A joint frailty-copula model for meta-analytic validation of failure time surrogate endpoints in clinical trials.

In a meta-analysis framework, the classical approach for the validation of time-to-event surrogate endpoint is based on a two-step analysis. This approach often raises estimation issues. Recently, we proposed a one-step validation approach based on a joint frailty model. This approach was quite time consuming, despite parallel computing, due to individual-level frailties used to take into account heterogeneity in the data at the individual level. We now propose an alternative one-step approach for evaluating surrogacy, using a joint frailty-copula model. The model includes two correlated random effects treatment-by-trial interaction and a shared random effect associated with the baseline risks. At the individual level, the joint survivor functions of time-to-event endpoints are linked using copula functions. We used splines for the baseline hazard functions. We estimated parameters and hazard function using a semiparametric penalized marginal likelihood method, considering various numerical integration methods. Both individual-level and trial-level surrogacy were evaluated using Kendall's tau and coefficient of determination. The performance of the estimators was evaluated using simulation studies. The model was applied to individual patient data meta-analyses in advanced ovarian cancer to assess progression-free survival as a surrogate for overall survival, as part of the evaluation of new therapy. The model showed good performance and was quite robust regarding the integration methods and data variation, regardless of the surrogacy evaluation criteria. Kendall's Tau was better estimated using the Clayton copula model compared to the joint frailty model. The proposed model reduces the convergence and model estimation issues encountered in the two-step approach.

Incorporation of zebularine from its 2'-deoxyribonucleoside triphosphate derivative and activity as a template-coding nucleobase.

Zebularine (1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one) was studied as both a 2 '-deoxyribosyl 5 '-triphosphate derivative and as a template incorporated into an oligonucleotide. Using a novel pyrosequencing assay, zebularine acted as cytosine analog and was incorporated into DNA with a template pairing profile most similar to cytosine, pairing with greatest efficiency opposite guanine in the template strand. Guanine was incorporated with greater affinity than adenine opposite a zebularine in the template strand. Computer modeling of base-pairing structures supported a better fit of zebularine opposite guanine than adenine. Zebularine acts as a cytosine analog, which supports its activity as an inhibitor of cytosine methyltransferase.

[Bacteremia due to Abiotrophia defectiva in a febrile neutropenic pediatric patient]. / Bacteriemia por Abiotrophia defectiva en un paciente pediótrico neutropénico febril.

The presence of Granulicatella spp. in bacteremic episodes of neutropenic patients was recently highlighted whereas Abiotrophia defectiva, was only isolated in cases of infectious endocarditis. The aim of this study is to describe a case of A.defectiva bacteremia in a leukemic and febrile (40 degrees C) neutropenic (200 GB/mm3) boy. A.defectiva was only isolated from one of the two processed blood samples. Although the patient was undergoing an episode of varicela which could have accounted as the possible cause of fever, A. defectiva was considered a significant finding because this species is not part of the commensal skin flora. This case suggests that both A. defectiva and Granulicatella spp. should be regarded as possible causes of bacteremia in immunocompromised patients.

Viridans streptococci bacteraemia in children with fever and neutropenia: a case-control study of predisposing factors.

Viridans streptococci (VS) are an increasing cause of bacteraemia in neutropenic patients with cancer. Case-control studies of predisposing factors for acquisition of this infection in children are not published. Between January 1989 and December 1999, 168 episodes of bacteraemia in 161 children with fever and neutropenia of haemato-oncology origin were analysed. 15 cases (9%) in 15 patients were caused by VS. Each case patient was compared with 6 matched control patients; 2 with other Gram-positive cocci (group 2), 2 with gram-negative bacilli bacteraemia (group 3) and two children with fever and neutropenia without bacteraemia (group 4). The median age of patients was 4.1 years (range: 2-15 years). 87% of children had acute leukaemia or lymphomas. Pneumonia was the predominant clinical focus (70%). Shock was observed in 13% of patients. ARDS was observed in one child who died of this complication. Multivariate analysis of risk factors for the development of VS bacteraemia showed that two factors were independent predictors: high doses of cytosine-arabinoside (ARA-C) as part of the chemotherapy treatment (Odds Ratio (OR): 9.3; Confidence Interval (CI) 1.56-55.5) (P<0.014) and the presence of pneumonia (OR: 1.36: CI 2.27-81.9) (P<0.0043). We propose that further studies are warranted to confirm these results.

