; however, 3 months after surgery, a necrosis of sclera recurred and the, patient underwent additional treatment with antifungal agents. No complication has been observed up to 3 months postoperatively. A 36-year-old male visited our clinic with ocular pain and decreased visual acuity associated with necrotizing scleritis which occurred after local conjunctival resection. After 4 weeks of antifungal treatments, scleral lesions were stabilized and the authors confirmed negative findings with repetitive fungus smear test. Therapeutic autologous tragal perichondrium graft was performed, and no complication was observed 3 months postoperatively. CONCLUSIONS: When treating a patient with fungal necrotizing scleritis, preoperative antifungal therapy and confirmation of negative findings in repetitive fungus smear test are important. Autologus tragal perichondrium graft accompanied with proper antifungal therapy is an effective treatment of fungal necrotizing scleritis.

Cryptococcal meningitis in HIV negative pregnant women: case report and review of literature / Meningite criptocóccica em gestante HIV negativa: relato de caso e revisão da literatura

INTRODUCTION: Cryptococcosis has become an important entity due to the epidemic of AIDS and therefore it is a significant opportunistic infection. However, there are case reports of cryptococcal meningitis in immune competent pregnant women. Since pregnancy is considered a period of relative immunosuppression, which likely prevents fetal rejection, this could explain the occurrence of opportunistic infections. OBJECTIVE: To report a case of cryptococcosis, and review all cases involving pregnancy and neurocryptococcal infection in immune competent pregnant patients. METHODS: Case report and systematic review of the literature using the MEDLINE and SciELO databases. DISCUSSION: A total of 27 patients were analyzed from 19 studies. The mean age at diagnosis was 26.4 years. There were six patients in their first trimester of pregnancy, 10 in the second, eight in the third and three post-partum. The most prevalent symptoms were headache (85.2 percent), altered vision (44.4 percent), altered mental status (44.4 percent), nausea (40.7 percent) and fever (33.3 percent). There were nine deaths (33.3 percent). Most of the patients received intravenous amphotericin B as treatment (77.8 percent). The majority (66.6 percent) of the patients accomplished a term delivery with healthy infants. CONCLUSION: Cryptococcal meningitis should be considered during pregnancy in cases of unexplained headache, altered vision, altered mental status, nausea and fever. Patients with a confirmed diagnosis should be admitted and treated with amphotericin B.

INTRODUÇÃO: Com a epidemia da AIDS, a neurocriptococose foi melhor estudada e considerada infecção fúngica oportunista. No entanto, há casos descritos de gestantes acometidas, apesar de imunocompetentes. A gestação, por si só, pode ser considerada um período de imunossupressão, para adaptação materno-fetal, o que poderia predispor à instalação de certas infecções. OBJETIVOS: Relato de caso de gestante com neurocriptococose e revisão sistemática dos casos descritos na literatura desta patologia durante a gestação, em pacientes imunocompetentes. METODOLOGIA: Revisão sistemática com busca MEDLINE e SciELO. RESULTADOS: Foram analisadas 27 pacientes com diagnóstico de neurocriptococse na gestação. A média de idade foi 26,4 anos. Seis pacientes estavam no primeiro trimestre de gravidez ao diagnóstico, 10 no segundo, oito no terceiro e três eram puérperas. O sintoma mais prevalente foi cefaléia (85,2 por cento), seguido por alteração visual (44,4 por cento), confusão mental (44,4 por cento), náusea (40,7 por cento) e febre (33 por cento). Houve nove óbitos maternos (33,3 por cento). Vinte e uma pacientes foram tratadas com anfotericina B (77,8 por cento). A maioria dos casos evoluiu com gestação a termo, com recém-nascidos saudáveis (66,6 por cento). CONCLUSÕES: Neurocriptococose deve ser um diagnóstico a se considerar na gestação, nos casos de cefaléia, alteração visual, confusão mental, náusea e febre persistentes, sendo indicada terapia intensiva e uso de anfotericina B.

Study of Empirical Antifungal Therapy in Febrile Neutropenia and Invasive Fungal Infection after Introduction of Novel Antifungal Agents / 대한의진균학회지

BACKGROUND: Patients with prolonged empirical broad spectrum antibiotics for febrile neutropenia (FN) with cancer, inevitably have increased risk of invasive fungal infections owing to the altered endogenous microbial environment. OBJECTIVE: The purpose of this study is to evaluate the impact of empirical antifungal therapy on occurrence of invasive fungal infections (IFIs) during FN with cancer. METHODS: We retrospectively reviewed medical records of patients with FN after cytotoxic chemotherapy due to cancer from July, 2003 to June, 2007. RESULTS: We identified 91 patients with FN after cytotoxic chemotherapy. Most common underlying conditions were lymphoma (20/91, 22%) and leukemia (20/91, 22%). IFIs occurred in 10% (9/91). In a comparison of patients with empirical antifungal therapy with no antifungal therapy, the duration of neutropenia was significantly increased with IFIs (p=0.09). The mortality of IFIs was 55.5% (5/9). CONCLUSION: We found that the duration of FN than empirical antifungal therapy affected occurrence of IFIs.

Chronic meningitis by histoplasmosis: report of a child with acute myeloid leukemia

Meningitis is a common evolution in progressive disseminated histoplasmosis in children, and is asymptomatic in many cases. In leukemia, the impaired of the T cells function can predispose to the disseminated form. The attributed mortality rate in this case is 20 percent-40 percent and the relapse rate is as high as 50 percent; therefore, prolonged treatment may be emphasized. We have described a child with acute myeloid leukemia (AML), that developed skin lesions and asymptomatic chronic meningitis, with a good evolution after prolonged treatment with amphotericin B deoxycholate followed by fluconazole.

Intravenous Itraconazole vs. Amphotericin B Deoxycholate for Empirical Antifungal Therapy in Patients with Persistent Neutropenic Fever

BACKGROUND: Amphotericin B dexoycholate is currently the standard empirical antifungal therapy for neutropenic patients with hematologic malignancies and who also have persistent fever that does not respond to antibacterial therapy. The antifungal triazoles offer a potentially safer and effective treatment alternative to Amphotericin B dexoycholate. METHODS: We assessed the efficacy and safety of intravenous itraconazole, as compared with the efficacy and safety of amphotericin B deoxycholate, as an empirical antifungal therapeutic agent in a matched case-control clinical trial from June 2004 to August 2005. RESULTS: Efficacy was evaluated in 96 patients (48 received itraconazole and 48 received amphotericin B deoxycholate) and all the patients who received the study drugs were evaluated for safety. The baseline demographic characteristics were well matched. The overall success rates were 47.9% for itraconazole and 43.8% for amphotericin B deoxycholate (% difference: 4.1 % [95% confidence interval for the difference: -15.8 to 24]), which fulfilled the statistical criteria for the non-inferiority of itraconazole. The proportions of patients who survived for at least seven days after discontinuation of therapy or who were prematurely discontinued from the study were not significantly different between the two groups. The rates of breakthrough fungal infections and resolution of fever during neutropenia were similar in both groups. More patients who received amphotericin B deoxycholate developed nephrotoxicity, hypokalemia or infusion-related events than did those patients who received itraconazole (nephrotoxicity: 16.7% vs. 1.8%, hypokalemia: 66.7% vs. 24.6%, and infusion-related events: 41.7% vs. 3.5%, respectively). CONCLUSIONS: Intravenous itraconazole is as effective as amphotericin B deoxycholate and it is generally better tolerated than amphotericin B deoxycholate when it is given as empirical antifungal therapy for Korean patients with persistent neutropenic fever.