Exploring avibactam and relebactam inhibition of Klebsiella pneumoniae carbapenemase D179N variant: role of the Ω loop-held deacylation water.

Klebsiella pneumoniae carbapenemase-2 (KPC-2) presents a clinical threat as this ß-lactamase confers resistance to carbapenems. Recent variants of KPC-2 in clinical isolates contribute to concerning resistance phenotypes. Klebsiella pneumoniae expressing KPC-2 D179Y acquired resistance to the ceftazidime/avibactam combination affecting both the ß-lactam and the ß-lactamase inhibitor yet has lowered minimum inhibitory concentrations for all other ß-lactams tested. Furthermore, Klebsiella pneumoniae expressing the KPC-2 D179N variant also manifested resistance to ceftazidime/avibactam yet retained its ability to confer resistance to carbapenems although significantly reduced. This structural study focuses on the inhibition of KPC-2 D179N by avibactam and relebactam and expands our previous analysis that examined ceftazidime resistance conferred by D179N and D179Y variants. Crystal structures of KPC-2 D179N soaked with avibactam and co-crystallized with relebactam were determined. The complex with avibactam reveals avibactam making several hydrogen bonds, including with the deacylation water held in place by Ω loop. These results could explain why the KPC-2 D179Y variant, which has a disordered Ω loop, has a decreased affinity for avibactam. The relebactam KPC-2 D179N complex revealed a new orientation of the diazabicyclooctane (DBO) intermediate with the scaffold piperidine ring rotated ~150° from the standard DBO orientation. The density shows relebactam to be desulfated and present as an imine-hydrolysis intermediate not previously observed. The tetrahedral imine moiety of relebactam interacts with the deacylation water. The rotated relebactam orientation and deacylation water interaction could potentially contribute to KPC-mediated DBO fragmentation. These results elucidate important differences that could aid in the design of novel ß-lactamase inhibitors.

Structural Characterization of the D179N and D179Y Variants of KPC-2 ß-Lactamase: Ω-Loop Destabilization as a Mechanism of Resistance to Ceftazidime-Avibactam.

Klebsiella pneumoniae carbapenemases (KPC-2 and KPC-3) present a global clinical threat, as these ß-lactamases confer resistance to carbapenems and oxyimino-cephalosporins. Recent clinically identified KPC variants with substitutions at Ambler position D179, located in the Ω loop, are resistant to the ß-lactam/ß-lactamase inhibitor combination ceftazidime-avibactam, but susceptible to meropenem-vaborbactam. To gain insights into ceftazidime-avibactam resistance conferred by D179N/Y variants of KPC-2, crystal structures of these variants were determined. The D179N KPC-2 structure revealed that the change of the carboxyl to an amide moiety at position 179 disrupted the salt bridge with R164 present in wild-type KPC-2. Additional interactions were disrupted in the Ω loop, causing a decrease in the melting temperature. Shifts originating from N179 were also transmitted toward the active site, including ∼1-Å shifts of the deacylation water and interacting residue N170. The structure of the D179Y KPC-2 ß-lactamase revealed more drastic changes, as this variant exhibited disorder of the Ω loop, with other flanking regions also being disordered. We postulate that the KPC-2 variants can accommodate ceftazidime because the Ω loop is displaced in D179Y or can be more readily displaced in D179N KPC-2. To understand why the ß-lactamase inhibitor vaborbactam is less affected by the D179 variants than avibactam, we determined the crystal structure of D179N KPC-2 in complex with vaborbactam, which revealed wild-type KPC-2-like vaborbactam-active site interactions. Overall, the structural results regarding KPC-2 D179 variants revealed various degrees of destabilization of the Ω loop that contribute to ceftazidime-avibactam resistance, possible substrate-assisted catalysis of ceftazidime, and meropenem and meropenem-vaborbactam susceptibility.

Treatment of classical Hodgkin lymphoma in the era of brentuximab vedotin and immune checkpoint inhibitors.

The majority of Hodgkin lymphoma patients are now cured with conventional first-line therapy; however, 10-15% of early-stage disease and less than 30% of advanced-stage patients are refractory(rare) or relapsed. Salvage second-line therapy combined with high-dose therapy and autologous stem-cell transplantation can cure 40-50% of patients. Recently novel agents (Brentuximab Vedotin and Immune Checkpoint inhibitors) have demonstrated evidence of therapeutic activity and are potential bridge to an allogeneic stem-cell transplantation. The review is aimed to present not only salvage strategies; indeed, the paper contains paragraphs about therapy and new treatment options at diagnosis.

Early reduction of serum TARC levels may predict for success of ABVD as frontline treatment in patients with Hodgkin Lymphoma.

