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Acta neurol. colomb ; 37(1,supl.1): 90-100, mayo 2021. tab, graf
Article in Spanish | LILACS | ID: biblio-1248585


RESUMEN La criptococosis es una enfermedad producida por levaduras encapsuladas que se adquiere por la inhalación de propágulos infectantes de Cryptoccoccus, principalmente por la C. neoformnas y en menor frecuencia por la C. gatti. La distribución de este hongo es global, pero se encuentra de manera habitual en excretas de aves como las palomas. El principal compromiso en las personas es a nivel de los pulmones, del cerebro o de forma diseminada. La criptococosis en el sistema nervioso central (SNQ se presenta con meningoencefalitis, rara vez en forma de lesiones localizadas granulomatosas conocidas como criptococoma. Esta micosis es una causa frecuente de meningitis que se encuentra, especialmente, en los pacientes con VIH/SIDA. Las manifestaciones clínicas de esta enfermedad en el SNC son: cefalea, alteración del estado mental, fiebre, náuseas, vómito, deterioro visual, parálisis del sexto nervio craneal y signos de irritación meníngea, entre otras. El diagnóstico se realiza por medio de cultivo, microscopía del líquido cefalorraquídeo (LCR) o detección del antígeno de criptococo. El tratamiento de la meningitis por criptococo se divide en tres fases: inducción, consolidación y mantenimiento. Los pilares del tratamiento son la anfotericina B, la flucitosina y el fluconazol.

SUMMARY Cryptococcosis is a disease produced by encapsulated yeast that is acquired by inhalation of infecting Cryp-tococcus propagules, mainly by C. neoformnas and less frequently by C gatti. The distribution of this fungus is global, but it is commonly found in the excreta of birds such as pigeons. The main commitment in people is at the level of the lungs, the brain or in a disseminated way. Cryptococcosis in the central nervous system (CNS) presents with meningoencephalitis, rarely as localized granulomatous lesions known as cryptococcoma. This mycosis is a frequent cause of meningitis especially found in patients with HIV / AIDS. The clinical manifestations of cryptococcosis in the CNS are: headache, altered mental status, fever, nausea, vomiting, visual impairment, sixth cranial nerve palsy, and signs of meningeal irritation, among others. Diagnosis is made by culture, cerebrospinal fluid (CSF) microscopy, or by detection of cryptococcal antigen. The treatment of cryptococcal meningitis is divided into three phases: induction, consolidation, and maintenance. The mainstays of treatment are amphotericin B, flucytosine, and fluconazole.

Article in Chinese | WPRIM | ID: wpr-911741


Twenty pediatric patients with kerion were treated in Department of Dermatology, Affiliated Hospital of Jining Medical University from January 2014 to June 2020. The general information, clinical manifestations, laboratory test results, treatment and prognosis were retrospectively analyzed. There were 13 males and 7 females aged from 2 to 10 years. Thirteen patients had a history of contact with animals, 4 had contact with parents with tinea. All patients had alopecia, 6 cases presented with inflammatory mass, 14 presented with abscessus; some patients had regional lymphadenopathy and febrile. Four cases were misdiagnosed as abscesses caused by bacterial infection and underwent incision leading to deep ulcers. A total of 13 fungal strains were isolated, including 4 strains of Microsporum gypseum, 3 strains of Trichophyton rubrum, 2 strains of Microsporum canis, the others were Trichophyton tonsurans and Trichophyton mentagrophytes and Fusarium. All patients were treated with fluconazole, concomitantly with topical antifungals and He-Ne laser, 19 of whom were cured. It is suggested that kerion characterized by inflammatory lesions is likely to be misdiagnosed. Fungal examination can confirm the diagnosis of kerion, and fluconazole is effective for treatment.

Article in Chinese | WPRIM | ID: wpr-908491


Objective:To investigate the clinical characteristics and influencing factors of mortality in patients with intra-abdominal candidiasis (IAC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 203 IAC patients who were admitted to 7 medical centers from June 2018 to June 2020 were collected, including 54 cases in Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, 31 cases in Fujian Medical University Union Hospital, 25 cases in Beijing Hospital, 25 cases in the First Affiliated Hospital of Xi'an Jiaotong University, 24 cases in China-Japan Friendship Hospital, 22 cases in General Hospital of Eastern Theater Command of Chinese PLA and 22 cases in Chongqing University Cancer Hospital. There were 130 males and 73 females, aged (64±15)years. Observation indicators: (1) candida infection and treatment of IAC patients; (2) analysis of influencing factors for mortality of IAC patients. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate and multivariate analyses were performed by Logistic regression model. Results:(1) Candida infection and treatment of IAC patients: 134 cases of candida albicans were cultured in the initial abdominal drainage fluid or intraoperative abdominal specimens of 203 patients, and 49 cases were treated with fluconazole. Of 69 cases infected with non candida albicans, 13 cases were treated with fluconazole. The resistance rate of candida albicans to fluconazole was 5.91%(12/203). Of 203 patients, there were 68 cases with infections shock, 53 cases with renal failure, 84 cases with respiratory failure and 63 cases with multiple organ failure, respectively. There were 148 of 203 patients admitted to intensive care unit for 9 days(range, 3-20 days), and the total hospital stay was 28 days(range, 17-50 days). Of 203 patients, 86 cases were cured and discharged, 50 cases were improved and transferred to local hospitals, 32 cases gave up treatment and discharged automatically, 19 cases died, 16 cases had no follow-up data. The mortality was 25.12%(51/203). (2) Analysis of influencing factors for mortality of IAC patients. Results of univariate analysis showed that acute physiology and chronic health evaluation score, sequential organ failure assessment score, the Cr, bilirubin, albumin, procalcitonin, and PLT on the first day of candida positive culture, of the lowest value in a week and the highest in a week, heart disease, diabetes, infections shock, renal failure, respiratory failure, multiple organ failure, anti-fungal therapy were the related factors for mortality of IAC patients ( t=-2.322, Z=-2.550, -2.262, -4.361, t=2.085, Z=-3.734, -5.226, -2.394, -5.542, t=3.462, Z=-4.957, -5.632, 3.670, -5.805, t=3.966, Z=-3.734, -5.727, χ2=4.071, 4.638, 27.353, 18.818, 13.199, 26.251, 13.388, P<0.05). Multivariate analysis showed that the bilirubin, procalcitonin on the first day of candida positive culture and infections shock were independent risk factors for mortality of IAC patients ( odds ratio=1.021, 1.022, 6.864, 95% confidence interval as 1.010-1.033, 1.001-1.044, 1.858-25.353, P<0.05). Conclusions:The common fungus of IAC was candida albicans, and fluconazole can be used as the initial empirical treatment. The prognosis of patients with abdominal candidiasis is poor. Bilirubin, procalcitonin on the first day of candida positive culture and infections shock are indepen-dent risk factors for mortality of IAC patients.

