Aspectos da abordagem terapêutica sobre candidíase vulvovaginal / Aspects of the therapeutic approach to vulvovaginal candidiasis / Aspectos del abordaje terapéutico de la candidiasis vulvovaginal

A candidíase vulvovaginal, é uma infecção da vulva e vagina causada por vários tipos de Candida spp. Essa patologia afeta 75% de todas as mulheres pelo menos uma vez durante a vida, ocorrendo com mais frequência durante a idade fértil. A transmissão dessa infeção fúngica ocorre por meio de contato com mucosas e secreções em pele de portadores ou doentes, contato sexual, água contaminada e transmissão vertical. Alguns outros sintomas característicos mais vistos em casos de CVV, são lesões brancas, cremosas e planas, sendo mais intensos no período pré-menstrual, quando a acidez vaginal aumenta. numerosos antifúngicos estão disponíveis no mercado, os quais são encontrados para administração oral na forma de comprimidos ou, para uso tópico, na forma de cremes, loções, comprimidos vaginais, supositórios e tampões revestidos. O objetivo geral do trabalho foi analisar através da revisão de literatura, tratamentos convencionais e alternativos para abordagem terapêutica da Candidíase Vulvovaginal contextuando a mesma, utilizando definições, dados epidemiológicos e sua sintomatologia frente à sociedade. O presente trabalho é uma revisão integrativa, que teve a coleta de dados realizada de março de 2021 a outubro de 2021 nas bases de dados Lilacs, Scielo, Google acadêmico, A busca resultou em 902 artigos, dos quais 14 atenderam ao critério de inclusão. A busca por tratamentos frente a candidíase vulvovaginal tem se mostrado ampla de acordo com os artigos selecionadas. Concluímos que a patologia candidíase vulvovaginal, vem apresentando resistência em algumas abordagens terapêuticas, assim como algumas mulheres não aderem há algum tipo de tratamento, devido à falta de conhecimento sobre a patologia.

Vulvovaginal candidiasis is an infection of the vulva and vagina caused by various types of Candida spp. This condition affects 75% of all women at least once in their lifetime, occurring more frequently during their childbearing years. The transmission of this fungal infection occurs through contact with mucous membranes and secretions on the skin of patients or patients, sexual contact, contaminated water and vertical transmission. Some other characteristic symptoms more seen in cases of VVC are white, creamy and flat lesions, being more intense in the premenstrual period, when the vaginal acidity increases. numerous antifungals are available on the market which are available for oral administration in tablet form or, for topical use, in the form of creams, lotions, vaginal tablets, suppositories and coated tampons. The general objective of the work was to analyze, through a literature review, conventional and alternative treatments for the therapeutic approach of Vulvovaginal Candidiasis in its context, using definitions, epidemiological data and its symptoms in society. The present work is an integrative review, which had data collection carried out from March 2021 to October 2021 in the Lilacs, Scielo, Google academic databases. The search resulted in 902 articles, of which 14 met the inclusion criteria. The search for treatments against vulvovaginal candidiasis has been shown to be wide according to the selected articles. We conclude that the vulvovaginal candidiasis pathology has been showing resistance in some therapeutic approaches, as well as some women do not adhere to any type of treatment, due to lack of knowledge about the pathology.

La candidiasis vulvovaginal es una infección de la vulva y la vagina cau- sada por diversos tipos de Candida spp. Esta afección afecta al 75% de las mujeres al menos una vez en la vida, siendo más frecuente durante la edad fértil. La transmisión de esta infección fúngica se produce por contacto con mucosas y secreciones de la piel de pacientes o enfermos, contacto sexual, agua contaminada y transmisión vertical. Otros síntomas característicos más observados en los casos de CVV son las lesiones blancas, cremosas y planas, siendo más intensas en el período premenstrual, cuando aumenta la acidez vaginal. Existen en el mercado numerosos antifúngicos disponibles para adminis- tración oral en forma de comprimidos o, para uso tópico, en forma de cremas, lociones, comprimidos vaginales, supositorios y tampones recubiertos. El objetivo general del tra- bajo fue analizar, a través de una revisión bibliográfica, los tratamientos convencionales y alternativos para el abordaje terapéutico de la Candidiasis Vulvovaginal en su contexto, utilizando definiciones, datos epidemiológicos y su sintomatología en la sociedad. El pre- sente trabajo es una revisión integradora, que tuvo recolección de datos realizada de marzo de 2021 a octubre de 2021 en las bases de datos académicas Lilacs, Scielo, Google. La búsqueda resultó en 902 artículos, de los cuales 14 cumplieron los criterios de inclu- sión. La búsqueda de tratamientos contra la candidiasis vulvovaginal se ha mostrado am- plia según los artículos seleccionados. Concluimos que la patología de la candidiasis vul- vovaginal viene mostrando resistencia en algunos abordajes terapéuticos, así como algu- nas mujeres no se adhieren a ningún tipo de tratamiento, debido al desconocimiento de la patología.