BACKGROUND: Many efforts have been made to predict prognosis of newly diagnosed Hodgkin Lymphoma (HL) patients. Objective of this study was to investigate the association between early reduction of Thymus and Activation-Regulated Chemokine after the first ABVD cycle (TARC-1) and prognosis of HL patients. METHODS: Serum samples of 116 HL patients were collected at baseline, after every ABVD cycle and during follow-up. The 99th centile of TARC distribution in a group of 156 independent healthy subjects (800pg/ml) was considered as cut-off for discriminating between abnormal and normal TARC values. FINDINGS: 101 patients out of 116 had baseline TARC above 800pg/ml (median value 27515pg/ml (IQR, 11001-68139)) and were the object of this analysis. TARC-1 significantly decreased to a median value of 556pg/ml (IQR, 378-977pg/ml). TARC-1 values below 800pg/ml were associated with success of therapy (p=0.0003) and PET-2 negativity (p=0.001). TARC-1≤800pg/ml identified a population with a significantly higher 5-years PFS in the whole cohort (90.1% vs 55.6%; p<0.0001) and in both subgroups of advanced (p=0.003) and early stage patients (p=0.021). At multivariable analysis, TARC-1 was significant independent predictor of PFS (p=0.0035). INTERPRETATION: Early reduction of TARC serum levels can predict success of treatment, being associated with achievement of interim PET-2 negative and favorable long-term outcome in HL patients receiving ABVD as front-line therapy.

Results of a randomized trial comparing high-dose chemotherapy plus Auto-SCT and R-FC in CLL at diagnosis.

The importance of early therapy intensification in B-cell CLL (B-CLL) patients remains to be defined. Even though several studies have been published, no randomized trials comparing directly autologous stem cell transplant (ASCT) and the accepted conventional therapy (that is, rituximab, fludarabine and CY; R-FC) have been reported so far. To assess the benefit of a first-line aggressive therapy, we designed a multicenter, randomized, phase 3 trial comparing R-FC and high-dose chemotherapy supported by ASCT in patients under 65 years of age, with stage B(II) or C B-CLL. Primary end point was CR: 96 patients were enrolled (48 in each arm). On an intent-to-treat basis, the CR rates in the ASCT and R-FC arms were 62.5% and 58%, respectively. After 5 years of follow-up, PFS was 60.4% in the ASCT arm and 65.1% in the R-FC arm, time to progression 65.8 and 70.5%, and overall survival 88% vs 88.1%, respectively. Our trial demonstrates, for the first time in a randomized manner, that frontline ASCT does not translate into a survival advantage when compared with benchmark chemoimmunotherapy in B-CLL patients; the possibility of its clinical benefit in certain subgroups remains uncertain.

O laço social na adolescência: a violência como ficção de uma vida desqualificada / Adolescence and social tie: violence as a fiction of a disqualified life / Lazo social y adolescencia: la violencia como ficción de una vida descalificada

Este trabalho discute as estratégias dos adolescentes dos grandes centros urbanos, periferias e favelas na sua inscrição no laço social. A partir de um trabalho clínico de orientação psicanalítica com adolescentes em ambiente escolar, formulamos a hipótese: diante da violenta desqualificação de suas vidas e da falta de perspectivas de inscrição em um laço indicador de participação fálica no social, alguns jovens fazem da violência sua própria ficção, de modo a inverter lugares - de passivos à violência passam a ativos, em uma produção fantasmática, na qual a violência se torna a modalidade normatizada de laço social.

This paper discusses the strategies of adolescents in large urban centers, suburbs and slums for subscribing to the social bond. Based on a clinical work, under a psychoanalytic orientation, with adolescents from a public school, we formulated the following hypothesis: in face of the violent disqualification of their lives and the lack of prospects of an inscription in a bond minimally indicative of phallic participation in the social field, some youth make violence their own fiction in order to reverse the places - from passive to violence they begin to be active in producing a fantasmatic production in which violence becomes the standardized form of social bond.

Este trabajo pretende discutir las estrategias de los adolescentes de los grandes centros urbanos, periferias y chabolas en su inscripción en el lazo social. A partir de un trabajo clínico, de orientación psicoanalítica, con adolescentes de una escuela municipal, pudimos formular la hipótesis: delante de la violenta descalificación de sus vidas y de la falta de perspectivas de una inscripción en un lazo mínimamente indicador de participación fálica en el campo social, algunos jóvenes hacen de la violencia su propia ficción, de modo a invertir los lugares - de pasivos a la violencia pasan a ser activos en una producción fantasmática en que la violencia se torna la modalidad normatizada de lazo social.

