Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries.

Transposition of the great arteries (TGA) is a congenital heart defect with a complex pathogenesis that has not been fully elucidated. In this study, we performed whole-exome sequencing (WES) in isolated TGA-diagnosed patients and analyzed genes of motile and non-motile cilia ciliogenesis and ciliary trafficking, as well as genes previously associated with this heart malformation. Deleterious missense and splicing variants of genes DNAH9, DNAH11, and ODAD4 of cilia outer dynein arm and central apparatus, HYDIN, were found in our TGA patients. Remarkable, there is a clustering of deleterious genetic variants in cilia genes, suggesting it could be an oligogenic disease. Our data evidence the genetic diversity and etiological complexity of TGA and point out that population allele determination and genetic aggregation studies are required to improve genetic counseling.

Calcinosis cutis congénita tumoral asociada con encefalopatía epiléptica infantil temprana con variante patogénica en el gen FGF12 / Tumorous congenital calcinosis cutis associated with early childhood epileptic encephalopathy with a pathogenic FGF12 gene variant

Resumen Introducción: La calcinosis cutis es el depósito de sales insolubles de calcio en la piel y se clasifica, de acuerdo con su patogénesis, en distrófica, metastásica, idiopática, iatrogénica y calcifilaxis. La calcinosis idiopática se presenta en pacientes sanos y es asintomática; incluye la calcinosis escrotal, la calcinosis nodular de Winer o nódulos calcificados subepidérmicos y la calcinosis tumoral familiar. Esta última es una condición rara que se caracteriza por el depósito de calcio periarticular en pacientes normocalcémicos sin conexión al hueso. Caso clínico: Paciente de sexo masculino de 5 meses de edad, quien al séptimo día de vida fue hospitalizado por ictericia multifactorial, sepsis neonatal tardía y apnea con crisis epilépticas. La evolución fue tórpida, con ingresos hospitalarios por crisis epilépticas de difícil manejo, respuesta parcial a la difenilhidantoína y descontrol electrolítico. Mediante la secuenciación del exoma dirigido se detectó una variante patogénica de sentido equivocado en FGF12 que confirmó el diagnóstico de encefalopatía epiléptica temprana número 47. Además, el paciente presentó dermatosis congénita diseminada a las extremidades inferiores con afección en muslos, asintomática, bilateral y simétrica, constituida por hipopigmentación y fóveas duras a la palpación profunda. La biopsia mostró calcificación distrófica. Conclusiones: Se presenta el caso de un lactante con calcinosis cutis congénita profunda asociada con una variante patogénica en el gen FGF12 y con encefalopatía epiléptica, situación clínica que, a la fecha, no había sido reportada en la literatura.

Abstract Background: Calcinosis cutis is the deposit of insoluble calcium salts in the skin. It is classified according to its pathogenesis in dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. Idiopathic calcinosis is asymptomatic, occurs in healthy patients, and includes scrotal calcinosis, Winer's nodular calcinosis or subepidermal calcified nodules, and familial tumor calcinosis. The latter is a rare condition characterized by periarticular calcium deposition in normocalcemic patients with no bone connection. Case report: The case of a 5-month-old male patient, who on the seventh day of life was hospitalized for multifactorial jaundice, late neonatal sepsis, and apnea with epileptic seizures is described. His evolution was torpid, with hospital admissions due to epileptic seizures that were difficult to manage with partial response to the use of diphenylhydantoin and electrolyte alterations. By means of exome sequencing directed, a pathogenic variant of wrong direction in FGF12 was detected and the diagnosis of early epileptic encephalopathy number 47 was confirmed. Also, the patient showed disseminated congenital dermatosis to lower extremities affecting thighs, asymptomatic, bilateral and symmetrical, constituted by hypopigmentation and fovea hard to deep palpation. The biopsy showed dystrophic calcification Conclusions: The case of an infant with deep congenital cutis calcinosis associated with a pathogenic variant in the FGF12 gene with epileptic encephalopathy is described. To date, this clinical situation has not been previously reported in the literature.

