Executive summary: Guidelines for the diagnosis and treatment of septic arthritis in adults and children, developed by the GEIO (SEIMC), SEIP and SECOT.

Infection of a native joint, commonly referred to as septic arthritis, is a medical emergency because of the risk of joint destruction and subsequent sequelae. Its diagnosis requires a high level of suspicion. These guidelines for the diagnosis and treatment of septic arthritis in children and adults are intended for use by any physician caring for patients with suspected or confirmed septic arthritis. They have been developed by a multidisciplinary panel with representatives from the Bone and Joint Infections Study Group (GEIO) belonging to the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Paediatric Infections (SEIP) and the Spanish Society of Orthopaedic Surgery and Traumatology (SECOT), and two rheumatologists. The recommendations are based on evidence derived from a systematic literature review and, failing that, on the opinion of the experts who prepared these guidelines. A detailed description of the background, methods, summary of evidence, the rationale supporting each recommendation, and gaps in knowledge can be found online in the complete document.

Epidemiology and clinical features of Streptococcus pyogenes bloodstream infections in children in Madrid, Spain.

Studies have shown increased invasive Group A Streptococcus (GAS) disease, including bloodstream infections (GAS-BSI). However, the epidemiological data of GAS-BSI are limited in children. We aimed to describe GAS-BSI in children in Madrid, over 13 years (2005-2017). Multicenter retrospective cohort study from 16 hospitals from Madrid, Spain. Epidemiology, symptomatology, laboratory, treatment, and outcome of GAS-BSI in children ≤ 16 years were analyzed. 109 cases of GAS-BSI were included, with incidence rate of 4.3 episodes/100,000 children attended at the emergency department/year. We compared incidence between two periods (P1: 2005-June 2011 vs P2: July 2011-2017) and observed a non-significant increase along the study period (annual percentage change: + 6.0% [95%CI: -2.7, + 15.4]; p = 0.163). Median age was 24.1 months (IQR: 14.0-53.7), peaking during the first four years of life (89/109 cases; 81.6%). Primary BSI (46.8%), skin and soft tissue (21.1%), and osteoarticular infections (18.3%) were the most common syndromes. We compared children with primary BSI with those with a known source and observed that the former had shorter hospital stay (7 vs. 13 days; p = 0.003) and received intravenous antibiotics less frequently (72.5% vs. 94.8%; p = 0.001) and for shorter duration of total antibiotic therapy (10 vs. 21 days; p = 0.001). 22% of cases required PICU admission. Factors associated with severity were respiratory distress, pneumonia, thrombocytopenia, and surgery, but in multivariate analysis, only respiratory distress remained significant (adjusted OR:9.23 [95%CI: 2.16-29.41]). Two children (1.8%) died.   Conclusion: We observed an increasing, although non-significant, trend of GAS-BSI incidence within the study. Younger children were more frequently involved, and primary BSI was the most common and less severe syndrome. PICU admission was frequent, being respiratory distress the main risk factor. What is known: • In recent decades, several reports have shown a worldwide increase in the incidence of invasive Group A streptococcal disease (GAS), including bloodstream infection (BSI). Recently, there have been a few reports showing an increase in severity as well. • There needs to be more information on the epidemiology in children since most studies predominantly include adults. What is new: • This study, carried out in children with GAS-BSI in Madrid, shows that GAS-BSI affects mostly younger children, with a broad spectrum of manifestations, needing PICU admission frequently. Respiratory distress was the leading risk factor for severity, whereas primary BSI seemed to be less severe. • We observed an increasing, although non-significant, trend of GAS-BSI incidence in recent years (2005-2017).

Acute Epstein-Barr virus infection: Diagnostic challenge in young children, risk factors for hospitalisation and cytomegalovirus co-detection.

