Collateral damage from oral ciprofloxacin versus nitrofurantoin in outpatients with urinary tract infections: a culture-free analysis of gut microbiota  A.J. Stewardson, N. Gaïa, P. François, S. Malhotra-Kumar, C. Delémont, B. Martinez de Tejada, J. Schrenzel, S. Harbarth, V. Lazarevic  Clinical Microbiology and Infection  Volume 21, Issue 4, Pages 344.e1-344.e11 (April 2015) DOI: 10.1016/j.cmi.2014.11.016 Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

FIG. 1 Summary of results of PERMANOVA comparing the 12 groups of samples (four groups of individuals, three time points). PERMANOVA test with 9999 permutations was performed on Bray-Curtis similarity matrix based on the square-root-transformed relative abundance of operational taxonomic units. p values for intergroup comparisons are indicated according to the colour scale given at left. CP, ciprofloxacin group; CTCP, household members of ciprofloxacin group; CRL, control group; NF, nitrofurantoin group. Antibiotic exposure occurred between sample 1 and 2. Sample 3 was collected about 28 days after sample 2. Clinical Microbiology and Infection 2015 21, 344.e1-344.e11DOI: (10.1016/j.cmi.2014.11.016) Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

FIG. 2 Principal coordinates analysis of samples taken at baseline (a) and at second (b) and third (c) sampling points. The analysis was done in PRIMER-E, based on square-root-transformed abundance of operational taxonomic units (OTUs) and Bray-Curtis similarity matrix. Vectors of Spearman correlations between OTUs with PCO1 and PCO2 axes (with lengths greater than 0.65) are overlaid onto the plot. Circles indicate antibiotic exposure between 2 and 12 months before the study. Clinical Microbiology and Infection 2015 21, 344.e1-344.e11DOI: (10.1016/j.cmi.2014.11.016) Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

FIG. 3 Families and genera differentially represented between before and after antibiotic treatment. Box plots show the range from second to third quartile divided by median. Square represents average. Whiskers correspond to maximum and minimum values. Boxes were coloured red and blue to indicate decrease and increase, respectively, in second time point samples relative to first and third time point samples. Taxa with significant (p < 0.05, Wilcoxon signed rank test) changes in any of the CP1–CP2, CP1–CP3, CP2–CP3, CP2–CTCP2, NF1–NF2, NF1–NF3 and NF2–NF3 comparisons are presented. CP, ciprofloxacin group; CRL, control group; CTCP, household members of ciprofloxacin group; NF, nitrofurantoin group. Clinical Microbiology and Infection 2015 21, 344.e1-344.e11DOI: (10.1016/j.cmi.2014.11.016) Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

FIG. 4 Bray-Curtis similarity within and between individuals. Average similarity and standard error bars are given. (a) Intraindividual (‘Intra’) vs. interindividual (‘Inter’) similarity. (b) Intraindividual microbiota similarity between different time points. Clinical Microbiology and Infection 2015 21, 344.e1-344.e11DOI: (10.1016/j.cmi.2014.11.016) Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

FIG. 5 Principal coordinates analysis of the four groups of samples. The first, second and third time point sample of the same individual are represented by the same symbol in black (first time point), dark gray (second time point) and light gray tones (third time point), respectively, and surrounded by an oval. Clinical Microbiology and Infection 2015 21, 344.e1-344.e11DOI: (10.1016/j.cmi.2014.11.016) Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

FIG. 6 Relative abundance of genera in ciprofloxacin-treated patients. Only genera with relative abundance of >5% in at least one of 18 samples are presented. Operational taxonomic units unassigned to a genus or assigned to low-abundance genera (<5% across all 18 samples) are summed to represent the category ‘other’. Clinical Microbiology and Infection 2015 21, 344.e1-344.e11DOI: (10.1016/j.cmi.2014.11.016) Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions