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Meropenem Dosage Regimen of Suppression Resistance Acinetobacter Baumannii Based on MPC

Author: WangLin
Tutor: LiuWei
School: Central South University
Course: Clinical
Keywords: Acinetobacter baumannii Meropenem Mutant preventionconcentration In vitro Pharmacoknetics/Pharmacodynamics model
CLC: R96
Type: Master's thesis
Year: 2013
Downloads: 16
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Abstract

Objective:Investigated the bactericidal activity of meropenem and its propensity to suppress Acinetobacter baumannii resistance in an in vitro hollow-fiber infection model. To determine the regimens of meropenem that can suppress the resistance of Acinetobacter baumannii in vitro.Method:One strains of Acinetobacter baumannii45791(MIC2ug/mL MPC32ug/mL). An HFIM inoculated with approximately2～3×109cfu/mL of bacteria was subjected to four various meropenem exposure: meropenem1.0g q8h as a0.5h infusion,1.0g q8h as a3h infusion,2.0g q8h as a0.5h infusion,2.0g q8h as a3h infusion. The experiment was conducted for7days. Serial samples were obtained over7days to quantify the meropenem concentrations. A high performance liquid chromatography method was used to determine meropenem concentrations. At0,24,48,72,96,120,144,168h bacterial samples was obtained to qualify the total bacterial population, and subpopulations with reduced susceptibilities.Results:For both meropenem2.0g q8h as a0.5h infusion and2.0g q8h as a3h infusion,a significant bacterial burden reduction (103cfu/mL) was seen individually at24h and48h;For both regimens bacterial burden reduced to103cfu/mL at120h and the subpopulations with reduced susceptibilities to meropenem were cleared at24h. For both meropenem1.0g q8h as a0.5h infusion and1.0g q8h as a3h infusion,a significant bacterial burden reduction (103cfu/mL) were seen individually at72h and48h; Then bacterial burden sustained higher than106cfu/mL;The subpopulations with reduced susceptibilities to meropenem regrowth individually at72h and24h and both to106cfu/mL at168h.Conclusion:The results suggest that the meropenem regimens dose2.0g q8h as a0.5h infusion and2.0g q8h as a3h infusion can not only kill the susceptible Acinetobacter baumannii but also suppress the Acinetobacter baumannii(MIC2ug/mL) resistance. The regimen of meropenem2.030min infusion can kill the susceptible Acinetobacter baumannii and suppress the resistance of Acinetobacter baumannii in vitro. Our data support2.0g q8h as a0.5h infusion and2.0g q8h as a3h infusion meropenem exposure for treatment of sever clinical Acinetobacter baumannii infection.%T> MPC≥18.75might be a PK/PD parameter of meropenem to suppress resistance of Acinetobacter baumannii.

Meropenem Dosage Regimen of Suppression Resistance Acinetobacter Baumannii Based on MPC

Abstract

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