[Treatment of urinary tract infections in febrile infants: experience of outpatient intravenous antibiotic treatment]. / Manejo de la infección del tracto urinario en lactantes febriles: Experiencia de tratamiento antimicrobiano intravenoso ambulatorio.

OBJECTIVE: To describe the feasibility, effectiveness and safety of intravenous (iv) outpatient treatment in 2 to 24 month-old children with febrile urinary tract infection (UTI). METHOD: Children presenting to the ER, between April 2003-2005, with fever and no identifiable focus who had a diagnosis of UTI were randomized to receive iv antibiotic in the hospital or in an outpatient facility. Children were started on amikacin or ceftriaxona according to physician criteria followed by antimicrobial adjustment based on urine culture result and a later switch to an oral antimicrobial. Urine cultures were performed during and after completing the antimicrobial course. Adherence and effectiveness of antimicrobial treatment and treatment-associated complications were analyzed. RESULTS: The study included 112 patients, 58 inpatient children and 54 outpatient children, with an average age of 7.7 months. Duration of iv treatment did not differ among groups (2.8 days (SD 1.2) 2.7 +0.91 days in inpatients vs 2.9 + 1.9 days in outpatients (p = 0.22). In 100% of outpatient children and 100% of inpatient children (overall 101/101) urine cultures were negative on day 5. None of the children had a treatment-associated complication. Cost analysis yielded 73% of saving money (overall cost for inpatient treatment US 9,815 vs outpatient treatment US 2,650). CONCLUSIONS: Outpatient iv treatment in patients between 2 and 24 months with UTI and fever was effective, safe and of lower cost.

Manejo de la infección del tracto urinario en lactantes febriles: experiencia de tratamiento antimicrobiano intravenoso ambulatorio / Treatment of urinary tract infections in febrile infants: experience of outpatient intravenous antibiotic treatment

Objective: To describe the feasibility, effectiveness and safety of intravenous (iv) outpatient treatment in 2 to 24 month-old children with febrile urinary tract infection (UTI). Method: Children presenting to the ER, between April 2003-2005, with fever and no identifiable focus who had a diagnosis of UTI were randomized to receive iv antibiotic in the hospital or in an outpatient facility. Children were started on amikacin or ceftriaxona according to physician criteria followed by antimicrobial adjustment based on uriñe culture result and a later switch to an oral antimicrobial. Uriñe cultures were performed during and after completing the antimicrobial course. Adherence and effectiveness of antimicrobial treatment and treatment-associated complications were analyzed. Results: The study included 112 patients, 58 inpatient children and 54 outpatient children, with an average age of 7.7 months. Duration of iv treatment didnot differ among groups (2.8 days (SD 1.2) 2.7 +0.91 days ininpatients vs 2.9 + 1.9 days in outpatients (p = 0.22). In 100 percent of outpatient children and 100 percent of inpatient children (overall 101/101) uriñe cultures were negative on day 5. None of the children had a treatment-associated complication. Cost analysis yielded 73 percent of saving money (overall cost for inpatient treatment US 9,815 vs outpatient treatment US 2,650). Conclusions: Outpatient iv treatment in patients between 2 and 24 months with UTI and fever was effective, safe and of lower cost.

Objetivo: Describir la factibilidad, efectividad y seguridad del tratamiento intravenoso (iv) ambulatorio en niños de 2 meses a 2 años con infección del tracto urinario (ITU) y fiebre. Método: Entre abril 2003 y abril 2005 se realizó un estudio prospectivo en pacientes con fiebre sin foco derivados de Emergencia Infantil, finalmente diagnosticados como ITU, estableciéndose dos grupos con tratamiento iv: uno hospitalizado y otro ambulatorio. Se administró amikacina o ceftriaxona según criterio del médico de turno, hasta obtener resultado del urocultivo, y posteriormente se cambió a tratamiento oral. Se controló urocultivo intra y post tratamiento registrándose adherencia, efectividad y complicaciones. Resultados: Se incluyeron 112 pacientes (58 hospitalizados y 54 ambulatorios), con edad promedio de 7,8 meses. El promedio de días de tratamiento iv fue 2,8 días (SD 1,2) sin diferencias significativas entre ambos grupos 2,7 +0,91 días en los internados vs 2,9 + 1,9 días en los ambulatorios (p = 0,22). En 100 por ciento de ambos grupos de pacientes (en globo 101/101) el urocultivo obtenido al día 5 fue estéril. No hubo complicaciones del tratamiento o sobre la vía venosa. El análisis de costos concluyó que en globo, el manejo ambulatorio representó un 73 por ciento de ahorro económico (1.430.000 pesos chilenos vs 5.300.000 pesos en el sólo rubro de día-cama Conclusiones: El tratamiento iv ambulatorio en pacientes con ITU febril entre 2 y 24 meses fue efectivo, seguro y a un menor costo.

