Antibiotic susceptibility and fosfomycin resistance characterization in a cohort of children older than 6 years of age with urinary tract infection.

Fosfomycin tromethamol (FT) was reintroduced as an option for the treatment of low urinary tract infection (UTI) in children. In this study, we described the antibiotic sensitivity and mechanisms of resistance to fosfomycin in isolates from children older than 6 years with UTI. Urine culture and antibiotic susceptibility study were performed. In fosfomycin resistant strains, PCR for fos, blaCTX-M was performed followed by classification by phylogenetic group and sequencetyping. Escherichia coli was the most frequent etiological agent (89.2%). The susceptibility percentages were: fosfomycin 97.9%; amoxicillin-clavulanate 92.7%; cefuroxime and ceftriaxone 99%; nitrofurantoin 94.4%. An E. coli strain (ST69, phylogenetic group D) was resistant to fosfomycin (MIC 256mg/l) and carried the blaCTX-M-14 and fosA3 genes in a 45kb IncN-type plasmid. This is the first report of E. coli ST69 with blaCTX-M-14/fosA3 of human origin.

[Multifocal hepatic hemangioendothelioma]. / Hemangioendotelioma hepático infantil multifocal.

INTRODUCTION: Hepatic hemangioendothelioma is a rare benign tumor in children, which frequently occurs in the first year of life. The clinical presentation is variable and the diagnosis is based on clinical suspicion, and laboratory and imaging studies. The objective was to describe a case of multifocal hepa tic hemangioendothelioma. CLINICAL REPORT: 3-month-old girl who presented hepatomegaly without elements of hepatic or heart failure. Abdominal ultrasound and CT scan were used to diagnose hepatic hemangioendothelioma, which was confirmed by CT abdominal angiography. The patient received glucocorticoid treatment at high doses for a prolonged period. A year and a half after treatment, there was evidence of tumor remission. She had side effects from the established treatment. CONCLUSIONS: In asymptomatic patients with isolated hepatomegaly, it should be considered a probable tumor patho logy, considering the clinic and imaging studies. Possible complications and treatments risks must always be assessed. In this case, the tumor extension and its probable complications justified the use of prolonged corticosteroid therapy at high doses despite its adverse effects.

Changes in Central Aortic Pressure Levels, Wave Components and Determinants Associated with High Peripheral Blood Pressure States in Childhood: Analysis of Hypertensive Phenotype.

The aims were to determine whether children's high peripheral blood pressure states (HBP) are associated with increased central aortic blood pressure (BP) and to characterize hemodynamic and vascular changes associated with HBP in terms of changes in cardiac output (stroke volume, SV), arterial stiffness (aortic pulse wave velocity, PWV), peripheral vascular resistances (PVR) and net and relative contributions of reflected waves to the aortic pulse amplitude. We included 154 subjects (mean age 11; range 4-16 years) assigned to one of two groups: normal peripheral BP (NBP, n = 101), defined as systolic and diastolic BP < 90th percentile, or high BP (HBP, n = 53), defined as average systolic and/or diastolic BP levels ≥90th percentile (curves for sex, age and body height). The HBP group included children with hypertensive and pre-hypertensive BP levels. After a first analysis, groups were compared excluding obese and dyslipidemic children. Peripheral and central aortic BP, PWV and pulse wave-derived parameters (augmentation index, forward and backward wave components' amplitude) were measured using gold-standard techniques, applanation tonometry (SphygmoCor) and oscillometry (Mobil-O-Graph). Independent of the presence of dyslipidemia and/or obesity, aortic systolic and pulse BP were higher in HBP than in NBP children. The increase in central BP could not be explained by an increase in the relative contribution of reflections to the aortic pressure wave, higher PVR or by an augmented peripheral reflection coefficient. Instead, the rise in central BP would be explained by an increase in the amplitude of both incident and reflected wave components.

Fibrodysplasia ossificans progressiva in a 3-year-old female patient.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disease affecting connective tissue, primarily caused by de novo mutations of the ACVR1 gene. FOP is a disease with congenital malformations of the toes and heterotopic ossification in characteristic patterns that progresses with flare-ups and remissions. Cumulative damage results in disability and, eventually, death. This report aimed to describe a case of FOP to highlight the importance of early diagnosis of this rare condition. CASE REPORT: We describe the case of a 3-year-old female diagnosed with congenital hallux valgus, who initially presented with soft tissue tumors, predominantly in the neck and chest, with partial remission. Multiple diagnostic tests were performed, including biopsies and magnetic resonance imaging, with nonspecific results. We observed ossification of the biceps brachii muscle during evolution. The molecular genetic study found a heterozygous ACVR1 gene mutation that confirmed FOP. CONCLUSIONS: Knowledge of this rare disease by pediatricians is critical for an early diagnosis and for avoiding unnecessary invasive procedures that may promote disease progression. In case of clinical suspicion, performing an early molecular study is suggested to detect ACVR1 gene mutations. The treatment of FOP is symptomatic and focused on maintaining physical function and family support.