Activador tisular del plasminógeno recombinante para el tratamiento de la vegetación intracardíaca en un lactante de muy bajo peso al nacer / Recombinant tissue plasminogen activator treatment for intracardiac vegetation in a very low birth weight infant

Las nuevas opciones de tratamiento prolongan la hospitalización y aumentan las infecciones intrahospitalarias bacterianas y fúngicas, pero también mejoran la sobrevida de los recién nacidos hospitalizados en la unidad de cuidados intensivos neonatales. Las infecciones fúngicas invasivas en neonatos están asociadas con una morbimortalidad significativa. También pueden diseminarse a órganos específicos y causar endocarditis, endoftalmitis, artritis séptica, nefropatía obstructiva y meningitis. En el caso de la endocarditis, se recomiendan tratamientos antimicóticos sistémicos agresivos y, en algunos casos, la intervención quirúrgica del neonato. Informamos el caso de un lactante prematuro, de bajo peso al nacer, con vegetación intracardíaca. Esta es una complicación rara y potencialmente mortal de infecciones fúngicas invasivas. El paciente recibió tratamiento con caspofungina y un activador tisular del plasminógeno recombinante, en vez de una intervención quirúrgica.

Developing treatment options have resulted in prolonged admission and increased bacterial and fungal nosocomial infections as well as improved survival in neonatal intensive care unit. Invasive fungal infections in newborns are associated with significant morbidity and mortality and can cause endorgan dissemination such as endocarditis, endophthalmitis, septic arthritis, obstructive nephropathy and meningitis. Endocarditis requires aggressive systemic antifungal therapy and sometimes surgical intervention in neonates. We report a low birth weight premature infant with intracardiac vegetation that is rare and a life-threatening complication of invasive fungal infections. He was treated with caspofungin and recombinant tissue plasminogen activator in stead of surgical intervention.

Antifungal activity of caspofungin in experimental infective endocarditis caused by Candida albicans

BACKGROUND Infective endocarditis is a disease characterised by heart valve lesions, which exhibit extracellular matrix proteins that act as a physical barrier to prevent the passage of antimicrobial agents. The genus Candida has acquired clinical importance given that it is increasingly being isolated from cases of nosocomial infections. OBJECTIVE To evaluate the activity of caspofungin compared to that of liposomal amphotericin B against Candida albicans in experimental infective endocarditis. METHODS Wistar rats underwent surgical intervention and infection with strains of C. albicans to develop infective endocarditis. Three groups were formed: the first group was treated with caspofungin, the second with liposomal amphotericin B, and the third received a placebo. In vitro sensitivity was first determined to further evaluate the effect of these treatments on a rat experimental model of endocarditis by semiquantitative culture of fibrinous vegetations and histological analysis. FINDINGS Our semiquantitative culture of growing vegetation showed massive C. albicans colonisation in rats without treatment, whereas rats treated with caspofungin showed significantly reduced colonisation, which was similar to the results obtained with liposomal amphotericin B. CONCLUSIONS The antifungal activity of caspofungin is similar to that of liposomal amphotericin B in an experimental model of infective endocarditis caused by C. albicans.