AIM: Acute Epstein-Barr virus (aEBV) and cytomegalovirus (CMV) infections frequently have similar manifestations. We aim to evaluate the characteristics of aEBV infection, risk factors for hospitalisation and differences according to CMV IgM detection (EBV-CMV co-detection) in children. METHODS: Retrospective, single-centre study including patients <16 years diagnosed with aEBV infection (positive anti-EBV IgM/Paul-Bunnell test and acute symptomatology). EBV-CMV co-detection was defined as positive CMV IgM. Factors associated with age, hospitalisation and EBV-CMV co-detection were analysed in a multivariate analysis. RESULTS: A total of 149 patients were included (median age 4.6 years). Most frequent manifestations were fever (77%), cervical lymphadenopathy (64%) and elevated liver enzymes (54%). Younger children had lower rate of positive Paul-Bunnell test (35% vs. 87%; p < 0.01), but higher rate of EBV-CMV co-detection (54% vs. 29%; p = 0.03). These children tended to have less typical symptoms of infectious mononucleosis and higher hospitalisation rate. The overall antibiotic prescription was 49%. Hospitalisation (27 children; 18%) was independently associated with prior antibiotic therapy and anaemia. Sixty-two cases (42%) had EBV-CMV co-detection, which was independently associated with elevated liver enzymes and younger age. CONCLUSION: In this study, younger children with aEBV infection presented more frequently with atypical clinical symptoms, had higher EBV-CMV co-detection rates and were more often hospitalised. Hospitalisation was associated with prior antibiotic prescription.

Colchicine as rescue treatment in two pediatric patients with chronic recurrent multifocal osteomyelitis (CRMO).

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare idiopathic autoinflammatory bone disease characterised by noninfective inflammation of bones. Diagnostic approach is challenging and requires exclusion of other causes such as malignancies or infections. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are usually applied as first-line therapy in CRMO patients; however, some cases require more intensive therapy with second-line agents to control disease activity. We hereby describe the use of colchicine as a nonconventional second-line disease-modifying antirheumatic drug in two pediatric patients with CRMO refractory to NSAIDs and corticosteroids. Our data indicate that colchicine might prove an important area for future research as a potential therapeutic option with easy administration, low cost, and a good safety profile in CRMO patients refractory to first-line therapy.

Oral Versus Intravenous Antibiotics for Pediatric Osteoarticular Infection: When and to Whom?

BACKGROUND: Osteoarticular infections (OAIs) are typically treated initially with intravenous antibiotics. The objective of this study was to evaluate whether an exclusive oral treatment in selected children may be appropriate. METHODS: The Spanish Network of Osteoarticular Infections is a nationwide multicenter registry comprising 37 hospitals in Spain. The registry prospectively includes clinical characteristics and outcome of children with OAI. One of the hospitals from RioPed offers oral treatment to children meeting certain criteria. Patients were classified into 2 groups. Group 1: management with initial intravenous antibiotic therapy. Group 2: patients exclusively treated with oral antibiotics. A comparison between the 2 groups was performed. RESULTS: We compared 893 children who initially received intravenous antibiotics (group 1) with 64 children who received exclusively oral therapy (group 2). Patients from group 2 were younger (33.9 vs. 20.3 months; P = 0.001), had a lower percentage of Staphylococcus aureus (23.3% vs. 3.1%; P < 0.001), a higher proportion of Kingella kingae (12.1% vs. 28.1%; P = 0.001), higher erythrocyte sedimentation rate/C-reactive protein (CRP) ratio (1.4 interquartile range 0.6-3.6 vs. 3.3 interquartile range 1.7-5.7; P < 0.001) and showed lower rate of fever (63% vs. 48.8%; P = 0.024) than in group 1. Complications were not found in group 2. CONCLUSIONS: An exclusively oral administration could be a safe option in selected patients with OAI. Low-risk criteria are proposed: good general condition, no underlying disease, 6 months to 3 years old, appropriate oral tolerance, C-reactive protein <80 mg/L, erythrocyte sedimentation rate/C-reactive protein ratio ≥0.67, no skin injury, no recent surgery, no cervical spondylodiscitis and no local complications at onset.

Interleukin 6 as a marker of severe bacterial infection in children with sickle cell disease and fever: a case-control study.

BACKGROUND: Etiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI). METHODS: A prospective, case-control study was carried out during 3 years, including patients younger than 18 years with SCD and fever (cases) and asymptomatic steady-state SCD children (controls). Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed. RESULTS: A total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7-7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI), 33 no proven infection (NPI) and 1 bacterial-viral coinfection (the latter excluded from the subanalyses). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p < 0.001), and undetectable in all controls. The rest of the cytokines analyzed did not show any significant difference. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL, with high PPV and NPV (PPV of 100% for a prevalence rate of 5, 10 and 15% and NPV of 98.7%, 97.3% and 95.8% for those prevalences rates, respectively). CONCLUSION: We found that IL-6 (with a cut-off value of 125 pg/ml) was an optimal marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, given its rapid elevation, IL-6 may be useful to early discriminate SCD children at risk of SBI, in order to guide their management.

