ArticleThe Journal of antimicrobial chemotherapy2025
The synergistic effect of the combination of polymyxin B and rifampicin in a murine neutropenic thigh infection model with E. coli and K. pneumoniae.
Article in The Journal of antimicrobial chemotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Recurrent mycotic aortic aneurysm withJournal of vascular surgery cases and innovative techniques · 2026Article
- Article
- Development of polymyxin- and aminoglycoside-based outer membrane permeabilizers: a review.Frontiers in microbiology · 2025Review
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Authors and funding
8 authors.
Funding
Abstract
backgroundAntibiotic 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.
methodsThe 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 interactions between polymyxin B and rifampicin were assessed using Loewe additivity and Bliss independence in both an E. coli and a K. pneumoniae strain.
resultsRifampicin monotherapy resulted in a static effect in E. coli but not against K. pneumoniae. When combined with polymyxin B, rifampicin fAUC/MIC needed for stasis, 1 log10 and 2 log10 kill effect decreased with increasing polymyxin B exposures for all strains. Synergy was confirmed in Loewe additivity (interaction indices 0.11-0.51 for E. coli and 0.04-0.19 for K. pneumoniae) and Bliss independence (267% and 863%). Maximal killing (>2 log10 kill) in combination therapy was found at rifampicin/polymyxin B fAUC/MIC of 0.68/32.56 for E. coli and 0.169/16.28 for K. pneumoniae.
conclusionsThese in vivo studies confirmed that there is a clear synergistic effect between polymyxin B and rifampicin, which was stronger for the K. pneumoniae strain than for the E. coli strain.
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