Variable antiviral activity of islatravir against M184I/V mutant HIV-1 selected during antiretroviral therapy.

BACKGROUND: Islatravir is a new antiretroviral drug that inhibits the reverse transcriptase (RT) of HIV-1 through multiple mechanisms. It is proposed to be used in combination with doravirine, a new NNRTI. M184V/I mutations have been shown to reduce the in vitro antiviral activity of islatravir, but their effect when pre-selected during ART has not been investigated. METHODS: HIV-1 rt sequences were obtained from four individuals of the Garrahan HIV cohort prior to, or during virological failure to ART. HIV-1 infectious molecular clones were constructed on an NL4-3 backbone, and infectious viruses were produced by transfection of 293T cells. Fold-changes in IC50 were calculated for each mutant versus the NL4-3 WT. HIV-1 phenotypic drug resistance was tested in vitro against NRTIs and NNRTIs. RESULTS: In all the cases, M184I/V, either alone or in the presence of other mutations, was associated with reduced susceptibility to islatravir, abacavir and lamivudine. Viruses carrying M184V/I showed variable levels of resistance to islatravir (4.8 to 33.8-fold). The greatest reduction in susceptibility was observed for viruses carrying the mutations M184V + V106I (33.8-fold resistance) or M184V + I142V (25.2-fold resistance). For NNRTIs, the presence of V106I alone did not affect susceptibility to doravirine or etravirine, but showed a modest reduction in susceptibility to efavirenz (6-fold). Susceptibility to doravirine was slightly reduced only for one of the mutants carrying V106I in combination with Y181C and M184V. CONCLUSIONS: Mutations and polymorphisms selected in vivo together with M184V/I depend on the viral genetic context and on ART history, and could affect the efficacy of islatravir once available for use in the clinic.

HIV-1 pretreatment drug resistance in vertically infected children is associated with poor virological response to protease inhibitor (PI)-based first-line antiretroviral therapy (ART): results from a cohort study in Argentina.

BACKGROUND: Increasing evidence from adult cohorts suggests an important role of HIV-1 pretreatment drug resistance (PDR) in ART failure, in spite of treatment being fully active according to baseline genotyping tests. Whether this is also true for children is unknown. METHODS: Virological and immunological parameters were longitudinally assessed in a group of 39 HIV-1 vertically infected children starting first-line lopinavir/ritonavir-based ART at a median of 5.0 months (IQR = 3.0-9.0). Evolution of viral load (VL) over time was compared between children with and without baseline PDR, as defined by the WHO mutation list. RESULTS: Resistance-associated mutations (RAMs) in the HIV-1 pol gene were present in nine HIV-1-infected children (23%) before initiation of first-line ART (PDR group). Of them, six carried RAMs associated with NNRTIs (NNRTI-PDR subgroup). At 4-8 weeks after ART initiation, the proportion of children achieving ≥1 log VL reduction was 87% for the no-PDR group versus 33% and 16.7% for the PDR group and the NNRTI-PDR subgroup, respectively. During follow-up, children with no PDR reached virological suppression almost four times faster than children with PDR or NNRTI-PDR [no-PDR = 631 days and PDR = 2134 days (P = 0.1249) and NNRTI-PDR = 2134 days (P = 0.0447)]. CD4 T cells remained similar between the study groups over time. CONCLUSIONS: HIV-1 baseline genotyping at diagnosis in vertically infected children is important for improved personalized medicine. While the mechanism is unclear, cases with PDR (particularly to NNRTIs) require closer monitoring of their first-line ART regimens in order to avoid early virological failures and prevent further accumulation of resistance.

[Paradoxical reaction during tuberculosis treatment in immunocompetent children: case report]. / Reacción paradojal al tratamiento antituberculoso en un paciente inmunocompetente: a propósito de un caso.

Tuberculosis is an important public health problem. It is estimated that around 5-10% of patients with tuberculosis present with central nervous system involvement; meningitis and tuberculoma being two of the most frequent manifestations. The paradoxical reaction in patients undergoing antituberculosis treatment is infrequent, nevertheless it is an important consideration in patients, who after an appropriate initial response to specific treatment, present with worsening clinical and radiological signs or the appearance of new lesions.

[Reasons for inappropriate prescribing of antibiotics in a high-complexity pediatric hospital]. / Motivos de la prescripción inadecuada de antibióticos en un hospital pediátrico de alta complejidad.

OBJECTIVE: Determine the reasons for inappropriate prescription of antibiotics and identify opportunities to improve prescription of these drugs in pediatric patients hospitalized in intermediate and intensive care units. METHODS: A prospective, descriptive longitudinal study was conducted of pediatric patients in intermediate and intensive care units who received parenteral administration of antibiotics, with the exception of newborns, burn unit patients, and surgical prophylaxis patients. A univariate analysis and multiple logistic regression were performed. RESULTS: A total of 376 patients with a median of age of 50 months were studied (interquartile range [IQR] 14.5-127 months). Out of the total patients studied, 75% had one or more underlying conditions. A total of 40.6% of these patients had an oncologic pathology and 33.5% had neurological conditions. The remaining 25.9% had other underlying conditions. Antibiotic treatment was inappropriate in 35.6% of the patients studied (N = 134). In 73 (54.4%) of the 134 cases, inappropriate use was due to the type of antibiotic prescribed, the dose administered, or the treatment period. The 61 (45.5%) remaining cases did not require antibiotic treatment. In the multivariate analysis, the risk factors for inappropriate use of antibiotics were: administration of ceftriaxone OR 2 (95% CI, 1.3-3.7; P = 0.02); acute lower respiratory tract infection OR 1.8 (95% CI, 1.1-3.3; P < 0.04); onset of fever of unknown origin in hospital inpatients OR 5.55 (95% CI, 2.5-12; P < 0.0001); and febrile neutropenia OR 0.3 (95% CI, 0.1-0.7; P = 0.009). CONCLUSIONS: Inappropriate use of antibiotics was less common in the clinical conditions that were well-characterized. Prescribing practices that could be improved were identified through the preparation and circulation of guidelines for antibiotic use in hospital inpatients.

