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OBJECTIVE: Previous reports have identified interleukin-2 (IL-2), quantified in the supernatants of QuantiFERON®-TB Gold In-tube (QFT) after 72 h of incubation, as a potential biomarker for distinguishing between latent and active tuberculosis (TB). However, its validity has not been tested in an appropriate clinical cohort. METHODS: A multicentre study of 161 consecutive adult patients undergoing evaluation for active TB at eight TB Units in Spain. Interferon-γ (IFN-γ) and IL-2 were assessed in the supernatant of QFT after 16-24 h and 72 h of incubation. The accuracy of IL-2 for indicating latent TB infection (LTBI) was assessed by receiving operating characteristic curves. . RESULTS: Twenty-eight participants were not infected, 43 had LTBI, 69 had TB, and 21 were not classifiable. Median (interquartile range) IL-2 concentrations after 72 h of incubation were 0.0 pg/mL (0.0-0.0) in uninfected individuals, 261.0 pg/mL (81.0-853.0) in LTBI individuals, 166.5 pg/mL (33.5-551.5) in patients with extrapulmonary TB, 95.0 pg/mL (26.0-283.0) in patients with smear-negative pulmonary TB, and 38.5 pg/mL (7.5-178.0) in patients with smear-positive pulmonary TB (p <0.0001). The area under the curve of the receiving operating characteristic curve (95% CI) of IL-2 after 72 h of incubation for the diagnosis of LTBI was 0.63 (0.53-0.74) when all TB cases were considered as a single group, ranging from 0.59 (0.47-0.71) to 0.72 (0.58-0.85) when only extrapulmonary and smear-positive pulmonary TB cases respectively were considered. CONCLUSIONS: Quantification of IL-2 in the supernatant of QFT after a prolonged incubation is not useful to distinguish between LTBI and active disease in clinical practice.
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Interleucina-2/sangre , Tuberculosis Latente/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Tuberculosis/diagnóstico , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Interferón gamma/sangre , Tuberculosis Latente/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , España , Tuberculosis/sangre , Tuberculosis Pulmonar/sangreRESUMEN
Ninety-six Streptococcus pneumoniae strains isolated between January 1989 and December 2000 from usually sterile sites of children aged < 5 years of age were included in the study. Resistance to penicillin (38.6% intermediate, 10.4% high-level), cefotaxime (20.8%), tetracycline (41.7%), chloramphenicol (33.3%) and erythromycin (27.1%), as well as serogroup/type, were related to age and pathology. Strains from children aged < 2 years showed the highest penicillin resistance rate. Resistance to penicillin, tetracycline, chloramphenicol and erythromycin was the most common pattern (18.8% of strains). Most isolates (80.2%) belonged to serogroups/types included in the heptavalent conjugate vaccine.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Infecciones Neumocócicas/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Preescolar , Humanos , Pruebas de Sensibilidad Microbiana , Serotipificación , España , Streptococcus pneumoniae/clasificaciónRESUMEN
We report one case of neonatal sepsis caused by Malassezia furfur in an infant who had been in the Intensive Care Unit for 64 days. She had received prolonged therapy with intravenous fat emulsion. We used Sabouraud's medium with an overlay of sterile olive oil for the blood culture, because we had observed yeast forms in one smear of peripheral blood. M. furfur was isolated after three days of incubation. The patient recovered following removal of the port-a-cath and antifungal treatment, and had no further evidence of fungal infection. The skin colonization by the same yeast was demonstrated.
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BACKGROUND: To describe the vertical transmission of HIV-1 by means of molecular methods. PATIENTS AND METHODS: A prospective study between 1995 and 1998 of two groups of patients, A: 107 newborn infants to HIV-1 infected mothers, and B: 11 infants with clinical suspicion of HIV infection, born to mothers who didn't know being infected. DNA and RNA PCR as well as reverse transcriptase gen mutations were tested. RESULTS: Eleven infected patients were identified, four from group A and seven from group B. Viral load at the moment of diagnosis was higher than 100,000 copies/ml in all patients. Genotypic mutations of the studied codons were not detected in ten patients. CONCLUSION: Molecular amplification techniques are useful for early diagnosis and follow-up of HIV infection acquired by vertical transmission.