Streptococcus agalactiae: causa de artritis séptica inusual a partir de los 3 meses de edad. Caso clínico / Streptococcus agalactiae: an unusual cause of septic arthritis beyond 3 months of age. Case report

La artritis séptica es una patología poco frecuente, pero con una alta morbilidad, debido a las importantes secuelas que puede originar. La etiología varía según la edad, y Staphylococcus aureus es el microorganismo más frecuente en todas ellas. Streptococcus agalactiae odel grupo B es una causa infrecuente de infección fuera del período neonatal; se asocia, a partir de los 3 meses de edad, con infecciones graves en pacientes inmunocomprometidos. El tratamiento de elección es penicilina G o ampicilina.Aquí se describe el caso de un niño de cuatro meses y medio de edad que desarrolló una artritis séptica por Streptococcus agalactiae odel grupo B, con inicio insidioso de la clínica. El diagnóstico etiológico obligó a descartar meningitis y una inmunodeficiencia asociada. La frecuencia extremadamente baja de dicha artritis a esta edad y la importancia de descartar una enfermedad diseminada son importantes puntos de aprendizaje en este caso.

Septic arthritis is not a very frequent disease, but with a high morbidity due to the important sequelae that it can cause. The etiology is age-specific, with Staphylococcus aureus being the most frequent microorganism in all ages. Streptococcus agalactiae or group B Streptococcus is an uncommon cause of infection outside the neonatal period. Beyond 3 months of age, infections by this pathogen are associated with serious infections in immunocompromised patients. The treatment of choice is penicillin G or ampicillin. A 4.5-month-old child who developed a group B Streptococcus septic arthritis is reported. The onset was insidious, and the etiological diagnosis prompted us to rule out meningitis and associated immunodeficiency. The extremely low frequency of group B Streptococcus septic arthritis at this age and the importance of ruling out a disseminated disease are crucial learning points in this case

Detection of Respiratory Viruses in the Clinical Outcome of Children With Fever and Neutropenia.

BACKGROUND: Several evidence-based guidelines for the management of children with febrile neutropenia (FN) have been published, with special focus in bacterial and fungal infections. However, the role of acute respiratory infections caused by respiratory viruses (RV) has not been clearly established. The aim of this study was to evaluate the epidemiology, clinical presentation and outcome of acute respiratory infections in children with FN. METHODS: Patients, <18 years of age admitted to the Pediatric Oncology-Hematology Unit after developing FN between November 2010 and December 2013, were prospectively included in the study. Children were evaluated by clinical examination and laboratory tests. Nasopharyngeal sample was obtained for detection of RV. RESULTS: There was a total of 112 episodes of FN in 73 children admitted to the hospital during a 32-month period. According to disease severity, 33% of the episodes were considered moderate or severe. Rhinovirus was the most frequently detected RV (66.6%; 24/36), followed by parainfluenza. On regard to clinical outcome, RV-infected children developed fewer episodes of moderate or severe FN compared with non-RV infected children (16.7% vs. 33.3%; P = 0.08). CONCLUSIONS: A great proportion of children with FN admitted to a tertiary hospital had a RV isolation. The rate of this RV isolation was significantly higher when a rapid molecular test was used compared with conventional microbiologic methods. Rhinovirus was the most frequently isolated, although its role as an active agent of acute infection was not clear. Children with FN and a RV isolate had a lower rate of severe disease.

[Evaluation of the impact of the Spanish consensus document on the approach to osteoarticular infections in Spain through the Paediatrics Osteoarticular Infections Network (RIOPED)]. / Evaluación del impacto del Documento de Consenso español sobre el abordaje de las infecciones osteoarticulares en nuestro medio a través de la Red de Infecciones Osteoarticulares Pediátricas (RIOPed).