Article in Chinese | WPRIM | ID: wpr-837458


Objective@#To investigate the in vitro interaction of amphotericin B (AmB) and fluconazole (FLC) at different time points and provide a reference for clinical combined treatment therapy of polyenes and azoles.@*Methods@#Candida albicans ATCC SC5314 was used in the study. The minimum inhibitory concentration (MIC) of antifungal drugs was determined using the double microdilution broth method. The same amount of DMSO and low concentration drugs were added to the DMSO treatment group at different time points (0, 2, 4, 6 h) to determine whether the solvent background environment affected the growth of Candida albicans. In the experimental group, to observe the effect of low concentration AmB on the antifungal effect of FLC, the experimental group was administered a low concentration of AmB (0.25 μg/mL or 0.125 μg/mL) added to FLC at different time points (0, 2, 4, 6 h), and the same amount of DMSO was added to FLC at different time points in the single drug control group. In the experimental group, to observe the effect of low concentration of FLC on the antifungal effect of AmB, the experimental group was administered a low concentration of FLC (0.06 μg/mL or 0.03 μg/mL) in AmB at different time points (0, 2, 4, 6 h), and the same amount of DMSO was used at different time points as the single drug control group. In the solvent group, the same amounts of DMSO and low concentration drugs were added at different time points. After resuscitation, the colony growth of each solvent control group, single-drug control group and experimental group was observed to evaluate the interaction between drug concentration and time. Compared with the AmB single-drug control group, there was no significant change in the experimental group with added low concentrations of FLC at 0 h (F=0.27, P=0.775), which was 1.74-1.93 times that of the control group at 2-4 h (P < 0.001), and there was no significant difference in colony count after 6 h (P > 0.05). @*Results@# Under the treatment of FLC at an inhibitory concentration (0.25 μg/ml), adding low concentration AMB did not affect the antifungal effect of FLC, and the multiple of colony count differences were not significant (P > 0.05).@*Conclusion@#The interaction between AmB and FLC was time-dependent. At the early stage (0 h), the interaction effect between fluconazole and amphotericin B was not clear. The fungicidal effect of AmB could be weakened when FLC was supplied at 2-4 h, and the effect of FLC on AmB was absent after 6 h.

Article in Chinese | WPRIM | ID: wpr-886872


Objective To investigate the main chemical constituents of the low polarity extracts from pinusmassoniana Lamb. leaves and their synergetic activity with fluconazole against fluconazole-resistant Candida albicans. Methods The pinusmassoniana leaves were extracted with 80% ethanol, and then the extracts were extracted by petroleum ether to obtain the low polarity extracts. The chemical components were detected by GC-MS and elucidated by the comparison with the standard mass spectral data. The relative contents in percentage were calculated using the area normalization method. The minimal inhibitory concentrations (MIC80) of fluconazole-resistant Candida albicans strains by the low polarity extracts in combination with fluconazole were determined by checkerboard microdilution assay. Results 30 components were detected from the low polarity extracts, and 17 components were identified. The minimum inhibitory concentration (MIC80) of the 80% ethanol extracts, the low polarity extracts and the petroleum ether extracts from the pinusmassoniana leaves combined with fluconazole against fluconazole-resistant Candida albicans were 7.81 μg/ml, 31.25 μg/ml and >250 μg/ml, respectively. Conclusion The 80% ethanol extracts of pinusmassoniana leaves and its low polarity extracts have synergistic activity combined with fluconazole onfluconazole-resistant Candida albicans. The diterpenoids (53.99%) may be the effective components of the low polarity extracts.