[Epidemiological characteristics according to the progress of SARS-CoV-2 pandemic in a highly complex pediatric hospital in Argentina: a descriptive study]. / Características epidemiológicas según el avance de la pandemia SARS-CoV-2 en un hospital pediátrico de alta complejidad en Argentina: estudio descriptivo.

BACKGROUND: The knowledge of the clinical and evolutionary characteristics of children with SARS-CoV-2 is continuously updated. The true impact of the disease in the pediatric population is still unknown. AIM: To describe the clinical characteristics, the use of resources and the evolution of children with COVID-19 in the Garrahan Pediatric Hospital, Buenos Aires, Argentina, in the first 20 weeks from the identification of the first case. METHODS: Descriptive, analytical, retrospective study. The epidemiological, clinical, evolutionary characteristics and the use of hospital resources of patients < 18 years with confirmed COVID-19 are described. In addition, these characteristics were compared according to whether they occurred in the first 10 epidemiological weeks from the first case of COVID-19 in the hospital or in the following ten weeks. RESULTS: n: 280. The median age was 83 months (IQR 33-144). 209 patients (74.6%) were hospitalized. The median days of hospitalization was 8 days (IQR 3-13). According to the WHO severity classification, there were 184 mild cases (65.7%), 3 moderate (1.1%), 16 severe (5.7%) and 20 critical patients (7.1%). The main reasons for admission to the ICU were not related to SARS-CoV-2 infection. When comparing the characteristics of the patients in the two periods, in the first period there was a higher frequency of underlying comorbidities, immunosuppressive treatment, the consultation was later and the patients had more requirements for ICU admission. Two children (0.7%) died in relation to the infection, both with severe comorbidities and severe bacterial coinfections. CONCLUSION: In this study, patients with underlying disease predominated. The mild form of the disease was the most frequent presentation. At the beginning of the pandemic, there were more patients under immunosuppressive treatment, the consultation was later and the hospitalization was more frequent, prolonged and with more serious clinical pictures.

Unraveling HIV-1 diagnosis in special pediatric cases.

BACKGROUND: Early HIV-1 diagnosis and initiation of antiretroviral treatment is essential to prevent AIDS, and reduce mortality in children. HIV-1 molecular diagnosis in children before 18 months of age require, two independent samples to confirm a result. However, some patients have discordant virologic results in different samples, raising uncertainty for a conclusive diagnosis. We defined these patients as "special pediatric cases". OBJECTIVES: The aim of our study was to characterize the "special pediatric cases" among HIV-1 infected children diagnosed in a five-year period at our laboratory and evaluate the impact on the time to HIV-1 diagnosis. STUDY DESIGN: A total of 44 perinatally HIV-1 infected infants with molecular diagnostic performed at the Pediatric Garrahan Hospital were analyzed from 2013 to 2017. RESULTS: We identified eight "special pediatric cases". In the first samples, all of them had negative results by different DNA-PCR assays. Three infants had undetectable plasma viral load (pVL), four had low detectable pVL value, and one infant had no available pVL. All samples with detectable pVL, including those with low pVL (ie: 65copies/mL), had high pVL values at the end of the diagnosis. Considering the age of the HIV-1 infected children at the end of the diagnosis, five "special pediatric cases" (62 %) had a "late" positive diagnosis [mean (range) = 146 (89-268) days old]. CONCLUSIONS: These "special pediatric cases" are not as unusual as previously thought and are important diagnostic challenges. Also, this study add evidence to include the viral load assay in the molecular diagnostic algorithm for perinatal HIV-1 infection.

Osteoarticular infections in a tertiary care children's hospital: Epidemiology and clinical characteristics in association with bacteremia. / Infecciones osteoarticulares en un hospital pediátrico de alta complejidad: epidemiología y características clínicas asociadas con bacteriemia.

INTRODUCTION: Osteoarticular infections are an important cause of morbidity and may present with bacteremia. The epidemiology has changed in recent years. OBJECTIVES: To describe the epidemiological, clinical, and evolutionary characteristics of children with osteoarticular infections and compare patients with and without bacteremia. POPULATION AND METHODS: Retrospective cohort. Patients younger than 18 years admitted between January 1st, 2016 and December 31st, 2016 suspected of osteoarticular infections who had undergone an arthrocentesis and/or joint biopsy were included. Clinical and laboratory characteristics were compared between patients with and without bacteremia. The Stata 10 software was used. RESULTS: N: 62. Patients' median age was 59.5 months (interquartile range [IQR]: 24-84). Fever developed in 44 patients (70%). Arthritis predominated (54 patients, 87%). An etiologic agent was identified in 29 patients (47%). Staphylococcus aureus was prevalent (n: 20, 32%). Among these, 15 developed bacteremia (24%). Clindamycin was administered to 56 patients (90%) as empirical therapy. The median intravenous treatment duration was 7 days (IQR: 5-11) and the median length of stay, 7 days (IQR: 4-12). Patients with bacteremia were younger (26 months versus 60 months, p < 0.05), had a higher baseline C-reactive protein level (101 U/L versus 33 U/L, p < 0.05), a lower hemoglobin level at the time of admission (10.8 g/dL versus 12.5 g/dL, p = 0.04), and a higher frequency of fever (100% versus 57%, p < 0.05). CONCLUSIONS: Staphylococcus aureus was prevalent. Children with bacteremia were younger, had a higher C-reactive protein level, a lower hemoglobin level at the time of admission, and 100% presented fever.

