Combination therapy strategies against multidrug resistant bacteria <i>in vitro</i> and <i>in vivo</i>

Exploring effective combination antibacterial therapies has become a research focus. This study selected seven common antibiotics to perform a series of tests on different Gram-negative bacteria isolated from clinical samples of chronic obstructive pulmonary disease patients. More than 70% of the strains exhibited multidrug resistance but remained sensitive to polymyxin B. The checkerboard assay revealed a significant synergistic effect between polymyxin B and tetracycline against different resistant strains, with fractional inhibitory concentration index values consistently below 0.5. Further time-kill curve analysis demonstrated that the use of minimal inhibit concentration of polymyxin B or tetracycline alone had limited bactericidal effects, while their combination significantly reduced bacterial counts by 2-3 log colony-forming units within 12 h. Additionally, the survival rate of larvae treated with the polymyxin B and tetracycline combination was significantly higher than that of the mono-therapy and untreated groups. In brief, this study demonstrates that the combination of polymyxin B and tetracycline exhibits potent antibacterial activity against multidrug resistant Gram-negative bacteria both in vitro and in vivo.