Especially critically ill children are exposed to antibiotic overtreatment, mainly caused by the fear of missing out a severe bacterial infection. Potential adverse effects and selection of multi-drug resistant bacteria play minor roles in decision making. This narrative review first describes harm from antibiotics and second focuses on different aspects that could help to reduce antibiotic overtreatment without harming the patient: harm from antibiotic treatment, diagnostic approaches, role of biomarkers, timing of antibiotic therapy, empiric therapy, targeted therapy, and therapeutic drug monitoring. Wherever possible, we linked the described evidence to the current Surviving Sepsis Campaign guidelines. Antibiotic stewardship programs should help guiding antibiotic therapy for critically ill children. Impact: Critically ill children can be harmed by inadequate or overuse of antibiotics. Hemodynamically unstable children with a suspicion of infection should be immediately treated with broad-spectrum antibiotics. In contrast, in hemodynamically stable children with sepsis and organ dysfunction, a time frame of 3 h for proper diagnostics may be adequate before starting antibiotics if necessary. Less and more targeted antibiotic treatment can be achieved via antibiotic stewardship programs.

Objectives: The Pediatric Sepsis Definition Task Force developed and validated a new organ dysfunction score, the Phoenix Sepsis Score (PSS), as a predictor of mortality in children with suspected or confirmed infection. The PSS showed improved performance compared with prior scores. However, the criteria were derived in a general pediatric population, in which only 10% had cancer. Given that pediatric cancer patients with sepsis have higher mortality compared with noncancer patients with sepsis, we aimed to assess the PSS in PICU patients with cancer and sepsis. Design: Retrospective multicenter cohort study. Setting: Twelve PICUs across Europe. Patients: Each PICU identified patients 18 years young or younger, with underlying malignancy and suspected or proven sepsis, and admission between January 1, 2018, and January 1, 2020. Interventions: None. Measurements and Main Results: The PSS and three other scores, including Phoenix-8, Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score, and pediatric Sequential Organ Failure Assessment (pSOFA) score, were calculated for comparison. The primary outcome was 90-day all-cause mortality. We compared score performance using area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC) analyses. Among 383 patients with proven or suspected sepsis, 90-day mortality was 19.3% (74/383). We failed to identify an association between a particular score and performance for 90-day mortality. The mean (95% CI) values for the AUROC of each score was: PSS 0.66 (0.59–0.72), Phoenix-8 0.65 (0.58–0.72), PELOD-2 0.64 (0.57–0.71), and pSOFA 0.67 (0.60–0.74) and for the AUPRC of each score: PSS 0.32 (0.23–0.42), Phoenix-8 0.32 (0.23–0.42), PELOD-2 0.32 (0.22–0.43), and pSOFA 0.36 (0.26–0.46). Similar results were obtained for PICU mortality or sepsis-related PICU mortality. Conclusions: Contrary to the general PICU population, our retrospective test of the PSS in a PICU oncology dataset with suspected or proved sepsis from European PICUs, 2018–2020, failed to identify improved performance in association with mortality. This unique patient population deserves development of organ dysfunction scores that reflect organ dysfunction and mortality data specifically from these patients and will require prospective validation in future studies.