INTRODUCCIÓN: Las infecciones osteoarticulares son una importante causa de morbilidad y pueden presentar bacteriemia. La epidemiología de estas infecciones se ha modificado en los últimos años. OBJETIVOS: Describir las características epidemiológicas, clínicas y evolutivas de los niños con infecciones osteoarticulares y comparar los pacientes con bacteriemia con los que no la presentaron. POBLACIÓN Y MÉTODOS: Cohorte retrospectiva. Se incluyeron pacientes menores de 18 años, admitidos en el Hospital Juan P. Garrahan entre el 1/1/2016 y el 31/12/2016 con sospecha de infecciones osteoarticulares en quienes se hubiese realizado artrocentesis y/o biopsia articular. Se excluyeron niños con patología previa. Se compararon las características clínicas y de laboratorio según tuvieran bacteriemia o no. Se utilizó Stata 10. RESULTADOS: N: 62. La mediana de edad fue 59.5 meses (rango intercuartilo -RIC- 24-84). Presentaron fiebre 44 pacientes (70%). Predominaron las artritis (54 pacientes, 87%). Se identificó un agente etiológico en 29 pacientes (47%). Predominó Staphylococcus aureus (n: 20, 32%). Tuvieron bacteriemia 15 de ellos (24%). Recibieron clindamicina como tratamiento empírico 56 pacientes (90%). La mediana de tratamiento endovenoso fue 7 días (RIC 5-11) y de internación, 7 días (RIC 4-12). Los pacientes con bacteriemia tuvieron menor edad (26 meses vs. 60, p < 0,05), mayor valor de proteína C reactiva inicial (101 vs. 33 U/L, p < 0,05), menor valor de hemoglobina al ingresar (10,8 g/dl vs. 12.5 g/dl, p 0,04) y mayor frecuencia de fiebre (100% vs. 57%, p < 0,05). CONCLUSIONES: Predominó Staphylococcus aureus. Los niños con bacteriemia tuvieron menor edad, mayor valor de proteína C reactiva, menos hemoglobina al ingresar y, más frecuentemente, fiebre.

[Epidemiology and risk factors for prolonged hospital length of stay in children with leukemia and bacteremia. Cohort study]. / Epidemiología y factores de riesgo de internación prolongada en niños con leucemia y bacteriemia. Estudio de cohorte.

INTRODUCTION: Bacteremia is a frequent complication in children with cancer, which is associated with greater severity, prolonged hospitalization and mortality. Prolonged hospitalization conditions greater morbidity and risk of acquisition of intranosocomial infections. AIM: To describe risk factors for prolonged hospital length of stay in children with leukemia and bacteremia. METHODS: Cohort study. Episodes of bacteremia in patients with leukemia at Garrahan Hospital from 1/1/2015 to 31/12/2016 were reviewed. We compared data from patients with a LOS of 14 days or more with those admitted for less than 14 days. Bivariate and logistic regression analysis was performed. We used Stata 13 statistical package. RESULTS: n = 121. Median age 59 months.81 patients (67%) had a diagnosis of acute lymphoblastic leukemia, followed by acute myeloid leukemia in 40 (33%). 96 patients (79%) had a central venous catheter (CVC), 94 patients (78%) were neutropenic. Blood cultures were positive for Enterobacteriaceae in 55 cases (45%), coagulase-negative staphylococci in 28 cases (23%), Group viridans Streptococcus in 19 (16%), Pseudomonas aeruginosa in 8 (7%). (9%). By the multivariate analysis, three factors remained significantly associated with length of stay of more than 14 days: CVC associated bacteremia (OR 21,73; CI95% 1.2-43.2; p 0.04), severe neutropenia (OR 1.75; CI95% 1.82-1.28; p 0.03) and coinfection (OR 27.4; CI95% 2.8-260.8; p 0.004). CONCLUSION: CVC associated bacteremia, severe neutropenia and viral coinfection were associated with hospital LOS of more than 14 days.

Risk factors for the appearance of secondary foci of infection in children with community-acquired Staphylococcus aureus bacteraemia. Cohort study 2010-2016. / Factores de riesgo de focos secundarios de infección en niños con bacteriemia por Staphylococcus aureus adquirida en la comunidad. Estudio de cohorte 2010-2016.

INTRODUCTION: Community-acquired Staphylococcus aureus (SA) bacteraemia is a common cause of hospitalisation in children. The occurrence of secondary foci (SF) of SA infection is associated with higher morbidity and mortality. OBJECTIVES: To identify risk factors for SF of infection in children with community-acquired SA bacteraemia. MATERIAL AND METHODS: Prospective cohort. All children aged from 30 days to 16 years admitted to a paediatric referral hospital between January 2010 and December 2016 for community-acquired infections, with SA isolated in blood cultures, were included. Microbiological, demographic and clinical characteristics were compared, with or without SF infection after 72hours of hospitalisation. RESULTS: A total of 283 patients were included, 65% male (n=184), with a median age of 60 months (IQR: 30-132). Seventeen per cent (n=48) had at least one underlying disease and 97% (n=275) had some clinical focus of infection, the most common being: osteoarticular 55% (n=156) and soft tissue abscesses 27% (n=79). A total of 65% (n=185) were resistant to methicillin. A SF of infection was found in 16% of patients (n=44). The SF identified were pneumonia 73% (n=32), osteoarticular 11% (n=5), soft tissue 11% (n=5) and central nervous system 5% (n=2). In the multivariate analysis, the persistence of positive blood cultures after the fifth day (OR: 2.40, 95%CI: 1.07-5.37, P<0.001) and sepsis (OR: 17.23, 95%CI 5.21-56.9, P<0.001) were predictors of SF. There was no association with methicillin sensitivity. CONCLUSIONS: In this cohort, methicillin-resistant SA infections predominated. The occurrence of SF of infection was associated with the persistence of bacteraemia after the fifth day and sepsis on admission.