Anidulafungina en niños: Experiencia en niños con trasplante de médula ósea / Anidulafungin in children: experience in children undergoing bone marrow transplantation

Introducción: Las infecciones fúngicas invasoras (IFI) son un problema de salud cada vez mayor, y se asocian con una alta morbilidad y mortalidad. Las nuevas opciones terapéuticas, tales como las equinocandinas y entre estos anidulafungina, se han utilizado en la población adulta, pero en pacientes pediátricos con trasplante de médula ósea la experiencia es escasa. Objetivo: El objetivo de este estudio descriptivo es presentar nuestra experiencia con el uso de la anidulafungina como profilaxis o tratamiento en pacientes con trasplante de médula ósea. Material y métodos: Entre enero hasta junio 2016, 29 pacientes trasplantados de médula ósea recibieron anidulafungina como profilaxis o tratamiento de infecciones fúngicas invasivas (IFI) probadas, probables o posibles. En todos los casos se monitorizó el valor de transaminasas, bilirrubina, creatinina y el recuento de glóbulos blancos al inicio y al final del tratamiento. Resultados: La anidulafungina se administró por vía intravenosa en una dosis de carga de 3 mg/kg/día, seguida de 1,5 mg/kg/día durante una mediana (Md) de 16 días (intervalo intercuartílico: 2-65 d). La Md de la edad de los pacientes fue de 97 meses (rango: 6-211m). La anidulafungina fue indicada como tratamiento en 7 casos (24%) y como profilaxis primaria o secundaria,en 22 (76%). En un paciente se confirmó microbiológicamente una IFI, por Candida albicans. Las Md de los parámetros bioquímicos en el inicio del tratamiento y al final, fueron: transaminasas GOT 29,5 U/l y 32 U/l (p 0,44); bilirrubina 0,35 y 0,30 mg/dL (p: 0,20); creatinina, 0,52 y 0,60 mg/dl (p:0,67). El recuento de glóbulos blancos mostró una gran variabilidad debido a la enfermedad subyacente, pero la diferencia de su valor entre el inicio y al final de la administración del fármaco, no fue significativo: Md 2810 células/mm3 y 5160 células/mm3, respectivamente (p: 0,07). Ninguno de los pacientes tuvo eventos adversos o murieron por causas relacionadas con anidulafungina. En el seguimiento a 30 días no se registró recaída de la infección o mortalidad relacionada a la droga. Conclusiones: Los resultados de nuestra serie sugieren que la anidulafungina podría ser una opción para la profilaxis o el tratamiento de las IFI en los niños con trasplante de médula ósea. Se requieren más estudios para confirmar estas observaciones (AU)

Introduction: Invasive fungal infections (IFI) are an increasing health problem associated with high morbidity and mortality. New treatment options, such as echinocandins and among these anidulafungin, have been used in the adult population, but experience in children undergoing bone marrow transplantation is scarce. Aim: The aim of this descriptive study is to present our experience with the use of anidulafungine as prophylaxis or treatment in patients undergoing bone marrow transplantation. Material and methods: Between January and June 2016, 29 patients who underwent bone marrow transplantation received anidulafungin as prophylaxis against or treatment for confirmed, probable, or possible (IFI). In all cases transaminase, bilirubin, and creatinine levels as well as total white blood cell count were monitored at treatment initiation and completion. Results: Anidulafungine is administered intravenously in a loading dose of 3 mg/kg/day, followed by 1.5 mg/kg/day for a mean of 16 days (interquartile range: 2-65 d). Mean age of the patients was 97 months (range: 6-211m). Anidulafungine was used as treatment in 7 cases (24%) and as primary or secondary prophylaxis in 22 (76%). IFI was microbiologically confirmed to be Candida albicans in one patient. Mean biochemical parameters at treatment onset and completion were: transaminases AST 29.5 U/l and 32 U/l (p 0.44); bilirubin 0.35 and 0.30 mg/dL (p 0.20); creatinine, 0.52 and 0.60 mg/dl (p : 0.67). White blood cell count was highly variable due to the underlying disease; however, the difference between values at treatment initiation and completion were not significant: Mean 2810 cells/mm3 and 5160 cells/mm3, respectively (p: 0.07). None of the patients had adverse effects or died because of anidulafungin-related causes. At 30 days of follow-up no relapse of infection or drug-related mortality was observed. Conclusions: The results in our series suggest that anidulafungin is an option for the prophylaxis against or treatment of IFI in children undergoing bone marrow transplantation. Further studies are necessary to confirm these findings (AU)

