Susceptibility Trends in Respiratory Pathogens: The Role of the Newer Fluoroquinolones

ABSTRACT: Resistance to the various classes of antimicrobials continues to increase in virtually all clinically significant gram-negative and gram-positive bacteria. In particular, rates of resistance to -lactam and macrolide antimicrobial agents are on the rise among the most common bacterial pathogens, including Streptococcus pneumoniae and Haemophilus influenzae. In the bacterial cell, the fluoroquinolones inhibit, to varying degrees, the enzymes DNA gyrase (topoisomerase II) and topoisomerase IV. The newer fluoroquinolones (such as gatifloxacin, gemifloxacin, and moxifloxacin) inhibit these enzymes more than the older agents in this class (ciprofloxacin and levofloxacin); gemifloxacin has a greater affinity for these 2 vital target enzymes. When both enzymes are strongly inhibited, any genetic mutation in a microorganism leads to a smaller increase in minimum inhibitory concentration (MIC) than would occur with a quinolone that targets only 1 enzyme. Gemifloxacin exhibits extremely low MIC results against the clinically significant respiratory pathogens—lowest among clinically available fluoroquinolones. Susceptibility Trends in Respiratory Pathogens: The Role of the Newer Fluoroquinolones