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Infecciones por VIH/diagnóstico , VIH-1 , Fármacos Anti-VIH/uso terapéutico , Resistencia a Medicamentos/genética , Femenino , Estudios de Seguimiento , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , VIH-1/genética , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Reacción en Cadena de la Polimerasa/métodos , Estudios Prospectivos , Estudios Retrospectivos , Carga ViralRESUMEN
The purpose of this study was to compare the diagnostic accuracy for the detection of infection between the culture of fluid obtained by sonication (SFC) and the culture of peri-implant tissues (PITC) in patients with early and delayed implant failure, and those with unsuspected and suspected septic failure. It was hypothesised that SFC increases the diagnostic accuracy for infection in delayed, but not early, implant failure, and in unsuspected septic failure. The diagnostic accuracy for infection of all consecutive implants (hardware or prostheses) that were removed for failure was compared between SFC and PITC. This prospective study included 317 patients with a mean age of 62.7 years (9 to 97). The sensitivity for detection of infection using SFC was higher than using PITC in an overall comparison (89.9% versus 67%, respectively; p < 0.001), in unsuspected septic failure (100% versus 48.5%, respectively; p < 0.001), and in delayed implant failure (88% versus 58%, respectively; p < 0.001). PITC sensitivity dropped significantly in unsuspected compared with suspected septic failure (p = 0.007), and in delayed compared with early failure (p = 0.013). There were no differences in specificity. Sonication is mainly recommended when there is implant failure with no clear signs of infection and in patients with delayed implant failure. In early failure, SFC is not superior to PITC for the diagnosis of infection and, therefore, is not recommended as a routine diagnostic test in these patients.
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Prótesis e Implantes/microbiología , Falla de Prótesis/etiología , Infecciones Relacionadas con Prótesis/diagnóstico , Sonicación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Introducción: Mycoplasma pneumoniae y adenovirus son dos de las causas más frecuentesde neumonía en la infancia. El objetivo del estudio es describir las características epidemiológicas,clínicas, radiológicas y analíticas de los casos de neumonía por dichos microorganismosen menores de 15 años en un hospital de Barcelona. Determinar si existen diferenciasentre etiologías y edades y conocer los casos de coinfección.Material y métodos: estudio retrospectivo, mediante revisión de las historias clínicas delos menores de 15 años atendidos en el periodo 2000-2007 en el hospital y cuya IgM paraM. pneumoniae y/o adenovirus fue positiva o se obtuvo inmunofluorescencia o cultivo positivopara adenovirus. Posteriormente se realizó un análisis estadístico mediante SPSS(R). Resultados: se diagnosticaron 153 neumonías: 73 por M. pneumoniae y 80 por adenovirus.La media de edad fue de 5,7 y 3,5 años respectivamente, siendo el 46% menores de 5 años en la neumonía por M. pneumoniae y el 71,3% por adenovirus. No se observó predominioestacional claro. Las manifestaciones clínicas más frecuentes fueron fiebre y tos, conbuen estado general. La auscultación pulmonar fue patológica en 141 casos, predominandola unilateralidad y crepitantes. La alteración radiológica fue mayoritariamente unilateral. Losresultados analíticos no fueron significativos. Se encontraron 23 coinfecciones entre ambos y 22 con otros microorganismos. Conclusiones: M. pneumoniae y adenovirus deben ser considerados como agentes causales de neumonías en cualquier edad de la infancia. Destaca la dificultad para establecerempíricamente el diagnóstico etiológico, la similitud clínica entre mayores y menores de 5 años y el porcentaje de coinfecciones (AU)
