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Experimental Therapeutics

Efficacy of Apramycin against Multidrug-Resistant Acinetobacter baumannii in the Murine Neutropenic Thigh Model

Anthony D. Kang, Kenneth P. Smith, Anders H. Berg, Katherine A. Truelson, George M. Eliopoulos, Christopher McCoy, James E. Kirby
Anthony D. Kang
aDepartment of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
eUnited States Army Medical Department Center and School, Fort Sam Houston, Texas, USA
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Kenneth P. Smith
aDepartment of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
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Anders H. Berg
aDepartment of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
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Katherine A. Truelson
aDepartment of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
dBoston University, Boston, Massachusetts, USA
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George M. Eliopoulos
bDivision of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
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Christopher McCoy
cDepartment of Pharmacy, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
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James E. Kirby
aDepartment of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
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DOI: 10.1128/AAC.02585-17
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ABSTRACT

Apramycin, an aminocyclitol aminoglycoside, was rapidly bactericidal against Acinetobacter baumannii. In a neutropenic murine thigh infection model, treatment-associated A. baumannii CFU reductions of >4 log10 per thigh were observed for all exposures for which area under the curve (AUC)/MIC ratio was >50 and maximum concentration of drug in serum (Cmax)/MIC was ≈10 or higher. Based on these findings, we suggest that apramycin deserves further preclinical exploration as a repurposed therapeutic for multidrug-resistant Gram-negative pathogens, including A. baumannii.

FOOTNOTES

    • Received 19 December 2017.
    • Returned for modification 8 January 2018.
    • Accepted 11 January 2018.
    • Accepted manuscript posted online 16 January 2018.
  • Supplemental material for this article may be found at https://doi.org/10.1128/AAC.02585-17.

  • Copyright © 2018 American Society for Microbiology.

All Rights Reserved.

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Efficacy of Apramycin against Multidrug-Resistant Acinetobacter baumannii in the Murine Neutropenic Thigh Model
Anthony D. Kang, Kenneth P. Smith, Anders H. Berg, Katherine A. Truelson, George M. Eliopoulos, Christopher McCoy, James E. Kirby
Antimicrobial Agents and Chemotherapy Mar 2018, 62 (4) e02585-17; DOI: 10.1128/AAC.02585-17

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Efficacy of Apramycin against Multidrug-Resistant Acinetobacter baumannii in the Murine Neutropenic Thigh Model
Anthony D. Kang, Kenneth P. Smith, Anders H. Berg, Katherine A. Truelson, George M. Eliopoulos, Christopher McCoy, James E. Kirby
Antimicrobial Agents and Chemotherapy Mar 2018, 62 (4) e02585-17; DOI: 10.1128/AAC.02585-17
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KEYWORDS

antimicrobial
apramycin
maximum tolerated dose
mouse thigh model
pharmacodynamics
pharmacokinetics
resistance
time-kill

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