caa a22 4500 606156879 CHVBK 20210128100610.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s10096-015-2441-7 doi (NATIONALLICENCE)springer-10.1007/s10096-015-2441-7 Target site antimicrobial activity of colistin might be misestimated if tested in conventional growth media [Elektronische Daten] [P. Matzneller, S. Strommer, Z. Österreicher, D. Mitteregger, M. Zeitlinger] Cation-dependent inhibition of antimicrobial activity was reported for polymyxin antibiotics. Ca2+ and Mg2+ concentrations recommended by the Clinical and Laboratory Standards Institute (CLSI) for the supplementation of Müller-Hinton broth (MHB) are markedly lower than interstitial space fluid (ISF) concentrations in vivo. Hence, it was speculated that the antimicrobial activity of colistin might be overestimated if tested using conventional cation-adjusted MHB. The antimicrobial activity of colistin against n = 100 clinical isolates of Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Escherichia coli (n = 25 each) was evaluated by broth microdilution and, for selected isolates, by time-kill curves, in MHB without cations (MHBONLY), MHB supplemented with 25mg/L Ca2+ and 12.5mg/LMg2+ according to CLSI recommendations (MHBCLSI), and in MHB adjusted to 50mg/L Ca2+ and 20mg/LMg2+ simulating ISF concentrations (MHBISF). The minimum inhibitory concentration (MIC) values of colistin against the vast majority of isolates of both P. aeruginosa and A. baumannii increased significantly with higher cation concentrations. The susceptibility of K. pneumoniae isolates to colistin did not show significant changes between cation-supplemented media, while the MICs of E. coli decreased with ascending cation concentrations. These findings were confirmed in time-kill studies, where colistin killing against P. aeruginosa 1514 and A. baumannii 1485 declined with increasing cation concentrations. Contrarily, the killing of selected concentrations of colistin against K. pneumoniae 15 and E. coli 16 was enhanced in the presence of increasing cation concentrations. The present data suggest that the clinical antimicrobial activity of colistin might be misestimated in vitro if tested in conventional growth media. Springer-Verlag Berlin Heidelberg, 2015 Matzneller P. Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut Strommer S. Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut Österreicher Z. Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut Mitteregger D. Clinical Division of Clinical Microbiology, Clinical Institute of Laboratory Medicine, Medical University of Vienna, Vienna, Austria aut Zeitlinger M. Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut European Journal of Clinical Microbiology & Infectious Diseases Springer Berlin Heidelberg 34/10(2015-10-01), 1989-1994 0934-9723 34:10<1989 2015 34 10096 https://doi.org/10.1007/s10096-015-2441-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10096-015-2441-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Matzneller P. Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Strommer S. Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Österreicher Z. Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Mitteregger D. Clinical Division of Clinical Microbiology, Clinical Institute of Laboratory Medicine, Medical University of Vienna, Vienna, Austria aut NATIONALLICENCE 700 1- Zeitlinger M. Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria aut NATIONALLICENCE 773 0- European Journal of Clinical Microbiology & Infectious Diseases Springer Berlin Heidelberg 34/10(2015-10-01), 1989-1994 0934-9723 34:10<1989 2015 34 10096