INTRODUCCIÓN: La fibrodisplasia osificante progresiva (FOP) es una enfermedad autosómica dominante rara que afecta el tejido conectivo, cuya causa principal son mutaciones de novo del gen ACVR1. Se trata de una enfermedad con malformaciones congénitas de los primeros ortejos y osificación heterotópica en patrones característicos que progresa en empujes y remisiones. El daño acumulativo provoca discapacidad y, eventualmente, la muerte. El objetivo de este trabajo fue describir un caso de FOP para favorecer el diagnóstico precoz de esta enfermedad infrecuente. CASO CLÍNICO: Se describe el caso de una paciente de 3 años, portadora de hallux valgus congénito, que inicialmente presentó tumoraciones dolorosas de tejidos blandos, de predominio en cuello y tórax, con remisión parcial de las mismas. Se realizaron múltiples pruebas diagnósticas, incluyendo biopsias e imágenes de resonancia magnética con resultados inespecíficos. En la evolución se observó osificación de músculo bíceps braquial. El estudio genético molecular encontró una mutación del gen ACVR1 en heterocigosis que confirmó el diagnóstico de FOP. CONCLUSIONES: El conocimiento de esta enfermedad por los pediatras es clave para realizar un diagnóstico precoz y evitar procedimientos invasivos innecesarios que pueden promover la progresión de la enfermedad. Ante la sospecha clínica, se sugiere realizar tempranamente el estudio molecular para detectar mutaciones del gen ACVR1. El tratamiento de la FOP es sintomático, centrado en el mantenimiento de la función física y el apoyo familiar.

[Epidemiological and clinical characteristics of children with COVID-19 cared for in a private health provider in Uruguay]. / Características epidemiológicas y clínicas de los niños con COVID-19 asistidos en un prestador de salud privado de Uruguay.

BACKGROUND: After the detection of the first cases of SARS-CoV-2 and the declaration of a health emergency in the country, community transmission of the virus remained low to moderate until November 2020, later becoming medium and high. Children under 15 years of age constitute the least affected group. The diagnosis is confirmed by RT-qPCR. The usefulness of the CT (cycle threshold) is discussed. AIM: To describe the epidemiological and clinical characteristics of children infected with SARS-CoV-2 and the relationship between the CT value and clinical presentation. METHOD: A descriptive, retrospective study was carried out in patients under 16 years of age with SARS-CoV-2 infection, assisted by a health provider in Montevideo between epidemiological week (EW) 3 of2020 and EW 9 of2021. Clinical variables, epidemiological notion, severity and evolution were described. The CT value at diagnosis was recorded and compared with the presence of symptoms. RESULTS: Patients under 16 years of age represented 16.6% of the total infected (794 in 4,792). 70% of the cases occurred between the months of January and February 2021. 67.6% presented intradomiciliary contact. The mean age was 7.5 ± 4.1 years, 51% were male. 55% presented symptoms and 45% were asymptomatic; no significant differences were observed in the mean, mode and age range of both groups. None presented comorbidities. In the group of 440 symptomatic patients, 55% presented fever: 32% associated with other symptoms, mainly upper respiratory symptoms, and 23% as the only symptom. The CT value was obtained in 536 of the 794 patients (67.5%). The mean CT was 29.7+5.8 in the symptomatic group vs. 31.5 ± 5.7 in asymptomatic patients (p > 0.05). Three patients were hospitalized, none required intensive care and none died. CONCLUSIONS: The prevalence and incidence of SARS-CoV-2 infection in children accompany that of adults and the majority had mild or asymptomatic forms, without complications. In this series, the CT value was not different in symptomatic and asymptomatic children. Close household contact was the main source of infection.

Vancomycin pharmacokinetic-pharmacodynamic parameters to optimize dosage administration in critically ill children.