Rev. cuba. invest. bioméd ; 40(supl.1): e1450, 2021. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1289473


Introducción: La Minthostachys mollises una planta aromática que crece en América Latina y produce aceites esenciales con acción antimicrobiana. Objetivo: Determinar la actividad del aceite esencial de Minthostachys mollis en diferentes concentraciones, comparado con doxiciclina y fluconazol frente a Porphyromonas gingivalis, Staphylococcus aureus y Candida albicans, a las 24, 48 y 72 horas. Métodos: Se realiza estudio experimental in vitro y longitudinal. Se prepararon 15 pocillos por subgrupo para evaluar el efecto inhibitorio de todas las concentraciones, dando un total de 360 pocillos. Por cromatografía de gases acoplada a espectrometría de masas se identificaron los componentes químicos del aceite esencial. Se analizó el efecto inhibitorio por el método de difusión de Kirby-Bauer en Agar Columbia y Agar Muller Hinton. El análisis estadístico se realizó mediante la prueba ANOVA y Tukey. Resultados: En el análisis químico se identificó principalmente pulegona (30,17 por ciento) y mentona (16,55 por ciento). Los halos de inhibición de Minthostachys mollis al 100 por ciento a las 24, 48 y 72 horas frente a la Porphyromonas gingivalis, midieron: 10,2 mm, 9,8 mm y 9,6 mm, respectivamente; frente al Staphylococcus aureus, midieron: 10,4 mm, 9,7 mm y 9,4 mm, respectivamente; y, por último, frente a Candida albicans midieron: 9,8 mm, 8,9 mm y 8,5 mm, respectivamente. Todas las concentraciones de Minthostachys mollis presentaron un efecto antimicrobiano significativamente menor que el fluconazol y la doxiciclina (p < 0,001). Conclusiones: El aceite esencial de Minthostachys mollis al 100 % presentó su mejor actividad inhibitoria frente al Staphylococcus aureus, la Porphyromonas gingivalis y la Candida albicans a las 24 horas. Sin embargo, este efecto antimicrobiano disminuye a medida que pasa el tiempo(AU)

Introduction: Minthostachys mollis is an aromatic plant species growing in Latin America which produces essential oils with antimicrobial activity. Objective: Determine the activity of essential oil from Minthostachys mollis at various concentrations as compared with doxycycline and fluconazole against Porphyromonas gingivalis, Staphylococcus aureus and Candida albicans at 24, 48 and 72 hours. Methods: An in vitro experimental longitudinal study was conducted. Fifteen wells were prepared per subgroup to evaluate the inhibitory effect of all concentrations, for a sum total of 360 wells. Chemical components of the essential oil were identified by gas chromatography-mass spectrometry. The inhibitory effect was analyzed with the Kirby-Bauer diffusion method in Mueller-Hinton and Columbia agar. Statistical analysis was based on ANOVA and Tukey's test. Results: Chemical analysis mainly found pulegone (30.17 percent) and menthone (16.55 percent). The inhibition halos of 100 percent Minthostachys mollis at 24, 48 and 72 hours against Porphyromonas gingivalis measured 10.2 mm, 9.8 mm and 9.6 mm, respectively, against Staphylococcus aureus they measured 10.4 mm, 9.7 mm and 9.4 mm, respectively, and against Candida albicans they measured 9.8 mm, 8.9 mm and 8.5 mm, respectively. The antimicrobial effect of Minthostachys mollis at all concentrations was significantly lower than that of fluconazole and doxycycline (p < 0.001). Conclusions: The essential oil from 100% Minthostachys mollis displayed its best inhibitory activity against Staphylococcus aureus, Porphyromonas gingivalis and Candida albicans at 24 hours. However, such antimicrobial effect decreases with the passing of time(AU)

Humans , Male , Female , In Vitro Techniques , Oils, Volatile , Fluconazole , Analysis of Variance , Chromatography, Gas , Porphyromonas gingivalis , Gas Chromatography-Mass Spectrometry , Longitudinal Studies , Chemical Phenomena
Infectio ; 24(4): 266-269, oct.-dic. 2020. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1114881


Resumen Introducción: La endocarditis fúngica es una enfermedad infecciosa agresiva e infrecuente, considerada una emergencia en los servicios hospitalarios. Se ha evidenciado una incidencia de 0-12% del total de las admisiones pediátricas por endocarditis infecciosa. La mortalidad por Candida spp se encuentra alrededor del 50-80% en todos los casos. La Candida lusitaniae afecta principalmente a pacientes inmunocomprometidos, con uso de dispositivos intravasculares y el empleo de antibióticos de amplio espectro. Reporte de caso: Se presenta el caso de un lactante menor quien es diagnosticado con fungemia y endocarditis infecciosa por Candida lusitaniae en válvula nativa posterior a cirugía de corrección por transposición de grandes vasos. Discusión y Conclusiones: La endocarditis infecciosa por Candida lusitaniae es una entidad poco frecuente, con una prevalencia menor al 2% constituyéndose un escenario desafiante en la práctica clínica. Se describen las características de un lactante menor quien presentó endocarditis fúngica ya definidas en la literatura mundial. Es imprescindible la detección temprana y una intervención terapéutica vertiginosa; puesto que, la persistencia del inoculo, la resistencia antimicótica y el retraso en el diagnóstico conllevan a una condición amenazante para la vida del paciente.

Abstract Introduction: Fungal infective endocarditis is an aggressive and infrequent disease, considered an emergency in hospital services. Candida mortality is around 50-80% in all cases. The Candida lusitaniae mainly affects immunocompromised patients with chronic venous access and the use of broad-spectrum antibiotics. Case report: A minor infant is presented who is diagnosed with fungemia and infective endocarditis due to Candida lusitaniae in a native valve secondary to surgery by transposition of large vessels. Discussion and Conclusions: Candida lusitaniae infectious endocarditis is very rare, with a prevalence of less than 2% constituting a challenging scenario in clinical practice. The characteristics of fungemia and endocarditis already defined in the world literature are described. Early detection and a vertiginous therapeutic intervention are essential, since; latent infection, antifungal resistance and delay in diagnosis lead to a threatening condition for the patient's life.

Humans , Infant , Candida , Endocarditis , Fungemia , Echinocandins , Infections/complications , Anti-Bacterial Agents
Rev. colomb. ciencias quim. farm ; 49(2): 401-431, May-Aug. 2020. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1144359


SUMMARY Aims: This study investigated the bioactivity of the crude leaf extract (CLE) and fractions hexane (HX) and ethyl acetate (EtOAc) from Talinum paniculatum alone and in association with fluconazole (FLC) against reference strain and clinical isolates of FLC-resistant Candida albicans. Furthermore, the antioxidant capability, chemical composition of this plant, and the effect's underlying mechanisms were evaluated. Methods: The antifungal activity was evaluated using checkerboard assay to establish the minimum inhibitory (MIC) and minimum microbicidal concen trations (MMC). During FLC and plant products challenges, the reactive oxygen species (ROS) generation (hydroxyl radicals [HO●]) were detected in C. albicans cells using the membrane-permeable fluorescent probes APF and HPF. High-performance liquid chromatography (HPLC) profile, quantitative analysis of antioxidant compounds, and free radical scavenging activity (DPPH assay) tests were performed. Results: The CLE and fractions presented outstanding antifungal activity and selectivity against C. albicans cells but had no synergistic effect's with FLC. The MIC values for CLE and its fractions against C. albicans reference strain were in the order of HX (31.25 µg ml-1) < EtOAc (62.5 μg ml-1) < CLE (500 μg ml-1), and against FLC-resistant C. albicans HX (125 μg ml-1) = EtOAc < CLE (500 μg ml-1). CLE and its fractions had more potent antifungal activities than FLC against the clinical isolates. Moreover, fungicidal effect's for these plant products were demonstrated against FLC-resistant C. albicans, which further conirmed an antifungal potential. Conversely, during association, plant products were shown to cause an increase in FLC MIC anywhere from 2- to 16-fold. FLC exposure led to an increase in the steady-state levels of ROS (HO●) in C. albicans cells. Next, we found that the increases in FLC MICs were owing to action of antioxidants containing-CLE and its fractions in preventing FLC-induced ROS-mediated growth inhibition of C. albicans. Conclusion: T. paniculatum can be a source of bioactive compounds with antifungal potential. However, because of the common use of its edible leaf, caution is advised during therapy with FLC (since it can decrease FLC susceptibility).

RESUMEN Objetivos: este estudio investigó la bioactividad del extracto de hoja en bruto (EHB) y las fracciones hexano (HX) y acetato de etilo (AcOEt) de Talinum paniculatum solo y en asociación con fluconazol (FLC) contra cepas de referencia y aislados clínicos de Candida albicans resistente a FLC. Además, evaluó la capacidad antioxidante, la composición química de esta planta y los mecanismos subyacentes del efecto fungicida. Métodos: la actividad antifúngica se evaluó mediante microdilución en caldo para establecer las concentraciones inhibitorias mínimas (CIM) y microbicidas mínimas (CMM). Durante el tratamiento con FLC y productos vegetales se detectó la generación de especies reactivas de oxígeno (ERO) (radicales hidroxilo [HO●]) en células de C. albicans utilizando las sondas fluorescentes permeables a la membrana APF y HPF. El perfil de cromatografía líquida de alta resolución (CLAR), el análisis cuantitativo de compuestos antioxidantes y el ensayo DPPH fueron evaluados. Resultados: el EHB y las fracciones presentaron una excelente actividad antifúngica y selectividad contra las células de C. albicans, pero no tuvieron efectos sinérgicos con FLC. Los valores de CIM para EHB y sus fracciones contra la cepa referencia de C. albicans fueron del orden de: HX (31,25 μg ml-1) < AcOEt (62,5 μg ml-1) < EHB (500 μg ml-1), y contra C. albicans resistente a FLC: HX (125 μg ml-1)= AcOEt < EHB (500 µg ml-1). EHB y sus fracciones fueron más potentes antifúngicos que FLC contra los aislados clínicos. Además, estos productos vegetales tienen efectos fungicidas contra C. albicans resistentes a FLC, esto conirmó el potencial antifúngico. Por el contrario, durante la asociación se demostró que los productos vegetales causan un aumento en la CIM de FLC de 2 a 16 veces. La exposición a FLC aumentó los niveles de ERO (HO●) en las células de C. albicans. Los aumentos en las CIM de FLC se debieron a la acción de los antioxidantes presentes en EHB y sus fracciones para prevenir la inhibición del crecimiento mediada por ERO inducida por FLC en C. albicans. Conclusión: T. paniculatum puede ser una fuente de compuestos bioactivos con potencial antifúngico. Sin embargo, debido al uso común de su hoja comestible, se recomienda usarla con precaución durante la terapia con FLC (ya que puede disminuir la susceptibilidad a FLC).