[Acute Q fever: study of 23 patients (author's transl)]. / Fiebre Q aguda: experiencia en 23 casos.

Twenty-three patients with Q fever who were diagnosed over a 3 year period are described. The majority came from the Madrid urban area and less than half had epidemiological antecedents. Nine patients presented with pulmonary infiltrations, 12 with suppressed fever and in 2 criteria for fever of unknown origin were met. The majority had clinical or analytic data of hepatic disease and liver biopsy practiced in 4 patients showed granulomas. Diagnosis was established through the increment of seric antibodies against antigens of phase II C. burnetii, detected by complement fixation test. Acute Q fever is not a rare disease in our environment and must be taken into account when a differential diagnosis is looked for in processes such as fever of short evolution, fever of unknown origin, pneumoniae and granulomatous hepatitis.

[Risk factors for nosocomial bacterial infection in children: a case-control study]. / Factores de riesgo de adquisición de bacteriemias intranosocomiales en niños. Un estudio de casos y controles.

With the objective to identify independent risk factors associated with the development of nosocomial bacteremia, we have performed a prospective, exploratory, case-control study. All non-neutropenic children with nosocomial bacteremia admitted during a seven-month period were eligible. All children non-neutropenic without nosocomial bacteremia were eligible as controls. The incidence of bacteremia in the study population was 11.3/1000 admissions. Ninety one cases and ninety nine controls were analyzed. In 46% of patients clinical foci were detected. The catheter-related infection was the most frequently founded. Staphylococcus spp coagulase negative, Staphylococcus aureus and Klebsiella pneumoniae were the microorganisms more frequently isolated. Multivariate analysis identified five risk factors independently associated with nosocomial bacteremia: admission outside of Intensive Care Units (ICU) (OR: 8.14, 2.60-25.5), previous antibiotic treatment (OR: 5.02, 2.18-11.5), invasive procedures (OR: 5.35, 1.70-16.8), without surgery (OR: 2.99, 1.37-6.52) and the presence of central venous lines (OR: 5.35, 2.13-12.4). Our data give strong support for the value of testing strict guidelines for limiting vascular catheter and antibiotic use, and limiting the invasive procedures.

[Community-acquired Staphylococcus aureus bacteremia in children: analysis of mortality risk factors]. / Bacteriemias en niños por Staphylococcus aureus adquiridas en la comunidad: análisis de los factores de riesgo de mortalidad.

Sixty episodes of community-acquired Staphylococcus aureus bacteremia (SaCB) were prospectively analyzed between January 1990 and December 1994. The mean age of the patients was 78 (1-180) months. Thirteen (55%) of the children had underlying disease, the most frequent one being acute lymphoblastic leukemia. In 83% of the episodes a primary site of infection was observed. Skin and osteoarticular foci were the most frequently encountered. Only two patients had endocarditis. Arterial hypotension was detected in 17% of the patients. Ninety two percent of S. aureus isolated were penicillin-resistant. Only two strains were methicillin-resistant. In 24 (40%) episodes where metastatic foci were detected, osteoarticular infections were predominant. Mortality due to SaCB was 20%. Multivariate analysis by logistic regression revealed that arterial hypotension (RR = 24.8; 4.77-128.9), leucopenia (RR = 10.3; 1.25-86.2) and non hemato-oncologic diseases (RR = 10.0; 1.09-92.2) correlated with high mortality rate (p = < 0.001).

[Criteria of low risk of mortality in children with neutropenia and fever during cancer chemotherapy]. / Criterios de bajo riesgo de mortalidad en niños con neutropenia y fiebre durante la quimioterapia por cáncer.

To validate the use of a lower-risk mortality profile in pediatric febrile neutropenia during anticancer therapy and to evaluate the efficacy of a sequential parenteral-oral antibiotic treatment for these children, a prospective study was conducted between May 1997 and December 1999. During this period 247 episodes in 215 patients were included in the present study. Children with neutropenia (ANC < 500/mm3) and fever (> 38 degrees C) due to anticancer therapy were eligible for the study if they presented the following lower-risk conditions: absence of severe co-morbidity factors, good clinical condition, no risk clinical foci, no bacteremia, and responsible parents. They were initially treated with inpatient parenteral short course of ceftriaxone and amikacin followed by ambulatory oral cefixime or ciprofloxacin to complete 7 days. Mean age was 64 (range: 8-200) months. The most common underlying malignant disease was acute lymphoblastic leukemia in 48% (118) of cases and 57% (141) of patients had an indwelling central venous catheter. Clinical evidence of infection was found in 47% (122) of children and the most common site was the upper respiratory tract (81%). Mean period of fever was 1.1 days (r: 1-8) and the duration of neutropenia was 3.9 days (r: 1-9). Sixty-one% (150) of children was discharged with neutropenia. Mean time of hospitalization was 1.5 days. Four clinical failures were detected (1.6%). They all were satisfactorily treated with a secondary treatment and none underwent any major complications or died. The lower-risk profile used was safe and the sequential antibiotic therapy was adequate to manage febrile neutropenia in this subset of children.