Tumorous congenital calcinosis cutis associated with early childhood epileptic encephalopathy with a pathogenic FGF12 gene variant.

Background: Calcinosis cutis is the deposit of insoluble calcium salts in the skin. It is classified according to its pathogenesis in dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. Idiopathic calcinosis is asymptomatic, occurs in healthy patients, and includes scrotal calcinosis, Winer's nodular calcinosis or subepidermal calcified nodules, and familial tumor calcinosis. The latter is a rare condition characterized by periarticular calcium deposition in normocalcemic patients with no bone connection. Case report: The case of a 5-month-old male patient, who on the seventh day of life was hospitalized for multifactorial jaundice, late neonatal sepsis, and apnea with epileptic seizures is described. His evolution was torpid, with hospital admissions due to epileptic seizures that were difficult to manage with partial response to the use of diphenylhydantoin and electrolyte alterations. By means of exome sequencing directed, a pathogenic variant of wrong direction in FGF12 was detected and the diagnosis of early epileptic encephalopathy number 47 was confirmed. Also, the patient showed disseminated congenital dermatosis to lower extremities affecting thighs, asymptomatic, bilateral and symmetrical, constituted by hypopigmentation and fovea hard to deep palpation. The biopsy showed dystrophic calcification. Conclusions: The case of an infant with deep congenital cutis calcinosis associated with a pathogenic variant in the FGF12 gene with epileptic encephalopathy is described. To date, this clinical situation has not been previously reported in the literature.

Background: Introducción">La calcinosis cutis es el depósito de sales insolubles de calcio en la piel y se clasifica, de acuerdo con su patogénesis, en distrófica, metastásica, idiopática, iatrogénica y calcifilaxis. La calcinosis idiopática se presenta en pacientes sanos y es asintomática; incluye la calcinosis escrotal, la calcinosis nodular de Winer o nódulos calcificados subepidérmicos y la calcinosis tumoral familiar. Esta última es una condición rara que se caracteriza por el depósito de calcio periarticular en pacientes normocalcémicos sin conexión al hueso. Caso clínico: Paciente de sexo masculino de 5 meses de edad, quien al séptimo día de vida fue hospitalizado por ictericia multifactorial, sepsis neonatal tardía y apnea con crisis epilépticas. La evolución fue tórpida, con ingresos hospitalarios por crisis epilépticas de difícil manejo, respuesta parcial a la difenilhidantoína y descontrol electrolítico. Mediante la secuenciación del exoma dirigido se detectó una variante patogénica de sentido equivocado en FGF12 que confirmó el diagnóstico de encefalopatía epiléptica temprana número 47. Además, el paciente presentó dermatosis congénita diseminada a las extremidades inferiores con afección en muslos, asintomática, bilateral y simétrica, constituida por hipopigmentación y fóveas duras a la palpación profunda. La biopsia mostró calcificación distrófica. Conclusiones: Se presenta el caso de un lactante con calcinosis cutis congénita profunda asociada con una variante patogénica en el gen FGF12 y con encefalopatía epiléptica, situación clínica que, a la fecha, no había sido reportada en la literatura.

Piperacillin/tazobactam plus amikacin vs. piperacilin/tazobactam: treatment for children with febrile neutropenia / Piperacilina/tazobactam más amikacina vs. piperacilina/tazobactam: tratamiento en niños con neutropenia febril

Background: Pediatric patients with febrile neutropenia usually receive a combination of broad spectrum antimicrobials. Treatment without aminoglycoside seems to have advantages. Objective: To compare the efficacy of piperacillin/tazobactam plus amikacin versus piperacillin/tazobactam. Methods: Randomized, open label, controlled clinical trial. Sample size for an efficacy of 55%, and delta of 25%; 80 episodes were required for each group. Selection criteria were patients with febrile neutropenia, candidates to receive parenteral antimicrobial treatment; they were randomized to one of two groups, piperacillin/tazobactam plus amikacin (Group A), or piperacillin/tazobactam (Group B). The outcomes were failure, adverse events and death. Mantel-Haenszel chi squaretest and exact Fisher test were used. Reduction of relative and absolute risk (RRR and ARR), 95% confidence intervals (CI 95%) and number needed to treat (NNT) were calculated. Results: 88 Episodes were analyzed in group A and 76 in group B. There was no statistical difference in general characteristics of patients or type of infections. There was not significant statistical difference in: failure 31.8% group A, 30.2% group B (RR 1.05, CI 95% 0.66-1.66, p = 0.86), or adverse events (one in each group). The RRR was 1.5%, and ARR 2%, with a NNT of 67. Conclusion: Piperacillin/tazobactam without amikacin was as effective as combination therapy in pediatric patients with febrile neutropenia.

