Effect of increasing meropenem MIC on the killing activity of meropenem in combination with amikacin or polymyxin B against MBL- and KPC-producing Enterobacter cloacae

Brandon Kulengowski; W. Cliff Rutter; Jeffrey J. Campion; Grace C. Lee; David J. Feola; David S. Burgess

doi:10.1016/j.diagmicrobio.2018.06.013

Effect of increasing meropenem MIC on the killing activity of meropenem in combination with amikacin or polymyxin B against MBL- and KPC-producing Enterobacter cloacae

Brandon Kulengowski, W. Cliff Rutter, Jeffrey J. Campion, Grace C. Lee, David J. Feola, David S. Burgess

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

24 Scopus citations

Abstract

Carbapenem resistant Enterobacteriaceae (CRE) are a growing threat worldwide. Infections caused by these organisms have exhibited high rates of mortality (50%) for which there is no standard of care and a dearth of clinical trials. Most in vitro data on CRE focus on Klebsiella pneumoniae, but it is known that effective therapy may depend on species or even strain. To address this, meropenem, amikacin, and polymyxin B alone and in combination were evaluated by time kill against four carbapenem-producing Enterobacter cloacae clinical isolates representing a range of meropenem nonsusceptibility (2–32 mg/L) and resistance mechanisms (KPC 2 and/or VIM 1). As meropenem minimum inhibitory concentration (MIC) increased, bactericidal activity and synergy were maintained for 48 hours in isolates exposed to meropenem and amikacin, but synergy and bactericidal activity were not maintained in all isolates exposed to meropenem and polymyxin B.

Original language	English
Pages (from-to)	262-266
Number of pages	5
Journal	Diagnostic Microbiology and Infectious Disease
Volume	92
Issue number	3
DOIs	https://doi.org/10.1016/j.diagmicrobio.2018.06.013
State	Published - Nov 2018

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Inc.

Funding

We thank Cynthia Mattingly for excellent technical assistance. We thank Dr. Sylvie Garneau-Tsodikova for her expertise in understanding aminoglycoside resistance genes. This material is, in part, the result of work supported with resources and use of facilities at the Lexington, KY VA Medical Center. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declarations of interest: none

Funders	Funder number
Durham VA Medical Center

Keywords

Amikacin
Carbapenem resistant Enterobacteriaceae
Meropenem
Polymyxin B
Time kill

ASJC Scopus subject areas

Microbiology (medical)
Infectious Diseases

UN SDGs

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

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10.1016/j.diagmicrobio.2018.06.013

Cite this

Kulengowski, B., Rutter, W. C., Campion, J. J., Lee, G. C., Feola, D. J., & Burgess, D. S. (2018). Effect of increasing meropenem MIC on the killing activity of meropenem in combination with amikacin or polymyxin B against MBL- and KPC-producing Enterobacter cloacae. Diagnostic Microbiology and Infectious Disease, 92(3), 262-266. https://doi.org/10.1016/j.diagmicrobio.2018.06.013

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title = "Effect of increasing meropenem MIC on the killing activity of meropenem in combination with amikacin or polymyxin B against MBL- and KPC-producing Enterobacter cloacae",

abstract = "Carbapenem resistant Enterobacteriaceae (CRE) are a growing threat worldwide. Infections caused by these organisms have exhibited high rates of mortality (50\%) for which there is no standard of care and a dearth of clinical trials. Most in vitro data on CRE focus on Klebsiella pneumoniae, but it is known that effective therapy may depend on species or even strain. To address this, meropenem, amikacin, and polymyxin B alone and in combination were evaluated by time kill against four carbapenem-producing Enterobacter cloacae clinical isolates representing a range of meropenem nonsusceptibility (2–32 mg/L) and resistance mechanisms (KPC 2 and/or VIM 1). As meropenem minimum inhibitory concentration (MIC) increased, bactericidal activity and synergy were maintained for 48 hours in isolates exposed to meropenem and amikacin, but synergy and bactericidal activity were not maintained in all isolates exposed to meropenem and polymyxin B.",

