Evolving Approach to Antibiotic Treatment of Pediatric Spondylodiscitis.

OBJECTIVE: To describe for intervertebral spondylodiscitis (IS) its clinical characteristics, treatment approaches with intravenous (IV) antibiotics, and clinical implications of changes in treatment approach. STUDY DESIGN: This retrospective study included all children aged 0-18 years diagnosed with imaging-confirmed thoracic and lumbar IS from 2000 to 2022 at a tertiary pediatric hospital. Patients with longer IV treatment regimen were compared with those with a shorter clinically directed IV to oral regimen. RESULTS: In all, 124 cases were included with median age 14.9 months (IQR, 12.7-19.4 months) at diagnosis. Irritability and pain while changing diapers were common symptoms (52.4% and 49.2%, respectively). Elevated erythrocyte sedimentation rate (ESR) was the most common laboratory finding (95%; median, 50 mm/h [IQR 34-64 mm/h]). Elevated erythrocyte sedimentation rate was found in higher proportions (95%) compared with elevated C-reactive protein (76%; median, 1.8 mg/dL; P < .001). Since implementing the shorter clinically directed IV treatment duration for patients with thoracic and lumbar IS, hospitalization duration was decreased from a median of 12 to 8 days (P = .008) and IV treatment duration by a median of 14 to 8 days (P < .001). Only 1 patient (1.6%) in the clinically directed treatment group required rehospitalization owing to failure of therapy. Conversely, 9 of 124 children in the cohort suffered from IV treatment-related complications; all had been treated IV for prolonged periods. CONCLUSIONS: Early transition to oral treatment in pediatric spondylodiscitis seems to be appropriate clinically and shortens hospital stay and IV treatment duration without major negative clinical impact.

Excellent response to treatment with hydroxychloroquine in pediatric patients with SLE-related immune thrombocytopenia.

BACKGROUND: Pediatric immune thrombocytopenia (ITP) may precede systemic autoimmune disorders. In adolescent patients with ITP, routine screening for systemic lupus erythematosus (SLE) may be performed by testing for antinuclear antibody (ANA) titer. Hydroxychloroquine (HCQ) is a safe and effective immunomodulatory drug in patients with SLE but rarely used in ITP. We analyzed the platelet count response and safety of HCQ in treating pediatric patients with SLE-related ITP. METHODS: A retrospective study including pediatric patients with ITP and definite or incomplete SLE, who were treated with HCQ during 2010-2021. SLE was defined by ANA titer ≥ 1:160 as measured by immunofluorescence and ≥10 points according to the 2019 EULAR/ACR 2019 classification criteria, while patients with incomplete SLE achieved a score < 10. Complete response (CR) of the platelet count was defined as platelet count > 100 × 109/L; partial response (PR) as platelet count 30-100 × 109/L and exceeding ≥ twice baseline counts. RESULTS: Of the 17 patients included (median age 15.5 years; IQR 3.6), 15 (88.2%) were female, 13 had definite SLE, and four had incomplete SLE. HCQ was initiated at a median of 17 months after ITP diagnosis with a median platelet count of 38 × 109/L (IQR 28). At 8 weeks, 8 (47.1%) patients responded, including 6 (35.3%) achieving CR. After one year, the overall response was 82.4%, with the remaining patients having stable platelet counts requiring no additional ITP therapy. The response was maintained at a median follow-up of 42 months. No adverse effects to HCQ were noted. CONCLUSION: Pediatric patients with SLE-related ITP may benefit from treatment with HCQ.

Pediatric chest radiograph interpretation in a real-life setting.