[False-positive cultures due to cross contamination in tuberculosis laboratories]. / Falsos cultivos positivos por contaminación cruzada en laboratorios de tuberculosis.

Fifteen episodes of Mycobacterium tuberculosis laboratory cross-contamination suspected between 1996 and 2001 at 6 laboratories in Buenos Aires City and suburbs were investigated by IS6110 RFLP. Thirteen episodes were confirmed. Even though BACTEC 460 produced the highest number of confirmed episodes in a single laboratory, the most extended one occurred while employing conventional culture procedures in solid medium. The double repetitive element-polymerase chain reaction (DRE-PCR) was applied to 8 of these episodes and produced concordant results with those of the RFLP. The DRE-PCR appears to be a valuable tool for the prompt identification of false positive cultures. The timely rectification of defects in laboratory protocols can avert false diagnoses of tuberculosis and unnecessary prolonged treatments.

[Bact-Alert automatized system for blood cultures: 5 vs 7 days of incubation. First Argentine multicentre study]. / Sistema automatizado de hemocultivos Bact-Alert: 5 vs 7 dias de incubación. Primer estudio multicéntrico argentino.

Bact-Alert automatized system for blood cultures: 5 vs 7 days of incubation. First Argentine multicentre study. Between January and December 2001, we analyzed 80,141 blood cultures by the Bact-Alert system (14,960 FAN aerobics, 3,855 FAN anaerobic, 11,114 standards aerobics, 11,367 standards anaerobic, 12,054 pediatrics and 26,791 FAN pediatrics bottles) and 44.235 series from 27.615 patients at eight hospitals of Buenos Aires city, one of La Plata city and three of the Buenos Aires province. A total of 13,657 blood cultures yielded a positive result. Only 181 of them had been detected as positive between the 5th and 7th day of incubation and only 26 (0.19%) had clinical significance (Staphylococcus aureus 3; coagulase negative staphylococci 2; Enterococcus faecalis 1; Streptococcus pneumoniae 2; Campylobacter spp 1; Escherichia coli 1; Enterobacter cloacae 1; Enterobacteraerogenes 1; Citrobacter freundii 1; Klebsiella pneumoniae 1; Proteus mirabilis 1; Serratia marcescens 4; yeasts 7, including one strain of Cryptococcus neoformans). Of the total of contaminants, 38% were isolated by the anaerobic standard (65% were Propionibacterium spp and 29% coagulase negative staphylococci), 31.2% by the FAN aerobic (33.3% difphteroids and 28.9% Bacillus spp), 11.8% by the pediatric, 9% by FAN pediatric, 8.33% by aerobic standard and 1.4% by FAN anaerobic bottle. Our results show that the prolonged incubation of blood cultures for more than 5 days using the Bact-Alert system is unnecessary.

Infecciones invasivas con bacteriemia por Streptococcus pneumoniae en niños: ¿qué pasó en los últimos 5 años? / Invasive infections with bacteremia due to Streptococcus pneumoniae in children: What has happened over the past 5 years?

