Comparative effectiveness and safety of antibiotic prophylaxis during induction chemotherapy in children with acute leukaemia: a systematic review and meta-analysis.

Background: Bacterial infections are common during induction therapy in children and adolescents with acute leukaemia and may cause infection-related mortality.

Aim: To determine the efficacy and safety of prophylactic antibiotics in paediatric patients with acute leukaemia receiving induction chemotherapy.

Methods: From three English databases and four Chinese databases, we searched for randomized controlled trials (RCTs) and cohort studies that compared prophylactic antibiotics to placebo, no prophylaxis, or that compared one antibiotic versus another in paediatric patients with acute leukaemia undergoing induction chemotherapy. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias using Cochrane Risk of Bias 2 tool and Newcastle-Ottawa Scale, and the certainty of evidence using Grading of Recommendations Assessment, Development, and Evaluation (GRADE).

Findings: Two RCTs and ten cohort studies were finally included. For children with acute lymphoblastic leukaemia, antibiotic prophylaxis, including levofloxacin, sulfamethoxazole-trimethoprim, or other antibiotics, probably reduced bacteraemia (risk ratio (RR): 0.44; 95% confidence interval (CI): 0.33-0.60; moderate certainty) without significantly increasing Clostridioides difficile infection (CDI) or invasive fungal infection. Levofloxacin reduced the CDI rate (RR: 0.08; 95% CI: 0.01-0.62; high certainty). Ciprofloxacin prophylaxis probably reduced infection-related mortality (RR: 0.12; 95% CI: 0.01-0.97; moderate certainty). In children with acute myeloid leukaemia, ciprofloxacin plus vancomycin may reduce febrile neutropenia (RR: 0.79; 95% CI: 0.66-0.94; low certainty). Individual studies indicated that prophylaxis increased antibiotic exposure but reduced non-preventive antibiotic exposure.

Conclusion: In children with acute leukaemia undergoing induction therapy, antibiotic prophylaxis may improve the bacterial infection and mortality.