Fluoroquinolone AUIC break points and the link to bacterial killing rates: In vitro models

Abstract

It is clear that the major cause of the development and propagation of fluoroquinolone-resistant S. pneumoniae is the dramatic inappropriate overuse of ciprofloxacin, especially for empiric treatment of community -acquired respiratory illness, which is not very effective at eradicating S. pneumoniae (due to low AUC24/MIC) and readily selects for both low- and high-level resistant mutants. What can we do to prevent further increases in fluoroquinolone-resistant S. pneumoniae as well as clinical failures even with the new fluoroquinolones? We should stop using ciprofloxacin for community-acquired respiratory infections in favor of the newer fluoroquinolones that are less likely to select for resistance at the target site and also are not susceptible to efflux in S. pneumoniae and not use any fluoroquinolones in patients who have recently clinically and/or bacteriologically failed a fluoroquinolone or perhaps received a fluoroquinolone for any purpose in the last 3 months. We should aggressively encourage the judicious use of all antibiotics. We should insist that surveillance studies not only report percent susceptible, intermediate, and resistant, but also describe MIC distributions over time to assess MIC shifts. We should perform ongoing DNA sequencing (minimally of the Quinolone Resistance Determining Region) on randomly selected S. pneumoniae isolates with fluoroquinolone MICs around the break point to assess the accumulation of silent mutations. We will be able to curtail fluoroquinolone-resistant S. pneumoniae only through such an aggressive multi-pronged action plan.