Echinococcosis in children: Experience in a tertiary care hospital outside the endemic area. / Hidatidosis en niños: experiencia en un hospital de alta complejidad fuera del área endémica.

Echinococcosis is a zoonotic disease that is widely spread across Argentina and worldwide. It is acquired during childhood but it is more common during adulthood. The pediatric population accounts for 10-20% of all cases. This study included 47 children diagnosed with echinococcosis over a 20-year period. Their median age was 8 years old (range: 3-17); most patients had some epidemiological history, such as having lived or living in an endemic or rural area and/ or having dogs that are fed with viscera. Findings included 85% of single cysts in only one parenchyma. Cysts were most commonly located in the liver and lungs. Medical/surgical treatment was carried out in 45 patients (96%). Subsequent complications were observed in 13 patients (28%), which were more common in those with lung cysts. Three patients (6%) relapsed 1-24 months later and required a new surgery. No patient died as a result of the parasitic disease.

La hidatidosis es una zoonosis con una amplia distribución en Argentina y en el mundo. Se adquiere en la infancia, pero se presenta, más frecuentemente, en la edad adulta. La población pediátrica representa el 10%-20% del total de los casos. Se presentan 47 niños con diagnóstico de hidatidosis durante un período de 20 años. La mediana de edad fue de 8 años (rango: 3-17) y, en su mayoría, tenían algún antecedente epidemiológico orientador, como la procedencia de un área endémica, rural y/o la tenencia de perros alimentados con visceras. El 85% fueron quistes únicos localizados en un solo parénquima. Las localizaciones quísticas pulmonares y hepáticas fueron las más frecuentemente encontradas. El tratamiento fue médico-quirúrgico en 45 pacientes (96%). Trece (28%) presentaron alguna complicación posterior, que fue más frecuente en aquellos con localización pulmonar. Tres (6%) recayeron entre el mes y los 24 meses, y requirieron una nueva cirugía. Ninguno falleció a causa de la enfermedad parasitaria.

Características epidemiológicas según el avance de la pandemia SARS-CoV-2 en un hospital pediátrico de alta complejidad en Argentina: estudio descriptivo / Epidemiological characteristics according to the progress of SARS-CoV-2 pandemic in a highly complex pediatric hospital in Argentina: a descriptive study

INTRODUCCIÓN: El conocimiento de las características clínicas y evolutivas de los niños con SARS-CoV-2 está siendo continuamente actualizado. El verdadero impacto de la enfermedad en la población pediátrica es todavía desconocido. OBJETIVO: Describir las características clínicas, el uso de recursos y la evolución de niños con COVID-19 en el Hospital de Pediatría Garrahan, Buenos Aires, Argentina, en las primeras 20 semanas desde la identificación del primer caso. PACIENTES Y MÉTODOS: Estudio descriptivo analítico, retrospectivo. Se describen las características epidemiológicas, clínicas, evolutivas y el uso de recursos hospitalarios de pacientes < 18 años con COVID-19 confirmado. Además, se compararon dichas características según se presentaran en las primeras 10 semanas epidemiológicas desde el primer caso de COVID-19 en el hospital o en las 10 siguientes. RESULTADOS: n: 280. La mediana de edad fue 83 meses (RIC 33-144). Fueron hospitalizados 209 pacientes (74,6 %). La mediana de días de internación fue de 8 días (RIC 3-13). Según la clasificación de gravedad de la OMS, fueron casos leves 184 (65,7%), moderados 3 (1,1%), graves 16 (5,7%) y 20 pacientes críticos (7,1%). Los principales motivos de ingreso a UCI no se relacionaron con la infección por SARS-CoV-2. Al comparar las características de los pacientes en los dos períodos, en el primer período hubo más frecuencia de comorbilidades subyacentes, tratamiento inmunosupresor, la consulta fue más tardía y los pacientes tuvieron más requerimientos de internación en UCI. Fallecieron en relación con la infección dos niños (0,7%), ambos con comorbilidades graves y coinfecciones bacterianas graves. CONCLUSIÓN: En este estudio predominaron los pacientes con enfermedad de base. La forma leve de la enfermedad fue la presentación más frecuente. Al inicio de la pandemia, hubo más pacientes bajo tratamiento inmunosupresor, la consulta fue más tardía y la internación fue más frecuente, prolongada y con cuadros clínicos más graves.

BACKGROUND: The knowledge of the clinical and evolutionary characteristics of children with SARS-CoV-2 is continuously updated. The true impact of the disease in the pediatric population is still unknown. AIM: To describe the clinical characteristics, the use of resources and the evolution of children with COVID-19 in the Garrahan Pediatric Hospital, Buenos Aires, Argentina, in the first 20 weeks from the identification of the first case. METHODS: Descriptive, analytical, retrospective study. The epidemiological, clinical, evolutionary characteristics and the use of hospital resources of patients < 18 years with confirmed COVID-19 are described. In addition, these characteristics were compared according to whether they occurred in the first 10 epidemiological weeks from the first case of COVID-19 in the hospital or in the following ten weeks. RESULTS: n: 280. The median age was 83 months (IQR 33-144). 209 patients (74.6%) were hospitalized. The median days of hospitalization was 8 days (IQR 3-13). According to the WHO severity classification, there were 184 mild cases (65.7%), 3 moderate (1.1%), 16 severe (5.7%) and 20 critical patients (7.1%). The main reasons for admission to the ICU were not related to SARS-CoV-2 infection. When comparing the characteristics of the patients in the two periods, in the first period there was a higher frequency of underlying comorbidities, immunosuppressive treatment, the consultation was later and the patients had more requirements for ICU admission. Two children (0.7%) died in relation to the infection, both with severe comorbidities and severe bacterial coinfections. CONCLUSION: In this study, patients with underlying disease predominated. The mild form of the disease was the most frequent presentation. At the beginning of the pandemic, there were more patients under immunosuppressive treatment, the consultation was later and the hospitalization was more frequent, prolonged and with more serious clinical pictures.

