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      615. Pharmacodynamics (PD) of the Beta-Lactamase Inhibitor Xeruborbactam When Administered in Combination with Meropenem

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      Open Forum Infectious Diseases
      Oxford University Press (OUP)

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          Abstract

          Background

          Xeruborbactam (XERU) is a member of a new class of cyclic boronic acid β-lactamase inhibitors with inhibitory activity against major members of Class A, B, C, and D beta-lactamases. The purpose of these studies was to determine the pharmacodynamic parameter that best described the activity of XERU against Enterobacterales and A. baumannii when administered in combination with a fixed dosage regimen of meropenem in the neutropenic mouse thigh infection model.

          24h Free Xeruborbactam AUC vs CRE

          24h Free Xeruborbactam AUC vs CRAB

          Methods

          Seven carbapenem resistant Enterobacterales (CRE) and six carbapenem-resistant A. baumannii (CRAB) isolates were used in these studies. Mice were rendered neutropenic, infected with ∼107 CFU/thigh and were treated with various doses of XERU in combination with meropenem (300 mg/kg q2h) by the IP route starting 2 hours post infection for 24 hours. The meropenem dosage regimen was fixed and designed to simulate 2 g every 8 hours by 3-hour infusion in humans. Plasma exposures (PK) were measured in neutropenic, infected mice. The relationship between XERU PK-PD indices and the reduction in the log number of CFU per thigh were analyzed by using the sigmoid Emax PD model.

          Results

          The activity of XERU was best described by the % 24h free XERU plasma concentrations exceeded 1 mg/L and 24h free xeru plasma AUC.

          Xeru PK-PD Parameters in Combination with Meropenem against CRE

          Xeru PK-PD Parameters in Combination with Meropenem against CRAB

          Conclusion

          The PK-PD of XERU was best described by the % 24h free XERU plasma concentrations exceeded 1 mg/L and 24h free XERU plasma AUC. The PK-PD of XERU in combination with meropenem and the clinical PK of both drugs support further clinical development for the treatment of carbapenem-resistant isolates of Enterobacterales and A. baumannii.

          Disclosures

          Ziad Tarazi, Qpex Biopharma: Employee Niki Roos, n/a, Qpex Biopharma: Employee Ted Page, n/a, Qpex Biopharma: Employee David Griffith, n/a, Qpex Biopharma: Employee.

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          Author and article information

          Journal
          Open Forum Infectious Diseases
          Oxford University Press (OUP)
          2328-8957
          December 01 2022
          December 15 2022
          December 01 2022
          December 15 2022
          December 15 2022
          : 9
          : Supplement_2
          Article
          10.1093/ofid/ofac492.667
          74d2036f-1cdf-4fd5-972f-ac2f1a25f99d
          © 2022

          https://creativecommons.org/licenses/by/4.0/

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