Use of Tamoxifen Derivatives in Combination with Colistin against Colistin-Resistant Acinetobacter baumannii

Drug repurposing has led to the identification of tamoxifen, a well-known chemotherapy drug, as a compound with relevant antibacterial properties. In this field, the development of new tamoxifen derivatives with antimicrobial activity, particularly against colistin-resistant , represents an important area of research. We evaluated the MICs of 22 and 3 tamoxifen derivatives against wild-type and colistin-resistant A. baumannii strains, respectively, using microdilution assays, either as monotherapy or in combination with colistin. While all derivatives showed MIC values above 64 mg/L when tested as monotherapy, combining derivatives 1, 14, and 18 with colistin reduced tamoxifen derivatives' MICs to 0.125-2 mg/L for the reference strain ATCC 17978 and to 0.5-1 mg/L for the colistin-resistant Ab22 strain. Growth assays showed that these derivatives delayed Ab22 proliferation during the first 4 h. Moreover, these derivatives increased membrane permeabilization without altering the expression of the outer membrane proteins (OMPs). These findings suggest that tamoxifen derivatives in combination with colistin exhibit antibacterial activity against a colistin-resistant A. baumannii, potentially broadening the spectrum of available drug treatments for combating MDR A. baumannii.