INTRODUCTION: In 2014 the Consensus Document produced by the Spanish Paediatric Societies (SEIP-SERPE-SEOP) was published to help in the diagnosis and treatment of osteoarticular infections (OAI). In 2015 the RIOPed was considered as a multidisciplinary national network for the investigation into OAI. The aim of this study was to assess the level of adaption to the recommendations established in the Consensus during one year of follow-up. MATERIAL AND METHODS: A prospective, national multicentre study was carried out in 37 hospitals between September 2015 and September 2016. The study included patients >16years-old with a diagnosis of OAI, confirmed by microbiological isolation, or probable: septic arthritis (SA) with >40,000 white cells in synovial fluid, or osteomyelitis (OM)/spondylodiscitis (SD) with a compatible imaging test. The results were compared with those obtained in a retrospective study conducted between 2008 and 2012. RESULTS: A total of 235 cases were included, of which 131 were OM, 79 SA, 30 OA, and 15 SD. As regards the complementary tests that the Consensus considered mandatory to perform, radiography was carried out on 87.8% of the cases, a blood culture on 91.6%, and culture of the synovial fluid in 99% of SA. A magnetic resonance (MR) was performed on 71% of the OM cases. The choice of intravenous empirical antibiotic treatment was adapted to the recommendations in 65.1% of cases, and in 62.3% for the oral treatment. Surgery was performed in 36.8% of SA cases (85.7% arthrotomy), with a significant decrease compared to the retrospective study (P=.014). Only 58.5% of cases followed the recommendations on the duration of the treatment; however, a lower duration of intravenous treatment was observed. CONCLUSIONS: In general, the level of adaptation to the recommendations that were set by the Expert Group, is good for the complementary tests, and acceptable as regards the choice of antibiotic treatment, although inadequate in almost 40% of cases. A decrease in hospital stay was achieved.

Effect of an intervention to improve the prescription of antifungals in pediatric hematology-oncology.

BACKGROUND: The use of antifungals has expanded in pediatric hematology-oncology, and the need to develop pediatric-based surveillance and education activities is becoming crucial. The aims of this study were to evaluate the impact of a multidisciplinary protocol on the adequacy of antifungal prescription in a pediatric hematology-oncology unit and to assess the effect of an educational intervention to improve the knowledge of prescribing pediatricians over time. METHODS: A multidisciplinary team established a protocol for the management of invasive fungal disease (IFD). The use of antifungals before (January 2012-May 2013) and after the protocol (June 2013-December 2015) was evaluated. Prescribing pediatricians attended a training course on IFD and were evaluated before 0, 6, and 12 months after the intervention. RESULTS: During the study period, antifungal agents were used in 185 episodes (56 children, 39.3% females), and were administered as prophylaxis (58.9%), empiric (34.6%), or targeted therapy (6.5%). Antifungal prescriptions were inadequate in 7% of the episodes, related to drug selection (53.8%), dosage (38.5%) and route of administration (7.7%). After protocol implementation, inadequate prescriptions decreased 9.9% (15.2% vs 5.3%; P = .04). Following the educational activity, the percentage of adequate responses to the questionnaire improved significantly compared to baseline, and persisted over time (19.7% improvement at 0 months [P < .0001]; 21.1% at 6 months [P < .0001]; 16.6% at 12 months [P = .002]). CONCLUSIONS: The establishment of multidisciplinary protocols and education activities improved the quality of antifungal prescription and the knowledge of prescribers regarding antifungal therapy. Therefore, these activities may be important for the implementation of antifungal stewardship programs in pediatrics.

[Invasive disease due to Streptococcus pyogenes: Changes in incidence and prognostic factors]. / Enfermedad invasiva por Streptococcus pyogenes: cambios en la incidencia y factores pronósticos.

INTRODUCTION: Invasive group A streptococcal disease (iGASD) is a serious infection in children. Several studies have shown an increased incidence in the past years. OBJECTIVE: To evaluate the characteristics and outcome of iGASD in children, and to determine changes in incidence or severity. MATERIAL AND METHODS: A retrospective study was conducted on children≤16 years evaluated in a tertiary paediatric hospital in Madrid, and diagnosed with iGASD (June 2005-July 2013). An analysis was made of the demographics, symptomatology, microbiology, and treatment. The changes throughout the period studied were evaluated, as well as parameters associated with disease severity. RESULTS: The study included a total of 55 children with iGASD, with 33 (60%) females, and a median age of 48.5 (20.5-88.9) months. The most frequent clinical syndromes were cellulitis/subcutaneous abscess (21.8%), ENT abscess (20%), pneumonia (16.4%), osteoarticular infection (16.4%), and mastoiditis (12.7%). The incidence of iGASD (cases/105 emergencies/year) increased from 5.6 (4.2-7.2) between June 2005-May 2009 to 18.9 (15.1-26) between June 2009-May 2013; P=.057. Surgery and admission to PICU was required by 35 (63.6%) and 10 (18.2%) patients, respectively. Children in PICU were younger (26.5 vs 52.6 months, P=.116), had a higher C-reactive protein (24.5 vs 10.7mg/dl, P<.001) and higher frequency of pneumonia (60 vs 7%, P<.001). In the multivariate analysis, only C-reactive protein was a risk factor for admission to PICU (OR: 1.14 [1.004-1.286], P=.04). There were no sequelae. CONCLUSIONS: An increased incidence of iGASD was observed in the children in this study. Lower age, pneumonia, and higher C-reactive protein were associated with disease severity in this series.