Introduction: Mycoplasma pneumoniae and adenovirus are two of the main causes ofpneumonia in children. The objectives of the study are to describe the epidemiological, clinical, radiological and laboratory characteristics of the cases of pneumonia caused by these microorganismsin children younger than 15 years in a Hospital of Barcelona. And also to knowif there are differences between both etiologies, between children with different ages and toknow the cases of coinfections. Methods: retrospective study of review of clinical histories of children under 15 who were visited from 2000 to 2007 in the hospital and whose IgM against M. pneumonia and/oradenovirus or the immunofluorescence or culture for adenovirus had been positive. A statisticalstudy with the program SPSS was performed. Results: seventy-three pneumonias caused by M. pneumoniae and 80 by adenovirus werediagnosed. Thirty-five were girls and 28 boys. The mean age was 5.7 and 3.5 years respectively;46.6% were younger than 5 years in M. pneumoniae and 71.3% in adenovirus infections.There was no clear stational prevalence. The most frequent clinical manifestationswere fever and cough, with good general aspect. The auscultatory findings were pathological in 141 cases, being crepitations and unilateral affectation the most frequent features. Chestx-rays showed predominantly unilateral affectation. Blood tests did not show significative alterations.There were 23 coinfections found with both microorganism and 22 with others.Conclusions: M. pneumoniae and adenovirus should be considered causal agents of paediatricpneumonias. Is remarkable the difficulty in the differential diagnosis with other pneumonias,the clinical similitude between younger and older than 5 years and the importantpercentage of coinfections (AU)
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Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Neumonía por Mycoplasma/epidemiología , Técnica del Anticuerpo Fluorescente Directa , beta-Lactamas/uso terapéutico , Penicilinas/uso terapéutico , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Ceftriaxona/uso terapéutico , Azitromicina/uso terapéutico , Infecciones por Adenovirus Humanos/complicaciones , Infecciones por Adenovirus Humanos/epidemiología , Adenovirus Humanos/aislamiento & purificación , Adenovirus Humanos/patogenicidad , Estudios Retrospectivos , Registros Médicos/estadística & datos numéricos , CefaleaRESUMEN
UNLABELLED: Neisseria meningitidis is the most prevalent micro-organism involved in paediatric bacterial meningitis in the Barcelona area in children over 3 mo of age and it is an important cause of morbidity and mortality in Spain. A total of 498 strains of N. meningitidis, obtained between the years 1986 and 1997 from children with sepsis and/or meningitis, were characterized according to their serogroup and penicillin resistance; their distribution in serotypes and subtypes was studied from 1990. A decreasing tendency in the number of annual isolates was observed in this period. Most isolates belonged to serogroups B (403 strains) and C (77 strains). Serogroup C accounted for 1.8% of the strains in 1986 and 57.1% in 1997. The most prevalent phenotype between 1990 and 1996 was B:4:P1.15. but C:2b:P1.2,5 was the most prevalent in 1997. Overall penicillin-resistance rates ranged from 9.1% in 1986 (when a non-susceptible strain was isolated for the first time in the Hospital Sant Joan de Déu, Barcelona, Spain) to 71.4% in 1997, and it was more common among strains belonging to serogroup C (52% of resistant strains) than to serogroup B (22.1 % of resistant strains). The penicillin-resistance level was low, MIC always < or = 0.5 microg/ml. The present increase in N. meningitidis group C isolates, mainly C:2b:P1.2,5, and the availability of preventive measures for this highly pathological and resistant phenotype, argues strongly for the establishment of an epidemiological monitoring system. Detection of penicillin resistance should be standardized worldwide in order to unify data from all laboratories. CONCLUSION: A shift between serogroups B and C is observed in Barcelona from 1986 to 1997, as well as a rapid distribution of decreased penicillin susceptibility.