keywords = "Amikacin, Carbapenem resistant Enterobacteriaceae, Meropenem, Polymyxin B, Time kill",

author = "Brandon Kulengowski and Rutter, \{W. Cliff\} and Campion, \{Jeffrey J.\} and Lee, \{Grace C.\} and Feola, \{David J.\} and Burgess, \{David S.\}",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2018",

month = nov,

doi = "10.1016/j.diagmicrobio.2018.06.013",

language = "English",

volume = "92",

pages = "262--266",

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}

Kulengowski, B, Rutter, WC, Campion, JJ, Lee, GC, Feola, DJ & Burgess, DS 2018, 'Effect of increasing meropenem MIC on the killing activity of meropenem in combination with amikacin or polymyxin B against MBL- and KPC-producing Enterobacter cloacae', Diagnostic Microbiology and Infectious Disease, vol. 92, no. 3, pp. 262-266. https://doi.org/10.1016/j.diagmicrobio.2018.06.013

Effect of increasing meropenem MIC on the killing activity of meropenem in combination with amikacin or polymyxin B against MBL- and KPC-producing Enterobacter cloacae. / Kulengowski, Brandon; Rutter, W. Cliff; Campion, Jeffrey J. et al.
In: Diagnostic Microbiology and Infectious Disease, Vol. 92, No. 3, 11.2018, p. 262-266.

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

TY - JOUR

T1 - Effect of increasing meropenem MIC on the killing activity of meropenem in combination with amikacin or polymyxin B against MBL- and KPC-producing Enterobacter cloacae

AU - Kulengowski, Brandon

AU - Rutter, W. Cliff

AU - Campion, Jeffrey J.

AU - Lee, Grace C.

AU - Feola, David J.

AU - Burgess, David S.

PY - 2018/11

Y1 - 2018/11

N2 - Carbapenem resistant Enterobacteriaceae (CRE) are a growing threat worldwide. Infections caused by these organisms have exhibited high rates of mortality (50%) for which there is no standard of care and a dearth of clinical trials. Most in vitro data on CRE focus on Klebsiella pneumoniae, but it is known that effective therapy may depend on species or even strain. To address this, meropenem, amikacin, and polymyxin B alone and in combination were evaluated by time kill against four carbapenem-producing Enterobacter cloacae clinical isolates representing a range of meropenem nonsusceptibility (2–32 mg/L) and resistance mechanisms (KPC 2 and/or VIM 1). As meropenem minimum inhibitory concentration (MIC) increased, bactericidal activity and synergy were maintained for 48 hours in isolates exposed to meropenem and amikacin, but synergy and bactericidal activity were not maintained in all isolates exposed to meropenem and polymyxin B.

AB - Carbapenem resistant Enterobacteriaceae (CRE) are a growing threat worldwide. Infections caused by these organisms have exhibited high rates of mortality (50%) for which there is no standard of care and a dearth of clinical trials. Most in vitro data on CRE focus on Klebsiella pneumoniae, but it is known that effective therapy may depend on species or even strain. To address this, meropenem, amikacin, and polymyxin B alone and in combination were evaluated by time kill against four carbapenem-producing Enterobacter cloacae clinical isolates representing a range of meropenem nonsusceptibility (2–32 mg/L) and resistance mechanisms (KPC 2 and/or VIM 1). As meropenem minimum inhibitory concentration (MIC) increased, bactericidal activity and synergy were maintained for 48 hours in isolates exposed to meropenem and amikacin, but synergy and bactericidal activity were not maintained in all isolates exposed to meropenem and polymyxin B.

KW - Amikacin

KW - Carbapenem resistant Enterobacteriaceae

KW - Meropenem

KW - Polymyxin B

KW - Time kill

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JF - Diagnostic Microbiology and Infectious Disease

IS - 3

ER -

Effect of increasing meropenem MIC on the killing activity of meropenem in combination with amikacin or polymyxin B against MBL- and KPC-producing Enterobacter cloacae

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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