Antifungal pharmacodynamics: Latin America's perspective

Abstract The current increment of invasive fungal infections and the availability of new broad-spectrum antifungal agents has increased the use of these agents by non-expert practitioners, without an impact on mortality. To improve efficacy while minimizing prescription errors and to reduce the high monetary cost to the health systems, the principles of pharmacokinetics (PK) and pharmacodynamics (PD) are necessary. A systematic review of the PD of antifungals agents was performed aiming at the practicing physician without expertise in this field. The initial section of this review focuses on the general concepts of antimicrobial PD. In vitro studies, fungal susceptibility and antifungal serum concentrations are related with different doses and dosing schedules, determining the PD indices and the magnitude required to obtain a specific outcome. Herein the PD of the most used antifungal drug classes in Latin America (polyenes, azoles, and echinocandins) is discussed.

Eficacia y seguridad de la caspofungina en pediatría: revisión sistemática y metaanálisis / Efficacy and safety of caspofungin in children: systematic review and meta-analysis

Las infecciones fúngicas invasivas son una importante causa de morbimortalidad en pediatría. La caspofungina es una equinocandina utilizada como alternativa en la prevención y/o tratamiento de ciertas infecciones fúngicas invasivas en niños, aunque con poca evidencia sobre su eficacia y seguridad en comparación con el tratamiento habitual. Objetivos. Evaluar la eficacia y seguridad de la caspofungina comparada con otros antifúngicos en la prevención y/o tratamiento de infecciones fúngicas invasivas en pediatría. Material y métodos. La estrategia de búsqueda inicial tuvo como objetivo identificar estudios controlados aleatorizados de aceptable calidad metodológica (escala de Jadad > 3) mediante la palabra clave "caspofungin" realizados en pacientes de entre los 0 y los 18 años. Resultados. Solo 3 publicaciones cumplieron los criterios de inclusión. De ellas, 2 fueron en población pediátrica y una en neonatal. No se documentó una mayor incidencia de efectos adversos para la caspofungina y su eficacia no se diferenció de otros antifúngicos (RR típico 1,47; IC 95%: 0,78-2,79). Conclusiones. Esta revisión sistemática sugiere que la caspofungina podría considerarse como una alternativa para su indicación en pediatría en la prevención y tratamiento de las infecciones fúngicas invasivas. Sin embargo, dado el pequeño número de publicaciones existentes, se requieren más estudios para alcanzar conclusiones definitivas.

Invasive fungal infections are a significant cause of morbidity and mortality in children. Caspofungin is an echinocandin used as an alternative treatment in the prevention and/or treatment of certain invasive fungal infections in children, although compared to the standard treatment there is little evidence on its efficacy and safety. Objectives. To evaluate the efficacy and safety of caspofungin compared with other antifungal drugs for the prevention and/or treatment of invasive fungal infections in children. Material and methods. The objective of the initial search strategy was to identify randomized controlled studies of acceptable methodological quality (Jadad scale >3), through the key word "caspofungin", conducted in patients with an age range from 0 to 18 years old. Results. Only 3 publications met the inclusion criteria. Two of them were studies conducted in children and one in newborn infants. A higher incidence of adverse events was not documented for caspofungin and its efficacy was not different from that of other antifungal drugs (typical RR 1.47; CI 95%: 0.78-2.79). Conclusions. This systematic review suggests that caspofungin could be considered as an alternative drug in children for the prevention and treatment of invasive fungal infections. However, given the small number of existing publications, more studies are required to reach definite conclusions.