Varicella at "Casa Garrahan", 2008-2013: Assessment of postexposure prophylaxis measures.

INTRODUCTION: Casa Garrahan (CG) accommodates children with complex conditions referred nationwide; these children are seen in children's hospitals located in the Autonomous City of Buenos Aires. Varicella is a highly-contagious disease, with attack rates of up to 90% among susceptible individuals. In closed communities, the implementation of outbreak control measures is critical. OBJECTIVES: To describe the characteristics of children exposed to varicella at CG, the implemented prophylaxis measures and their effectiveness. METHODS: Prospective, cohort study. Children exposed to varicella at CG between2008 and 2013, their demographic and clinical characteristics, immunization and/or history of varicella, prophylaxis measures, and secondary attack rate were assessed. RESULTS: N: 107. Fifty-three percent (n: 57) were girls. Their median age was 84 months old [interquartile range (IQR): 24-144]. Ninety-five percent (n: 102) had an underlying disease [hemato-oncological disease: 39% (n: 42); neurological disease: 18% (n: 19); congenital heart disease: 9% (n: 10); and post-operative period: 65 (n: 6)]. Fifty percent had some degree of immunosuppression (n: 54). Twenty-nine percent (n: 31) referred to have had varicella; 27% (n: 29) indicated that they never had the infection; and 41% (n: 44) did not recall a history of varicella. Only 3% (n: 3) had been vaccinated. Based on their immune status, age and history of varicella, acyclovir was indicated as prophylaxis in 61% (n: 65); immunization in 10% (n: 10); and gamma globulin in 1 patient. No adverse effects were observed in relation to the different prophylaxis measures. No secondary cases were observed at 30 days. CONCLUSIONS: Implemented measures were effective to prevent secondary cases. Among healthy and immunocompromised children, prophylaxis with acyclovir was effective and well-tolerated.

Assessment of C-reactive protein and procalcitonin levels to predict infection and mortality in burn children.

UNLABELLED: C-reactive protein (CRP) and procalcitonin(PCT) levels may distinguish between a systemic inflammatory response and an infection in burn children. OBJECTIVES: To establish the operative capability of CRP and PCT to diagnose infections and mortality. METHODS: Burn patients admitted to the hospital with clinical suspicion of an infection were included. CRP and PCT were measured and their operative diagnostic capabilities were calculated. RESULTS: Forty-eight patients (p) were included.Their median age was 49 months old (r: 17-86).The median burned surface area was 40% (r: 30-48%); 28 p (58%) had type AB and type B burn wounds. Infection was confirmed in 32 p (66.7%);the most common infection was burn-related sepsis (24 p, 75%), followed by burn wound infection (6 p, 19%). Eight patients (17%) died.It was not possible to establish CRP sensitivity and specificity because it was high in all patients,regardless of mortality, survival or the presence of infection. In relation to infections, PCT had a 90.6% sensitivity (95% confidence interval [CI]:75.8-96.8%), a 18.8% specificity (95% CI: 6.6-43%),a 69% positive predictive value (PPV) and a 50%negative predictive value (NPV). In relation to 30-day mortality, sensitivity was 100% (95% CI:67.6-100%), specificity 15% (95% CI: 7.1-29.1%),PPV 19% (95% CI: 10-33.3%) and NPV 100%(95% CI: 61-100%). CONCLUSIONS: In pediatric burn patients, neither CRP nor PCT showed an adequate operative capability to detect an infection or a fatal outcome.

[Paracoccidioidomycosis in pediatric patients: a description of 4 cases]. / Paracoccidioidomicosis en pediatría: descripción de 4 casos.

BACKGROUND: Paracoccidioidomycosis is the most frequent systemic mycosis in Latin America, caused by the dimorphic fungus Paracoccidioides. Paracoccidioidomycosis in children is uncommon. Our aim is to describe clinical features of patients who had a confirmed diagnosis of paracoccidioidomycosis in our hospital in the last 10 years. CASE REPORTS: We describe 4 cases of paracoccidioidomycosis in previously healthy children from the north of our country. Diagnoses were made by biopsy or culture. CONCLUSIONS: The diagnosis of paracoccidioidomycosis should be considered in a patient coming from regions where Paracoccidioides is endemic, and presenting with a lymphoproliferative syndrome, anemia, eosinophilia and hypergammaglobulinemia.

Effectiveness of a program to improve antibiotic use in children hospitalized in a children's tertiary care facility in Argentina.

INTRODUCTION: Inadequate antibiotic use is associated with an increased emergence of resistant microorganisms, higher morbidity and mortality rates, and an impact on public health. OBJECTIVE: To assess the effectiveness of a program aimed at improving the use of antimicrobials in patients hospitalized at Hospital Garrahan. MATERIAL AND METHODS: Prospective, longitudinal, before and after study with no control group. STUDY PERIOD: From November 1st, 2010 to June 30th, 2011. Patients receiving parenteral antibiotics were included. Newborn infants, burned patients and those receiving prophylactic antibiotics were excluded. The periods before and after implementing discussion and monitoring workshops for antibiotic prescription and distributing treatment guidelines were compared. An univariate analysis and a multiple logistic regression study were performed (STATA 8.0). RESULTS: In the pre-intervention period,376 patients were included; of them, 35.6% had received inadequate treatment. The multiple regression analysis showed that the endpoints for inadequate antibiotic use were acute lower respiratory tract infection (OR: 3.80; 95% CI: 1.35-3.26; p=0.04), fever without a source in hospitalized patients (OR: 5.55; 95% CI: 2.43-12.6; p < 0.01), and febrile neutropenia (OR: 0.29; 95% CI: 0.10-0.7; p < 0.01). In the post-intervention period, 357 patients were included; 21.5% had received inadequate treatment. A reduction in inadequate antibiotic prescription was observed compared to the pre-intervention period (p < 0.01). The multiple regression analysis showed that endpoints for inadequate use were skin and soft tissue infections (OR: 0.33; 95% CI: 0.13-0.93; p = 0.035), and febrile neutropenia (OR: 0.48; 95% CI: 0.220.94; p= 0.04). CONCLUSION: The program was effective and allowed to improve antibiotic prescription practices in hospitalized children.

