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In vitro microdialysis membrane efficiency of broad-spectrum antibiotics in combination and alone

Authors MacVane SH, Housman ST, Nicolau DP

Received 2 April 2014

Accepted for publication 16 April 2014

Published 5 June 2014 Volume 2014:6 Pages 97—101

DOI https://doi.org/10.2147/CPAA.S65389

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Shawn H MacVane,1 Seth T Housman,1 David P Nicolau1,2

1Center for Anti-Infective Research and Development, 2Division of Infectious Diseases, Hartford Hospital, Hartford, CT, USA

Purpose: Microdialysis is a valuable technique for studying the distribution of drugs into interstitial fluid, the target site for a pharmacologic effect. Due to incomplete equilibrium, retrodialysis is a method used to correct for relative recovery. The impact of two-drug combinations on probe recovery, however, remains unknown.
Methods: In vitro microdialysis was conducted for five antibiotics (avibactam, cefepime, ceftaroline, piperacillin-tazobactam, and vancomycin), representing three empiric antimicrobial regimens, to assess the impact of two-drug combinations on probe recovery. Recoveries were compared between single and two-drug treatments.
Results: Recoveries by gain and loss were linear with their molecular weight. During all gain experiments, recoveries were similar when tested alone or in combination with another antibiotic. Unacceptable differences in recovery by loss were observed for cefepime in the presence of vancomycin (-21%) and vancomycin in the presence of piperacillin-tazobactam (-22%).
Conclusion: Differences among in vitro recovery by loss suggest two-drug combinations may impact dialysate recovery during in vivo retrodialysis procedures, particularly when larger molecular weight drugs (ie, vancomycin) are involved. Importantly, there were no differences during gain experiments. In vitro studies, as performed here, should be conducted for each potential two-drug combination, prior to their combined use for in vivo retrodialysis.

Keywords: microdialysis, retrodialysis, combination therapy

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