Journal: Antibiotics
Article Title: TXA11114 : Discovery of an In Vivo Efficacious Efflux Pump Inhibitor (EPI) That Potentiates Levofloxacin Against Pseudomonas aeruginosa
doi: 10.3390/antibiotics15040346
Figure Lengend Snippet: In vivo efficacy in murine thigh and lung infection models. ( A ) Efficacy of TXA11114 /levofloxacin combination murine thigh infection model: In this model, mice were inoculated intramuscularly (IM) in the right thigh with 5.75 log 10 CFU of P. aeruginosa ATCC 27853. Pretreatment control was determined 6.08 log 10 CFU at 2 h (baseline). Then, 24 h after infection, the mean bacterial thigh titers reached 8.82 log 10 CFU at 24 h (untreated control), confirming successful colonization. Mice were treated 2 h after infection with vehicle, TXA11114 (fixed 30 mg/kg, IV, Q6H), levofloxacin alone (10, 15, and 20 mg/kg, SC, Q6H) or in combination for 24 h. CFU/thigh was determined at 24 h after infection. Relative changes in CFU with treatment to baseline were plotted. Five mice were used per group. Tukey’s multiple comparisons test was used after an ANOVA to determine which specific pairs of group means were statistically different. * p < 0.05; † p < 0.01 (vs. control). ( B ) In vivo efficacy of TXA11114 /levofloxacin in murine lung model. In the lung infection model, mice were inoculated intranasally with 4.83 log 10 CFU of P. aeruginosa ATCC 27853. Pretreatment bacterial load in lung was 4.59 log 10 CFU/lung determined 2 h. after infection (baseline). Bacterial load was increased to 8.89 log 10 CFU at 24 h post-infection in the untreated control set. Mice for each group were treated with vehicle, TXA11114 (30 mg/kg, IV, Q6H), levofloxacin alone (30 mg/kg, SC, Q6H) or in combination for 24 h. Post-treatment, bacterial lung burden was determined 24 h after infection and changes in bacterial counts are represented relative to baseline. Data are represented as the mean ± standard deviation (SD), within an experimental group. A p value < 0.05 was considered statistically significant. Five mice were used per group. Tukey’s multiple comparisons test was used after an ANOVA to determine which specific pairs of group means were statistically different.
Article Snippet: Type strain P. aeruginosa ATCC 27853 cells were incubated with EtBr to allow for intracellular accumulation and treated with carbonyl cyanide 3-chlorophenylhydrazone (CCCP) to inhibit active efflux.
Techniques: In Vivo, Infection, Control, Standard Deviation