Introducción: los pacientes pediátricos con neutropenia febril habitualmente reciben una combinación de antimicrobianos de amplio espectro. La terapia sin aminoglucósido parece tener ventajas. Objetivo: comparar la eficacia de piperacilina/tazobactam más amikacina frente a la de piperacilina/tazobactam. Métodos: ensayo clínico controlado aleatorizado. Tamaño de muestra para una eficacia de 55%, y delta de 25%; se calcularon 80 episodios por grupo. Fueron seleccionados pacientes con neutropenia febril, candidatos a recibir antimicrobiano parenteral; se aleatorizaron a recibir piperacilina/tazobactam más amikacina (grupo A) o piperacilina/tazobactam (grupo B). Los desenlaces fueron falla, eventos adversos y muerte. Se emplearon las pruebas Chi cuadrada de Mantel-Haenszel y exacta de Fisher. Se calculó la reducción de riesgo relativo y absoluto (RRR y RRA), intervalos de confianza 95% (IC 95%) y número necesario a tratar (NNT). Resultados: se analizaron 88 episodios en el grupo A y 76 en el grupo B. No hubo diferencias estadísticas en características generales ni en el tipo de infecciones. No se encontró diferencia significativa en: falla 31.8% grupo A, 30.2% grupo B (RR 1.05, IC 95% 0.66-1.66, p = 0.86), ni en los eventos adversos (uno en cada grupo). La RRR fue de 1.5%, RRA de 2%, con un NNT de 67. Conclusión: la terapia con piperacilina/tazobactam sin amikacina fue tan efectiva como la terapia combinada para pacientes pediátricos con neutropenia febril.

Relación entre sobrecarga hídrica y mortalidad en niños conshock séptico / Relation between fluid overload and mortality in children with septic shock

El shock séptico es una de las principales causas que puede llevar a la muerte. La reanimación hídrica constituye un destacado tratamiento para poder disminuir la mortalidad. Objetivo: determinar la relación entre el porcentaje de sobrecarga hídrica (%SH) y la mortalidad en niños con shock séptico. Métodos. Estudio de cohorte en pacientes con shock séptico de entre 1 y 17 años, posterior a la reanimación hídrica con presión venosa central ≥ 5 mmHg con monitoreo invasivo y registro completo de %SH hasta las 96 h. El seguimiento y la variable de desenlace se completaron hasta el día 28. Se registraron las siguientes variables del shock séptico, shock refractario, causa de la insuficiencia renal aguda, anemia, desnutrición, el tiempo de inicio de antimicrobiano, presión oncótica y puntaje de gravedad. Análisis estadístico: Se calculó el hazard ratio (HR) y se construyeron tres modelos pronósticos por riesgos proporcionales de Cox. Resultados. La población fue de 263 pacientes; con un promedio de edad de 8 ± 3 años y con mortalidad del 33 %. El %SH ≥ 10,1 acumulado a las 96 h fue el único asociado; el HR (IC 95 %) ajustado fue perfil hemodinámico HR = 2,6 (1,95,6); por shock refractario, HR = 2,5 (1,6-5,6) y por desnutrición, HR = 8,3 (3,5-14). Conclusiones. El %SH > 10,1 % se relacionó con una mayor mortalidad a 28 días de ajustado al perfil hemodinámico, la refractariedad del shock y el estado nutricional.

