Background: Antimicrobial resistance (AMR) is a global health crisis, with broad-spectrum antibiotic overuse contributing significantly to multidrug-resistant organisms. Pediatric patients with newly diagnosed acute lymphoblastic leukemia (ALL) often present with fever, prompting empiric broad spectrum antibiotic therapy due to perceived infection risk. However, emerging evidence suggests that many fevers in this population may be noninfectious, driven by leukemic cytokine release rather than microbial infection. This study evaluates the prevalence of confirmed infections and compares fever resolution after antibiotics versus anti-leukemic therapy.
Methods: A retrospective, single-center cohort study was conducted at Children’s Hospital Los Angeles from 2019 to 2021. Patients younger than 18 years with a new leukemia diagnosis and fever ≥38°C during initial hospitalization were included; exclusion criteria were prior leukemia, age >18 years, or Pediatric Early Warning Score ≥2 on two consecutive occasions. After exclusions, 30 patients met study criteria. Data collected included demographics, frequency of fever following antibiotic and anti-leukemic therapy, microbiology results, and imaging findings. Statistical analyses comprised relative risk reduction and paired t-test. Institutional Review Board approval was obtained prior to study initiation in accordance with ethical standards for research involving human subjects.
Results: Among 30 pediatric patients with newly diagnosed acute leukemia, 63% had documented fever during initial hospitalization, yet 92.8% received broad-spectrum antibiotics. Notably, 30% were prescribed antibiotics without a recorded fever. Microbiologic evaluation revealed no positive blood, urine, or sputum cultures; only two patients had possible clinical infection (one otitis media, one abnormal chest radiograph). Fever resolution was markedly greater after initiation of anti-leukemic therapy compared with antibiotics: 89.5% of patients continued to have fever following antibiotics, whereas only 26.3% remained febrile after anti-leukemic treatment. Relative risk of persistent fever after antibiotics versus anti-leukemic therapy was 3.4, with a relative risk reduction of 70.6%. Paired t-test confirmed statistical significance (mean fever episodes post-antibiotics 4.05 vs 0.42 post-anti-leukemic; p = 0.000189), supporting the hypothesis that fever reduction is primarily attributable to anti-leukemic therapy rather than antibiotics.
Conclusions: Fevers in pediatric patients with newly diagnosed acute lymphoblastic leukemia (ALL) prior to induction chemotherapy are rarely infectious, and anti-leukemic therapy appears more effective than antibiotics in reducing fever frequency. This raises concerns that routine empiric broad-spectrum antibiotic use may be excessive when infection risk is low. The Pediatric Early Warning Score (PEWS) may offer a practical approach to identifying low-risk febrile patients who could safely avoid broad spectrum antibiotics. Further multi-center studies are needed to confirm the utility of PEWS in this population and to explore the safety and effectiveness of narrower-spectrum antibiotic strategies in this setting.
.png)
.png)