OBJECTIVE: Critically ill children may present changes in pharmacokinetic parameters and may not reach effective concentrations of vancomycin with current dosages. The objective of this study is to calculate vancomycin pharmacokinetic parameters in critically ill children and to estimate area under the curve at 24 hrs/minimal inhibitory concentration reached for Staphylococcus aureus. DESIGN, SETTING, AND PATIENTS: Children treated with vancomycin, hospitalized in the Intensive Care Unit of the Pediatric Hospital-Centro Hospitalario Pereira Rossell, were included. Samples to determine vancomycin serum concentration were obtained on first and third days of treatment, 1 hr after the end of the third daily dose administration (maximum drug concentration) and 15 mins before the fourth (minimum drug concentration). Half-life elimination, volume of distribution, clearance, and area under the curve at 24 hrs were estimated. Vancomycin concentration values of 20-40 µg/mL (maximum drug concentration) and 5-10 µg/mL (minimum drug concentration) were considered therapeutic. MEASUREMENTS AND MAIN RESULTS: Twenty-two children were included. On day 1, seven of 18 children for maximum drug concentration and 16 of 22 for minimum drug concentration reached concentrations in therapeutic range; on day 3, seven of 16 children for maximum drug concentration and 11 of 17 for minimum drug concentration did. Mean values of maximum drug concentration and minimum drug concentration were higher in children with negative water balance. Mean value of half-life elimination increased from day 1 to day 3. Considering a value of minimal inhibitory concentration for S. aureus of 1 µg/mL, nine of 18 children reached a relationship area under the curve at 24 hrs/minimal inhibitory concentration >400 on day 1 and seven of 15 on day 3. Considering a minimal inhibitory concentration of 2 µg/mL, one child reached it on day 1 and one on day 3. CONCLUSIONS: Critically ill children show changes in pharmacokinetic parameters. Serum concentration monitorization is necessary for dosage individualization. Most children do not reach an area under the curve at 24 hrs/minimal inhibitory concentration >400 with current dosage.

Children hospitalized for myiasis in a reference center in Uruguay.

BACKGROUND: Myiasis is an emerging disease caused by tissue invasion of dipteran larvae. In Uruguay, Cochliomyia hominivorax and Dermatobia hominis are the most frequent species. This study aimed to describe the epidemiological and clinical characteristics and the follow-up of children < 15 years hospitalized for myiasis in a reference center in Uruguay between 2010 and 2019. METHODS: We conducted a descriptive and retrospective study by reviewing medical records. We analyzed the following variables: age, sex, comorbidities, origin, the month at admission, clinical manifestations, other parasitoses, treatments, complications, and larva species identified. RESULTS: We found 63 hospitalized children: median age of 7 years (1 month-14 years), 68% of females. We detected risk comorbidities for myiasis (33%), of which chronic malnutrition was the most frequent (n = 6); 84% were from the south of the country; 76% were hospitalized during the summer. Superficial and multiple cutaneous involvements were found in 86%: of the scalp 50, furunculoid type 51, secondary to C. hominivorax 98.4%, and to D. hominis in 1.6%. As treatments, larval extraction was detected in all of them, surgical in 22%. Asphaltic products for parasites were applied in 94%, ether in 49. Antimicrobials were prescribed in 95%; cephradine and ivermectin were the most frequent. About 51% presented infectious complications, impetigo was found in 29, cellulitis in 2, and abscess in 1. CONCLUSIONS: Myiasis predominantly affected healthy schoolchildren during the summer months and was frequently associated with ectoparasites. Superficial infestation of the furuncle-like scalp by C. hominivorax was the most frequent form. Infectious complications motivated hospitalizations.

Primary meningococcal arthritis of the hip due to serogroup W in a pediatric patient.

BACKGROUND: Primary meningococcal arthritis (PMA) is defined as the presence of acute septic arthritis with the identification of Neisseria meningitidis in synovial fluid or blood cultures but no clinical evidence of sepsis or meningitis. This report aimed to describe a clinical case of PMA caused by serogroup W, an uncommon etiology of this disease in Uruguay, and review the available literature. CASE REPORT: We report the case of a 5-year-old female, with no past medical history, admitted to the emergency department with a 12-hour history of fever of 39 °C and a limp. The patient was hemodynamically stable and had no clinical evidence of meningitis. Hip ultrasound showed an increase in synovial fluid. Arthrocentesis showed purulent exudate and synovial fluid culture showed no growth after five days. The blood culture showed isolates of N. meningitidis, serogroup W. The patient received treatment with ceftriaxone, and drainage of the affected joint was performed with excellent clinical response. CONCLUSIONS: Primary meningococcal arthritis is a rare presentation of meningococcal disease. Systematic arthrocentesis and the adequacy of antibiotic therapy when septic arthritis is clinically suspected are essential for confirming the diagnosis and decompressive drainage of the involved joint. This report is the first of PMA caused by serogroup W in Uruguay. Although the most common serogroup involved in meningococcal arthritis is serogroup B in Uruguay, an increase in serogroup W-related diseases has been reported in Chile and Argentina, emphasizing the need for epidemiological surveillance.

[SARS-CoV-2 infection in children: Clinical characteristics and dynamics of SARS-CoV-2 transmission in a private health center. Uruguay]. / Infección por SARS-CoV-2 en niños: Características clínicas y dinámica de la transmisión de SARS-CoV-2 en un centro de salud privado. Uruguay.

BACKGROUND: To date, the prevalence and severity of the COVID-19 disease in children is lower than in adults. There are controversies regarding the dynamics of transmission and the role they play in the spread of the disease. AIM: To describe the clinical characteristics and transmission dynamics of patients under 15 years of age reported for suspicion and/or contact for COVID-19 in the period March 13 - November 20, 2020, in a private comprehensive health provider (Médica Uruguaya Medical Assistance Corporation, MUCAM). METHODS: Descriptive, retrospective study, in which clinical manifestations, epidemiological notion, secondary cases, severity and evolution are described. The risk and rate of secondary intradomiciliary attack were estimated. RESULTS: 539 patients met the inclusion criteria. The diagnosis was confirmed in 29 (5.3%): 13 (7.0%) of the 351 symptomatic children and 16 (4.5%) of the 188 asymptomatic. 100% of the confirmed cases and 85% of the unconfirmed cases had the notion of contact (p < 0.05). The OR for infection from an indoor contact was 26.5 (9.8-71.7) and the rate of secondary indoor attack 23% ± 4.1. CONCLUSIONS: In this series, mild and asymptomatic forms predominated in patients under 15 years of age. One in five exposed indoors contracted the disease, this notion of contact being decisive to indicate confirmatory studies. Most of the children did not continue the chain of transmission.

[Actinomyces sp. brain abscess: a rare infection in children. A case report]. / Absceso cerebral por Actinomyces sp.: una infección infrecuente en niños. A propósito de un caso.

Despite advances in diagnostic and treatment techniques, intracranial infections remain serious diseases with an estimated incidence of between 0.3 and 1.3 cases/100,000 inhabitants. We present a previously healthy patient with an intraoperative diagnostic of brain abscess, in whom although the culture showed polymicrobial development, Actinomyces sp was presumptively identified in the pathological anatomy. Given this finding, prolonged combined antibiotic therapy was performed with good evolution. Absceso cerebral por Actinomyces sp.: una infección infrecuente en niños. A propósito de un caso Actinomyces sp. brain abscess: a rare infection in children. A case report The presentation of this suppurative process was nonspecific and the contribution of the anatomopathology in the etiological diagnosis was relevant. The identification of an unusual microorganism defined the need to deepen the identification of predisposing factors.

A pesar de los avances en las técnicas de diagnóstico y tratamiento, las infecciones intracraneanas son aún enfermedades graves con una incidencia estimada entre 0,3 y 1,3 casos por cada 100 000 habitantes. Se presenta un paciente previamente sano con un absceso cerebral de diagnóstico intraoperatorio en quien, si bien el cultivo evidenció desarrollo polimicrobiano, se identificó presuntivamente Actinomyces sp. en la anatomía patológica. Dado este hallazgo, se realizó antibioticoterapia combinada prolongada con buena evolución. La presentación de este proceso supurado fue inespecífica y la contribución de la anatomía patológica en el diagnóstico etiológico fue relevante. La identificación de un microorganismo inhabitual definió la necesidad de profundizar en la determinación de factores predisponentes.

[Characterization of hypotonia-hyporesponsiveness after pentavalent vaccine and neurodevelopmental screening in children under 6 years of age, 2013-2018, Uruguay]. / Caracterización de la hipotonía-hiporrespuesta post vacuna pentavalente y tamizaje del neurodesarrollo en niños bajo 6 años de edad, 2013-2018, Uruguay.

BACKGROUND: Hypotonic-hyporesponsive episodes (HHE) is one frequently reported neurologic adverse effect supposedly attributable to vaccination and immunization. Its long-term impact on neurodevelopment is not completely known. AIM: To characterize the post-pentavalent vaccine HHE events reported to the Uruguayan Ministry of Health (M of H) between 2014 and 2018. To perform neurodevelopment screening of those who were under 6 years of age at the time of evaluation. METHODS: Descriptive study of the reports made to the National Farmacosurveillance System of the M of H. Neurodevelopment screening was performed using the National Guidelines for Developmental Surveillance. RESULTS: 30 cases were studied. Most cases occurred after the first doses, were of short duration and during the first hours after vaccination, with spontaneous recovery. Median time between the event and this evaluation was 2 years and 2 months. Screening tests were normal in 15. Delay in the language area was detected in one case. CONCLUSIONS: HHE events had similar characteristics to those described in the literature, with no severe short-term complications. Despite the limitations of the present study, no delays nor deviations were found in the development of the children who were evaluated.

[Peritoneal tuberculosis. A rare form of presentation of an emerging disease in pediatrics]. / Tuberculosis peritoneal. Una forma de presentación poco frecuente de una enfermedad emergente en pediatría.