Low-risk factors for severe bacterial infection and acute chest syndrome in children with sickle cell disease.

INTRODUCTION: The rate of bacterial infections in children with sickle cell disease (SCD) has decreased in recent years, mainly due to penicillin prophylaxis and vaccination. OBJECTIVES: To determine the rate of severe bacterial infection (SBI) in a cohort of children with SCD and to describe low-risk factors for confirmed SBI (CSBI) and acute chest syndrome (ACS). METHODS: This 11-year retrospective cohort study included children with febrile SCD admitted to a reference hospital in Spain. A case-control study was performed comparing patients diagnosed with SBI to those without SBI, and subanalyses for groups with CSBI and ACS were carried out. RESULTS: A total of 316 febrile episodes were analyzed; 69 (21.8%) had confirmed or possible SBI. Thirteen of those had CSBI (4.1%), eight urinary tract infection, and five bacteremia/sepsis. Among the cases of possible SBI, the majority had ACS (54/56; 96.4%). Age >3 years, absence of central venous catheter, hemodynamic stability, and procalcitonin <0.6 ng/ml were low-risk factors for CSBI, whereas normal oxygen saturation and C-reactive protein <3 mg/dl were low-risk factors for ACS, with negative predictive values (NPV) of 98.3%, 97.4%, 96%, 97.2%, 87.5%, and 85.8%, respectively. CONCLUSION: In this cohort of children with SCD who were well vaccinated and received adequate prophylaxis, we found a low rate of bacteremia and CSBI. We described several low-risk factors for CSBI and ACS, all of them with a high NPV. These findings may help to develop a risk score to safely select the patients that could be managed with a more conservative approach.

Characteristics and Disease Course in a Cohort of Children With PFAPA Syndrome in the Community of Madrid, Spain. / Características y evolución de una cohorte de niños con síndrome PFAPA en la Comunidad de Madrid.

INTRODUCTION: PFAPA syndrome is an autoinflammatory disease whose diagnosis is mainly clinical. Several treatments have been proposed; among them, tonsillectomy could be an effective one. MATERIAL AND METHODS: Retrospective multicenter study. Patients included were diagnosed with PFAPA syndrome, according to the Thomas criteria, in 3 hospitals in Madrid between 2009-2013. RESULTS: Thirty-two cases were included. Median age at onset and at diagnosis were 32 months (IQR 24-44) and 47.5 months (IQR 37-60), respectively. There were increases in leukocytes (13,580/µL [IQR 8,200-16,600] vs. 8,300/µL [IQR 7,130-9,650], P=.005), neutrophils (9,340/µL [IQR 5,900-11,620] vs. 3,660/µL [IQR 2,950-4,580], P=.002) and C-reactive protein (11.0mg/dL [IQR 6.6-12.7] vs. 0.2mg/dL [IQR 0.1-0.6], P=.003) during febrile episodes. In all, 80.8% of patients reported remission of symptoms within 24h after oral corticosteroid therapy. Fourteen patients were tonsillectomized. In 11, the febrile episodes stopped while, in 3, the frequency was reduced; there were 2 cases of postoperative bleeding. The disease was resolved in 56.3% of the patients, at a median age of 60 months (IQR 47-95), with similar duration in patients who were tonsillectomized and those who were not. CONCLUSIONS: We present a large cohort of children with PFAPA syndrome, with clinical and analytical features similar to those described in the literature, and a good response to corticosteroids and a high resolution rate of symptoms after tonsillectomy.

Epidemiology and Management of Acute, Uncomplicated Septic Arthritis and Osteomyelitis: Spanish Multicenter Study.

