Risk-score based strategy to minimize antibiotic exposure in children with sickle cell disease and fever.

Severe bacterial infections (SBI) have become less frequent in children with sickle cell disease (SCD) in the last decades. However, because of their potential risk of SBI, they usually receive empirical therapy with broad-spectrum antibiotics when they develop fever and are hospitalized in many cases. We performed a prospective study including 79 SCD patients with fever [median age 4.1 (1.7-7.5) years, 78.5% males; 17 of the episodes were diagnosed with SBI and 4 of them were confirmed] and developed a risk score for the prediction of SBI. The optimal score included CRP > 3 mg/dl, IL-6 > 125 pg/ml and hypoxemia, with an AUC of 0.91 (0.83-0.96) for the prediction of confirmed SBI and 0.86 (0.77-0.93) for possible SBI. We classified the patients in 3 groups: low, intermediate and high risk of SBI. Our risk-score-based management proposal could help to safely minimize antibiotic treatments and hospital admissions in children with SCD at low risk of SBI.

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.

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.

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.

[Immunisation schedule of the Spanish Association of Paediatrics: 2017 recommendations]. / Calendario de vacunaciones de la Asociación Española de Pediatría (CAV-AEP): recomendaciones 2017.

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV- AEP) annually publishes the immunisation schedule which, in our opinion, is considered optimal for children resident in Spain, taking into account the evidence available on current vaccines. Pneumococcal and varicella immunisation in early childhood is already included in all funded vaccines present in the regional immunisation programmes. Furthermore, this committee establishes recommendations on vaccines not included in official calendars (non-funded immunisations), such as rotavirus, meningococcal B, and meningococcal ACWY. As regards funded immunisations, 2+1 strategy (2, 4, 11-12 months) with hexavalent (DTaP-IPV-Hib-HB) and 13-valent pneumococcal vaccines is recommended. Administration of the 6-year booster dose with DTaP is recommended, as well as a poliomyelitis dose for children who had received the 2+1 scheme, with the Tdap vaccine for adolescents and pregnant women between 27 and 32 weeks gestation. The two-dose scheme should be used for MMR (12 months and 2-4 years) and varicella (15 months and 2-4 years). Coverage of human papillomavirus vaccination in girls aged 12 with a two-dose scheme (0, 6 months) should be improved. Information and recommendations for male adolescents about potential beneficial effects of the tetravalent HPV vaccine should also be provided. ACWY meningococcal vaccine is the optimal choice in adolescents. For recommended unfunded immunisations, the CAV-AEP recommends the administration of meningococcal B vaccine, due to the current availability in Spanish community pharmacies, with a 3+1 scheme. CAV-AEP requests the incorporation of this vaccine in the funded unified schedule. Vaccination against rotavirus is recommended in all infants.