Tuberculosis constitutes an important health problem, affecting one third of the world's population. The pulmonary localization is the most frequent one, being rare the peritoneal presentation. Clinical manifestations are non-specific so the diagnosis requires a high level of suspicion. The case of a 13-year-old teenager hospitalized for peritoneal tuberculosis is reported. The objective is to describe a rare form of extra-pulmonary manifestation of M. tuberculosis infection in the pediatric age and to sensitize the medical community, in the current epidemiological context, to the reemergence of this disease and the importance of timely diagnosis and treatment as well as strengthening control and prevention measures.

La tuberculosis constituye un importante problema sanitario, que afecta a un tercio de la población mundial. La localización pulmonar es la más frecuente, y es rara la presentación peritoneal. Las manifestaciones clínicas son inespecíficas, por lo que el diagnóstico requiere de un alto nivel de sospecha. Se comunica el caso de una adolescente de 13 años hospitalizada por tuberculosis peritoneal. El objetivo es describir una forma poco frecuente de manifestación extrapulmonar de la infección por M. tuberculosis en la edad pediátrica y concien-tizar a la comunidad médica, en el contexto epidemiológico actual, sobre la reemergencia de esta enfermedad y la importancia del diagnóstico y tratamiento oportunos, así como de reforzar las medidas de control y prevención.

[Intestinal parasites in schoolchildren, public health problem. Intervention from the National Integrated Health System of Uruguay]. / Enteroparasitosis en escolares, problema de salud pública. Intervención desde el Sistema Nacional Integrado de Salud de Uruguay.

OBJECTIVES: To generate a model of intervention, from the National Integrated Health System (NIHS, Uruguay), with school facilitators of health, web resources and approach from the schools to the community. MATERIALS AND METHODS: Descriptive cross-sectional study of population base using a random sampling, non-clustered, during the months of April and December 2016. This was based in the model of schoolchildren health promoters, the use of web resources and community approach with the school as the centre of actions. RESULTS: The prevalence of parasites was 14% for Giardiasis (6,5 and 22%) (IC95%: 11-17) and 26% for Oxiurosis (IC95%: 22-30) (20 and 44%). Soil transmitted helminthiases were geo-referenced: we found 45 clusters, mainly in slums without basic services. CONCLUSIONS: These worrying results show that there are regions in Montevideo (Uruguay) with high levels of faecal home and environmental contamination. Community approaches with prevention activities from NIHS may have a positive impact on these vulnerable populations.

OBJETIVOS: Generar un modelo de intervención en promoción de salud, desde el Sistema Nacional Integrado de Salud (SNIS) de Uruguay, con promotores escolares de salud, recursos web y abordaje desde los centros educativos a la comunidad. MATERIALES Y MÉTODOS: Estudio descriptivo transversal, de base poblacional, mediante un muestreo aleatorio, no agrupado, durante los meses de abril y diciembre de 2016. Se llevó a cabo una capacitación para escolares en promoción de salud, encuesta poblacional, herramientas web, exámenes parasitológicos y georreferenciación. RESULTADOS: Se observaron prevalencias de giardiasis, del 14% (IC95%: 11-17) (6,5 a 22%); y oxiurosis 26% (IC95: 22-30) (20 a 44%). Se visualizaron 45 conglomerados de geohelmintiasis (HTS), la mayoría en zonas con asentamientos poblacionales carentes de servicios básicos. CONCLUSIONES: La existencia de sectores poblacionales vulnerables con índices de contaminación fecal intradomiciliaria y ambientales hace necesario que el SNIS realice de forma sistemática actividades de promoción de salud que puedan aportar datos relevantes para intervenciones gubernamentales intersectoriales y para mejorar la salud de estos sectores desprotegidos.

[Extrapulmonary tuberculosis in children under the age of 15 hospitalized at the Pereira Rossell Hospital Center, Uruguay]. / Tuberculosis extra-pulmonar en niños bajo 15 años de edad internados en el Centro Hospitalario Pereira Rossell, Uruguay.

