Association of daptomycin use with resistance development in Enterococcus faecium bacteraemia—a 7-year individual and population-based analysis  A. Egli, H. Schmid, E. Kuenzli, A.F. Widmer, M. Battegay, H. Plagge, R. Frei, R. Achermann, M. Weisser  Clinical Microbiology and Infection  Volume 23, Issue 2, Pages 118.e1-118.e7 (February 2017) DOI: 10.1016/j.cmi.2016.10.003 Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

Fig. 1 Distribution of daptomycin MIC. Distribution of MIC values measured by Etest in Enterococcus faecium isolates from positive blood cultures. White bars denote episodes with strains fully susceptible according to CLSI. Light grey bars indicate a MIC of 4 mg/L (at the breakpoint towards resistance) and dark grey bars represent resistant strains according to CLSI (MIC >4 mg/L). Clinical Microbiology and Infection 2017 23, 118.e1-118.e7DOI: (10.1016/j.cmi.2016.10.003) Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

Fig. 2 Daptomycin MIC and daptomycin consumption. (a) Distribution of MIC values for each year. Each circle shows an individual measurement. Black bars represent median values, whiskers are showing inter quartile ranges. (b) Consumption of daptomycin indicated with defined daily dosages (DDDs). Clinical Microbiology and Infection 2017 23, 118.e1-118.e7DOI: (10.1016/j.cmi.2016.10.003) Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

Fig. 3 Multiple episodes of Enterococcus faecium bacteraemia. The MIC difference between the first and second episode of E. faecium bacteraemia is shown as box plots with median and interquartile range and in addition to the individual measurements. Patients who did not receive daptomycin during the first episode are shown on the left side and patients who received daptomycin during the first episode on the right side. Of note, one outlier in the group without daptomycin (MIC 12 mg/μL) showed in the PFGE a different clonal pattern, thereby indicating that this clone was independent and did not evolve due to daptomycin treatment. Clinical Microbiology and Infection 2017 23, 118.e1-118.e7DOI: (10.1016/j.cmi.2016.10.003) Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

Fig. 4 Clonal evolution over time measured with pulsed-field gel electrophoresis (PFGE). Using PFGE, each isolate could be grouped into arbitrary named clones (Clonal ID 1, 2, 3, 4, etc.), shown for the whole population (left) and for the haematological ward (right). The numbers in the boxes indicate the number of isolates within the same clone for a particular year e.g. “3” indicates that three isolates with the same PFGE pattern were found within this year. The colour code indicates the mean MIC level for a particular clone within 1 year. Clone number 15 was present from 2008 to 2014. After 2009 this clone showed a slight rise in the MIC. Clinical Microbiology and Infection 2017 23, 118.e1-118.e7DOI: (10.1016/j.cmi.2016.10.003) Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions

Fig. 5 Index of Diversity over different MICs. Solid line shows a best-fit curve for linear regression, dashed lines indicate the respective 95% CI. Simpon's index of diversity over the study follow up significantly increased. Clinical Microbiology and Infection 2017 23, 118.e1-118.e7DOI: (10.1016/j.cmi.2016.10.003) Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases Terms and Conditions