Investigation of different group A immunoassays following one dose of meningococcal group A conjugate vaccine or A/C polysaccharide vaccine in adults.

A double-blind, randomized, controlled phase I study to assess the safety, immunogenicity, and antibody persistence of a new group A conjugate vaccine (PsA-TT) in volunteers aged 18 to 35 years was previously performed. Subjects received one dose of either the PsA-TT conjugate vaccine, meningococcal A/C polysaccharide vaccine (PsA/C), or tetanus toxoid vaccine. The conjugate vaccine was shown to be safe and immunogenic as demonstrated by a standardized group A-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and by a serum bactericidal antibody (SBA) assay using rabbit complement (rSBA). This report details further analysis of the sera using four additional immunologic assays to investigate the relationship between the different immunoassays. The immunoassays used were an SBA assay that used human complement (hSBA), a group A-specific IgG multiplexed bead assay, and two opsonophagocytic antibody (OPA) assays which used two different methodologies. For each vaccine group, geometric mean concentrations or geometric mean titers were determined for all assays before and 4, 24, and 48 weeks after vaccination. Pearson's correlation coefficients were used to assess the relationship between the six assays using data from all available visits. An excellent correlation was observed between the group A-specific IgG concentrations obtained by ELISA and those obtained by the multiplexed bead assay. hSBA and rSBA titers correlated moderately, although proportions of subjects with putatively protective titers and those demonstrating a > or = 4-fold rise were similar. The two OPA methods correlated weakly and achieved only a low correlation with the other immunoassays. The correlation between hSBA and group A-specific IgG was higher for the PsA-TT group than for the PsA/C group.

Cardiopulmonary response to exercise in patients with different degrees of lung toxicity after radio-chemotherapy for Hodgkin's disease.

The combination of mediastinal radiotherapy (RT) and polychemotherapy (CT) regimens can produce late toxic pulmonary and cardiac effects which often remain at the subclinical level. The aim of the present study was to investigate the cardiopulmonary response to exercise in this kind of patient. Therefore, 126 patients suffering from Hodgkin's disease were investigated after a follow-up of at least 5 years from the completion of the combined treatment. Sixty-two patients had been submitted to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)-RT, 40 to ABVD-MOPP (mechloretamine, vincristine, procarbazine, prednisone)-RT and 24 to VEBEP (vincristine, epidoxorubicin, bleomycin, cyclophosphamide, etoposide, prednisone)-RT. The patients were divided into three groups on the basis of respiratory function: group 1 (67 patients), normal spirometry and lung transfer function for carbon monoxide (DLCO); group 2 (52 patients), normal spirometry and DLCO less than 80% of predicted; and group 3 (7 patients), total lung capacity and DLCO less than 80% of predicted. The patients were submitted to respiratory function evaluation and 2D-echocardiography before exercise, and to the determination of cardiac output by the acetylene rebreathing method before and during symptom-limited exercise on a cycloergometer using an incremental protocol. The patients of group 3 and to a lesser extent the patients of group 2 showed, in comparison to patients of group 1, a lower tolerance to exercise, a lower oxygen consumption, a higher respiratory rate, a lower O2 pulse and a lower cardiac output per oxygen uptake. These data indicated an abnormal exercise physiology in the patients with persistent pulmonary impairment, especially when the reduction of DLCO was associated with a decrease of total lung capacity. The lower exercise capacity seems to be due to a combination of decreased cardiac performance and an impairment of gas diffusion capacity.

Viver em tempos sombrios: a experiência e os laços com os contemporâneos / Living in gloomy times: experience and bonds with our contemporaries / Vivir en tiempos sombríos: la experiencia y los vínculos con los contemporáneos

Neste artigo, vamos examinar, apoiadas em convergências ético-políticas de autores de diversas áreas de conhecimento, as estratégias de poder e os impasses do sujeito contemporâneo nestes tempos sombrios. Apontaremos algumas das consequências desse poder para o sujeito no capitalismo avançado, particularmente as que incidem sobre o sentido da vida, sobre a historização do sujeito. Indicaremos algumas modalidades de resistência que supõem o deslocamento do gozo monitorado politicamente e mortífero para o desejo, para uma práxis caracterizada pelo resgate da experiência compartilhada do mundo, em que os processos coletivos e a reabilitação do espaço público possam tornar possível a construção de projetos comuns. O artigo recoloca a noção de contemporâneo pela via da conjugação de diversas temporalidades, afirmando a construção de um modo particular de atribuir sentido ao presente. Entende que, resgatando a experiência compartilhada com os contemporâneos, pode-se reinventar a vida e criar mecanismos de pressão contra a submissão ao poder soberano.