Article | IMSEAR | ID: sea-214966


With increasing use of antibacterial and cytotoxic drugs, lethal invasive Candidiasis is on the rise, with almost half of the cases being caused by non albicans Candida species (NAC). Frequent use of azoles for empirical therapy has also led to their increased resistance. We wanted to characterise Candida species isolated from various clinical specimens and assess their susceptibility pattern to Fluconazole and Voriconazole.METHODSA total of 100 consecutive Candida species isolated from various clinical specimens in our institute from January 2016 to December 2016 were included in the study. Standard yeast identification protocol and CHROM agar were used for speciation and their antifungal susceptibility pattern was found by disc diffusion method.RESULTSOut of the 100 isolates, C. tropicalis was the predominant isolate (47%), followed by C. albicans (31%), C. parapsilosis (16%) and C. krusei (6%). Females (57%) were more affected and maximum number of patients was above 60 years (24%). Diabetes mellitus (21%) was the major predisposing factor for Candida, followed by broad spectrum antibiotic therapy (14%). Isolates were more susceptible to Voriconazole (99%) than Fluconazole (87%). NAC spp. showed more resistance to Fluconazole (17.4%) than C. albicans (3.3%). Only one isolate of C. krusei (16.6%) showed resistance to Voriconazole.CONCLUSIONSDue to the increasing incidence of azole resistant NAC spp., the species level identification of Candida species, along with their anti-fungal susceptibility patterns can help the clinicians in formulating a treatment protocol and can help in decreasing the mortality and morbidity.

Biomédica (Bogotá) ; 40(1): 153-165, ene.-mar. 2020. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1089112


Resumen Introducción. Las infecciones oportunistas asociadas con Candida albicans han tenido gran repercusión en la salud pública por la mortalidad que generan en determinados grupos poblacionales. Aunque existen tratamientos farmacológicos disponibles, es evidente el aumento de la resistencia desarrollada por el agente patógeno, por lo que la determinación de los mecanismos de resistencia de las cepas presentes en las áreas hospitalarias es importante, ya que permitiría plantear mejores esquemas de tratamiento. Objetivo. Analizar la expresión de los genes ERG11, CDR1 y MDR1 en cepas de C. albicans aisladas de adultos mayores a su ingreso en la unidad de cuidados intensivos del Hospital Santa Sofía de Manizales, Colombia. Materiales y métodos. Se seleccionaron 29 muestras (21 resistentes y 8 sensibles) y se conformaron dos grupos de trabajo, uno de muestras con exposición al fluconazol y el otro sin esta. El ARN extraído se cuantificó mediante reacción en cadena de la polimerasa con transcriptasa inversa en tiempo real (RT-qPCR). Resultados. Se encontraron diferencias significativas en la expresión del gen MDR1 en el grupo de cepas de C. albicans resistentes. Dos de las cepas resistentes (104 y 62-2) expuestas al antifúngico presentaron valores muy elevados en la expresión de este gen. La expresión del ERG11 y del CDR1 no fue significativa en los grupos estudiados. Conclusión. El aumento de sobreexpresión del gen MDR1 indica que este puede ser el responsable de la resistencia; sin embargo, algunas cepas resistentes no sobreexpresaron los genes analizados, lo que indica que puede haber otros genes involucrados en la resistencia de las cepas estudiadas.

Abstract Introduction: Opportunistic infections associated with Candida albicans have had a great impact on public health due to the mortality they generate in certain population groups. Although pharmacological treatments are available, the resistance developed by the pathogen has become increasingly evident. For this reason, determining the mechanisms of resistance associated with the strains found in different hospital areas is important since it would help improving treatment plans. Objective: To analyze the expression of ERG11, CDR1, and MDR1 genes in strains of C. albicans isolated from elderly patients at admittance in the intensive care unit of Hospital Santa Sofía in Manizales, Colombia. Materials and methods: A total of 29 samples (21 resistant and 8 sensitive) were selected and distributed in two working groups: with and without exposure to fluconazole. The extracted RNA was quantified by real-time reverse transcription polymerase chain reaction (RT-qPCR). Results: Significant differences were found in the expression of the MDR1 gene in the group of resistant C. albicans strains. Two of the resistant strains (104 and 62-2) exposed to the antifungal showed very high values in the expression of this gene. The expression of ERG11 and CDR1 was not significant among the groups studied. Conclusion: The increased overexpression of the MDR1 gene indicates that it may be responsible for the resistance. However, some resistant strains did not overexpress any of the genes analyzed, which indicates that there may be other genes involved in the resistance of the strains under study.

China Pharmacy ; (12): 1118-1123, 2020.
Article in Chinese | WPRIM | ID: wpr-821504