Introducción: Las infecciones por Streptococcus pneumoniae (Spn) constituyen enfermedades de alta prevalencia y representan una de las principales causas de morbimortalidad en pediatría. La resistencia antibiótica de S. pneumoniae es variable según las características del huésped, serotipos predominantes y la circulación de clones determinados. El objetivo del estudio fue evaluar las características de los niños con infecciones invasivas con bacteriemia por Spn, la sensibilidad a los antibióticos betalactámicos (penicilina y ceftriaxona) de las cepas, los serotipos identificados y la frecuencia de los serotipos en el período pre-vacunación universal para neumococo (2008 ­ 2011) versus pos vacunal (2012 ­ 2013). Material y métodos: estudio prospectivo. Se incluyeron todos los <18 años internados con documentación de Spn en hemocultivos en el Hospital de Pediatría J. P. Garrahan en el periodo 2008-2013.Se utilizó el programa Epi info versión 3.2.2 (Epi Info 7).Resultados: se incluyeron 171 pacientes, con 52,6% de varones, mediana de edad de 31 meses (RIC 12-61); 116 niños tenían co-morbilidad asociada (67,8%). Las formas clínicas de infección más frecuentes fueron neumonía (n: 68; 39,8%), supuración pleuropulmonar en 12,3% (n:21) y fiebre sin foco clínico en 18,7% (n: 32). La mortalidad fue del 8,2% (n: 14). Todos los aislamientos de Spn fueron sensibles a la penicilina y a las cefalosporinas de tercera generación. No se identificaron Spn con sensibilidad disminuida a los betalactámicos. Los serotipos predominantes fueron el 14, 1, 6A, 7F, 12F, 19A y 23F. Se identificaron serotipos incluidos en la vacuna neumocóccica 13­ V (VNC13) en el período pre vacunal en el 71.1% (n:74) versus 59.7% (n:40) en el período pos vacunal; dicha diferencia no fue estadísticamente significativa. Conclusiones: la mayoría de los pacientes con infecciones invasivas por Spn incluidos en este estudio presentaban enfermedades subyacentes. En el periodo observado no se identificaron cepas de Spn con sensibilidad disminuida a los beta- lactámicos. Aunque la incorporación de la vacuna VNC13 es reciente, la frecuencia de identificación de serotipos incluidos en la VNC-13 disminuyó un 11,4% en relación al periodo pre vacunal (71,1% vs 59,7%) (AU)

Introduction: Infections due to Streptococcus pneumoniae (Spn) are highly prevalent diseases that account for one of the main causes of morbidity and mortality in pediatrics. Resistance to antibiotics of S. pneumoniae is variable according to host characteristics, predominant serotypes, and circulation of dominant clones. The aim of this study was to assess the characteristics of children with invasive infections and bacteremia due to Spn, sensitivity of the strains to beta-lactam antibiotics (penicillin and ceftriaxone), the identified serotypes, and the incidence of serotypes in the pre-universal vaccination for pneumococcus period (2008 ­ 2011) versus the post-vaccination period (2012 ­ 2013). Material and methods: A prospective study. All children <18 years of age with documented Spn in hemocultures admitted to the Pediatric Hospital J. P. Garrahan between 2008 and 2013 were included. Epi info 3.2.2 (Epi Info 7) was used for statistical analysis. Results: We included 171 patients, 52.6% of whom were boys, with a mean age of 31 months (IQR 12-61); 116 children had associated comorbidities (67.8%). The most common clinical manifestations of infection were pneumonia (n: 68; 39.8%), inflammatory-purulent pleuropulmonary disease (n:21; 12.3%), and fever without a clinical focus (n: 32; 18.7%). Mortality was 8.2% (n: 14). All Spn isolates were sensitive to penicillin and third-generation cephalosporins. No Spn with reduced sensitivity to beta-lactams were found. Predominant serotypes were 14, 1, 6A, 7F, 12F, 19ª, and 23F. Serotypes included in the pneumococcal vaccine 13­ V (VNC13) were identified in the pre-vaccination period in 71.1% (n:74) versus 59.7% (n:40) in the post-vaccination period; this difference was not statistically significant. Conclusions: The majority of patients with invasive infections due to Spn included in this study had underlying diseases. In the study period no strains of Spn with diminished sensitivity to beta-lactams were observed. Although the VNC13 vaccine has been recently incorporated, the incidence of identification of serotypes included in the VNC-13 vaccine has decreased 11.4% compared to the pre-vaccine period (71.1% vs 59.7%)

Neumonía de la comunidad en pediatría: Estudio descriptivo en un hospital de alta complejidad / Community-acquired pneumonía in pediatrics: Descriptive study in a tertiary-care hospital