Based on ethical and political viewpoints of authors from various fields and on psychoanalysis, this article examines power strategies and the contemporary subject's predicaments in these gloomy times. It points out some of the consequences of power to the subject of today's advanced capitalism, particularly those affecting life's meaning and history. It indicates some means of resistance that entail the displacement of a politically monitored jouissance, lethal to desire, onto a praxis characterized by the rescue of a shared world experience, in which collective processes and the rehabilitation of public spaces may enable the construction of common projects. The article reshapes the notion of contemporariness by connecting several temporalities, thus asserting the construction of an individual way of ascribing meaning to the present. It demonstrates that, by rescuing the experience with one's contemporaries, it is possible to reinvent life and create pressure mechanisms against submission to a sovereign power.

En este artículo vamos a examinar, apoyados en autores de diversas áreas y en el psicoanálisis, las estrategias de poder y los impasses del sujeto contemporáneo en estos tiempos sombríos. Apuntaremos algunas consecuencias de este poder para el sujeto en el capitalismo avanzado, particularmente aquellas que inciden sobre el sentido de la vida y la historicidad del sujeto. Indicaremos algunas modalidades de resistencia que suponen el desplazamiento del gozo monitorizado políticamente, mortífero para el deseo, para una praxis que rescate la experiencia compartida del mundo, donde los procesos colectivos y la rehabilitación del espacio público posibiliten la construcción de proyectos en común. El artículo recoloca la noción de contemporáneo vía la conjugación de diversas temporalidades, afirmando la construcción de un modo particular de atribuir sentido al presente. Entiende que rescatando la experiencia compartida con los contemporáneos, se puede reinventar la vida y crear mecanismos de presión contra la sumisión al poder soberano.

Síndrome febril sin foco y sospecha de infección bacteriana en niños entre 6 semanas y 36 meses / Clinical presentation of febrile syndrome without apparent focus and bacterial infection suspicion in children between 6 weeks and 36 months-old

Background: Unknown fever (UF) is a frequent pathology in children and its main etiology are viral infections. The identification of bacterial infection with antibiotics requirements is still on debate. Objective: Determine the characteristics of patients with suspicion of an invasive bacterial infection (IBI) and evaluate the contribution of C reactive protein (CRP) and leukocytes with absolute neutrophyl count (ANC). Method: Prospective-descriptive study of 640 patients between 6 weeks and 36 months-old, with UF and IBI suspicion, admitted in Infectology from the Emergency Room of Hospital Sotero del Rio between 2005 - 2007. Results: 53,7 percent of cases had a confirmed IBI, most commonly urinary tract infection (80,17 percent). A significantly difference was found between CRP, leukocytes and ANC, but the Roe curve did not show a relevant difference. It was not possible to determine a specific level of CRP, leukocytes and ANC for a better IBI discrimination.

Introducción: El síndrome febril sin foco (SFSF) es una patología frecuente en niños, su principal causa son infecciones virales. La identificación de los pacientes que requieren antibióticos, sigue siendo un tema de debate. Objetivo: Evaluar parámetros clínicos y de laboratorio y su utilidad para la decisión de indicación de antibiótico en niños de 6 semanas a 3 años que consultan al servicio de urgencia y su diagnóstico es un SFSF con sospecha de infección bacteriana. Pacientes y Métodos: Estudio descriptivo prospectivo realizado en 640 pacientes entre 6 semanas y 36 meses de edad, hospitalizados o derivados a infectología desde la urgencia del Hospital Dr. Sótero del Río, en quienes se sospechó IBI, durante los años 2005 a 2007. Resultados: Se confirmó IBI en 53,7 por ciento de los pacientes, siendo la localización más frecuente la vía urinaria (80,17 por ciento), bacteriemia (9 por ciento) y neumonía (8,75 por ciento). Hubo diferencia estadísticamente significativa entre el promedio de PCR, RAN y leucocitos entre los pacientes con IBI confirmadas y el resto, sin embargo, en las curvas de ROC estas diferencias no son relevantes. Conclusión: En los pacientes con SFSF y sospecha de IBI la principal causa es la ITU. No fue posible determinar un punto de corte de PCR, RAN o leucocitos para este grupo de pacientes, pues la curva de ROC no resultó significativa.

[Short duration of initial intravenous treatment in 70 pediatric patients with osteoarticular infections]. / Tratamiento intravenoso inicial abreviado en 70 pacientes pediátricos con infecciones osteo-articulares.