OBJECTIVE:To excavate the safety warning signals induced by azole antifungal agents ,including fluconazole , ketoconazole,itraconazole and voriconazole after marketing ,and to provide references for rational drug use in the clinic. METHODS:Reporting odds ratio (ROR)data mining algorithm was used to investigate signals of adverse drug event (ADE)for fluconazole,ketoconazole,itraconazole and voriconazole from FDA Adverse Event Reporting System (FAERS)during January 1st,2004 to March 30th,2019. ROR data mining method was used to excavate the ADR signals of the drugs ,and main ADR involved in the safety information of azole antifungal agents instructions were analyzed. RESULTS :A total of 27 831,5 712, 5 381 and 11 333 reports were picked out for fluconazole ,ketoconazole,itraconazole and voriconazole ,respectively. All of these drugs had exhibited high-risk signals detection by ROR ,including medical examination ,blood and lymphatic system disorders , renal and urinary disorders ,endocrine diseases ,hepatobiliary disorders. The hepatotoxic-related ADR signals were mainly concentrated in fluconazole and voriconazole (fluconazole ROR =6.51,voriconazole ROR =14.65);ADR detection results of Cushing’s-like syndrome (ROR=24.86) and adrenal suppression (ROR=44.06) by itraconazole showed high-risk signals ; ketoconazole and itraconazole had showed a strong ADR signal in adrenocortical dysfunction (ketoconazole ROR =15.64, itraconazole ROR =23.26),and the signal intensity of ketoconazole (ROR=2.81)in skin and subcutaneous tissue disorders was significantly higher than that of other drugs . In addition ,hemorrhagic cystitis caused by fluconazole,itraconazole and voriconazole were not included in the drug instructions (fluconazole ROR =17.73,itraconazole ROR =31.43,voriconazole ROR =17.06); netted green spot caused by fluconazole (ROR=10.50)were not included in the drug instructions . CONCLUSIONS:Clinical staff should pay more attention to the differences in serious ADR related to fluconazole ,ketoconazole,itraconazole and voriconazole ; particularly some ADRs not mentioned in the drug instructions but have high incidence such as hemorrhagic cystitis caused by fluconazole,itraconazole,voriconazole and netted green spot caused by fluconazole ,as well as ADRs mentioned in the drug instructions but have abnormally high signal ,such as Cushing ’s-like syndrome and adrenal suppression caused by itraconazole .

Article in Chinese | WPRIM | ID: wpr-855798


AIM: To compare the bioequivalence of two brands of fluconazole capsules (50 mg) made in Chengdu Brilliant Pharmaceutical Co., Ltd and Pfizer Pharmaceuticals Ltd. (held in France) in healthy volunteers under fasted and fed conditions. METHODS: The study was an open-label, randomized, two way-crossover study involving 52 healthy Chinese volunteers. A single oral test and reference fluconazole capsules (50 mg) were given to the volunteers under fasted and fed conditions. The plasma concentration of fluconazole was determined by LC-MS/MS method. The non-compartment model pharmacokinetic parameter calculation method was applied to calculate pharmacokinetic parameters and perform statistical analysis.RESULTS: The main pharmacokinetic parameters after oral administration of test and reference fluconazole capsules under fasted conditions were as follows, Cmax (1.32±0.21) μg/mL and (1.15±0.20) μg/mL; AUC0-t (52.84±7.91) μg•h•mL-1 and (51.49±8.15) μg•h•mL-1; AUC0-∞ (58.07±9.30) μg•h•mL-1 and (56.99±10.13) μg•h•mL-1, respectively. The main pharmacokinetic parameters after oral administration of test and reference fluconazole capsules under fed conditions were as follows, Cmax (1.04±0.14) μg/mL and (1.04±0.15) μg/mL; AUC0-t (50.64±7.08) μg•h•mL-1 and (49.91±9.13) μg•h•mL-1; AUC0-∞(56.79±9.26) μg•h•mL-1 and (56.06±11.58) μg•h•mL-1, respectively. The 90% confidential intervals of the geometric mean ratios of Cmax, AUC0-t, AUC0-∞ under fasted and fed conditions were all between 80% and 125%. CONCLUSION: The two brands of fluconazole capsules were bioequivalent under fasted and fed conditions.

Braz. J. Pharm. Sci. (Online) ; 56: e18069, 2020. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1089210


Present study was aimed to prepare and characterize fluconazole loaded nanostructured lipid carriers (FLZ-NLCs) for the treatment of fungal infections. Fungal infections are tremendously widespread and are the often faced dermatological condition worldwide. FLZ-NLCs was prepared by ultrasonication emulsion technique using stearic acid (SA) as solid lipid, castor oil as liquid lipid and tween 20 as a surfactant. The mean diameter of optimized FLZ-NLCs were found to be 359.15 ± 9.83 nm. The drug content and entrapment efficiency of NLCs was found to be 102.97 ± 7.45% and 87 ± 0.59%, respectively. In vitro drug release studies of FLZ-NLCs showed 37.34 ± 2.08% drug release over a period of 72 h. The above studies confirmed the prepared FLZ-NLCs may be useful for the treatment of fungal infections.

Braz. J. Pharm. Sci. (Online) ; 56: e18599, 2020. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1132042


The present study investigated the association of the non-steroidal anti-inflammatory drug ibuprofen with itraconazole, fluconazole and amphotericin B against Cryptococcus neoformans isolates. The minimal inhibitory concentration (MIC) was found according to M27-A3 protocol and in vitro interactions were evaluated using checkerboard microdilution method. Synergism was demonstrated between azoles and ibuprofen for most isolates. However, no synergistic effects were seen when amphotericin B was combined with ibuprofen. Therefore, our results suggest that ibuprofen presents clinical potential when combined with azole drugs in the treatment of cryptococcosis.

Colomb. med ; 50(4): 293-298, Oct.-Dec. 2019.
Article in English | LILACS-Express | LILACS | ID: biblio-1114722


Abstract Background: Candida auris is an emerging yeast frequently reported as resistant to multiple antifungal drugs commonly used to treat Candida infections. This specie can colonize the patient's skin and has great ability for producing outbreaks in hospitals. C. auris is phylogenetically related to other Candida species, can be misidentified using conventional biochemical or commercial methods and requires specific technology for its identification. Case report: We report the first isolate of C. auris in Cali, Colombia, from a central venous catheter in a 37-year-old patient with rheumatoid arthritis and endocarditis who did not have symptoms of sepsis. The yeast was initially misidentified as C. haemulonii using the Phoenix system and subsequently identified as C. auris by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). The broth microdilution method was used to determine the minimum inhibitory concentration; the isolate was susceptible to fluconazole, itraconazole, voriconazole and amphotericin B. Conclusions: This report contributes to knowledge of the epidemiology of C. auris infections in individuals with underlying disease and describes an isolate with a behavior different from what is usually reported.