BACKGROUND: Acute osteoarticular infection (OAI) is a potentially severe disease. The aim of this study was to evaluate the etiology, clinical characteristics and therapeutic approach of OAI in children in Spain. METHODS: Medical records from children <14 years with OAI from 25 hospitals between 2008 and 2012 were reviewed. Confirmed osteomyelitis (OM) and septic arthritis (SA) required a positive bacterial isolate; otherwise, they were considered probable. Probable SA with <40,000 cells/mm in joint fluid was not included. RESULTS: A total of 641 children were evaluated. Two hundred and ninety-nine cases (46%) were OM, 232 (36%) SA, 77 (12%) osteoarthritis and 33 (5%) spondylodiscitis. Children with OM were older (63 vs. 43 months for SA; P < 0.001). Magnetic resonance imaging and bone scintigraphy had the highest yield for OM diagnosis (94%). Arthrocentesis was performed in 96% of SA. A microorganism was isolated in 246 patients (38%: 33% OM vs. 55% SA; P < 0.001): Staphylococcus aureus was the most common (63%), followed by Kingella kingae (15%) and Streptococcus pyogenes (9%). Ninety-five percent of children initially received IV antibiotics, mostly cefotaxime + cloxacillin (60%) or cloxacillin (40%). Total treatment duration was 38 (±31) days for OM and 28 (±16) days for SA (P < 0.0001). Twenty percent of children with OM (46% because of complications) and 53% with SA (95% initial arthrotomy) underwent surgery. Patients with SA were compared according to initial arthrotomy (n = 123) versus arthrocentesis (n = 109), and no clinical differences were observed, except for higher rate of hip SA in the former (50% vs. 9%; P < 0.001). Children with arthrocentesis had less sequelae [6.6% vs. 1%; P = 0.03, odds ratio = 0.58 (95% confidence interval: 0.45-0.76)], but not in the multivariate analysis. CONCLUSIONS: This is the largest pediatric cohort of OAI in Spain. S. aureus was the most common isolate, although K. kingae was recovered in a high proportion of cases. Conservative management was applied in half of the patients. There was a low rate of sequelae, even with nonsurgical approaches.

Comparison of Mycobacterium lentiflavum and Mycobacterium avium-intracellulare complex lymphadenitis.

BACKGROUND: Mycobacterium lentiflavum is considered a rare pathogen causing nontuberculous mycobacterial (NTM) lymphadenitis. METHODS: A multicenter, retrospective study was performed in immunocompetent children <14 years of age with microbiologically confirmed NTM lymphadenitis treated at 6 hospitals in Madrid, Spain, during 2000-2010. We compared children with M. lentiflavum and Mycobacterium avium-intracellulare complex infection. RESULTS: Forty-five microbiologically confirmed NTM lymphadenitis patients were identified: 19 (45.2%) caused by M. avium-intracellulare complex, 17 (40.5%) by M. lentiflavum, 1 by both and 5 by other mycobacteria. Out of 17 M. lentiflavum cases, 14 were diagnosed in the past 5 years. Regarding M. lentiflavum cases, median age was 23 months. Submandibular nodes were the most frequently involved (76.5%), with multiple locations seen in 41% of the children and spontaneous drainage in 41% of them. Drug susceptibility tests were performed in 14 isolates and showed a complete susceptibility to clarithromycin and cycloserine, whereas 93% were resistant to rifampin, 33% to quinolones and full resistance to other tested antimycobacterial drugs was detected. All but 1 child required surgery and 11 were treated additionally with various drug combinations. Total resolution was achieved in 50% of children within 6 months.Compared with M. avium-intracellulare complex cases, children were younger and laterocervical nodes were significantly less frequently involved. No statistically significant differences were found related to clinical characteristics, treatment and outcome. CONCLUSIONS: M. lentiflavum is an emerging pathogen producing NTM lymphadenitis in Madrid.

Interferon-γ release assay for the diagnosis of tuberculosis in children.

AIMS: To compare the QuantiFERON-TB GOLD In Tube test (QTF) and the tuberculin skin test (TST) in children. METHODS: A prospective study was carried out in nine hospitals in Madrid, Spain. TST and QTF were performed in immigrants, tuberculosis (TB) contacts and patients with TB disease (TBD). RESULTS: 459 children were included. Disagreement between the tests was more frequently observed among latent tuberculosis infection (LTBI) cases (54%; 38/70) than in non-infected or TBD cases (0.8%; 3/369) (p<0.01). There were more BCG-vaccinated children among LTBI cases with negative QTF (76%) than among LTBI cases with positive QTF (40%) (p<0.001). Agreement between tests in BCG-vaccinated children was lower than in non-vaccinated cases (p<0.05). Tests in TB exposed patients showed better agreement than in non-exposed children (p<0.05). CONCLUSIONS: Agreement of both tests was excellent in TBD cases, non-vaccinated children and non-infected patients. A significant number of QTF negative results were observed among LTBI cases, especially in BCG-vaccinated children. Agreement was better in exposed children.