Epidemiología y factores de riesgo de internación prolongada en niños con leucemia y bacteriemia: estudio de cohorte / Epidemiology and risk factors for prolonged hospital length of stay in children with leukemia and bacteremia: cohort study

Resumen Introducción: La bacteriemia constituye una complicacion frecuente en los niños con cáncer, que se asocia a mayor gravedad, internación prolongada y mortalidad. La internación prolongada condiciona mayor morbilidad y riesgo de adquisición de infecciones intranosocomiales. Objetivo: Analizar factores de riesgo de internación prolongada en niños con leucemia y bacteriemia. Pacientes y Métodos: Cohorte retrospectiva. Se incluyeron niños con leucemia internados en el Hospital Garrahan entre 1/1/2015 y 31/12/2016 con bacteriemia. Se compararon características de pacientes con internaciones menores o mayores a 14 días. Se realizó un análisis bivariado y modelo de regresión logística. Se utilizó Stata 13. Resultados: n = 121. Mediana de edad 59 meses. Tenían leucemia linfoblastica 81 pacientes (67%) y leucemia mieloblástica 40 (33%). Tenían catéter venoso central (CVC) 96 de los niños (79%), neutropenia 94 (78%), neutropenia menor a 100 neutrófilos 79 (65%). La identificación en hemocultivos fue: 55 casos (45%) enterobacterias, 28 (23%) Staphylococcus coagulasa negativa, Streptococcus spp grupo viridans 19 (16%), Pseudomonas aeruginosa 8 (7%). Huo co-infección viral en 14 pacientes (12%).Tuvieron menos de 14 días de internación 71 pacientes (59%) y mayor período 50 (41%). En el análisis multivariado la bacteriemia asociada a CVC (OR 21,73; IC95% 1,2-43,20; p 0,04), neutropenia profunda al ingreso (OR 1,75; IC95% 1,82-1,28; p 0,03) y co-infección viral (OR 27,42; IC95% 2,88-260,83; p 0,004) fueron factores de riesgo de internación > 14 días. Conclusiones: La bacteriemia asociada a CVC, la neutropenia profunda al ingreso y la co-infección se asociaron con una internación igual o mayor a 14 días.

ABSTRACT Introduction: Bacteremia is a frequent complication in children with cancer, which is associated with greater severity, prolonged hospitalization and mortality. Prolonged hospitalization conditions greater morbidity and risk of acquisition of intranosocomial infections. Aim: To describe risk factors for prolonged hospital length of stay in children with leukemia and bacteremia. Methods: Cohort study. Episodes of bacteremia in patients with leukemia at Garrahan Hospital from 1/1/2015 to 31/12/2016 were reviewed. We compared data from patients with a LOS of 14 days or more with those admitted for less than 14 days. Bivariate and logistic regression analysis was performed. We used Stata 13 statistical package. Results: n = 121. Median age 59 months.81 patients (67%) had a diagnosis of acute lymphoblastic leukemia, followed by acute myeloid leukemia in 40 (33%). 96 patients (79%) had a central venous catheter (CVC), 94 patients (78%) were neutropenic. Blood cultures were positive for Enterobacteriaceae in 55 cases (45%), coagulase-negative staphylococci in 28 cases (23%), Group viridans Streptococcus in 19 (16%), Pseudomonas aeruginosa in 8 (7%). (9%). By the multivariate analysis, three factors remained significantly associated with length of stay of more than 14 days: CVC associated bacteremia (OR 21,73; CI95% 1.2-43.2; p 0.04), severe neutropenia (OR 1.75; CI95% 1.82-1.28; p 0.03) and coinfection (OR 27.4; CI95% 2.8-260.8; p 0.004). Conclusion: CVC associated bacteremia, severe neutropenia and viral coinfection were associated with hospital LOS of more than 14 days.

Infecciones osteoarticulares en un hospital pediátrico de alta complejidad: epidemiología y características clínicas asociadas con bacteriemia / Osteoarticular infections in a tertiary care children's hospital: Epidemiology and clinical characteristics in association with bacteremia

Introducción. Las infecciones osteoarticulares son una importante causa de morbilidad y pueden presentar bacteriemia. La epidemiología de estas infecciones se ha modificado en los últimos años. Objetivos. Describir las características epidemiológicas, clínicas y evolutivas de los niños con infecciones osteoarticulares y comparar los pacientes con bacteriemia con los que no la presentaron. Población y métodos. Cohorte retrospectiva. Se incluyeron pacientes menores de 18 años, admitidos en el Hospital Juan P. Garrahan entre el 1/1/2016 y el 31/12/2016 con sospecha de infecciones osteoarticulares en quienes se hubiese realizado artrocentesis y/o biopsia articular. Se excluyeron niños con patología previa. Se compararon las características clínicas y de laboratorio según tuvieran bacteriemia o no. Se utilizó Stata 10. Resultados. N: 62. La mediana de edad fue 59.5 meses (rango intercuartilo -RIC- 24-84). Presentaron fiebre 44 pacientes (70%). Predominaron las artritis (54 pacientes, 87%). Se identificó un agente etiológico en 29 pacientes (47%). Predominó Staphylococcus aureus (n: 20, 32%). Tuvieron bacteriemia 15 de ellos (24%). Recibieron clindamicina como tratamiento empírico 56 pacientes (90%). La mediana de tratamiento endovenoso fue 7 días (RIC 5-11) y de internación, 7 días (RIC 4-12). Los pacientes con bacteriemia tuvieron menor edad (26 meses vs. 60, p < 0,05), mayor valor de proteína C reactiva inicial (101 vs. 33 U/L, p < 0,05), menor valor de hemoglobina al ingresar (10,8 g/dl vs. 12.5 g/dl, p 0,04) y mayor frecuencia de fiebre (100% vs. 57%, p < 0,05). Conclusiones. Predominó Staphylococcus aureus. Los niños con bacteriemia tuvieron menor edad, mayor valor de proteína C reactiva, menos hemoglobina al ingresar y, más frecuentemente, fiebre.

