Minimizing quinolone resistance: are the new agents more or less likely to cause resistance?

The introduction of oral antimicrobial agents with broad-spectrum activity extending to methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and other multiply antibiotic-resistant pathogens made the fluoroquinolones an attractive choice for empirical therapy for an extensive range of conditions. As a consequence there has been heavy and indiscriminate use of these agents in some centres 1–6 resulting in fluoroquinolone resistance emerging more rapidly than anticipated in certain pathogens , especially those that were only marginally susceptible. 3,4,7–9 With the recent releases of more potent agents such as trovafloxacin, grepafloxacin, sparfloxacin and levo-floxacin, and others under development, there is now a concern that resistance to the newer agents may also develop. Two factors will be critical in determining the rate at which resistance to these agents develops—the manner in which fluoroquinolones (old and new) are used, and whether or not there are differences between the agents in their propensity to promote the development and spread of resistance. The fluoroquinolones represented a new class of antimicro-bial when they were introduced and there was, initially, a poorer understanding of their limitations compared with other more familiar classes of antibiotics. A high level of optimism arising from early publications, marketing launches and post-marketing activities probably contributed to fluoroquinolone overuse. Today, there is considerable experience with these agents and a better understanding of their optimal uses, benefits and limitations. For example, it is now understood that the factors responsible for the development of resistance to other antibiotic classes apply also to the fluoroquinolones. This now intuitively obvious fact is contrary to early speculations that the emergence of resistance to fluoroquinolones would be less common than occurred with other drug classes. 4 Therefore, as with other drug classes, attempts to minimize resistance must aim to restrict fluoroquinolone use to situations in which these agents are necessary, and to contain resistance that emerges by proven infection control procedures. 6 With this understanding firmly established, fluoroquinolones should now be used with greater wisdom than in the past. These considerations apply to all antibiotic classes, but there are also fluoroquinolone-specific considerations , in that some agents may retard the development of resistance more than others. Such agents can, therefore, be regarded as ecologically less harmful than others. This concept is discussed below. That is, if fluoroquinolone use can be restricted to appropriate indications, and ecologically preferable agents are used, it should be possible to reduce the selection pressure, and extend the …