Research from JAMA Pediatrics — Serum Procalcitonin Level and Other Biological Markers to Distinguish Between Bacterial and Aseptic Meningitis in Children — A European Multicenter Case Cohort Study

Fidaxomicin, a narrow-spectrum antibiotic approved for Clostridioides (Clostridium) difficile infection (CDI) in adults, is associated with lower rates of recurrence than vancomycin; however, pediatric data are limited. This multicenter, investigator-blind, phase 3, parallel-group trial assessed the safety and efficacy of fidaxomicin in children. Patients aged <18 years with confirmed CDI were randomized 2:1 to 10 days of treatment with fidaxomicin (suspension or tablets, twice daily) or vancomycin (suspension or tablets, 4 times daily). Safety assessments included treatment-emergent adverse events. The primary efficacy end point was confirmed clinical response (CCR), 2 days after the end of treatment (EOT). Secondary end points included global cure (GC; CCR without CDI recurrence) 30 days after EOT (end of study; EOS). Plasma and stool concentrations of fidaxomicin and its active metabolite OP-1118 were measured. Of 148 patients randomized, 142 were treated (30 <2 years old). The proportion of participants with treatment-emergent adverse events was similar with fidaxomicin (73.5%) and vancomycin (75.0%). Of 3 deaths in the fidaxomicin arm during the study, none were CDI or treatment related. The rate of CCR at 2 days after EOT was 77.6% (76 of 98 patients) with fidaxomicin and 70.5% (31 of 44) with vancomycin, whereas the rate of GC at EOS was significantly higher in participants receiving fidaxomicin (68.4% vs 50.0%; adjusted treatment difference, 18.8%; 95% confidence interval, 1.5%–35.3%). Systemic absorption of fidaxomicin and OP-1118 was minimal, and stool concentrations were high. Compared with vancomycin, fidaxomicin was well tolerated and demonstrated significantly higher rates of GC in children and adolescents with CDI. NCT02218372

Background Clinical decision rules (CDRs) could be helpful to safely distinguish between bacterial and aseptic meningitis (AM). Objective To compare the performance of two of these CDRs for children: the Bacterial Meningitis Score (BMS) and the Meningitest. Design Secondary analysis of retrospective multicentre hospital-based cohort study. Setting Six paediatric emergency or intensive care units of tertiary care centres in five European countries. Patients Consecutive children aged 29 days to 18 years presenting with acute meningitis and procalcitonin (PCT) measurement. Intervention None. Main outcome measures The sensitivity and specificity of the BMS (start antibiotics in case of seizure, positive cerebrospinal fluid (CSF) Gram staining, blood neutrophil count ≥10 ×10⁹/l, CSF protein level ≥80 mg/dl or CSF neutrophil count ≥1000 ×10⁶/l) and the Meningitest (start antibiotics in case of seizure, purpura, toxic appearance, PCT level ≥0.5 ng/ml, positive CSF Gram staining or CSF protein level ≥50 mg/dl) were compared using a McNemar test. Results 198 patients (mean age 4.8 years) from six centres in five European countries were included; 96 had bacterial meningitis. The BMS and Meningitest both showed 100% sensitivity (95% CI 96% to 100%). The BMS had a significantly higher specificity (52%, 95% CI 42% to 62% vs 36%, 95% CI 27% to 46%; p<10⁻8). Conclusion The Meningitest and the BMS were both 100% sensitive. This result provides level II evidence for the sensitivity of both rules, which can be used cautiously. However, use of the BMS could safely avoid significantly more unnecessary antibiotic treatments for children with AM than can the Meningitest in this population.

Community-acquired bacterial pneumonia (CABP) remains a major infection among children, despite the use of pneumococcal vaccination. Ceftaroline fosamil is a broad-spectrum cephalosporin antibiotic with activity against many bacteria, including Streptococcus pneumoniae (both penicillin-nonsusceptible and multidrug-resistant strains) and Staphylococcus aureus (including methicillin-resistant S. aureus). This article describes the safety, tolerability, and effectiveness of ceftaroline fosamil in the treatment of pediatric patients hospitalized with CABP, from a randomized, active-controlled, observer-blinded clinical study (registration number NCT01530763). Pediatric patients were stratified into 4 age cohorts and randomized (3:1) to receive either intravenous ceftaroline fosamil or ceftriaxone, with optional oral switch for a total treatment duration of 5-14 days. Enrollment was planned for 160 patients. Data collected included demographics, infection characteristics and pathogens. Treatment-emergent adverse events, clinical outcomes, and microbiologic responses were assessed. Ceftaroline fosamil was well tolerated. Similar percentages of patients in the ceftaroline fosamil (55/121; 45%) and ceftriaxone (18/39; 46%) groups reported treatment-emergent adverse events. Coombs seroconversion was observed in 17% of patients in the ceftaroline fosamil group; however, no evidence of hemolytic anemia or hemolysis was found. No deaths were reported during the study. Ceftaroline fosamil had similar effectiveness to ceftriaxone, with high clinical cure rates at test-of-cure in the modified intent-to-treat population (94/107; 88% and 32/36; 89%, respectively). Three documented S. aureus infections were successfully treated in the ceftaroline group, including one caused by methicillin-resistant S. aureus. The results of this study suggest that ceftaroline fosamil may be an important treatment option for pediatric patients hospitalized with CABP.