Do high doses of quinolones decrease the emergence of antibacterial resistance? A systematic review of data from comparative clinical trials

Summary Objective To evaluate whether the use of high doses of quinolones may reduce the development of antimicrobial resistance. Data sources Relevant studies were identified from PubMed and the Cochrane Central Register of Controlled Trials (until June 2006). Study selection and data extraction We performed a systematic review of the available data from comparative clinical studies reporting on the emergence of resistance when using different daily doses of quinolones. Data synthesis Twelve studies reported comparative data regarding the emergence of antimicrobial resistance. Development of resistance occurred in patients of 5/12 studies included in the review, with no statistical difference between the compared arms. Conclusions Although data from laboratory studies are indicative of a benefit from using high daily doses of quinolones in order to minimize the emergence of antimicrobial resistance, the data from the reviewed trials are limited and can neither support nor reject this finding. However, it seems that if a true benefit exists this is rather small and regards mainly isolates with initially high minimum inhibitory concentrations. Further comparative clinical studies focusing on this issue are justified.