Rare severe mycotic infections in children receiving empirical caspofungin treatment for febrile neutropenia

ABSTRACTEmpirical antifungal therapy is most often given to patients with leukemia. However breakthrough fungal infections under antifungal therapy are not uncommon. Four children, with hematologic malignant disease developed mycotic breakthrough infections while on empirical caspofungin treatment for a median of 14 (range 11-19) days. Trichosporon asahii was detected in the blood culture of two patients and Geotrichum capitatum in the other two (one patient also had positive cerebrospinal fluid culture). Because the patients' clinical situation worsened, voriconazole was empirically added for two patients three and five days before the agent was detected. The first sterile blood culture was obtained 3-7 days of voriconazole treatment. All patients reached clear cultures but one patient died. One patient with central nervous system infection with G. capitatum had severe neurological sequelae. Very severe fungal infections can occur during empirical caspofungin therapy. Therefore, patients should be followed closely.

Tratamiento exitoso de una mucormicosis rinocerebral persistente en un paciente pediátrico durante el debut de una leucemia aguda / Successful treatment of a persistent rhino-cerebral mucormycosis in a pediatric patient with a debut of acute lymphoblastic leukemia

The fungi of the order Mucorales cause mucormycosis, which usually presents as an invasive fungal disease with rapid angioinvasion in immunocompromised patients. Rhinocerebral is the most common presentation. The lipid formulations of amphotericin B are used as primary treatment in invasive mucormycosis; the combined use of posaconazole could allow a reduction in the dose of amphotericin B improving tolerance and adherence to treatment. Caspofungin and amphotericin B association has been shown to be synergistic in vitro and effective in murine models. We present the case of a preschool patient that during the debut of acute lymphoblastic leukemia developed a rhinocerebral mucormycosis successfully responding to antifungal treatment with the combination of liposomal amphotericin and caspofungin.

Los hongos del orden Mucorales causan la mucormicosis, que se presenta habitualmente como una enfermedad fúngica invasora con rápida angioinvasión en pacientes inmunocomprometidos. La presentación rino-cerebral es la más frecuente. Las formulaciones lipídicas de anfotericina B se usan como tratamiento primario en las mucormicosis invasoras; el uso combinado de posaconazol podría permitir reducir la dosis de anfotericina B generando una mejor tolerancia y adherencia al tratamiento. La asociación de caspofungina con anfotericina ha demostrado acción sinérgica in vitro y eficacia en modelos murinos. Se presenta el caso de una niña preescolar que durante el debut de una leucemia linfoblástica aguda evolucionó con una mucormicosis rino-cerebral persistente, que respondió en forma exitosa al tratamiento antifúngico combinado de anfotericina liposomal y caspofungina.

Invasive infection due to Saprochaete capitata in a young patient with hematological malignancies

We report a case of invasive infection due to Saprochaete capitata in a patient with hematological malignancies after chemotherapy treatment and empiric antifungal therapy with caspofungin. Although severely immunocompromised the patient survived been treated with amphotericin B lipid complex associated with voriconazole.

Antifúngicos em infecções oculares: drogas e vias de administração / Antifungals in eye infections: drugs and routes of administration

O tratamento das infecções oculares por fungos representa um desafio à prática oftalmológica. Para obtermos resposta terapêutica adequada, além do uso da droga correta, é necessária a administração desta de forma eficaz. Este manuscrito reúne informações a respeito das principais drogas antifúngicas utilizadas em infecções oculares, suas concentrações e principais vias de administração.

Treatment of fungal eye infections represents a challenge to the ophthalmology practice. For an adequate therapeutic response, besides correct drug choice, it is necessary an effectively administration. This script gathers information about the major antifungal drugs used in eye infections, their concentrations and main administration routes.

Catheter-related Candidemia Caused by Candida haemulonii in a Patient in Long-term Hospital Care

Candida haemulonii, one of the non-albicans Candida species, is an emerging yeast pathogen that is known to be resistant to amphotericin B and other antifungal agents such as azoles. These anti-fungal agents have often been associated with clinical treatment failure, so no treatment regimen has been clearly established for invasive C. haemulonii infections. We investigated a catheter-related infection of C. haemulonii candidemia in an adult patient in long-term hospital care. In the early stages, the candidemia remained persistent despite treatment with fluconazole. However, after changing the antifungal agent to caspofungin, the candidemia was resolved. Fluconazole and amphotericin B are not reliable empirical antifungal agents for invasive C. haemulonii infections, as shown in previous case reports. An echinocandin such as caspofungin may be an appropriate empirical choice of antifungal agent for an invasive C. haemulonii infection.