UNLABELLED: Osteoarticular infections (OAI) are infrequent in pediatrics and there is controversy on the need for prolonged use of intravenous antimicrobials. OBJECTIVE: To characterize and describe evolution and complications of a regimen of 7 days initial intravenous antibiotic treatment for OAI in children, completing 4-6 weeks of total treatment. PATIENTS AND METHODS: In a large pediatric hospital, 70 children younger than 15 years of age were diagnosed with OAI between March 2003 and December 2004. Children received 7 days of intravenous antibiotics followed by 3 to 5 weeks of oral treatment. RESULTS: Incidence of OAI in this hospital was 1.8:10000. Patients mean age was 6.4 +/-4.4 years and 60% presented with septic arthritis, 36% osteomyelitis and 4% osteoarthritis. In 80% of cases, the infection was located in the lower extremity. Positive cultures were obtained in 59% predominating Staphylococcus aureus (46.5%). Seven patients had prolonged pain or persistently high or increasing serum C reactive protein levels and were maintained on prolonged intravenous therapy. None of the 63 children with 7 day intravenous antimicrobials nor the 7 children with prolonged intravenous use developed a complication in the short-term follow up. CONCLUSIONS: Seven days of intravenous antibiotic for the initial phase of OAI treatment was effective in a majority of children and may be recommended.

Tratamiento intravenoso inicial abreviado en 70 pacientes pediátricos con infecciones osteo-articulares / Short duration of initial intravenous treatment in 70 pediatric patients with osteoarticular infections

Osteoarticular infections (OAI) are infrequent in pediatrics and there is controversy on the need for prolonged use of intravenous antimicrobials. Objective: To characterize and describe evolution and complications of a regimen of 7 days initial intravenous antibiotic treatment for OAI in children, completing 4-6 weeks of total treatment. Patients and methods: In a large pediatric hospital, 70 children younger than 15 years of age were diagnosed with OAI between March 2003 and December 2004. Children received 7 days of intravenous antibiotics followed by 3 to 5 weeks of oral treatment. Results: Incidence of OAI in this hospital was 1.8:10000. Patients mean age was 6.4 ±4.4 years and 60 percent presented with septic arthritis, 36 percent osteomyelitis and 4 percent osteoarthritis. In 80 percent of cases, the infection was located in the lower extremity. Positive cultures were obtained in 59 percent predominating Staphylococcus aureus (46.5 percent). Seven patients had prolonged pain or persistantly high or increasing serum C reactive protein levels and were maintained on prolonged intravenous therapy. None of the 63 children with 7 day intravenous antimicrobials nor the 7 children with prolonged intravenous use developed a complication in the short-term follow up. Conclusions: Seven days of intravenous antibiotic for the initial phase of OAI treatment was effective in a majority of children and may be recommended.

Las infecciones osteoarticulares (IOA) son poco frecuentes en pediatría. Existe controversia acerca de la óptima duración y la vía de administración de la terapia antimicrobiana. Objetivo: Caracterizar y describir la evolución y complicaciones en niños con IOA que recibieron 7 días iniciales de terapia endovenosa, completando 4 a 6 semanas de terapia total. Pacientes y Métodos: Estudio descriptivo, que incluyó a 70 niños con diagnóstico de IOA, entre marzo de 2003 y diciembre de 2004 en un hospital pediátrico, quienes recibieron tratamiento endovenoso abreviado a 7 días, seguido de terapia oral por 3 a 5 semanas. Resultados: La incidencia de IOA fue de 1,8: 10.000 niños bajo 15 años de edad. El promedio de edad fue 6,4 ± 4,4 años. Sesenta por ciento presentaba artritis séptica, 36 por ciento osteomielitis y 4 por ciento osteoartritis. En 80 por ciento la infección se localizó en extremidades inferiores. Los cultivos fueron positivos en 59 por ciento. En 46,5 por ciento se aisló Staphylococcus aureus. Siete niños evolucionaron con dolor persistente o elevación significativa de PCR y requirieron prolongar la terapia endovenosa y/o total, sin presentar complicaciones a corto plazo. Conclusiones: Siete días de terapia antimicrobiana intravenosa parece ser efectivo y recomendable para el tratamiento, en su fase inicial, de las infecciones osteo-articulares.