Septic shock is one of the main causes of mortality. Fluid replacement stands out as the treatment of choice to reduce mortality. Objective. To determine the relation between the percentage of fluid overload (%FO) and mortality in children with septic shock. Methods. Cohort study in patients aged 1-17 years with septic shock, after fluid replacement with central venous pressure ≥ 5 mmHg, invasive monitoring, and complete recording of %FO up to 96 h. Follow-up and outcome measures were recorded up to day 28. The following outcome measures of septic shock were recorded: refractory shock, cause of acute kidney injury, anemia, malnutrition, time to antibiotic initiation, oncotic pressure, and severity score. Statistical analysis. The hazard ratio (HR) was estimated and three Cox proportional hazard models were developed. Results. The population included 263 patients; their average age was 8 ± 3 years. Mortality was 33 %. A %FO ≥ 10.1 % accumulated at 96 h was the only associated outcome measure; the HR (95 % confidence interval) was adjusted for hemodynamic profile, HR = 2.6 (1.95.6); refractory shock, HR = 2.5 (1.6-5.6); and malnutrition, HR = 8.3 (3.5-14). Conclusions. A %FO > 10.1 % was related to a higher mortality at 28 days of adjustment for hemodynamic profile, refractory shock, and nutritional status.

Relation between fluid overload and mortality in children with septic shock. / Relación entre sobrecarga hídrica y mortalidad en niños conshock séptico.

INTRODUCTION: Septic shock is one of the main causes of mortality. Fluid replacement stands out as the treatment of choice to reduce mortality. OBJECTIVE: To determine the relation between the percentage of fluid overload (%FO) and mortality in children with septic shock. METHODS: Cohort study in patients aged 1-17 years with septic shock, after fluid replacement with central venous pressure ≥ 5 mmHg, invasive monitoring, and complete recording of %FO up to 96 h. Follow-up and outcome measures were recorded up to day 28. The following outcome measures of septic shock were recorded: refractory shock, cause of acute kidney injury, anemia, malnutrition, time to antibiotic initiation, oncotic pressure, and severity score. STATISTICAL ANALYSIS AND METHODS: The hazard ratio (HR) was estimated and three Cox proportional hazard models were developed. RESULTS: The population included 263 patients; their average age was 8 ± 3 years. Mortality was 33 %. A %FO ≥ 10.1 % accumulated at 96 h was the only associated outcome measure; the HR (95 % confidence interval) was adjusted for hemodynamic profile, HR = 2.6 (1.95.6); refractory shock, HR = 2.5 (1.6-5.6); and malnutrition, HR = 8.3 (3.5-14). CONCLUSIONS: A %FO > 10.1 % was related to a higher mortality at 28 days of adjustment for hemodynamic profile, refractory shock, and nutritional status.

El shock séptico es una de las principales causas que puede llevar a la muerte. La reanimación hídrica constituye un destacado tratamiento para poder disminuir la mortalidad. Objetivo: determinar la relación entre el porcentaje de sobrecarga hídrica (%SH) y la mortalidad en niños con shock séptico. Métodos. Estudio de cohorte en pacientes con shock séptico de entre 1 y 17 años, posterior a la reanimación hídrica con presión venosa central ≥ 5 mmHg con monitoreo invasivo y registro completo de %SH hasta las 96 h. El seguimiento y la variable de desenlace se completaron hasta el día 28. Se registraron las siguientes variables del shock séptico, shock refractario, causa de la insuficiencia renal aguda, anemia, desnutrición, el tiempo de inicio de antimicrobiano, presión oncótica y puntaje de gravedad. Análisis estadístico: Se calculó el hazard ratio (HR) y se construyeron tres modelos pronósticos por riesgos proporcionales de Cox. Resultados. La población fue de 263 pacientes; con un promedio de edad de 8 ± 3 años y con mortalidad del 33 %. El %SH ≥ 10,1 acumulado a las 96 h fue el único asociado; el HR (IC 95 %) ajustado fue perfil hemodinámico HR = 2,6 (1,95,6); por shock refractario, HR = 2,5 (1,6-5,6) y por desnutrición, HR = 8,3 (3,5-14). Conclusiones. El %SH > 10,1 % se relacionó con una mayor mortalidad a 28 días de ajustado al perfil hemodinámico, la refractariedad del shock y el estado nutricional.

