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

doi:10.1128/AAC.02053-17

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 journal › Article › Research › peer-review

9 Citations (Scopus)

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, ∼10^7.2 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 language	English
Article number	e02053-17
Number of pages	8
Journal	Antimicrobial Agents and Chemotherapy
Volume	62
Issue number	4
DOIs	https://doi.org/10.1128/AAC.02053-17
Publication status	Published - 1 Apr 2018

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1128/AAC.02053-17

247901350-oaFinal published version, 1.55 MB

Cite this

Landersdorfer, C. B., Yadav, R., Rogers, K. E., Kim, T. H., Shin, B. S., Boyce, J. D., Nation, R. L., & Bulitta, J. B. (2018). Combating Carbapenem-Resistant Acinetobacter baumannii by an Optimized Imipenem-plus-Tobramycin Dosage Regimen: Prospective Validation via Hollow-Fiber Infection and Mathematical Modeling. Antimicrobial Agents and Chemotherapy, 62(4), Article e02053-17. https://doi.org/10.1128/AAC.02053-17

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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.}",

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Landersdorfer, CB, Yadav, R, Rogers, KE, Kim, TH, Shin, BS, Boyce, JD , Nation, RL & Bulitta, JB 2018, 'Combating Carbapenem-Resistant Acinetobacter baumannii by an Optimized Imipenem-plus-Tobramycin Dosage Regimen: Prospective Validation via Hollow-Fiber Infection and Mathematical Modeling', Antimicrobial Agents and Chemotherapy, vol. 62, no. 4, e02053-17. https://doi.org/10.1128/AAC.02053-17

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

Research output: Contribution to journal › Article › Research › peer-review

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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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KW - Pharmacodynamics

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KW - Synergy

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ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Targeting hypermutable 'superbugs' in chronic respiratory infections by optimised antibiotic combination dosage regimens

Targeting bacterial 'superbugs' by innovative combination dosing strategies and new antibiotics

Combating bacterial 'superbugs' by innovative antibiotic combination strategies

Cite this

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

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Projects

Targeting hypermutable 'superbugs' in chronic respiratory infections by optimised antibiotic combination dosage regimens

Targeting bacterial 'superbugs' by innovative combination dosing strategies and new antibiotics

Combating bacterial 'superbugs' by innovative antibiotic combination strategies

Cite this