Etiología del síndrome febril prolongado en niños / Etiology of prolonged fever in children

Background: Prolonged fever (PF) is an uncommon entity in children, produced by diverse etiologies that differ according to geographic areas and national socioeconomical status. Objective: To determine etiologic diagnosis of PF in children from the southeast area of Santiago. Methods: A prospective-descriptive study performed in 35 patients with PF, age between 6 months - 15 years, referred to the Pediatrics Infectious Diseases Unit of Hospital Sótero del Rio during 2005 and 2006. Results: In 74 percent of cases an etiologic diagnosis was established, predominantly infectious diseases (68 percent) and rheumatologic disorders (6 percent). The most frequent infections observed were Bartonella henselae (17 percent), urinary tract infection (11 percent) and Epstein Barr virus infection (5.7 percent). Conclusions: PF in children from the southeast area of Santiago is caused by multiple etiologies, mainly infections with a high incidence of Bartonella henselae.

Introducción: El síndrome febril prolongado (SFP) es una patología infrecuente en niños, que incluye una amplia gama de etiologías que difieren según área geográfica y nivel socioeconómico del país. Objetivo: Determinar el diagnóstico etiológico específico de SFP en niños del sector sur-oriente de Santiago. Pacientes y Métodos: Se realizó un estudio descriptivo prospectivo en 35 pacientes con SFP, entre seis meses a quince años de edad, derivados a la Unidad de Infectología Pediátrica del Hospital Dr. Sótero del Río durante los años 2005 y 2006. Resultados: Se obtuvo diagnóstico etiológico definitivo en 74 por ciento de los pacientes. Las etiologías más frecuentes fueron infecciosas (68 por ciento) o reumatológicas (6 por ciento). Las etiologías específicas más frecuentes fueron Bartonella henselae (17 por ciento), infección del tracto urinario (11 por ciento) e infección por virus Epstein Barr (5,7 por ciento). Conclusión: El SFP en el grupo de niños estudiados del sector sur-oriente de Santiago se debe a múltiples etiologías, principalmente de origen infeccioso, destacando Bartonella henselae.

[Pulmonary complications in children with human immunodeficiency virus infection]. / Compromiso pulmonar en la infección por virus de inmunodeficiencia humana en niños.

Pulmonary complications in children infected by human immunodeficiency virus (HIV) are common and may be the first manifestation of acquired immunodeficiency syndrome (AIDS). The aim of our study was to review pulmonary diseases and complications in pediatric patients with HIV infection in a large tertiary hospital in Santiago, Chile. We performed a retrospective, descriptive analysis of 17 patients with HIV infection controlled at the Hospital Dr. Sótero del Rio. Respiratory complications/diseases were: overall pneumonia (n: 14), recurrent pneumonia (n: 10), citomegalovirus associated pneumonia (n: 4), Pneumocystis jiroveci associated pneumonia (n: 1) pulmonary tuberculosis (n: 1), lymphoid interstitial pneumonia (n: 3) and chronic pulmonary disease (n: 7). Microorganisms isolated were mostly atypical and frequently associated with severe and chronic pulmonary damage. A high degree of suspicion is required to detect atypical microorganisms promptly, in order to rapidly implement pathogen targeted therapy that could potentially decrease the possibility of sequelae.

Compromiso pulmonar en la infección por virus de inmunodeficiencia humana en niños / Pulmonary complications in children with human immunodeficiency virus infection

Pulmonary complications in children infected by human immunodeficiency virus (HIV) are common and may be the first manifestation of acquired immunodeficiency syndrome (AIDS). The aim of our study was to review pulmonary diseases and complications in pediatric patients with HIV infection in a large tertiary hospital in Santiago, Chile. We performed a retrospective, descriptive analysis of 17 patients with HIV infection controlled at the Hospital Dr. Sótero del Rio. Respiratory complications/diseases were: overall pneumonia (n: 14), recurrent pneumonia (n: 10), citomegalovirus associated pneumonia (n: 4), Pneumocystis jiroveci associated pneumonia (n: 1) pulmonary tuberculosis (n: 1), lymphoid interstitial pneumonia (n: 3) and chronic pulmonary disease (n: 7). Microorganisms isolated were mostly atypical and frequently associated with severe and chronic pulmonary damage. A high degree of suspicion is required to detect atypical microorganisms promptly, in order to rapidly implement pathogen targeted therapy that could potentially decrease the possibility of sequelae.