Resumen Antecedentes: Candida auris es una levadura emergente, informada con frecuencia como resistente a diversos antifúngicos usados comúnmente para tratar infecciones por Candida. Esta especie puede colonizar la piel y tiene gran capacidad de producir brotes en ambientes hospitalarios. Está filogenéticamente relacionada con otras especies de Candida, es mal identificada por los métodos bioquímicos o comerciales, y requiere tecnología específica para su identificación. Reporte de caso: Se informa el primer aislamiento de C. auris en Cali, Colombia en un paciente de 37 años con artritis reumatoide y endocarditis, sin síntomas de sepsis, a partir de la punta de catéter venoso central. La levadura inicialmente se identificó como C. haemulonii por el sistema Phoenix® y posteriormente como C. auris por espectrometría de masas desorción/ionización láser asistida por una matriz con detección de masas por tiempo de vuelo (MALDI-TOF MS). Se determinó la concentración inhibitoria mínima por el método de microdilución en caldo que mostró un aislamiento sensible a fluconazol, itraconazol, voriconazol y anfotericina B. Conclusión: Este informe contribuye al conocimiento de la epidemiología de las infecciones por C. auris en individuos con enfermedad subyacente y describe un aislamiento con un comportamiento diferente a lo indicado en otros estudios.

Article | IMSEAR | ID: sea-203461


Background: Candida species is known as the most commonopportunistic yeast affecting the genitourinary tract. Thetriazoles are commonly used for the treatment of candidiasis.But the increasing resistance of Candida to different azolescreated a demand for newer drugs.Objective: Voriconazole is a second generation azoleantifungal agent that shows excellent in vitro activity against awide variety of yeast and moulds. This study was done toassess the therapeutic efficacy of Voriconazole in Fluconazoleresistant vaginal candidiasis.Material and Methods: This one-group pretest-posttest quasiexperiment was conducted in a specialized private chamber ofFaridpur, Bangladesh from January 2018 to July 2019. Vaginalcandidiasis was diagnosed by clinical features, microscopicexamination, culture and sensitivity of high vaginal swab.Voriconazole was used only in Fluconazole resistant vaginalcandidiasis.Results: During the study period, 568 patients were presentedwith vulvovaginitis. Among them, in 267 (47%) patients,Candida albicans were isolated. All patients were treated byFluconazole as first-line treatment. 160 (60%) of those patientsdid not improve clinically and were treated by Voriconazole.Success rate was 93% (149). Regarding side effects ofVoriconazole, transient visual disturbance occurred in 35% ofthe patients, nausea and vomiting in 20% of the patients.Conclusion: Due to wide species variety of Candida andincreasing resistance, Voriconazole may be the second linetreatment of vaginal candidiasis.

Int J Pharm Pharm Sci ; 2019 Aug; 11(8): 26-34
Article | IMSEAR | ID: sea-205930


Objective: The objective of the study was to develop and validate a new rapid and more sensitive Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) method for the simultaneous estimation of azithromycin, fluconazole and ornidazole in bulk and pharmaceutical dosage forms. Methods: Separation was achieved with a cap cell pack C18 column (4.6 x 250 mm, 5μ) with an isocratic mobile phase containing a mixture of acetonitrile and phosphate buffer pH 4.8 [adjusted with ortho-phosphoric acid] (50:50 % v/v) at the flow rate of 1 ml/min and detection was monitored at 210 nm. Results: The retention time (Rt) of azithromycin, fluconazole and ornidazole were found to be 4.82±0.01, 5.25±0.01 and 6.33±0.01 min respectively. The precision was found with<1.5% of %RSD. The calibration curve was linear over the concentration ranging from 500-1000 µg/ml for azithromycin, 75-150 µg/ml for fluconazole and 375-750 µg/ml for ornidazole with the correlation coefficient (r2) of 0.999. The percentage recovery was found to be within the specified range i.e., 98-102 % for three drugs. Limit of detection (LOD) was found to be 5.810, 1.790 and 4.924 µg/ml, whereas Limit of quantification limits (LOQ) was found to be 9.834, 2.667 and 7.980 µg/ml, respectively. Conclusion: A simple isocratic liquid chromatographic method was developed and validated for simultaneous estimation of azithromycin, fluconazole and ornidazole in their formulations. Due to its simplicity, rapidness and specificity, it can be applied for routine quality control analysis of these drugs.