Introduction. Osteoarticular infections are an important cause of morbidity and may present with bacteremia. The epidemiology has changed in recent years. Objectives. To describe the epidemiological, clinical, and evolutionary characteristics of children with osteoarticular infections and compare patients with and without bacteremia. Population and methods. Retrospective cohort. Patients younger than 18 years admitted between January 1st, 2016 and December 31st, 2016 suspected of osteoarticular infections who had undergone an arthrocentesis and/or joint biopsy were included. Clinical and laboratory characteristics were compared between patients with and without bacteremia. The Stata 10 software was used.Results. N: 62. Patients' median age was 59.5 months (interquartile range [IQR]: 24-84). Fever developed in 44 patients (70%). Arthritis predominated (54 patients, 87%). An etiologic agent was identified in 29 patients (47%). Staphylococcus aureus was prevalent (n: 20, 32%). Among these, 15 developed bacteremia (24%). Clindamycin was administered to 56 patients (90%) as empirical therapy. The median intravenous treatment duration was 7 days (IQR: 5-11) and the median length of stay, 7 days (IQR: 4-12). Patients with bacteremia were younger (26 months versus 60 months, p < 0.05), had a higher baseline C-reactive protein level (101 U/L versus 33 U/L, p < 0.05), a lower hemoglobin level at the time of admission (10.8 g/dL versus 12.5 g/dL, p = 0.04), and a higher frequency of fever (100% versus 57%, p < 0.05).Conclusions. Staphylococcus aureus was prevalent. Children with bacteremia were younger, had a higher C-reactive protein level, a lower hemoglobin level at the time of admission, and 100% presented fever

Hidatidosis en niños: experiencia en un hospital de alta complejidad fuera del área endémica / Echinococcosis in children: Experience in a tertiary care hospital outside the endemic area

La hidatidosis es una zoonosis con una amplia distribución en Argentina y en el mundo. Se adquiere en la infancia, pero se presenta, más frecuentemente, en la edad adulta. La población pediátrica representa el 10%-20% del total de los casos. Se presentan 47 niños con diagnóstico de hidatidosis durante un período de 20 años. La mediana de edad fue de 8 años (rango: 3-17) y, en su mayoría, tenían algún antecedente epidemiológico orientador, como la procedencia de un área endémica, rural y/o la tenencia de perros alimentados con visceras. El 85% fueron quistes únicos localizados en un solo parénquima. Las localizaciones quísticas pulmonares y hepáticas fueron las más frecuentemente encontradas. El tratamiento fue médico-quirúrgico en 45 pacientes (96%). Trece (28%) presentaron alguna complicación posterior, que fue más frecuente en aquellos con localización pulmonar. Tres (6%) recayeron entre el mes y los 24 meses, y requirieron una nueva cirugía. Ninguno falleció a causa de la enfermedad parasitaria.

Echinococcosis is a zoonotic disease that is widely spread across Argentina and worldwide. It is acquired during childhood but it is more common during adulthood. The pediatric population accounts for 10-20% of all cases. This study included 47 children diagnosed with echinococcosis over a 20-year period. Their median age was 8 years old (range: 3-17); most patients had some epidemiological history, such as having lived or living in an endemic or rural area and/or having dogs that are fed with viscera. Findings included 85% of single cysts in only one parenchyma. Cysts were most commonly located in the liver and lungs. Medical/surgical treatment was carried out in 45 patients (96%). Subsequent complications were observed in 13 patients (28%), which were more common in those with lung cysts. Three patients (6%) relapsed 1-24 months later and required a new surgery. No patient died as a result of the parasitic disease.

Evaluación del valor de la proteína C reactiva y de la procalcitonina en la predicción de infección y mortalidad en los niños quemados / Assessment of C-reactive protein and procalcitonin levels to predict infection and mortality in burn children

Los niveles de proteína C reactiva (PCR) y procalcitonina (PrC) podrían diferenciar la respuesta inflamatoria sistémica de la infección en niños quemados. Objetivos. Determinar la capacidad operativa de PCR y PrC para el diagnóstico de infecciones y de mortalidad. Métodos. Se incluyeron pacientes quemados admitidos en el Hospital y que tuvieran sospecha clínica de infección. Se realizó dosaje de PCR y PrC, y se calcularon las capacidades operativas diagnósticas de ambas. Resultados. Se incluyeron 48 pacientes (p). La mediana de edad fue de 49 meses (r: 17-86). La mediana de superficie quemada fue 40% (r: 3048%); 28 p (58%) tuvieron quemaduras AB y B. Treinta y dos (66,7%) tuvieron infección; la sepsis relacionada con la quemadura fue la más común (24 p, 75%), seguida por infección de la quemadura (6 p, 19%). Ocho pacientes (17%) murieron. La sensibilidad y la especificidad de la PCR no pudieron ser determinadas porque estuvo elevada en todos los pacientes, independientemente de la presencia de infección, mortalidad o supervivencia. Para infección, la PrC tuvo una sensibilidad de 90,6% (IC95% 75,8-96,8), especificidad de 18,8% (IC95% 6,643%), valor predictivo positivo (VPP) de 69% y valor predictivo negativo (VPN) de 50%. Para mortalidad a los 30 días, la sensibilidad fue de 100% (IC95% 67,6-100%), especificidad de 15% (IC95% 7,1-29,1%), VPP de 19% (IC95% 10-33,3%) y VPN de 100% (IC95% 61-100%). Conclusiones. En pacientes pediátricos quemados, ni la PCR ni la PrC presentaron una capacidad operativa apropiada para la detección de infección o desenlace fatal.