Genotype-guided antiretroviral regimens in children with multidrug-resistant HIV-1 infection.

BACKGROUND: Genotyping tests were developed to attenuate the impact of viral resistance. Information about the efficacy in genotype base antiretroviral therapy in children is rare and even more in low- and middle-income countries. METHODS: Sixteen children with antiretroviral therapy (ART) failure and triple-class drug-resistant viruses were included in this study. Protease and retrotranscriptase genotypes were available for all patients. Switch of ART regimen was guided by genotyping data. The primary end point was virological suppression (<50 copies/ml) and immunological improvement after 48 wk of treatment with the new ART regimen. RESULTS: The median age of the patients was 14.5 y (interquartile range (IQR) 11-16.5). Median HIV-1 RNA viral load was 4.2 log10 (IQR: 3.4-4.8). The primary end point was found in 11 children (69%), and 13 children (81%) had an HIV-1 RNA viral load <200 copies/ml. Median (IQR) for the baseline CD4(+) cell count was 382 cells/µl (281-686 cells/µl), whereas after 48 wk of treatment with the new ART regimen, it was 640 cells/µl (361-936 cells/µl) (P < 0.001). CONCLUSION: Darunavir/ritonavir, raltegravir, and etravirine were well tolerated in the present pediatric population. These drugs provide good options for children exposed to extensive ART. Regimens guided by genotyping data were effective for children who had ART failure and multidrug-resistant HIV-1 infection.

[Risk factors for nosocomial infection in a level III Neonatal Intensive Care Unit]. / Factores de riesgo asociados a infección nosocomial (IN) en una Unidad de Cuidados Intensivos Neonatales (UCIN) de tercer nivel.

INTRODUCTION: Nosocomial infections are a major and a frequent problem in neonatal intensive care units and increase morbidity, mortality, and costs. The objective of this study was to identify the risk factors associated with nosocomial infections in a neonatal intensive care unit. METHODS: Nested case control study. Records from patients were registered: gestational age, sex, birth weight, central venous catheter and other devices, congenital malformations, surgeries, mechanical ventilation, steroid use, H2 blockers, length of stay in neonatal intensive care unit, type of infection, and etiological agent. RESULTS: We studied 188 cases with nosocomial infections and 192 controls without nosocomial infections. The most frequent infection was sepsis (34.8%) and coagulase negative Staphylococcus was the principal etiological agent (37.2%). The risk factors associated with nosocomial infection were central venous catheter (OR: 7.3; 95% CI: 2.3-22.8), duration of neonatal intensive care unit stay>14 days (OR: 3.4; 95% CI: 1.7-6.7), H2 blockers (OR: 2.3; 95% CI: 1.2-4.2), number of surgeries≥2 (OR: 3; 95% CI: 1.1-7.9) and mechanical ventilation>7 days (OR: 2.1; 95% CI: 1.1-4.2). CONCLUSIONS: Some risk factors associated to nosocomial infections in this study are similar to those found previously, with the exception of the number of surgeries that was not reported in previous studies.

[Epidemiology of nosocomial infections in a neonatal intensive care unit]. / Epidemiología de las infecciones nosocomiales en una unidad de cuidados intensivos neonatales.

BACKGROUND: Newborns who are admitted to neonatal intensive care units are at a high risk for the development of a nosocomial infection. The purpose of this study was to record the incidence and the type of nosocomial infections, the isolated microorganisms and the susceptibility profile of these newborns in a neonatal intensive care unit. METHODS: A descriptive, prospective, longitudinal study was conducted over a 1-year period. Out of 113 newborns with nosocomial infection, demographic variables, antibiotic use prior to admission, central venous catheter use, type of nosocomial infection, isolated microorganism and susceptibility profile were recorded. RESULTS: One hundred and forty nine nosocomial infection episodes were recorded, with an incidence of 37.7 × 100 discharges and an incidence density rate of 25.6 × 1000 patient-days. The most common nosocomial infections were central venous catheter colonization related bacteremia (35.5 %) and sepsis (28.8 %). The most common microorganisms were coagulase-negative Staphylococcus (43.4 %) and Klebsiella pneumoniae (21 %), out of which 97.3 % were extended-spectrum beta-lactamase-producers. CONCLUSIONS: The incidence of nosocomial infection was similar to that reported in developing countries. Central venous catheter colonization-related bacteremia and gram-positive bacteria were the most common nosocomial infection and causative microorganisms, respectively.