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Meningitis Meningocócica/tratamiento farmacológico , Neisseria meningitidis/clasificación , Resistencia a las Penicilinas , Penicilinas/uso terapéutico , Adolescente , Técnicas de Tipificación Bacteriana , Niño , Preescolar , Hospitalización , Humanos , Lactante , Meningitis Meningocócica/microbiología , Meningitis Meningocócica/mortalidad , Pruebas de Sensibilidad Microbiana , Neisseria meningitidis/efectos de los fármacos , Neisseria meningitidis/aislamiento & purificación , Fenotipo , Prevalencia , España/epidemiologíaRESUMEN
BACKGROUND: The purpose of this study was to set up the current level of Streptococcus pyogenes sensitivity, in pediatric patients in our community, to penicillin, clindamycin, clarithromycin, erythromycin and azithromycin. MATERIAL AND METHODS: 100 strains were collected between October 1996 to July 1997. 79 were pharyngeal and 21 were non-pharyngeal strains. The MICs were obtained by the E-test method, and furthermore the results were compared by the Kirby-Bauer method. RESULTS: All strains were sensitive to penicillin and except one (inducible resistance) to clindamycin. 19% were resistant to macrolide, without differences among clarithromycin, erythromycin and azithromycin. From 13 strains (16.5%) of pharyngeal and 6 (28.5%) from non-pharyngeal samples, 4 of these from cutaneous samples, showed resistance. 18 of the resistance strains belonged to novel resistance fenotip and one to 10 inducible fenotip. Only minor discrepancies about erythromycin and clindamycin were observed between E-test and Kirby-Bauer methods. CONCLUSIONS: This study confirms a remarkable level of resistance to macrolides in pediatric patients, mainly in the cutaneous samples. Due to the reduced prevalence of macrolide-susceptible strains, in vitro susceptibility testing appears necessary in case of macrolide chemotherapy.
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Farmacorresistencia Microbiana , Infecciones Estreptocócicas/microbiología , Streptococcus pyogenes/efectos de los fármacos , Adolescente , Azitromicina/farmacología , Niño , Preescolar , Claritromicina/farmacología , Clindamicina/farmacología , Resistencia a Múltiples Medicamentos , Eritromicina/farmacología , Femenino , Humanos , Lactante , Masculino , Penicilinas/farmacología , Fenotipo , Streptococcus pyogenes/aislamiento & purificación , Tonsilitis/microbiologíaRESUMEN
BACKGROUND: The aim of this study is to evaluate a new diagnostic test to detect Helicobacter pylori antigen in stool samples (HpSA), and compare the results with those obtained by standard techniques (rapid urease test,culture, histological examination of gastric biopsy specimens,13C-urea breath test and serology), in a paediatric population with gastrointestinal symptomatology. PATIENTS AND METHODS: Sixty patients with dyspeptic symptoms (37 females and 23 males;mean age 10.9 years) attending the Gastroenterology Service were included in the study. Exclusion criterium was previous treatment with proton pump inhibitors, bismuth compounds or antibiotics. Rapid urease test, culture and histologic study of gastric biopsies,13C-urea breath test and serology, as well as HpSA, were performed to all patients. RESULTS: Forty seven patients were considered infected by H.pylori on the basis of bacterium isolation and 13C-urea breath test positivity. HpSAwas detected in 45 of the 47 H.pylori positive patients(95.7%). There were no HpSA false positive. CONCLUSION: Our results show that this new test is highly sensitive (95%) and specific(100%) for detection of H. pylori infection. It has some advantages over other non invasive techniques: it is easy to perform,requires no blood samples and its cost is lower than that of 13C-urea breath test.
