Combating Carbapenem-Resistant Acinetobacter baumannii by an Optimized Imipenem-plus-Tobramycin Dosage Regimen: Prospective Validation via Hollow-Fiber Infection and Mathematical Modeling

Cornelia B. Landersdorfer, Rajbharan Yadav, Kate E. Rogers, Tae Hwan Kim, Beom Soo Shin, John D. Boyce, Roger L. Nation, Jürgen B. Bulitta

Research output: Contribution to journalArticleResearchpeer-review

Abstract

We aimed to prospectively validate an optimized combination dosage regimen against a clinical carbapenem-resistant Acinetobacter baumannii (CRAB) isolate (imipenem MIC, 32 mg/liter; tobramycin MIC, 2 mg/liter). Imipenem at constant concentrations (7.6, 13.4, and 23.3 mg/liter, reflecting a range of clearances) was simulated in a 7-day hollow-fiber infection model (inoculum, ∼107.2 CFU/ml) with and without tobramycin (7 mg/kg q24h, 0.5-h infusions). While monotherapies achieved no killing or failed by 24 h, this rationally optimized combination achieved >5 log10 bacterial killing and suppressed resistance.

Original languageEnglish
Article numbere02053-17
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume62
Issue number4
DOIs
Publication statusPublished - 1 Apr 2018

Keywords

  • Acinetobacter baumannii
  • Carbapenem resistance
  • Dynamic hollow-fiber infection model
  • Mathematical modeling
  • Mechanism based
  • Mechanistic
  • Pharmacodynamics
  • Pharmacokinetics
  • Synergy

Cite this

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title = "Combating Carbapenem-Resistant Acinetobacter baumannii by an Optimized Imipenem-plus-Tobramycin Dosage Regimen: Prospective Validation via Hollow-Fiber Infection and Mathematical Modeling",
abstract = "We aimed to prospectively validate an optimized combination dosage regimen against a clinical carbapenem-resistant Acinetobacter baumannii (CRAB) isolate (imipenem MIC, 32 mg/liter; tobramycin MIC, 2 mg/liter). Imipenem at constant concentrations (7.6, 13.4, and 23.3 mg/liter, reflecting a range of clearances) was simulated in a 7-day hollow-fiber infection model (inoculum, ∼107.2 CFU/ml) with and without tobramycin (7 mg/kg q24h, 0.5-h infusions). While monotherapies achieved no killing or failed by 24 h, this rationally optimized combination achieved >5 log10 bacterial killing and suppressed resistance.",
keywords = "Acinetobacter baumannii, Carbapenem resistance, Dynamic hollow-fiber infection model, Mathematical modeling, Mechanism based, Mechanistic, Pharmacodynamics, Pharmacokinetics, Synergy",
author = "Landersdorfer, {Cornelia B.} and Rajbharan Yadav and Rogers, {Kate E.} and Kim, {Tae Hwan} and Shin, {Beom Soo} and Boyce, {John D.} and Nation, {Roger L.} and Bulitta, {J{\"u}rgen B.}",
year = "2018",
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language = "English",
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journal = "Antimicrobial Agents and Chemotherapy",
issn = "1098-6596",
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Combating Carbapenem-Resistant Acinetobacter baumannii by an Optimized Imipenem-plus-Tobramycin Dosage Regimen : Prospective Validation via Hollow-Fiber Infection and Mathematical Modeling. / Landersdorfer, Cornelia B.; Yadav, Rajbharan; Rogers, Kate E.; Kim, Tae Hwan; Shin, Beom Soo; Boyce, John D.; Nation, Roger L.; Bulitta, Jürgen B.

In: Antimicrobial Agents and Chemotherapy, Vol. 62, No. 4, e02053-17, 01.04.2018.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Combating Carbapenem-Resistant Acinetobacter baumannii by an Optimized Imipenem-plus-Tobramycin Dosage Regimen

T2 - Prospective Validation via Hollow-Fiber Infection and Mathematical Modeling

AU - Landersdorfer, Cornelia B.

AU - Yadav, Rajbharan

AU - Rogers, Kate E.

AU - Kim, Tae Hwan

AU - Shin, Beom Soo

AU - Boyce, John D.

AU - Nation, Roger L.

AU - Bulitta, Jürgen B.

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Y1 - 2018/4/1

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KW - Mathematical modeling

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KW - Synergy

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