Chest radiography is a frequently used imaging modality in children. However, only fair to moderate inter-observer agreement has been reported between chest radiograph interpreters. Most studies were not performed in real-world clinical settings. Our aims were to examine the agreement between emergency department pediatricians and board-certified radiologists in a pediatric real-life setting and to identify clinical risk factors for the discrepancies. Included were children aged 3 months to 18 years who underwent chest radiography in the emergency department not during the regular hours of radiologist interpretation. Every case was reviewed by an expert panel. Inter-observer agreement between emergency department pediatricians and board-certified radiologists was assessed by Cohen's kappa; risk factors for disagreement were analyzed. Among 1373 cases, the level of agreement between emergency department pediatricians and board-certified radiologists was "moderate" (k = 0.505). For radiographs performed after midnight, agreement was only "fair" (k = 0.391). The expert panel identified clinically relevant disagreements in 260 (18.9%) of the radiographs. Over-treatment of antibiotics was identified in 121 (8.9%) of the cases and under-treatment in 79 (5.8%). In a multivariable logistic regression, the following parameters were found to be significantly associated with disagreements: neurological background (p = 0.046), fever (p = 0.001), dyspnea (p = 0.014), and radiographs performed after midnight (p = 0.007). CONCLUSIONS: Moderate agreement was found between emergency department pediatricians and board-certified radiologists in interpreting chest radiographs. Neurological background, fever, dyspnea, and radiographs performed after midnight were identified as risk factors for disagreement. Implementing these findings could facilitate the use of radiologist expertise, save time and resources, and potentially improve patient care. WHAT IS KNOWN: • Only fair to moderate inter-observer agreement has been reported between chest radiograph interpreters. • Most studies were not performed in real-world clinical settings. Clinical risk factors for disagreements have not been reported. WHAT IS NEW: • In this study, which included 1373 cases at the emergency department, the level of agreement between interpreters was only "moderate." • The major clinical parameters associated with interpretation discrepancies were neurological background, fever, dyspnea, and interpretations conducted during the night shift.

Clinical implications of extremely elevated C-reactive protein among febrile immunocompetent children.

AIM: To identify the various diagnoses associated with extremely elevated C-reactive protein (CRP) (>30 mg/dL) among immunocompetent children and to evaluate its clinical implications during emergency department (ED) workup and hospital management. METHODS: Children (3 months-18 years) with fever in ED were included, retrospectively. The cohort was divided into two groups-'extremely elevated CRP' (>30 mg/dL) and 'highly elevated CRP' (15-30 mg/dL). RESULTS: Included were 1173 patients with CRP 15-30 mg/dL and 221 with CRP > 30 mg/dL. Bacterial infection was more prevalent among the extremely elevated CRP group (94.1% vs. 78.5%, respectively, p = 0.002). Specifically, bacterial pneumonia (52%), cellulitis (7.2%) and sepsis (4.1%) were more prevalent among this group. More of these patients were reported as 'Ill appearing' [78 (35.3%) vs. 166 (17.4%), p < 0.001]. They were more often treated with fluids [33 (14.9%) vs. 50 (5.3%), p < 0.001] and a higher portion of them required admission to an intensive care unit [11 (5.0%) vs. 16 (1.7%), p = 0.007]. CONCLUSION: Febrile children with extremely elevated CRP showed greater illness severity (haemodynamic instability, PICU admissions), thus careful clinical attention is desirable in these cases. More than half of them had bacterial pneumonia, which reinforces the importance of relevant investigation when diagnosis is unclear.

Differential Serum Phosphate Levels in Pediatric Febrile Syndromes and Their Clinical Significance.

BACKGROUND: The potential of hypophosphatemia (HP) to differentiate between febrile syndromes and its clinical significance in children without sepsis were not previously described. METHODS: Data were retrospectively collected of febrile children aged 3 months to 18 years, hospitalized at general pediatric wards during 2010-2019. Phosphate levels were compared between bacterial infection (BI), viral infection (VI), and Kawasaki disease (KD). Regression analyses were used to evaluate the relationship between HP and outcome. RESULTS: Of 3963 febrile children, 559 had BI, 3271 had VI, and 133 had KD. In BI compared to VI and KD, HP was more prevalent (49.2%, 19.7%, and 31.6%, respectively; P<0.001) and more severe [median (interquartile range) phosphate standard deviation score: -1.85 (2.08), -0.56 (2.08), and -1.20 (2.28), respectively; P<0.001]. In the BI group, Pi-SDS level was lower among patients with than without bacteremia (-2.33 ± 1.8 vs. -0.79 ± 1.68; P<0.001). Phosphate levels displayed discriminatory potential between bacterial and viral etiologies, with an area under the curve of 0.719 (95% CI, 0.697-0.742). Minimal phosphate standard deviation score values had a negative weak correlation with the maximal C-reactive protein levels and white blood cell count. Univariate and multivariate analyses showed an association of HP with a more severe disease course, manifested by longer hospital stay [+2.10 (95% CI, 0.75-3.46) days; P=0.003] and a higher rate of intensive care unit admission [odds ratio, 2.63 (95% CI, 1.94-3.56); P<0.001). CONCLUSIONS: Hypophosphatemia rates were highest in bacterial etiology, intermediate in KD, and lowest in viral etiology and were associated with poorer outcomes. Phosphate level may serve as a marker for ruling out a bacterial etiology.

