ArticleThe Journal of antimicrobial chemotherapy2026
The pharmacodynamics of polymyxin B in Acinetobacter baumannii in murine thigh and lung infection models.
Article in The Journal of antimicrobial chemotherapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesPolymyxin B has been used for many years to treat Acinetobacter baumannii, but little is known about its pharmacodynamics (PD). We aimed to describe the PD of polymyxin B in treating A. baumannii infections.
methodsUsing the murine neutropenic thigh and lung infection models we determined the magnitude of the pharmacokinetic (PK)/PD index correlating with efficacy for eight A. baumannii strains. PD was analysed using the Emax model to determine PD targets. Using published human PK data the PTAs were calculated.
resultsIn the thigh infection model, stasis, 1-log10 and 2-log10 kill were reached for all strains. Median (range) fAUC/MIC (area under the unbound concentration-time curve divided by the MIC) targets for stasis, 1-log10 kill and 2-log10 kill were 2.1 (1.0-11), 2.9 (1.0-15) and 4.0 (1.1-20), respectively. In contrast, in the lung model, 2-log10 kill was reached in 2/8 strains only, and there was insufficient killing at tolerated exposures to determine PD fAUC/MIC targets. For the standard human dosing regimen, PTAs derived from the thigh model were inadequate at the USCAST (United States Committee on Antimicrobial Susceptibility Testing) clinical breakpoint and a protein binding of 90%.
conclusionsWhereas polymyxin B treatment had good efficacy in the murine thigh infection model, in the lung infection model its effect was limited. PD targets, with MICs of circulating A. baumannii isolates of ≤2 mg/L, are not reached with a standard human dosing regimen and will probably exceed threshold values for toxicity. These data suggest that the efficacy of polymyxin B as monotherapy for A. baumannii infections is questionable.
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