Factores de riesgo y letalidad asociados a candidemia neonatal en una unidad de neonatología / Risk factors and lethality associated with neonatal candidemia in a neonatal unit

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.

Non-culture-based diagnostic methods for the diagnosis of invasive candidiasis: are they helpful to clinicians?

Invasive candidiasis in immune-compromised patients is associated with high attributable mortality. Early detection of candidemia and accurate identification of Candida species are essential pre-requisites for improved prognosis. Since clinical presentation is non-specific and blood culture-based methods lack sensitivity, detection of immunological and molecular markers has provided an alternative for early diagnosis of invasive candidiasis. Serial estimations of these biomarkers have also proved useful to initiate pre-emptive therapy in suspected patients before clinical signs appear and to monitor response to therapy. Antigen-based methods include detection of beta-D-glucan [panfungal marker] and Candida mannan [genus-specific marker]. Detection of both, Candida mannan and anti-mannan antibodies has higher sensitivity. While false positive / negative results remain a problem, these markers provide a useful adjunct to the diagnosis if performed in select patient population. Recent advances have also been made in nucleic acid-based detection methods. A commercial real-time PCR assay [Light Cycler Septi Fast] for detection of clinically important Candida spp. in blood specimens within six hours is now available. Molecular methods have also resulted in speciesspecific identification of yeast isolates within an hour. While these advances aid in early and specific diagnosis of candidemia and invasive candidiasis, further evaluation of these approaches in different clinical settings is also needed

The First Korean Case of Candidemia due to Candida dubliniensis

Candidemia due to uncommon Candida spp. appears to be increasing in incidence. C. dubliniensis has been increasingly recovered from individuals not infected with HIV. Identification of C. dubliniensis can be problematic in routine clinical practice due to its phenotypic resemblance to C. albicans. We report the first case of C. dubliniensis candidemia in Korea, which occurred in a 64-yr-old woman who presented with partial seizure, drowsiness, and recurrent fever. Germ-tube positive yeast that was isolated from blood and central venous catheter tip cultures formed smooth, white colonies on sheep blood agar and Sabouraud agar plates, indicative of Candida spp. C. dubliniensis was identified using the Vitek 2 system (bioMerieux, USA), latex agglutination, chromogenic agar, and multiplex PCR. The blood isolate was susceptible to flucytosine, fluconazole, voriconazole, and amphotericin B. After removal of the central venous catheter and initiation of fluconazole treatment, the patient's condition gradually improved, and she was cleared for discharge from our hospital. Both clinicians and microbiologists should be aware of predisposing factors to C. dubliniensis candidemia in order to promote early diagnosis and appropriate treatment.

Métodos diagnósticos en candidemia: una revisión sistemática de la literatura con meta-análisis / Diagnostic methods in candidemia: a systematic review of literature with meta-analysis

Candidemia is a disease with high morbidity and mortality especially in critical care patients. Early diagnosis enables early treatment. Objectives: To conduct a systematic review of the literature in order to establish the best laboratory tests for the diagnosis of candidemia in critical patients. Materials and Methods: We conducted a systematic review of available literature in PubMed. Serological studies were subjected to meta-analysis in metadisk-Beta 1.1.1. Results: 4 studies of 1286 reviewed were included. Three were about serological tests and one about molecular testing (RT-PCR). The sensitivity and specificity for RT-PCR, antibody testing and antigen and antibody tests were 87 percent and 100 percent, 47.5 percent and 82.6 percent, 96 percent and 81 percent, respectively. Diagnostic Odds Ratio of antigenemia was 1.51 (95 percent CI = 0,032-70,964, p = 0.001). Conclusions: RT-PCR has better diagnostic performance, measuring antigenemia plus antibodies improves sensitivity, specificity, LR + and LR-- . There is insufficient evidence to support this.

La candidemia es una patología con alta morbilidad y mortalidad, especialmente en los pacientes sometidos a servicios de cuidado crítico. El diagnóstico precoz permite realizar tratamiento temprano. Objetivos: Realizar una revisión sistemática de la literatura para establecer cuáles son las pruebas de laboratorio con mejor rendimiento diagnóstico y operativo para el diagnóstico de candidemia en cuidado intensivo. Materiales y Métodos: Se realizó una revisión sistemática de la literatura disponible en PubMed, se sometieron a meta-análisis estudios de pruebas serológicas en MetaDisc-Beta 1.1.1. Resultados: Se incluyeron 4 estudios de 1.286 revisados, 3 de pruebas serológicas y 1 de RPC-RT. La sensibilidad y especificidad fue de 87 y 100 por ciento para RPC-RT, 47,5 y 82,6 por ciento para pruebas de anticuerpos, 96 y 81 por ciento para pruebas de antígeno y anticuerpo. La ORD de antigenemia 1,51(IC95 por ciento = 0,03270,964; p = 0,001). Conclusiones: RPC-RT tiene mejor rendimiento diagnóstico, la medición de antigenemia más anticuerpos mejora la sensibilidad, especificidad, LR+ y LR-. No hay suficiente evidencia que soporte esto.