Introducción: La neumonía adquirida en la comunidad (NAC) representa una de las principales causas de morbi-mortalidad en Pediatría. Su etiología es variable. Material y métodos: Cohorte prospectiva.1/04/2012 al 31/03/2013. Criterios de inclusión: edad entre 1 mes y 15 años, internados en el Hospital de Pediatría Juan P. Garrahan, Rx de tórax y clínica compatible con NAC. Análisis estadístico: Epi info 3.2.2. Resultados: n: 305, 55,4% (n: 169) varones. Edad (mediana) 13,3 meses (rango: 1-180). Enfermedad de base 47,9% (n: 146). Se identificó agente etiológico de NAC en 50,8% (n: 155); de ellos 79,3% (n: 119) fueron virus y 31,3% (n: 47) bacterias. En 11 pacientes (7,1%), ya incluidos en las cifras anteriores, se detectó una coinfección bacteria-virus. Tuvieron bacteriemia 7,9% (n: 24). Los virus identificados más frecuentemente fueron VSR (60,5%; n: 72), ADV (18,5%; n: 22) y Parainfluenza (8,4%; n: 10). Streptococcus pneumoniae representó el 38,2% (n: 18) y Staphylococcus aureus 36.2% (n: 17) de los aislamientos bacterianos (n: 47). Requirieron UCI el 17% (n: 52) de los niños y 1,6% (n: 5) fallecieron por una causa relacionada con la infección. La duración de la internación fue 11,02 días (r: 2-104). Predominaron los menores de 2 años (68,5%; n: 209). Los mayores de 2 años tuvieron más derrame pleural (13,4% vs 39,6%; OR 0,3; IC 95% 0,2 a 0,5; p 0,001), condensación lobar (37,3% vs 49%; OR 0,76; IC 95% 0,58 a 0,99) y pulmonar (5,3% vs 12,5%; OR 0,42; IC 95% 0,14 a 0,92) que los menores. Los virus fueron más frecuentes en los menores de 2 años que en los mayores. (51,1% vs 13,5%; OR 6,5; IC 95% 3,43 a 12,48). Conclusiones: La identificación del agente etiológico es alta si se emplean métodos convencionales (cultivos) y de biología molecular. Las infecciones virales predominaron en los menores de 2 años (AU)

Introduction: Community-acquired pneumonia (CAP) is one of the main causes of morbidity and mortality in pediatrics. Its etiology is variable. Material and methods: Prospective cohort study.1/04/2012 to 31/03/2013. Inclusion criteria: Age between 1 month and 15 years, admission to the Pediatric Hospital Juan P. Garrahan, chest x-rays and clinical features compatible with CAP. Statistical analysis: Epi info 3.2.2. Results: n: 305, 55.4% (n: 169) boys. Age (median) 13.3 months (range: 1-180). Underlying disease 47.9% (n: 146). The etiological agent of CAP was identified in 50.8% (n: 155); of which 79.3% (n: 119) were viruses and 31.3% (n: 47) bacteria. In 11 patients (7.1%), included in the previous numbers, a bacteria-virus coinfection was found. Bacteremia was observed in 7.9% (n: 24). The most frequently identified viruses were SRV (60.5%; n: 72), ADV (18.5%; n: 22), and parainfluenza (8,4%; n: 10). Streptococcus pneumoniae accounted for 38.2% (n: 18) and Staphylococcus aureus for 36.2% (n: 17) of the bacterial isolates (n: 47). Of all children, 17% (n: 52) required ICU admission and 1.6% (n: 5) died because of infection-related causes. Median hospital stay was 11,02 days (r: 2-104). There was a predominance of children under 2 years of age (68.5%; n: 209). Children older than 2 years more frequently had pleural effusion (13.4% vs 39.6%; OR 0.3; 95% CI 0.2 to 0.5; p 0001), and lobular (37.3% vs 49%; OR 0.76; 95% CI 0.58 to 0.99) and pulmonary condensation (5.3% vs 12.5%; OR 0.42; 95% CI 0.14 to 0.92) than younger patients. Viruses were more frequently found in children under 2 years of age than in the older patients (51.1% vs 13.5%; OR 6.5; 95% CI 3.43 to 12.48). Conclusions: The possibility to identify the etiological agent is high when using conventional methods (cultures) and molecular biology. Viral infections predominated in children younger than 2 years of age (AU)

Brote de Ralstonia mannitolilytica a partir de bacteriemias asociadas a catéteres implantables y semiimplantables en un hospital pediátrico / Outbreak of Raistonia mannitolilytica by implantable and semi-implantable catheter-related bacteremia in a pediatric hospital

