biostudies-literatureUnknown80(5)Van Den Berg Sthe Joint Programming Initiative on Antimicrobial Resistance (JPIAMR)ZonMwthe Joint Programming Initiative on Antimicrobial Resistance<h4>Background</h4>Antibiotic combination therapy is increasingly used to treat MDR pathogens. In vitro studies suggest that the polymyxin B/rifampicin combination might be synergistic. Therefore, the pharmacodynamics of rifampicin as monotherapy and combined with polymyxin B were studied in Escherichia coli- and Klebsiella pneumoniae-infected mice.<h4>Methods</h4>The rifampicin pharmacokinetics (oral doses 0.5-64 mg/kg) in murine plasma were studied to estimate the exposures to rifampicin. These exposures were subsequently correlated with the antibacterial effect in a sigmoid maximum-effect model. The minimum exposures needed for a static, 1 log10 and 2 log10 kill effect in two E. coli and two K. pneumoniae strains were determined for monotherapy and the combination. The pharmacodynamic iThe Journal of antimicrobial chemotherapy1248-1255https://www.ebi.ac.uk/biostudies/studies/S-EPMC12046403biostudies-literatureThe synergistic effect of the combination of polymyxin B and rifampicin in a murine neutropenic thigh infection model with E. coli and K. pneumoniae.PMC12046403Marchand STen Kate MTMuller AESassen SDTCouet WMeletiadis JVan Den Berg SVan Der Spek HfalseThe synergistic effect of the combination of polymyxin B and rifampicin in a murine neutropenic thigh infection model with E. coli and K. pneumoniae.<h4>Background</h4>Antibiotic combination therapy is increasingly used to treat MDR pathogens. In vitro studies suggest that the polymyxin B/rifampicin combination might be synergistic. Therefore, the pharmacodynamics of rifampicin as monotherapy and combined with polymyxin B were studied in Escherichia coli- and Klebsiella pneumoniae-infected mice.<h4>Methods</h4>The rifampicin pharmacokinetics (oral doses 0.5-64 mg/kg) in murine plasma were studied to estimate the exposures to rifampicin. These exposures were subsequently correlated with the antibacterial effect in a sigmoid maximum-effect model. The minimum exposures needed for a static, 1 log10 and 2 log10 kill effect in two E. coli and two K. pneumoniae strains were determined for monotherapy and the combination. The pharmacodynamic i2025-01-01T00:00:00Z2025 May2025-07-08T03:10:56.559Z2025-07-08T03:10:56.559ZS-EPMC120464034003626010.1093/jac/dkaf056