Expresiones cutáneas de candidiasis sistémica en pacientes inmunosuprimidos / Cutaneous expression of systemic candidiasis in immunosuppressed patients

La candidiasis sistémica constituye una importante causa de morbimortalidad en pacientes internados en centros de alta complejidad. Las expresiones cutáneas de la infección son múltiples y se observan en un pequeño porcentaje de pacientes. Se presentan cinco casos de candidiasis sistémica con compromiso cutáneo en pacientes inmunosuprimidos: un paciente trasplantado de médula ósea, dos pacientes con leucemia mieloide aguda, un caso de sepsis bacteriana y un paciente con linfoma linfocítico. Todos los pacientes presentaron fiebre persistente y lesiones cutáneas que se biopsiaron para estudio histológico y cultivo. La histopatología mostró seudohifas en tres de los casos. En los cultivos de piel se identificó a Candida tropicalis, Candida Krusei y Candida albicans en dos pacientes. El incremento de cepas resistentes hace necesario el empleo de nuevos antifúngicos como las equinocandinas para el tratamiento de esta entidad.

Systemic candidiasis is a signifi cant cause of morbidity and mortality in immunosuppressed hospitalized patients. Skin signs of systemic candi-diasis are numerous although they can be observed in a small percent-age of patients. We report fi ve cases of systemic candidiasis with cutaneous manifestations in immunosuppressed patients: one case of bone- marrow transplantation, two patients with acute myeloid leukaemia, one with bacterial sepsis and one patient with lymphocitic lymphoma. The patients presented persistent fever and cutaneous lesions. Skin biopsy for histopathological study and cultures were carried out. The histological examination showed yeasts in three of the cases. Skin culture revealed: Candida tropicalis, Candida krusei and Candida albicansin two cases. Due to the increase of resistant species new drugs such as echinocandins are currently available for the treatment of this entity.

New Antifungal Agents in Pediatric Practice.

Clinical needs for new antifungal agents have steadily increased with the rise and alteration in spectrum of invasive mycoses in children and neonates having AIDS, malignancies and undergoing immunosuppressive therapies. Several new options are now available for management of serious fungal infections. The aim of this review is to summarize the key features of the new antifungal agents and novel targets being investigated for the treatment of fungal infections, with special reference to its use in the treatment of pediatric fungal infections. New triazoles have broad spectrum of activity with voriconazole presently being the drug of choice against invasive aspergillosis, and posaconazole is the possible first substitute of amphotericin B against zygomycosis. Echinocandins with new mode of action of inhibition of fungal cell wall polysaccharide synthesis are effective in treating candidemia and invasive candidiasis. Some of these agents are however, still awaiting FDA approval for their use in pediatric practice.

Acute monoblastic leukemia with t(10;11)(p12;q23) presenting with pulmonary involvement: a case report and literature review.

A forty-three-year-old Thai man presented with acute fever and dyspnea for one week with bilateral patchy infiltration, pancytopenia with monoblast. Bone marrow study was consistent with acute monoblastic leukemia. Lung lesions rapidly progressed to acute respiratory failure, which required intubation. Bronchoscopy with bronchoalveolar lavage revealed monotonous monoblast infiltration. Induction chemotherapy with 7 + 3 regimen was administered to halt the progression of leukemic pulmonary infiltration. Although there was clinical improvement, the chest radiograph developed crescent formation in the right upper lung field. Invasive pulmonary aspergillosis was suspected and successfully treated with antifungal agent. After peripheral blood recovery, bone marrow evaluation was performed and complete remission was established. HLA matching was sent to prepare for hematopoietic stem cell transplantation (HSCT). The literature review showed that the appropriate treatment for the patients with t(10;11)(p12;q23) was HSCT, but there was no data concerning correlation of t(10;11)(p12;q23) and pulmonary infiltration. This may be due to the low incidence of leukemic infiltration of acute leukemia patients, which is 0.48% and 3.06% in acute myeloid leukemia and acute monoblastic leukemia, respectively.