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

M Yang; X Lu; L Xin; J Luo; S Diao; Z Jia; G Cheng; L Zeng; L Zhang

doi:10.1016/j.jhin.2023.03.003

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

J Hosp Infect. 2023 Jun:136:20-29. doi: 10.1016/j.jhin.2023.03.003. Epub 2023 Mar 13.

Authors

M Yang¹, X Lu², L Xin³, J Luo⁴, S Diao⁵, Z Jia⁴, G Cheng⁶, L Zeng⁷, L Zhang⁸

Affiliations

¹ Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China; Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China; NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation, Chengdu, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China; West China School of Medicine, Sichuan University, Chengdu, China.
² Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China; Department of Paediatric Haematology and Oncology, West China Second Hospital, Sichuan University, Chengdu, China.
³ Department of Clinical Pharmacy, The Affiliated Hospital of Yunnan University, Kunming, China.
⁴ Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China; Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China; NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation, Chengdu, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China; West China School of Pharmacy, Sichuan University, Chengdu, China.
⁵ Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China; Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China; NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation, Chengdu, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China.
⁶ Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China; Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China; Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Sichuan University, Chengdu, China.
⁷ Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China; Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China; NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation, Chengdu, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China. Electronic address: LinanZeng@scu.edu.cn.
⁸ Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China; Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China; NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation, Chengdu, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China; Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu, China. Electronic address: zhanglingli@scu.edu.cn.

PMID: 36921630
DOI: 10.1016/j.jhin.2023.03.003

Abstract

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.

Keywords: Acute leukaemia; Antibacterial prophylaxis; Bacterial infection; Induction chemotherapy; Meta-analysis; Paediatrics.

Publication types

Meta-Analysis
Systematic Review
Review

MeSH terms

Acute Disease
Adolescent
Anti-Bacterial Agents / adverse effects
Antibiotic Prophylaxis
Bacterial Infections* / drug therapy
Child
Ciprofloxacin / adverse effects
Humans
Induction Chemotherapy
Leukemia, Myeloid, Acute* / complications
Leukemia, Myeloid, Acute* / drug therapy
Levofloxacin

Substances

Anti-Bacterial Agents
Ciprofloxacin
Levofloxacin