Investigation of in vitro effects of cationic steroid antibiotics against burkholderia cepacia complex strains

Burkholderia cepacia complex (Bcc) species are aerobic, Gram negative and non-fermentative bacillus. Bcc can cause asymptomatic carriage to fatal pneumonia patients with cystic fibrosis. This bacterial complex is intrinsically resistant to antibiotics and the possibility of transmission from hospital, increases the importance of diagnosis and treatment. Infections that are difficult to treat revealed the need for alternative antimicrobial agents. One of these alternative substances is ceragenins which are similar to antimicrobial peptids and act on bacterial wall. In our study, in vitro effects of CSA-13, CSA-131, CSA-131-P, levofloxacin and trimethoprim-sulfamethoxazole (SXT) alone and combination against 42 Bcc strains isolated from clinical samples were investigated. MIC and MBC values were determined by broth microdilution method and combination antimicrobial effects by time-kill method. MIC50 (μg/ml) values for CSA-13, CSA-131, CSA-131-P, levofloxacin and SXT were 16, 16, 16, 2 and 1/19, respectively. MBC values of ceragenins were determined as twice the MIC values. According to the time-kill experiments, CSA-13 and CSA-131-P showed bactericidal effect in the first six hours. In the combinations of CSA-13 with levofloxacin and SXT, synergistic effect was observed not only in 4xMIC but also in 1xMIC. In addition, when CSA-131 was used in combination with levofloxacin, synergistic effect was detected. Antagonistic effect was not observed. As a result, we think that the use of CSAs, especially CSA-13 and CSA-131, alone or combination will be good candidates for the treatment of Bcc infections. However, deficiencies in the stability properties, efficacy and pharmacokinetics of CSAs require further research in the future.