Antibiotic prophylaxis and the gastrointestinal resistome in paediatric patients with acute lymphoblastic leukaemia: a cohort study with metagenomic sequencing analysis
Abstract
Summary Background Although antibiotic prophylaxis with levofloxacin can reduce the risk of serious infection in immunocompromised patients, the potential contribution of prophylaxis to antibiotic resistance is a major drawback. We aimed to identify the effects of levofloxacin prophylaxis, given to paediatric patients with acute lymphoblastic leukaemia to prevent infections during induction chemotherapy, on antibiotic resistance in gastrointestinal microbiota after completion of induction and consolidation therapy. Methods This prospective, single-centre (St Jude Children’s Research Hospital, Memphis, TN, USA) cohort study included children (≤18 years) receiving therapy for newly diagnosed acute lymphoblastic leukaemia and who received either primary levofloxacin prophylaxis or no antibacterial prophylaxis (aside from Pneumocystis jirovecii prophylaxis with trimethoprim-sulfamethoxazole) and provided at least two stool samples, including one after completion of induction therapy. We used metagenomic sequencing to identify bacterial genes that confer resistance to fluoroquinolones, trimethoprim-sulfamethoxazole, or other antibiotics, and to identify point mutations in bacterial topoisomerases (gyrA, parC) that confer resistance to fluoroquinolones. We then used generalised linear mixed models to compare the prevalence and relative abundance of antibiotic resistance gene groups after completion of induction and consolidation therapy between participants who had received…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 49 participants or records.
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