Rev. chil. pediatr ; 90(2): 186-193, abr. 2019. tab
Article in Spanish | LILACS | ID: biblio-1003736


OBJETIVO: Determinar los principales factores de riesgo asociados a candidemia en neonatos. PACIENTES Y MÉTODO: Se realizó un estudio de casos y controles retrospectivo pareado, desde enero de 2014 a diciembre de 2016. Los casos fueron pacientes con aislamiento en hemocultivo y/o líquido cefalorraquídeo de Candida spp. luego de sus primeras 48 horas intrahospitalarias y los controles fueron neonatos escogidos del censo estadístico de la sala de neonatología pareados según su fecha de admisión a sala (rango de 30 días), peso al nacer, edad gestacional y condición de egreso (vivo o fallecido). Por cada caso seleccionamos dos controles. Los factores de riesgo evaluados fueron la estancia intrahospitalaria mayor a 7 días, el uso de antibióticos de amplio espectro, ventilación mecánica, nutrición parenteral mayor a 5 días, procedimientos invasivos como colocación de accesos venosos centrales y cirugías abdominales y torácicas, enterocolitis necrosante y crecimiento de microorganismo bacteriano en hemocultivo previo a la candidemia. RESULTADOS: Durante el período de estudio hubo aislamiento de Candida spp. en 141 neonatos. Se encontró que el 49% fue de Candida parapsilosis con la mayor letalidad asociada. En el análisis multivariado se identificaron como factores de riesgo la estancia intrahospitalaria mayor a 7 días (OR = 17,0, 95% IC = 2,36-122,4), uso de líneas umbilicales (OR = 9,04, 95% IC = 1,55-52,5), exposición a cirugía (OR = 12,4, 95% IC = 1,76-87,3) y el uso de meropenem (OR = 4,62, 95% IC = 1,34-15,9). CONCLUSIÓN: La estancia intrahospitalaria prolongada mayor a 7 días y la exposición a cirugía fueron los factores de riesgo más importantes en este estudio para el desarrollo de candidemia neonatal.

OBJECTIVE: To identify the main risk factors associated with neonatal candidemia. PATIENTS AND METHOD: A retrospective paired case-control study was conducted from January 2014 to December 2016. The cases were patients with isolation in blood culture and/or cerebrospinal fluid of Candida spp. after their first 48 hours in the hospital and the controls cases were neonates chosen from the statistical census of neonatology paired according to their admission date (30-day range), birth weight, gestational age, and discharge condition (alive or deceased). For each case, we select two controls. The risk factors evaluated were intrahospital stay over seven days, use of broad-spectrum antibiotics, mechanical ventilation, parenteral nutrition longer than five days, invasive procedures such as central venous access and abdominal and thoracic surgeries, necrotizing enterocolitis and growth of bacterial microorganisms in blood culture before candidemia. RESULTS: During the study period, 141 patients developed candidemia. 49% of the cases corresponded to Candida parapsilosis with the highest associated lethality rate. The multivariate analysis identified as risk factors hospital stay longer than seven days (OR = 17.0, 95% CI = 2.36-122.4), use of umbilical lines (OR = 9.04, 95% CI = 1.55-52.5), abdominal and/or thoracic surgery (OR = 12.4, 95% CI = 1.76-87.3), and treatment with Meropenem (OR = 4.62, 95% CI = 1.34-15.9). CONCLUSION: Prolonged intrahospital stay longer than seven days and thoracic and/or abdominal surgery were the most significant risk factors in this study for the development of neonatal candidemia.

Humans , Male , Female , Infant, Newborn , Candidemia/etiology , Panama/epidemiology , Intensive Care Units, Neonatal , Case-Control Studies , Logistic Models , Odds Ratio , Retrospective Studies , Risk Factors , Candidemia/diagnosis , Candidemia/mortality
Article | IMSEAR | ID: sea-203141


Objectives: The study aimed at comparing the therapeuticefficacy of Terbinafine and Itraconazole in terms of clinical curein the treatment of Fluconazole resistant Tinea corporis andTinea cruris.Materials and Methods: A clinical trial with 154 patients’having Tinea corporis and Tinea cruris was performed. All thepatients were treated with fluconazole. The resistant patientswere randomly divided into two groups. The first group wastreated with Terbinafine 250mg daily for 4 weeks, whereassecond group was treated by Itraconazole for 4 weeks. Theparticipants were followed up till the end of treatment and onemonth after treatment.Results: At the end of the trial, terbinafine group developed78.84% clinical response, while Itraconazole treated groupdeveloped only 39.13%.Conclusion: Based on the marked observed difference, it maybe concluded that Terbinafine is more effective in treatingfluconazole resistant Tinea corporis and Tinea cruris.

China Pharmacy ; (12): 235-239, 2019.
Article in Chinese | WPRIM | ID: wpr-816728


OBJECTIVE: To establish a method for determination of fluconazole concentration in human plasma. METHODS: UPLC-MS/MS method was adopted to determine plasma after precipitated with acetonitrile. Using isotope fluconazole-d4 as internal standard, the determination was performed on ACQUITY UPLC BEH C18 column with mobile phase consisted of 0.1% formic acid-acetonitrile (gradient elution) at the flow rate of 0.3 mL/min. The column temperature was 40 ℃, and the sample size was 3 μL. ESI was used for positive ion scanning by multiple reaction monitoring mode. The ion pairs for quantitative analysis were m/z 307.1→220.0 (fluconazole) and m/z 311.1→223.0 (internal standard). RESULTS: The linear range of fluconazole was 10-5 000 ng/mL (r=0.998 1). The limits of quantitation was 10 ng/mL. RSDs of intra-day and inter-day were less than 8%; accuracy ranged 95.8%-106.7%. The extraction recovery ranged 97.3%-107.3% (RSD<5.0%, n=6), and matrix effect, dilution effect and residual effect didn’t influence quantitative analysis of the substance to be measured. CONCLUSIONS: The method is simple, rapid, specific and accurate, which can be used for therapeutic drug monitoring and pharmacokinetic study of fluconazole.