A-290 Impact of oxidative and iron-depleted stress on ceftazidime and levofloxacin susceptibility of Stenotrophomonas maltophilia

Background Stenotrophomonas maltophilia is recognized as a multidrug-resistant opportunistic pathogen. Ceftazidime (CAZ) and levofloxacin (LEV) are the common choices for the treatment of S. maltophilia infection. Antibiotic susceptibility test (AST) is the currently used method to determine the susceptibility of pathogens to antibiotics in vitro. AST procedure is well standardized according to the guidelines of internationally authorized institutions. However, the assay conditions of AST do not completely reflect the infection niches that pathogens may encounter. For a pathogen, oxidative stress and iron-depleted stress imposed by host cells are inevitable during the infection course. In this study, the influence of oxidative and iron-depleted stress on determining the susceptibility of S. maltophilia toward CAZ and LEV was investigated. Methods Menadione (MD) and 2,2-dipyridyl (DIP) were used as additives for the generation of oxidative and iron-depleted stress, respectively. The minimal inhibition concentration (MIC) values of 224 clinical S. maltophilia isolates toward CAZ and LEV were determined by agar dilution method with and without MD and DIP. The breakpoints for CAZ and LEV susceptible are MIC8 ?g/ml and MIC2 ?g/ml, respectively. Results In the MD- and DIP-free conditions, 11.1% (n?=?25/224) of the isolates assessed displayed susceptible to CAZ. Furthermore, 13.3% (n=30/224) and 10.3% (n=23/224) of the isolates were susceptible to CAZ in DIP- and MD-containing medium, respectively. Nevertheless, the susceptible rate decreased to 7.1% (16/224) when these isolates were tested in the medium with both stressors. The susceptible rate of the 224 isolates against LEV were 75% (n=168/224), 75.4% (n=169/224), 73.2% (n=164/224), and 75% (n=168/224) in non-additive, DIP-, MD-, and DIP/MD-containing medium, respectively. Conclusion The susceptibility of S. maltophilia toward CAZ decreases in the presence of oxidative and iron-depleted stress. However, oxidative and iron-depleted stress hardly makes impacts on the LEV susceptibility of S. maltophilia.