Killing of nongrowing and adherent Escherichia coli determines drug efficacy in device-related infections

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Abstract
Antimicrobial therapy of device-related infections often fails, despite the in vitro susceptibility of the infecting strain. Therefore, alternative laboratory-based in vitro tests are required to predict the outcome. Fleroxacin, ciprofloxacin, aztreonam, and co-trimoxazole were tested against Escherichia coli ATCC 25922 in vitro and in the tissue-cage animal model. The importance of early treatment was evaluated by starting the drugs either 30 min before or 4, 12, and 24 h after bacterial challenge. Results were compared with the in vitro drug efficacy against nongrowing and adherent Escherichia coli ATCC 25922. The alternative in vitro tests correlated highly with the outcome in the tissue-cage animal model. In the prophylaxis group (drug given 30 min before bacterial challenge), co-trimoxazole was less efficacious than the other three drugs (P less than 0.001). In delayed treatment, ciprofloxacin showed the highest cure rate. It was also more potent than the other drugs against nongrowing and adherent E. coli ATCC 25922. The efficacies of aztreonan, fleroxacin, and ciprofloxacin dropped significantly (P less than 0.01) when the time interval between bacterial challenge and the start of treatment was delayed to greater than 4 h. These data emphasize (i) the need for proper timing of prophylaxis in patients undergoing implant surgery, and (ii) the possibility of successful treatment of established device-related infections with drugs which kill not only growing but also nongrowing and adherent bacteria.