BACKGROUND: Tuberculosis is a public health problem. Children constitute a population at risk of becoming ill and evolving into serious forms. AIM: To describe the frequency, epidemiological, clinical and evolutionary characteristics of children under 15 years of age hospitalized for extrapulmonary tuberculosis (EPTB) at the Pereira Rossell Hospital-Uruguay, during 2009-2019. METHODS: Descriptive, retrospective study, review of medical records and records of the Honorary Commission for the Fight Against Tuberculosis. VARIABLES: age, sex, epidemiological and clinical link, diagnostic confirmation, treatment and complications. RESULTS: 77 cases of EPTB were registered, 45 (58%) were hospitalized in this center. Average age 7 years, males 25 (56%). All received the Bacillus Calmette-Guérin vaccine. An epidemiological link was identified in 28 (62%). The forms of EPTB were: pleural 26 (58%), central nervous system (CNS) 9 (20%), lymphoganglionic 4 (9%), cutaneous 2 (5%), bone 1 (2%), peritoneal 1 (2%), pleural- peritoneal 1 (2%), bone-CNS 1 (2%). Etiology was confirmed in 23 (51%): by culture 16, GeneXpert 5, by both 2. Thirty-six (80%) patients completed treatment. Four (9%) presented complications: convulsive state 2, cerebral hemorrhage 1, multiple organ failure 1. CONCLUSIONS: EPTB occurred in previously healthy children. The diagnosis requires a high index of suspicion and the confirmation of the simultaneous use of several diagnostic techniques.

Haemophilus influenzae type b invasive infections in children hospitalized between 2000 and 2017 in a Pediatric Reference Hospital (PRH).

BACKGROUND: Uruguay incorporated the conjugate vaccine against Haemophilus influenzae b (Hib) in 1994. In 2008, the vaccine was changed from one with natural conjugated capsular polysaccharide to one with a synthetic polysaccharide component. We describe the frequency and characteristics of invasive Hib infections in children hospitalized in a Pediatric Reference Hospital (PRH) between January 1st, 2000 and December 31st, 2017. METHODS: Sterile site Hib isolations from hospitalized children were included. Clinical and microbiological characteristics were analyzed. Favorable conditions for the infection were considered: incomplete immunization, immunodeficiencies and associated pathologies. Two periods are described: 1, prior to vaccine change (1/1 st/2000- 12/31/08) and 2, post-change (1/1 st/09- 12/31st/17). RESULTS: 45 children were hospitalized: 5 in the first period and 40 in the second. The hospitalization rate per 10,000 discharges was 0.41 (95% CI 0.05-0.77) and 4.2/10,000 (95% CI 2.89-5.48), respectively (p < 0.01). The diagnoses at discharge were: meningitis/ventriculitis (20), pneumonia (16), bacteremia (3), epiglottitis (1), arthritis (1), cellulitis (3) and obstruction of the upper airway (1). Four children presented comorbidities. Twenty seven received less than 3 doses of anti-Hib vaccination and 18 were properly vaccinated (2 were immunodeficient). The median hospitalization was 14 days, 18 children required intensive therapy. CONCLUSIONS: Observed change may be due to: incomplete primary series, inhomogeneous vaccine coverage and immunogenicity of the synthetic polysaccharide. To reduce this public health problem, epidemiological surveillance.

[Antibiotic consumption and antimicrobial susceptibility evolution in the Centro Hospitalario Pereira Rossell in methicillin resistant Staphylococcus aureus era]. / Evolución del consumo de antibióticos y de la susceptibilidad antimicrobiana en el Centro Hospitalario Pereira Rossell en la era de Staphylococcus aureus resistente a meticilina.

INTRODUCTION: In the past few years, an increase in methicillin resistant-not multiresistant Staphylococcus aureus was observed in Uruguay among children with community acquired infections. Recommendations for empiric antibiotic treatment required adjustments and new national guidelines were recommended in July 2004. Adherence to these guidelines was indirectly performed by monitoring antibiotic consumption and antimicrobial susceptibility patterns in Uruguay. OBJECTIVE: To describe and compare antibiotic consumption and antimicrobial susceptibility of Staphylococcus aureus in a Pediatric Hospital of the Centro Hospitalario Pereira Rossell (PH-CHPR) between 2001 and 2006. METHODS: Antibiotic consumption in hospitalized children was calculated using the Defined Daily Dose per 100 bed-days (DDD/100). Reference values were obtained from the World Health Organization Collaborating Center for Drug Statistics Methodology of. Consumption. Data were obtained using the WinPharma programme of the Pharmacy Department of CHPR. The fraction of annual occupancy of hospital beds was obtained from the Statistic Division of CHPR. Antibiotic consumption was evaluated between 2001 and 2006 and expressed as DDD/100 and percent change. Antimicrobial susceptibility was evaluated using CHPR's Microbiology Laboratory data during the same time period. RESULTS: After 2003 a significant increase in consumption of clindamycin, ceftriaxone, trimethoprim-sulphamethoxazole, cefuroxime, vancomycin and gentamycin was observed, except for cephradine. Consumption of clindamycin, ceftriaxone and trimethoprim-sulphamethoxazole showed the highest increase (6.15%; 1.44% and 1.17% respectively). Detection of Staphylococcus aureus increased significantly mostly from skin and soft tissue infections. Oxacillin susceptibility of S. aureus strains obtained from different sites had a significant and persistent decrease after 2003 (from 81 % during year 2001 to 40% in year 2006 (p < 0.05). Susceptibility to others antibiotics did not decrease. Between 2004 and 2006 the "D effect" decreased from 28% to 21 %. Antimicrobial susceptibility patterns did not differ by site of infection. CONCLUSIONS: Methicillin resistant-not multiresistant Staphylococcus aureus has established itself as a regular community pathogen in Uruguayan children. Changes in antimicrobial consumption patterns reflect the impact of this pathogen in clinical practice and the overall adherence to new recommendations. This change was not associated with an increase in antibiotic resistance. Clindamycin is an alternative treatment although Clindamycin inducible resistance is a worry. Continuous monitoring of antibiotic consumption and local susceptibility patterns are required to promote rational use of antibiotics.