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Antígenos Bacterianos/análisis , Heces/microbiología , Gastritis/diagnóstico , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/inmunología , Adolescente , Anticuerpos Antibacterianos/sangre , Proteínas Bacterianas/análisis , Pruebas Respiratorias , Isótopos de Carbono , Niño , Preescolar , Femenino , Gastritis/microbiología , Gastroscopía , Infecciones por Helicobacter/microbiología , Helicobacter pylori/aislamiento & purificación , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Urea , Ureasa/análisisRESUMEN
BACKGROUND: The purpose of this study was to evaluate the use of polymerase chain reaction (PCR) applied to the diagnosis Helicobacter pylori infection in the pediatric population, by means of a rapid and simple method of extraction and posterior detection by a colorimetric hybridation of amplified H. pylori DNA. METHODS: Fifty three gastric biopsies, obtained through upper gastrointestinal endoscopy from 53 patients with gastric pathology (45 recidivant abdominal pain and eight hematemesis), were processed from october 1995 to july 1996. Three non invasive tests were performed: detection of IgG by (Cobas) Core Anti-H. pylori EIA (Roche), breath test with 13C-urea and PCR of dental plaque, as well as four invasive ones: histologic study, culture into selective (Pylori Agar, bioMérieux) and non selective media (Columbia Agar with 5% sheep blood, bioMérieux), test of rapid urease and PCR of gastric biopsies. A 20% solution of Chelex 100 resin (DNA Extraction Reagen, Perkin Elmer) was used for DNA extraction, amplification was performed from gen ureA (Clayton, 1992) and amplified DNA was detected by colorimetric hybridation (PCR ELISA, Boehringer, Mannheim). Duration of the PCR process was: extraction 25 min, amplification two hours and detection three hours. RESULTS: Results of culture and PCR from gastric biopsies agreed in 84.3% of cases (27 positives, 16 negatives and two not determined). Two samples were positive by culture and negative by PCR, and were considered as PCR false negatives due to positivity of three or more other tests. Six samples were negative by culture and positive by PCR, being considered as culture false negatives due to positivity of three or more other tests. Sensitivity of PCR and culture was 94.2 and 82.8%. Specificity was 100% for both tests. None of the dental plaque samples was positive. CONCLUSIONS: When invasive techniques are to be done for microbiologic diagnose of H. pylori, PCR increases the confirmation rate of infection; the present procedure enables daily routine work due to its simplicity and its short turnaround time.
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Infecciones por Helicobacter/diagnóstico , Helicobacter pylori , Reacción en Cadena de la Polimerasa/métodos , Adolescente , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Malassezia spp. is a lipophilic yeast considered to be a normal component of the human skin flora. It has been associated with sepsis in patients receiving intravenous infusion of lipid emulsions through central venous catheters (CVC). Current evidence indicates a high rate of skin colonization in healthy adults, in contrast with the low rate of colonization in prepubertal children. Of note is the high prevalence of colonized infants in the neonatal intensive care unit (NICU). METHODS: We performed a prospective open observational study of colonization in all infants admitted to the NICU during a nine-month period (October 1997-June 1998). Length of stay in the unit, birthweight and the use of CVC for parenteral fat infusion were evaluated. RESULTS: Seventy-seven neonates were included in the study. The mean length of stay in the NICU was 24 days. A total of 63.6 % weighed less than 2,500 g at birth and 72 % were given parenteral nutrition supplemented with fat emulsion through a CVC. The overall rate of colonization in the unit was 41.5 and 75 % of the patients became colonized within the first two weeks of admission. CONCLUSIONS: These data emphasize the need for preventive measures to reduce the transmission of these yeasts in the NICU and to prevent the occurrence of neonatal sepsis due to Malassezia spp. in immunologically immature infants.
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Dermatomicosis/epidemiología , Fungemia/epidemiología , Unidades de Cuidado Intensivo Neonatal , Malassezia , Fungemia/microbiología , Humanos , Recién Nacido , Malassezia/aislamiento & purificación , Estudios Prospectivos , Factores de Riesgo , Piel/microbiologíaRESUMEN
OBJECTIVE: To study the possible viral etiology in 139 infants with lower respiratory tract infection who required hospitalization in the Infant Unit of our hospital, from October 1994 to June 1995. PATIENTS AND METHODS: 139 patients were admitted, aged from 13 days to 14 months, during this period. The etiological agent was detected by direct immunofluorescence from nasopharyngeal secretions. Monoclonal antibodies were used against Respiratory Syncitial Virus, Influenza A Virus, Influenza B Virus, Adenovirus and Parainfluenza 3 Virus. Antibody detection against these viruses by Complement Fixation Test was done on 29 of these patients, with paired sera (acute and convalescent phase). RESULTS: In 82 patients (59%) we found at least one viral agents from the nasopharyngeal specimens, but in 64 of these only one was detected, in the remaining 18, there were more than one. Significant levels of antibodies were detected in only six of the 29 patients tested. Serology was negative in the remaining 23 patients. CONCLUSIONS: Syncitial Respiratory Virus is the first virus responsible for the lower respiratory tract infection in this age group (49%). There was no correlation between serological diagnosis and antigen detection.