C-reactive protein (CRP) and procalcitonin (PCT) levels may distinguish between a systemic inflammatory response and an infection in burn children.Objectives. To establish the operative capability of CRP and PCT to diagnose infections and mortality. Methods. Burn patients admitted to the hospital with clinical suspicion of an infection were included. CRP and PCT were measured and their operative diagnostic capabilities were calculated. Results. Forty-eight patients (p) were included. Their median age was 49 months old (r: 17-86). The median burned surface area was 40% (r: 30-48%); 28 p (58%) had type AB and type B burn wounds. Infection was confirmed in 32 p (66.7%); the most common infection was burn-related sepsis (24 p, 75%), followed by burn wound infection (6 p, 19%). Eight patients (17%) died. It was not possible to establish CRP sensitivity and specificity because it was high in all patients, regardless of mortality, survival or the presence of infection. In relation to infections, PCT had a 90.6% sensitivity (95% confidence interval [CI]: 75.8-96.8%), a 18.8% specificity (95% CI: 6.6-43%), a 69% positive predictive value (PPV) and a 50% negative predictive value (NPV). In relation to 30-day mortality, sensitivity was 100% (95% CI: 67.6-100%), specificity 15% (95% CI: 7.1-29.1%), PPV 19% (95% CI: 10-33.3%) and NPV 100% (95% CI: 61-100%).Conclusions. In pediatric burn patients, neither CRP nor PCT showed an adequate operative capability to detect an infection or a fatal outcome.

Varicela en la Casa Garrahan, 2008-2013: Evaluación de las medidas de profilaxis posexposición / Varicella at "Casa Garrahan", 2008-2013: Assessment of postexposure prophylaxis measures

Introducción. La Casa Garrahan (CG) aloja a niños con patologías complejas de todo el país, atendidos en los hospitales pediátricos de la Ciudad Autónoma de Buenos Aires. La varicela es una enfermedad muy contagiosa, cuya tasa de ataque alcanza el 90% en susceptibles. En comunidades cerradas, es fundamental implementar medidas de prevención ante brotes. Objetivos. Describir las características de los niños expuestos a casos de varicela en la CG, las medidas de profilaxis implementadas y su efectividad. Métodos. Estudio de cohorte prospectivo. Se evaluaron los niños expuestos a varicela en la CG entre 2008 y 2013, sus características demográficas, clínicas y vacunación y/o varicela previa, medidas de profilaxis y tasa de ataque secundaria. Resultados. N: 107. El 53% (n: 57) eran niñas. La mediana de edad fue 84 meses (RIC: 24144). El 95% (n: 102) teman enfermedad de base [oncohematológica: 39% (n: 42); neurológica: 18% (n: 19); cardiopatías congénitas: 9% (n: 10); y posoperatorios: 65 (n: 6)]. Tenían algún grado de inmunosupresión el 50% (n: 54). El 29% (n: 31) referían haber tenido varicela; el 27% (n: 29) referían no haber padecido la enfermedad; y el 41% (n: 44) no recordaban el antecedente. Solo 3% (n: 3) estaban vacunados. Sobre la base del estado inmunológico, edad y antecedentes de varicela previa, se indicó aciclovir como profilaxis en 61% (n: 65); vacuna, en 10% (n: 10); y gammaglobulina, en 1 paciente. No se observaron efectos adversos relacionados con las profilaxis. No se observó ningún caso secundario a los 30 días. Conclusiones. Las medidas implementadas resultaron efectivas en la prevención de casos secundarios. En niños sanos e inmunocomprometidos, la profilaxis con aciclovir fue efectiva y bien tolerada.

Introduction. Casa Garrahan (CG) accommodates children with complex conditions referred nationwide; these children are seen in children's hospitals located in the Autonomous City of Buenos Aires. Varicella is a highly-contagious disease, with attack rates of up to 90% among susceptible individuals. In closed communities, the implementation of outbreak control measures is critical. Objectives. To describe the characteristics of children exposed to varicella at CG, the implemented prophylaxis measures and their effectiveness. Methods. Prospective, cohort study. Children exposed to varicella at CG between2008 and 2013, their demographic and clinical characteristics, immunization and/or history of varicella, prophylaxis measures, and secondary attack rate were assessed. Results. N: 107. Fifty-three percent (n: 57) were girls. Their median age was 84 months old [interquartile range (IQR): 24-144]. Ninety-five percent (n: 102) had an underlying disease [hemato-oncological disease: 39% (n: 42); neurological disease: 18% (n: 19); congenital heart disease: 9% (n: 10); and post-operative period: 65 (n: 6)]. Fifty percent had some degree of immunosuppression (n: 54). Twenty-nine percent (n: 31) referred to have had varicella; 27% (n: 29) indicated that they never had the infection; and 41% (n: 44) did not recall a history of varicella. Only 3% (n: 3) had been vaccinated. Based on their immune status, age and history of varicella, acyclovir was indicated as prophylaxis in 61% (n: 65); immunization in 10% (n: 10); and gamma globulin in 1 patient. No adverse effects were observed in relation to the different prophylaxis measures. No secondary cases were observed at 30 days. Conclusions. Implemented measures were effective to prevent secondary cases. Among healthy and immunocompromised children, prophylaxis with acyclovir was effective and well-tolerated.