Ralstonia mannitolilytica junto con Ralstonia pickettii han sido asociadas con brotes hospitalarios relacionados con la contaminación de algún dispositivo o fluido. El objetivo de este trabajo fue describir un brote por R. mannitolilytica a partir de bacteriemias asociadas a catéteres implantables y semiimplantables ocurrido en un hospital pediátrico de alta complejidad y evaluar la utilidad del empleo de métodos moleculares para su investigación.Se detectó la presencia de bacilos gram negativos no fermentadores, con igual antibiotipo, en hemocultivos y retrocultivos a partir de dos pacientes que tenían catéteres implantables y estaban atendidos en una misma área del hospital. Se realizaron estudios microbiológicos de muestras de frascos de heparina, soluciones de dextrosa y soluciones antisépticas con resultado negativo. Algunos pacientes tuvieron signos y/o síntomas clínicos de bacteriemia al habilitar los catéteres para su uso. Se citaron para su estudio a todos los pacientes que habían tenido un procedimiento de apertura y cierre de catéter durante las fechas cercanas a los hallazgos en hemocultivos (N expuestos = 45). Ocurrieron 17 casos (infectados), a partir de los cuales se analizaron 23 aislamientos, en los que se pudo documentar la presencia de R. mannitolilytica (23 aislamientos). Por métodos moleculares se determinó que los aislamientos provenientes de muestras de pacientes involucrados en el brote se encontraban estrechamente relacionados y podrían representar una misma cepa o clon. Por evidencia circunstancial se consideró a la "solución heparínica de cierre" como fuente posible del brote (AU)

Both Ralstonia mannitolilytica and Ralstonia pickettii have been associated with hospital outbreaks due to device or fluid contamination. The aim of this study was to describe an implantable- or semi-implantable-catheter-related bacteremia outbreak by R. mannitolilytica in a tertiary-care hospital and to assess the usefulness of molecular analysis for the identification of the organism. Non-fermenting gram-negative bacilli, with identical antibiotypes, were detected in hemocultures of two patients with implantable catheters in the same hospital area. Microbiological studies of heparin and dextrose and antiseptic solution vials were negative. Some of the patients had clinical signs and/or symptoms of bacteremia when the catheter was prepared for use. All patients who underwent a procedure of accessing or locking the port of the catheter around the time of the positive hemoculture findings were contacted (N exposed = 45). Seventeen infections were detected, of which 23 isolates were analyzed. The presence of R. mannitolilytica was recorded in 23 isolates. Molecular analysis showed that the isolates from the samples of the patients involved in the outbreak were closely related and might represent the same strain or clone. Circumstantial evidence suggested that the heparin-lock solution may have been the source of the outbreak (AU)

Programa de prevención de las bacteriemias asociadas a catéteres venosos centrales / Program for prevention of central venous catheter-related bacteremia

Introducción: Las infecciones son las complicaciones más importantes asociadas al uso de los Catéteres Venosos Centrales (CVC), representan un riesgo 20 veces mayor de bacteriemias que los catéteres venosos periféricos. El objetivo de este estudio fue evaluar el efecto de la implementación de un paquete de medidas o "bundle" en las infecciones asociadas a catéteres venosos centrales (BACT- CVC) en la Unidad de Cuidados Intensivos del Hospital Garrahan (UCI). Métodos: El Programa de Intervención para disminuir las bacteriemias asociadas a catéteres venosos centrales requirió de la aplicación de cuatro paquetes de medidas y un subprograma para aumentar la adherencia a la higiene de manos. Se aplicó en todas las UCI, pero en el presente estudio se presenta como modelo de referencia el que se llevó a cabo en una de ellas. Período del estudio: se compararon 2 períodos: basal (1º Agosto de 2008 - 31 de Diciembre de 2009) y intervención (1º de Enero 2010 al 31 de Diciembre de 2011). La tasa de BACT - CVC se calculó en concordancia con los protocolos utilizados por el sistema NHSN - CDC de los Estados Unidos y el sistema nacional VIHDA. La base de datos utilizada para el estudio fue el software provisto por el programa VIHDA. Se compararon las tasas de BACT - CVC en el período previo y posterior a las intervenciones realizadas. Para el análisis estadístico se utilizó el programa EPIINFO. Se consideró estadísticamente significativo un valor de p < 0.05. Resultados: en el primer período (Agosto 2008 - Diciembre 2009) se produjeron un total de 44 BACT - CVC, con una tasa promedio de 9.64 BACT-CVC por 1000 días-catéter versus 17 BACT - CVC, tasa promedio de 4.41 BACT-CVC por 1000 días-catéter en el período en que se desarrolla el programa de intervención. Esta disminución resulta estadísticamente significativa (Chi cuadrado; valor P= 0,0048; RR 0,46; IC 95%: 0,26 - 0,80). Conclusiones: La aplicación de los combos y el subprograma para mejorar la adherencia a la higiene de manos según orientación de la OMS y aplicando Estrategias Multimodales, resultaron en una mejora significativa en la tasa de BACT- CVC (AU)

