Quinolones in 2005: an update F. Van Bambeke, J.-M. Michot, J. Van Eldere, P.M. Tulkens  Clinical Microbiology and Infection  Volume 11, Issue 4, Pages 256-280 (April 2005) DOI: 10.1111/j.1469-0691.2005.01131.x Copyright © 2005 European Society of Clinical Infectious Diseases Terms and Conditions

Fig. 1 Pharmacophore and structures of the main quinolones that have been approved for human use. Names in bold refer to compounds in large-scale clinical use in Europe. Names in italic refer to compounds for which commercialisation has been suspended or severely reduced because of side-effects and/or a decision of their registration holders (the development of garenoxacin in Europe and North America is at present uncertain). Clinical Microbiology and Infection 2005 11, 256-280DOI: (10.1111/j.1469-0691.2005.01131.x) Copyright © 2005 European Society of Clinical Infectious Diseases Terms and Conditions

Fig. 2 Structure–e relationships in quinolones. The central part of the molecule refers to the pharmacophore shown in Fig. 1. Clinical Microbiology and Infection 2005 11, 256-280DOI: (10.1111/j.1469-0691.2005.01131.x) Copyright © 2005 European Society of Clinical Infectious Diseases Terms and Conditions

Fig. 3 Cumulative MIC distributions for wild-type populations of four major pathogens (redrawn from data obtained and made publicly available by the European Committee on Antimicrobial Susceptibility Testing (EUCAST); see http://www.eucast.org). Each reference distribution is the result of aggregated MIC data obtained from publications in international journals, national breakpoint committees, reference laboratories, international antimicrobial surveillance systems, such as EARSS (http://www.earss.rivm.nl) or those sponsored by pharmaceutical companies, and antimicrobial susceptibility testing device manufacturers. As such, the data are meant to represent the natural variability in the susceptibility of organisms without specific, acquired resistance mechanisms to the corresponding drugs. Clinical Microbiology and Infection 2005 11, 256-280DOI: (10.1111/j.1469-0691.2005.01131.x) Copyright © 2005 European Society of Clinical Infectious Diseases Terms and Conditions

Fig. 4 Cross-resistance and dissociated resistance in quinolones. QA and QB illustrate a situation of cross-resistance: although the initial susceptibility of the strain may be different for molecules A and B, mutations in the target enzymes lead to similar changes in the susceptibility to both drugs. QC illustrates a situation of dissociated resistance: the susceptibility to molecule C does not change in spite of the acquisition of a first mutation, and will increase only upon acquisition of a second mutation. Clinical Microbiology and Infection 2005 11, 256-280DOI: (10.1111/j.1469-0691.2005.01131.x) Copyright © 2005 European Society of Clinical Infectious Diseases Terms and Conditions