Antibiotic prophylaxis and the gastrointestinal resistome in paediatric patients with acute lymphoblastic leukaemia: a cohort study with metagenomic sequencing analysis.

backgroundAlthough 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.

methodsThis 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

findingsBetween Feb 1, 2012, and April 30, 2016, 118 stool samples (32 baseline, 49 after induction, and 37 after consolidation) were collected from 49 evaluable participants; of these participants, 31 (63%) received levofloxacin prophylaxis during induction therapy and 18 (37%) received no antibacterial prophylaxis. Over the course of induction therapy, there was an overall increase in the relative abundance of trimethoprim-sulfamethoxazole resistance genes (estimated mean fold change 5·9, 95% CI 3·6-9·6; p<0·0001), which was not modified by levofloxacin prophylaxis (p=0·46). By contrast, the prevalence of topoisomerase point mutations increased over the course of induction therapy in levofloxacin recipients (mean prevalence 10·4% [95% CI 3·2-25·4] after induction therapy

interpretationAnalysing the gastrointestinal resistome can provide insights into the effects of antibiotics on the risk of antibiotic-resistant infections. In this study, antibiotic prophylaxis with trimethoprim-sulfamethoxazole or levofloxacin during induction therapy for acute lymphoblastic leukaemia appeared to increase the short-term and medium-term risk of colonisation with bacteria resistant to these antibiotics, but not to other drugs. More research is needed to determine the longer-term effects of antibacterial prophylaxis on colonisation with antibiotic-resistant bacteria.

fundingChildren's Infection Defense Center at St Jude Children's Research Hospital, American Lebanese Syrian Associated Charities, and National Institutes of Health.