INTRODUCCIÓN: el recién nacido hospitalizado en una unidad de cuidados intensivos tiene alto riesgo de desarrollar una infección nosocomial. El objetivo de este estudio fue registrar la incidencia y el tipo de infecciones nosocomiales, los microorganismos aislados y el perfil de susceptibilidad de estos en recién nacidos atendidos en una unidad de cuidados intensivos neonatales. MÉTODOS: se llevó a cabo un estudio descriptivo prospectivo longitudinal durante un año. De 113 recién nacidos que presentaron infección nosocomial, se registraron variables demográficas, uso de antibióticos antes del ingreso y de catéter venoso central, tipo de infección, microorganismo aislado y perfil de susceptibilidad. RESULTADOS: se registraron 149 infecciones nosocomiales, cuya incidencia fue de 37.7 × 100 egresos y su densidad de incidencia fue de 25.6 por cada 1000 días-paciente. Las infecciones nosocomiales más frecuentes fueron bacteriemia relacionada con la colonización del catéter venoso central (35.5 %) y la sepsis (28.8 %). Los principales microorganismos fueron los Sthapylococcus coagulasa negativa (43.4 %), todos resistentes a meticilina, y Klebsiella pneumoniae (21 %); 97.3 % de estos era productor de betalactamasas de espectro extendido. CONCLUSIONES: la incidencia de la infección nosocomial fue similar a la informada en los países en desarrollo. La bacteriemia relacionada con la colonización del catéter venoso central y los grampositivos fueron la infección nosocomial y los microorganismos causales más frecuentes.

[Antimicrobial resistance in uropathogens isolated in a pediatric hospital]. / Resistencia antimicrobiana de los uropatógenos aislados en un hospital pediátrico.

BACKGROUND: Urinary tract infection is one of the most common infections at all ages. Antimicrobial resistance has increased in the past few years. The aim of this study was to determine the most common etiologic agents of urinary tract infections and their antimicrobial susceptibility profiles. METHODS: A descriptive, cross-sectional survey was conducted. Patients with a urinary tract infection identified over a 1-year period were included. The type of infection, risk condition, antimicrobial treatment, microorganism and antimicrobial susceptibility were recorded. STATISTICAL ANALYSIS: descriptive statistics. RESULTS: One hundred and seventy four patients with infection, 31.4 % with urinary tract malformation, 56 % with functional abnormalities. 76.4 % were receiving antimicrobial prophylaxis. Escherichia coli was the most common agent isolated with 67%, followed by Klebsiella spp. 9 %, Pseudomonas spp. 7 % and others less frequently. Escherichia coli resistance to cephalotin was 58.7%, to norfloxacin 51 %, nitrofurantoin 15.5 %, cefuroxime 12.5 %, cefotaxime 15.5 %, cefepime 5 % and to amikacin 0 %. CONCLUSIONS: Escherichia coli was the most common causative agent, and resistance to quinolones and cephalotin was higher than 50 %. Most patients had urinary tract functional abnormalities and a history of prophylactic treatment use. Options other than quinolones need to be assessed due to the high resistance identified in uropathogens.