Las complicaciones pulmonares en niños infectados con virus de inmunodeficiencia humana (VIH) son frecuentes, pudiendo ser la primera manifestación del síndrome de inmunodeficiencia adquirida (SIDA). El objetivo de nuestro estudio fue revisar las complicaciones y patologías pulmonares que presentan estos pacientes, para lo cual se realizó un estudio retrospectivo, descriptivo de 17 pacientes con esta infección, controlados en el Hospital Dr. Sótero del Río. Las patologías respiratorias fueron: neumonía (n: 14), neumonía a repetición (n: 10), neumonía por citomegalovirus (n: 4), neumonía por Pneumocystis jiroveci (n: 1), tuberculosis pulmonar (n: 1), neumonía intersticial linfoide (n: 3) y daño pulmonar crónico (n: 7). En conclusión, una forma frecuente de debut de la infección por VIH es la patología pulmonar. Los agentes suelen ser atípicos y pueden producir infecciones graves y secuelares hasta llegar al daño pulmonar crónico. Un alto grado de sospecha puede permitir detectar las enfermedades respiratorias inter-currentes, tratarlas precozmente y evitar el deterioro posterior.

Endocarditis por Streptococcus pneumoniae en niños: presentación de un caso clínico y revisión de la literatura / Endocarditis caused by Streptococcus pneumoniae in children: case report and review

La endocarditis causada por Streptococcus pneumoniae es una patología muy poco frecuente en niños, correspondiendo sólo a 3 - 7 por ciento de los casos. Sin embargo, su importancia radica en que se puede presentar de forma muy agresiva, con complicaciones como destrucción valvular y abscesos, y con una mortalidad reportada hasta 61 por ciento, de no mediar tratamiento antimicrobiano precoz y muchas veces cardiocirugía. En más del 50 por ciento se puede asociar a otros focos infecciosos, como meningitis, neumonía, sinusitis o mastoiditis. Se describe el caso de una lactante de 10 meses que presentó una meningitis asociada a endocarditis debidas a S. pneumoniae, con grave compromiso cardíaco, y que requirió reemplazo valvular. Se realizó una revisión de la literatura médica acerca de endocarditis por S. pneumoniae en niños.

Adenoflegmón cervical por Streptococcus intermedius en una niña de 3 años: caso clínico / Cervical lymphadenitis due to Streptococcus intermedius in a 3 years-old girl: case report

Objetivo: Comunicar el caso de un adenoflegmón cervical por Streptococcus intermedius y caracterizar aspectos clínicos y microbiológicos de la infección por esta bacteria. Caso: Niña de 3 años, con historia de fiebre y aumento de volumen cervical anterior y supraclavicular izquierdo de 5 días de evolución, diagnosticándose adenoflegmón cervical; la punción revela Streptococcus intermedius. Se trató con cloxacilina y luego penicilina EV y completó tratamiento de 10 días con cotrimoxazol. Discusión: Streptococcus intermedius corresponde a una de las tres especies del grupo “anginosus” o “milleri”, integrante a su vez del grupo viridans. Forma parte de la flora bacteriana habitual orofaringea, de tubo digestivo y vagina. Tiene capacidad de migrar a otros parénquimas, produciendo infecciones abscedantes, a veces polimicrobianas y de difícil erradicación. Estudios nacionales de susceptibilidad antimicrobiana reportan sensibilidades cercanas al 100 por ciento a Penicilina y Cefotaxima. Diversos protocolos microbiológicos de identificación rápida permiten su diferenciación bacteriológica, ayudando a establecer alternativas terapéuticas más adecuadas.

Tratamiento selectivo de los episodios de neutropenia febril en niños con cáncer: Comité de Infectología, Programa Infantil Nacional de Drogas Antineoplásicas (PINDA) / Selective treatment of febrile neutropenia in pediatric cancer patients

El manejo de los pacientes pediátricos con cáncer y neutropenia febril (NF) requiere de su clasificación en alto o bajo riesgo de adquirir infecciones bacterianas invasoras (IBI), con el fin de implementar estrategias selectivas de tratamiento. Basados en nuestra experiencia y publicaciones internacionales al respecto, proponemos recomendaciones para el diagnóstico y manejo de niños con cáncer y NF, categorizadas según riesgo de IBI. Todos los pacientes pediátricos que presenten episodios de NF deben ser ingresados al hospital por al menos 24 horas. Durante este lapso se efectuará su evaluación clínica y de laboratorio con el objeto de clasificar el riesgo de este episodio y precisar el (los) posible(s) foco(s). Los pacientes de alto riesgo deben continuar internados hasta su recuperación. Los de bajo riesgo pueden ser manejados en forma ambulatoria. La elección de la terapia antimicrobiana inicial y los criterios para su ajuste deberán basarse en el hallazgo o no de focos infecciosos y en los patrones epidemiológicos e institucionales de susceptibilidad. La reevaluación de ambos grupos debe ser periódica (al menos en los días 3, 5 y 7 de evolución), y la respuesta terapéutica será clasificada como favorable o desfavorable según criterios clínicos y parámetros de laboratorio preestablecidos.