Levaquin Gets a Pass

Abstract

Antibiotic-induced gut microbiota disruptions contributes to consequences such as bloodstream infection and GVHD. Our recent survey of CTN centers showed that levofloxacin (LEVO) is the most commonly used prophylactic antibacterial antibiotic during allo-HCT (PMID:30058189). LEVO is also the most commonly used prophylactic antibacterial antibiotic during anti-leukemia induction therapy. LEVO effect on the gut microbiota during intensive therapy has not been systematically evaluated. We compared microbiota dynamics before vs. during single-agent LEVO (250 mg/day) exposure until antibiotic escalation in 40 intensively treated patients (20 allo-HCT and 20 acute leukemia patients; 176 samples). A protocol of 3-times-weekly stool sample collection beginning with hospital admission permitted this analysis. Samples underwent 16S rRNA gene sequencing. Time windows for each patient with ≥2 samples before LEVO exposure or ≥2 samples during exposure to LEVO, but before any other antibacterial antibiotics were considered. The median (range) length of these windows was 6 (3-18) and 8 (3-24) days, respectively. A mixed effect model was developed with the sample's Shannon diversity as the dependent variable, and sample day, cohort, and LEVO exposure on sample day (yes/no) as predictors. Interaction terms for day*cohort and day*LEVO, and a random effect for patient number were included. A similar model was developed for the relative abundance of each of the 10 most abundant genera as the dependent variable. We determined whether 99% confidence intervals (from 1000 bootstraps) for regression coefficients (β) for LEVO and day*LEVO contained 0. The only variable influenced by LEVO was <i>Parabacteroides</i> (β = -0.085 [99%CI: -0.147 to -0.023]; Table 1). LEVO exposure was associated with a lower abundance of <i>Parabacteroides</i>, independent of time and cohort. However, alpha diversity and all other genera were unaffected. In summary, LEVO effect on microbiota during intensive therapy is marginal. We recommend continuing to use LEVO as antibiotic prophylaxis as it permits continued microbiota diversity.