INTRODUCCIÓN: la infección urinaria es una de las más comunes en todas las edades. Recientemente se ha incrementado la resistencia antimicrobiana. El objetivo del estudio fue determinar los agentes etiológicos más frecuentes de infección urinaria y sus perfiles de susceptibilidad antimicrobiana. MÉTODOS: se llevó a cabo una encuesta transversal descriptiva. Se incluyeron los pacientes con infección urinaria identificados durante un año. Se registró tipo de infección, condición de riesgo, tratamientos antimicrobianos, microorganismos y resistencia antimicrobiana. El análisis de los datos se llevó a cabo mediante estadística descriptiva. RESULTADOS: se identificaron 174 pacientes con infección, 31.4 % con malformación del tracto urinario y 56 % con alteraciones funcionales; 76.4 % recibía profilaxis antimicrobiana. Escherichia coli fue el agente más frecuente (67 %), seguido de Klebsiella spp. (9 %) y Pseudomonas spp. (7 %). Se observó resistencia de Escherichia coli a cefalotina (58.7 %), norfloxacina (51 %), nitrofurantoína (15.5 %), cefuroxima (12.5 %), cefotaxima (15.5 %) y cefepime (5 %). CONCLUSIONES: Escherichia coli fue el agente causal más frecuente y la resistencia a quinolonas y cefalotina fue superior a 50 %. La mayoría de los pacientes tenían alteraciones funcionales de la vía urinaria y antecedente de uso de tratamiento profiláctico. Es necesario evaluar opciones diferentes a las quinolonas, dada la elevada resistencia que se identificó en los uropatógenos.

Production of icaADBC-encoded polysaccharide intercellular adhesin and therapeutic failure in pediatric patients with Staphylococcal device-related infections.

BACKGROUND: Biofilm production has been established as a virulence factor which allows Staphylococcus to adhere and persist in medical devices. The objective was to determine whether therapeutic failure in patients infected with Staphylococcus spp. is linked to biofilm production, the presence of the ica operon, and the bacterial insertion sequence element IS256. METHODS: Staphylococcus spp. isolates from patients with device-related infections were collected. Therapeutic failure with proper antimicrobial treatment was registered. Biofilm phenotype was determined by Congo red test agar and Christensen assay. Presence of the ica operon genes A-D and IS256 was detected by PCR. Differences were compared through x2. RESULTS: 100 isolates from staphylococcal infections episodes were included: 40 sepsis/bacteremia, 32 ependymitis, and 28 peritonitis. 73.77% of CoNS and 79.5% of S. aureus isolates harbored the icaD gene, 29% of all isolates IS256-A+ IS256-D genes, icaA and icaB genes were only found in CoNS (27.8% and 21.3% respectively). Therapeutic failure occurred in 95.4.% of patients with a positive IS256-A+ IS256-D S. epidermidis isolate, RR 5.49 (CI 95% 2.24-13.44 p < or = 0.0001), and 85.76% in CoNS isolates, RR 2.57 (CI 95% 0.97-6.80, p = 0.05). Although none S. aureus was positive for IS256-A + IS256-D, therapeutic failure was observed in 35.8%. CONCLUSIONS: The presence of icaA/D genes along with the sequence element IS256 was associated with therapeutic failure in most CoNS infections, even though its absence in S. aureus isolates does not ensure therapeutic success.

An outbreak due to Serratia marcescens in a neonatal intensive care unit typed by 2-day pulsed field gel electrophoresis protocol.

BACKGROUND: Serratia marcescens is a well-recognized nosocomial pathogen. The objective of the study was to describe typing results using a rapid pulsed field gel electrophoresis (PFGE) protocol and infection control measures during an outbreak of Serratia marcescens in a 24-bed, referral, neonatal intensive care unit (NICU) of a tertiary-care pediatric hospital. METHODS: Two patients with S. marcescens sepsis were identified in the NICU. Health care personnel of the unit were requested to reinforce infection control measures. Active surveillance was established to detect infected and/or colonized patients and environmental and staff reservoirs. Infected and colonized patients were cohorted on one side of the unit; admissions to NICU were limited. Isolates were typed with a short 2-day pulsed-field gel electrophoresis (PFGE) protocol. RESULTS: Thirty three patients were exposed during a period of 20 days. Ten S. marcescens isolates were obtained from six patients, in two from blood culture and in three from stool culture; a single clone was identified in four. S. marcescens was not isolated from environmental or staff cultures. CONCLUSIONS: PFGE results were obtained in 2 days, infection control measures were reinforced, outbreak was promptly interrupted, and the NICU remained opened.