Intoxicación por paracetamol en adolescentes. Reporte de una serie de casos

Introducción: la intoxicación por paracetamol puede producir falla hepática aguda. El pronóstico depende del diagnóstico precoz e inicio oportuno de las medidas terapéuticas. Objetivo: sensibilizar acerca del adecuado abordaje diagnóstico-terapéutico de la intoxicación aguda por paracetamol. Casos clínicos: se trata de 10 adolescentes de sexo femenino, mediana de edad 13,5 años, con intoxicación aguda intencional. Presentaban psicopatología 9; intentos de autoeliminación (IAE) previos 5, y seguimiento por equipo de salud mental 7. Cuatro recibían tratamiento con psicofármacos. Mediana de dosis de paracetamol 10 g (5 - 40). Se realizó carbón activado en ocho, asociado a lavado gástrico en seis pacientes. Mediana de tiempo entre ingesta y rescate 2,5 horas (1 - 3,5). Presentaron síntomas digestivos seis, fueron asintomáticas tres. Se dosificó el paracetamol luego de las 4 horas y en las primeras 24 horas de la ingesta en siete, siendo indetectable en una paciente. En las restantes, el riesgo de toxicidad hepática fue: posible en dos, probable en tres y sin riesgo en una. Se administró dosis carga de n-acetil cisteína a siete pacientes y tratamiento completo de mantenimiento a seis. Nueve ingresadas a cuidados moderados y una paciente a cuidados intensivos. No hubo complicaciones, ni fallecimientos. Se abordaron junto al toxicólogo. Conclusiones: la intoxicación aguda por paracetamol en adolescentes es habitualmente secundaria a IAE. La prevalencia de los problemas de salud mental y de IAE en esta población constituye una alerta para los profesionales de la salud que deben conocer el perfil de los fármacos utilizados y el abordaje diagnóstico-terapéutico de las posibles intoxicaciones. Dado el riesgo de hepatotoxicidad severa es necesario actuar rápidamente considerando dosis ingerida, tiempo desde la ingesta y factores de riesgo de hepatotoxicidad.

Introduction: Paracetamol poisoning can produce acute liver failure. Its prognosis depends on early diagnosis and timely initiation of specific therapeutic measures. Objective: To make health professionals aware of the appropriate diagnostic-therapeutic approach to acute paracetamol poisoning. Clinical cases: These are ten female adolescents, median age 13.5 years, with acute and intentional poisoning. 9 presented psychopathology, 5 previous self-elimination attempts (AEIs), and 7 were monitored by a mental health team. 4 received treatment with psychoactive drugs. Median dose of paracetamol 10 g (5-40 g). Drug rescue was performed with activated charcoal in 8, associated with gastric lavage in 6. The median time between intake and rescue was 2.5 hours (1-3.5 hours). They presented digestive symptoms 6 and were asymptomatic 3. Paracetamol was dosed after 4 hours and in the first 24 hours of ingestion in 7, being undetectable in 1. In the remainder, the risk of liver toxicity was classified as: possible 2, probable 3 and 1 without risk. A loading dose of n-acetyl cysteine was administered to 7 and full maintenance treatment to 6. 9 were admitted to moderate care and 1 to intensive care. There were no complications or deaths. Discussion/Conclusions: Acute paracetamol poisoning in adolescents is usually secondary to AEI. The prevalence of mental health problems and AEI in this population constitutes an alert for health professionals who must know the profile of the drugs used and the diagnostic-therapeutic approach to possible poisoning. Given the risk of severe hepatotoxicity, it is necessary to act quickly considering the dose ingested, time since ingestion, and risk factors for hepatotoxicity.