Pathogens Causing Pediatric Community Acquired Urinary Tract Infections and Their Increasing Antimicrobial Resistance: A Nationwide Study.

Urinary tract infections (UTIs) in childhood are common and are associated with considerable acute morbidity and long-term complications. The need for updated data to optimize empiric antibiotic therapy is crucial. We aimed to investigate the pathogens causing pediatric community acquired UTIs, their correlation with demographic characteristics, and trends in their antimicrobial resistance. This nationwide cross-sectional study included all 53,203 children (<18 years) diagnosed with UTI in community outpatient clinics in the following selected years: 2007, 2011, 2015, 2019 and 2021. Escherichia coli (E. coli) (82.1%) was the most common uropathogen, followed by Enterobacter, Klebsiella, Proteus, Pseudomonas, and Enterococcus species. The bacterial distribution displayed statistically significant (p < 0.0001) gender- and sector-specific patterns with a higher relative prevalence of non-E. coli UTI in Jewish and males. The rate of extended-spectrum beta-lactamase-positive E. coli increased substantially and significantly (p < 0.001) from only 6.1% in 2007 to 25.4% in 2021. Most non-E. coli uropathogens exhibited resistance to commonly used empiric antibiotics for UTIs in children. These findings are significant in guiding optimal empiric antibiotic treatment for pediatric community acquired UTIs. The resistance of uropathogens to antimicrobials is region- and time-dependent. Therefore, the periodic and local assessment of antibiotic resistance trends is essential to update guidelines and provide the most appropriate antibacterial therapy for children with UTIs.

An "On Demand" canakinumab regimen for treating children with Colchicine-Resistant familial Mediterranean fever - A multicentre study.

OBJECTIVES: Canakinumab, a human monoclonal antibody targeted at interleukin-1 beta, has demonstrated safety and efficacy in preventing familial Mediterranean fever (FMF) attacks among individuals with colchicine-resistant (crFMF). The manufacturer orders prescribe monthly subcutaneous injections. However, a subset of our patients is treated with an "canakinumab on demand " (COD) strategy, with wider intervals between drug administrations. Therefore, we aimed to compare disease activity and drug safety between COD and "canakinumab fixed frequency" (CFF) policies. METHODS: This retrospective study collected data from three Israeli paediatric rheumatology centres, of children with crFMF who were treated with canakinumab. Epidemiological and clinical parameters, cumulative drug dosages, and adverse events were compared between children treated by both policies. RESULTS: Twenty-five (49 %) children were treated according to COD policy and 26 according to CFF policy. Demographic parameters and most of the disease features did not differ significantly between the groups. Both groups showed significant reduction in attacks after canakinumab introduction. The median number (interquartile range) of attacks per month did not differ significantly between the COD and CFF groups (0.33 (0.08, 0.58) and 0.13 (0, 0.5), respectively, p = 0.485 (even though, per definition, COD patients presumably had an attack before receiving the second canakinumab dose). The mean monthly dose was lower for the COD than the CFF group (1.13 ± 1.13 vs. 3.16 ± 1.46 mg/kg, p < 0.001). Adverse events were similar between the groups. CONCLUSION: For individuals with crFMF, COD compared to CFF policy can achieve similar efficacy and safety, with a lower accumulated canakinumab dose, rendering it less immunosuppressive and less expensive.