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Infecciones del Sistema Respiratorio/virología , Virosis/diagnóstico , Antígenos Virales/análisis , Femenino , Técnica del Anticuerpo Fluorescente Directa , Hospitalización , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
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Humanos , Masculino , Femenino , Lactante , Bacteriemia/complicaciones , Bacteriemia/diagnóstico , Kingella kingae/aislamiento & purificación , Kingella kingae/patogenicidad , Extremidad Inferior , beta-Lactamas/uso terapéutico , Artritis Infecciosa/complicaciones , Osteomielitis/complicaciones , Fiebre/complicaciones , Estomatitis Aftosa/complicaciones , Estomatitis Aftosa/diagnóstico , Pruebas de Función Respiratoria/métodosAsunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Terapia Antirretroviral Altamente Activa , ADN Viral/sangre , VIH-1/efectos de los fármacos , Transmisión Vertical de Enfermedad Infecciosa , Provirus/efectos de los fármacos , ARN Viral/sangre , Carga Viral , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/transmisión , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Lactante , Estudios Longitudinales , Reacción en Cadena de la Polimerasa/métodos , Provirus/genética , Provirus/aislamiento & purificación , ARN Viral/genética , Sensibilidad y EspecificidadAsunto(s)
Kingella kingae/patogenicidad , Infecciones por Neisseriaceae/microbiología , Osteomielitis/microbiología , Astrágalo/microbiología , Amoxicilina/uso terapéutico , Biopsia , Neoplasias Óseas/diagnóstico , Cefotaxima/uso terapéutico , Terapia Combinada , Diagnóstico Diferencial , Quimioterapia Combinada/uso terapéutico , Humanos , Inmovilización , Lactante , Kingella kingae/aislamiento & purificación , Imagen por Resonancia Magnética , Masculino , Infecciones por Neisseriaceae/diagnóstico , Infecciones por Neisseriaceae/tratamiento farmacológico , Infecciones por Neisseriaceae/cirugía , Osteomielitis/diagnóstico , Osteomielitis/tratamiento farmacológico , Osteomielitis/cirugía , Astrágalo/diagnóstico por imagen , Astrágalo/patología , Tomografía Computarizada por Rayos XRESUMEN
Fundamentos: Malassezia spp. es una levadura que forma parte de la microflora cutánea. Está demostrado que puede ser agente etiológico de sepsis en pacientes portadores de catéter venoso central (CVC) que reciben emulsiones lipídicas por vía parenteral. Se conoce que las personas adultas sanas están altamente colonizadas en las zonas con mayor densidad de glándulas sebáceas, en contraste con la baja densidad de colonización en niños por debajo de la edad puberal. Cabe destacar la elevada densidad de colonización en niños ingresados en unidades neonatales de cuidados intensivos (UCI). Métodos: Se realizó un estudio prospectivo observacional abierto de la colonización cutánea de todos los recién nacidos ingresados en la UCI, durante un período de 9 meses (octubre de 1997-junio de 1998) valorando el tiempo de permanencia en la unidad, el peso al nacimiento y la presencia de CVC por el que se administraba la alimentación parenteral. Resultados: Se controlaron 77 recién nacidos, cuya permanencia media en la unidad fue de 24 días. El 63,6% pesaban menos de 2.500 g al nacer y el 72% precisaron alimentación parenteral suplementada con lípidos, suministrada a través del CVC. La colonización global en esta unidad fue del 41,5% de los que el 75% se positivizó antes de las 2 semanas del ingreso. Conclusiones: El conocimiento de esta elevada tasa de colonización en la UCI neonatal implica extremar todas las medidas preventivas necesarias para reducir al mínimo la transmisión de esta levadura a través de la unidad, con el fin de prevenir una eventual sepsis neonatal por Malassezia spp. en este grupo de pacientes (AU)