[Children with cancer and respiratory viral infection: epidemiology, diagnosis and treatment options]. / Niños con cáncer e infección viral respiratoria: epidemiología, diagnóstico y posibles tratamientos.

Community-adquired respiratory viral infection is the most common cause of febrile infection in children, and an important cause of infection to consider in children with cancer. Nevertheless, there are few well-designed, controlled studies in this population, which makes it difficult to understand the importance, behaviour and management of these viruses in immunocompromised children. New diagnostic techniques in PCR-based microbiology, could provide many opportunities for early diagnosis, preventing the spread of the virus and to implement the correct therapy. It is important to design appropriate prospective studies to assess these types of infections in children with cancer. In this review we analyse the main studies published in the literature, evaluating the epidemiology, diagnosis and management of children with cancer and respiratory viral infection.

Salvage therapy with abacavir and other reverse transcriptase inhibitors for human immunodeficiency-associated encephalopathy.

BACKGROUND: HIV-associated encephalopathy (HIV-AE) is a severe neurologic condition that affects HIV-infected children. The potential benefit of antiretroviral (ARV) agents with good cerebrospinal fluid (CSF) penetration remains to be defined. Abacavir (ABC) achieves good CSF concentrations and studies of high-dose ABC showed benefit in adults with HIV dementia. The present study evaluated the safety and virologic, immunologic and neuropsychological responses of an ARV regimen including high-dose ABC in children with HIV-AE. METHODS: Children between 3 months and 18 years old and abacavir-naive with HIV-AE and virologic failure were eligible. RESULTS: : Seventeen children (16 ARV-experienced) were enrolled and 14 children completed 48 weeks of therapy. The overall tolerability was good; 2 children had a possible hypersensitivity reaction. At week 48, 53% and 59% of the children achieved HIV RNA levels below the limit of quantitation in plasma and CSF, respectively. The median (25%-75% range) change of HIV RNA from baseline to week 48 was -2.29 (-0.81 to -2.47) log10 copies/mL in plasma and -0.94 (0 to -1.13) log10 copies/mL in CSF. The mean increases in CD4 (+/-standard error of mean) cell count and CD4% were 427 (+/-169) cells/mm and 8% (+/-2), respectively. Concentrations of soluble tumor necrosis factor receptor II were reduced in plasma and CSF. Children less than 6 years of age demonstrated significant neuropsychological improvement at week 48. CONCLUSIONS: In the present study with a limited number of children, highly active ARV therapy including high-dose ABC showed a safety profile similar to standard dose ABC and provided clinical, immunologic and virologic response in children with HIV-AE at week 48. Children less than 6 years of age also demonstrated significant neuropsychological improvement.

Cerebrospinal fluid and plasma concentrations of proinflammatory mediators in human immunodeficiency virus-infected children.

BACKGROUND: The pathogenesis of HIV encephalopathy is poorly understood especially in children. Studies suggest that HIV replication and the release of proinflammatory mediators in the central nervous system contribute to the pathogenesis of HIV dementia in adults. METHODS: Cerebrospinal fluid (CSF) and plasma samples from 23 HIV-infected children were longitudinally analyzed at Weeks 0, 8, 16 and 48 for HIV RNA and concentrations of the following proinflammatory mediators: monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha, regulated upon activation, normal T cell expressed and secreted (RANTES), macrophage-inflammatory protein (MIP)-1-alpha, MIP-1-beta and matrix metalloproteinase-9 (MMP-9). RESULTS: All 23 children had detectable concentrations of MCP-1 in the CSF at all time points evaluated. However, of the remaining of proinflammatory mediators measured in CSF at baseline, only a few children had detectable concentrations: tumor necrosis factor-alpha, n = 1; RANTES, n = 5; MMP-9, n = 9; MIP-1-alpha and MIP-1-beta, n = 0. A reduction from baseline to Week 48 was observed in CSF concentrations of MCP-1 and, among children with detectable values, MMP-9, which paralleled declines in CSF HIV RNA. CONCLUSION: These results suggest that MCP-1 and MMP-9 may be involved in the pathogenesis of central nervous system disease in HIV-infected children.