Introdução: O envenenamento por paracetamol pode levar à insuficiência hepática aguda. O prognóstico depende do diagnóstico precoce e do início oportuno das medidas terapêuticas. Objetivo: Aumentar a conscientização sobre a abordagem diagnóstica e terapêutica adequada para a intoxicação aguda por paracetamol. Casos clínicos: Dez adolescentes do sexo feminino, com idade média de 13,5 anos, com intoxicação agudada intencional. Nove apresentavam psicopatologia, 5 haviam feito tentativas anteriores de automutilação (SAI) e 7 tinham acompanhamento pela equipe de saúde mental, 44 recebiam tratamento com drogas psicotrópicas. Dose média de paracetamol 10 g (5 - 40 g). O carvão ativado foi usado em 8, associado à lavagem gástrica em 6. O tempo médio entre a ingestão e o resgate foi de 2,5 horas (1 a 3,5 horas). O paracetamol foi dosado após 4 horas e dentro de 24 horas da ingestão em 7, sendo indetectável em 1 caso. Nas demais pacientes, o risco de toxicidade hepática foi: possível em 2, provável em 3 e sem risco em 1. Uma dose de ataque de n-acetilcisteína foi administrada a 7 e o tratamento de manutenção completo a 6. Nove foram admitidas em cuidados moderados e 1 em cuidados intensivos. Esses dados foram discutidos com o toxicologista. Discussão/Conclusões: A intoxicação aguda por paracetamol em adolescentes geralmente é secundária a tentativa de autoextermínio (TAE). A prevalência de problemas de saúde mental e TAE nessa população é um alerta para os profissionais de saúde, que devem estar cientes do perfil dos medicamentos utilizados e da abordagem diagnóstica-terapêutica de possíveis intoxicações. Dado o risco de hepatotoxicidade grave, é necessário agir rapidamente, considerando a dose ingerida, o tempo decorrido desde a ingestão e os fatores de risco para hepatotoxicidade.

Population Pharmacokinetics of Clozapine and Norclozapine and Switchability Assessment between Brands in Uruguayan Patients with Schizophrenia.

Clozapine (CZP) is an atypical antipsychotic agent commonly used in the treatment of schizophrenia. It is metabolized primarily by CYP1A2 enzyme, yielding a pharmacologically active metabolite, norclozapine (NCZP). Significant intra- and interindividual pharmacokinetic (PK) variability for CZP and NCZP has been observed in routine therapeutic drug monitoring. So the goal of this study was to evaluate the magnitude and variability of concentration exposure to CZP and its active metabolite NCZP on pharmacokinetic parameters in Uruguayan patients with schizophrenia with a focus on covariates such as cigarette smoking, age, sex, caffeine consumption, brands available of CZP, and comedication using population PK (PPK) modeling methodologies. Patients with a diagnosis of schizophrenia treated with brand-name CZP (Leponex®) for more than a year were included in the study. Then these patients were switched to the similar brand of CZP (Luverina®). Morning predose blood samples for determination of CZP and NCZP using a HPLC system equipped with a UV detector were withdrawn on both occasions at steady state and under the same comedication. Ninety-eight patients, 22 women and 76 men, took part in the study. Mean ± standard deviation for CZP and NCZP concentration was 421 ± 262 ng/mL and 275 ± 180 ng/mL, respectively. After covariate evaluation, only smoking status remained significant in CZP apparent clearance, inducing a mean increment of 32% but with no clinical impact. The results obtained with the two brands of CZP should ensure comparable efficacy and tolerability with the clinical use of either product. Smoking was significantly associated with a lower exposure to CZP due to higher clearance. The results obtained with the two brands commercialized in our country hint a bioequivalence scenario in the clinical setting.

[Active surveillance of febrile seizures associated to DPT vaccines in a sentinel hospital in Uruguay]. / Vigilancia activa de convulsiones febriles vinculadas a vacuna pentavalente en un hospital centinela en Uruguay.

BACKGROUND: Febrile seizures are VAERS often associated with whole-cells Diphtheria-Pertussis-Tetanus vaccines. AIM: To analyze the association of febrile seizures with the administration of pentavalent vaccine in children under two-years-old assisted in the Centro Hospitalario Pereira Rossell (CHPR), in Montevideo during 2014. METHODS: Self-controlled case series study. We included children from Montevideo from two to 24-month-old at the time of admission, with diagnosis of febrile seizure at the time of discharge. We estimated the relative risk in three time periods: 0 to 3 days (risk period), 4 to 14 days (wash-out) and more than 14 days after vaccination (no-risk). RESULTS: We recorded 135 febrile seizures in 114 children, 16 of whom presented two or more events. The total number of events was 7 (5.2%) in risk periods and 8 (5.9%) in wash-out periods. The risk period showed a significantly increased risk (RR = 4.14, CI 95% = [1.73; 8.36]). CONCLUSIONS: This work allowed us to establish a national base line for the risk of febrile seizures associated with pentavalent vaccination, by using for the first time in the country a methodology specifically designed for this goal.