Introduction: Infections are the main complication associated with the use of central venous catheters (CVC), accounting for an infection risk about 20 times that of peripheral venous catheters. The aim of this study was to assess the effect of the implementation of sets of measures or "bundle" for the prevention of CVC-associated bacteremia (CVC-BACT) in the ICU. Methods: The intervention program for the reduction of CVC-BACT consisted of four sets of measures and a sub-program to increase adherence to hand hygiene. Bundle use was started in all PICUs, however, in this study implementation of the program in one of them was used as a reference model. Study period: Two periods were compared: Baseline (August 1, 2008 ­ December 31, 2009) and intervention (January 1, 2010 ­ December 31, 2011). The CVC-BACT rate was calculated according to the NHSN-CDC protocols of the United States and the Argentine VIHDA system. For the data base of the study software provided by the VIHDA program was used. CVC-BACT rates before and after the intervention period were calculated. For statistical analysis the EPIINFO program was used. A p < 0.05 was considered significant. Results: In the first period (August 2008 - December 2009) 44 CVC-BACT occurred, with a mean CVC-BACT rate of 9.64 per 1000 catheter days versus 17 CVC-BACT, mean CVC-BACT rate of 4.41 per 1000 catheter days, in the intervention period. This decrease was statistically significant (Chi square 7.94; p = 0.0048; RR 0.46; 95% CI: 0.26 ­ 0.80). Conclusions: Bundle use and the subprogram for better adherence to hand hygiene, according to WHO guidelines and applying multimodal strategies, resulted in a significantly lower CVC-BACT rate (AU)

Utilización de un método molecular para la detección de kingella kingae en muestras osteoarticulares / The Use of a molecular method for the detection of Kingella kingae in bone and joint samples

Kingella kingae es un agente causal de infecciones osteoarticulares especialmente en niños menores de 4 años. En este trabajo se ha realizado un estudio comparativo entre un método molecular [reacción en cadena de la polimerasa (PCR) en tiempo real y dos métodos microbiológicos habitualmente empleados para el estudio de las infecciones osteoarticulares. Sólo se obtuvo resultado positivo para K. kingae por el método de PCR en 3 de las 60 muestras analizadas. Los pacientes evolucionaron sin secuelas aparentes con tratamiento antibiótico. Es importante destacar, como ya lo han hecho otros autores, que adicionando métodos moleculares se puede aumentar sensiblemente la recuperación de este patógeno.

Utilización de un método molecular para la detección de kingella kingae en muestras osteoarticulares / The Use of a molecular method for the detection of Kingella kingae in bone and joint samples

Kingella kingae es un agente causal de infecciones osteoarticulares especialmente en niños menores de 4 años. En este trabajo se ha realizado un estudio comparativo entre un método molecular [reacción en cadena de la polimerasa (PCR) en tiempo real y dos métodos microbiológicos habitualmente empleados para el estudio de las infecciones osteoarticulares. Sólo se obtuvo resultado positivo para K. kingae por el método de PCR en 3 de las 60 muestras analizadas. Los pacientes evolucionaron sin secuelas aparentes con tratamiento antibiótico. Es importante destacar, como ya lo han hecho otros autores, que adicionando métodos moleculares se puede aumentar sensiblemente la recuperación de este patógeno

Thirteen years of culture-positive M. bovis-BCG infection in an IL-12Rbeta1 deficient patient: treatment and outcome.

Patients with mutations in the IFNgamma/IL-12 pathway show an exquisite susceptibility to mycobacterial diseases. An IL-12Rbeta1 deficient patient with impaired intestinal absorption suffered from a 13 year culture-positive Mycobacterium bovis-BCG infection with acquired multidrug resistance. A combined parenteral and enteral anti-mycobacterial treatment, including recombinant IFNgamma, helped to clear his infection.