Fig. 2.

Antibiotic impact on the gut resistome. a Stacked bar chart of summed length-corrected relative abundances (LCRA) of major antimicrobial resistance gene (ARG) classes at baseline (T0) and over the treatment period (T1–T3). The following ARG classes are depicted: aminoglycosides (AGly), beta-lactamases (Bla), fluoroquinolones (Flq), glycopeptides (Gly), macrolide-lincosamide-streptogramin (MLS), nitroimidazoles (Ntmdz), phenicols (Phe), sulfonamides (Sul), tetracyclines (tet), and trimethoprim (Tmt). b Trajectories of antimicrobial resistance genes quantification by LCRA before treatment (T0) and at the end of the observation period (T3) are shown for both antibiotic treatments. Pink data points are measurements at T0, purple data points at T3. Boxplots indicate the distribution of data. The connecting magenta line shows the means at each time point and their development under treatment. The p value is displayed at the top of each box and indicates statistical significant differences between T0 and T3 within each treatment cohort (paired t-test). Trends for LCRA changes are prominent but do not reach statistical significance. c Two-dimensional kernel estimation density of square root transformed LCRA values of sulfonamide and trimethoprim ARG classes in relation to the administered cumulative antibiotic dose in defined daily doses (DDD). ARG LCRA rises significantly with increasing doses of cotrimoxazole, but not under ciprofloxacin. d Based on multivariate regression modeling, the average percentage change of ARG class LCRA per defined daily dose (DDD) is illustrated for each treatment cohort. Bonferroni-corrected statistically significant differences between both antibiotics (LR p < 0.002) are presented by single asterisks. Significant differences in antimicrobial selection pressure were observed for aminoglycoside, CTX-M, glycopeptide, MLS, nitroimidazole, phenicol, sulfonamide, and trimethoprim ARGs. If an additional impact of concurrent medication was detected beside antibiotics in the multivariate models, this has been illustrated by different filling pattern. e Fluoroquinolone resistance-mediating mutation frequencies increase under ciprofloxacin exposure in patient 512 comparing baseline (T0) and endpoint (T3)