Colistin-sparing regimens against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae isolates

Combination of tigecycline or doxycycline and gentamicin or amikacin

Hung Jen Tang, Chih Cheng Lai, Chi Chung Chen, Chun Cheng Zhang, Tzu Chieh Weng, Yu Hsin Chiu, Han Siong Toh, Shyh Ren Chiang, Wen Liang Yu, Wen Chien Ko, Yin Ching Chuang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background/Purpose: In vitro studies of the combination of an aminoglycoside with tigecycline or doxycycline against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates are rarely published. The goal of this study was to evaluate the antibacterial activity of the combination regimens. Methods: Thirteen genetically different KPC-producing K. pneumoniae isolates were randomly selected. Drug concentrations of amikacin, gentamicin, tigecycline, and doxycycline were adjusted to 1-, 1/2-, and 1/4-fold of respective minimum inhibitory concentrations (MICs). Each drug alone or the combinations of amikacin or gentamicin with tigecycline or doxycycline were tested by combination studies. Results: Treatment with the 1× MIC concentration in combinations of amikacin or gentamicin and tigecycline or doxycycline for 24 hours resulted in bactericidal activity of 84-100% in the isolates. Treatment with 1/2× MIC combinations resulted in synergism of 69-100% in the isolates. Notably, doxycycline plus gentamicin or amikacin was synergistic for all tested isolates. However, bactericidal or synergistic effect was barely evident following 1/4× MIC combinations. There was no antagonism in any of the combination regimens. Conclusion: Enhanced activity was noted following treatment with doxycycline combined with gentamicin or amikacin against KPC-producing K. pneumoniae isolates, warranting further in vitro and animal investigations before clinical application.

Original languageEnglish
Pages (from-to)273-281
JournalJournal of Microbiology, Immunology and Infection
Volume52
Issue number2
DOIs
Publication statusPublished - Apr 1 2019
Externally publishedYes

Fingerprint

Colistin
Amikacin
Doxycycline
Klebsiella pneumoniae
Gentamicins
Microbial Sensitivity Tests
Aminoglycosides
Pharmaceutical Preparations
tigecycline
carbapenemase

Keywords

  • Aminoglycoside
  • Doxycycline
  • KPC
  • Synergism
  • Tigecycline

ASJC Scopus subject areas

  • Microbiology (medical)
  • Immunology and Allergy
  • Immunology and Microbiology(all)
  • Infectious Diseases

Cite this

Colistin-sparing regimens against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae isolates : Combination of tigecycline or doxycycline and gentamicin or amikacin. / Tang, Hung Jen; Lai, Chih Cheng; Chen, Chi Chung; Zhang, Chun Cheng; Weng, Tzu Chieh; Chiu, Yu Hsin; Toh, Han Siong; Chiang, Shyh Ren; Yu, Wen Liang; Ko, Wen Chien; Chuang, Yin Ching.

In: Journal of Microbiology, Immunology and Infection, Vol. 52, No. 2, 01.04.2019, p. 273-281.

Research output: Contribution to journalArticle

Tang, Hung Jen ; Lai, Chih Cheng ; Chen, Chi Chung ; Zhang, Chun Cheng ; Weng, Tzu Chieh ; Chiu, Yu Hsin ; Toh, Han Siong ; Chiang, Shyh Ren ; Yu, Wen Liang ; Ko, Wen Chien ; Chuang, Yin Ching. / Colistin-sparing regimens against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae isolates : Combination of tigecycline or doxycycline and gentamicin or amikacin. In: Journal of Microbiology, Immunology and Infection. 2019 ; Vol. 52, No. 2. pp. 273-281.
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abstract = "Background/Purpose: In vitro studies of the combination of an aminoglycoside with tigecycline or doxycycline against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates are rarely published. The goal of this study was to evaluate the antibacterial activity of the combination regimens. Methods: Thirteen genetically different KPC-producing K. pneumoniae isolates were randomly selected. Drug concentrations of amikacin, gentamicin, tigecycline, and doxycycline were adjusted to 1-, 1/2-, and 1/4-fold of respective minimum inhibitory concentrations (MICs). Each drug alone or the combinations of amikacin or gentamicin with tigecycline or doxycycline were tested by combination studies. Results: Treatment with the 1× MIC concentration in combinations of amikacin or gentamicin and tigecycline or doxycycline for 24 hours resulted in bactericidal activity of 84-100{\%} in the isolates. Treatment with 1/2× MIC combinations resulted in synergism of 69-100{\%} in the isolates. Notably, doxycycline plus gentamicin or amikacin was synergistic for all tested isolates. However, bactericidal or synergistic effect was barely evident following 1/4× MIC combinations. There was no antagonism in any of the combination regimens. Conclusion: Enhanced activity was noted following treatment with doxycycline combined with gentamicin or amikacin against KPC-producing K. pneumoniae isolates, warranting further in vitro and animal investigations before clinical application.",
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T1 - Colistin-sparing regimens against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae isolates

T2 - Combination of tigecycline or doxycycline and gentamicin or amikacin

AU - Tang, Hung Jen

AU - Lai, Chih Cheng

AU - Chen, Chi Chung

AU - Zhang, Chun Cheng

AU - Weng, Tzu Chieh

AU - Chiu, Yu Hsin

AU - Toh, Han Siong

AU - Chiang, Shyh Ren

AU - Yu, Wen Liang

AU - Ko, Wen Chien

AU - Chuang, Yin Ching

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Background/Purpose: In vitro studies of the combination of an aminoglycoside with tigecycline or doxycycline against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates are rarely published. The goal of this study was to evaluate the antibacterial activity of the combination regimens. Methods: Thirteen genetically different KPC-producing K. pneumoniae isolates were randomly selected. Drug concentrations of amikacin, gentamicin, tigecycline, and doxycycline were adjusted to 1-, 1/2-, and 1/4-fold of respective minimum inhibitory concentrations (MICs). Each drug alone or the combinations of amikacin or gentamicin with tigecycline or doxycycline were tested by combination studies. Results: Treatment with the 1× MIC concentration in combinations of amikacin or gentamicin and tigecycline or doxycycline for 24 hours resulted in bactericidal activity of 84-100% in the isolates. Treatment with 1/2× MIC combinations resulted in synergism of 69-100% in the isolates. Notably, doxycycline plus gentamicin or amikacin was synergistic for all tested isolates. However, bactericidal or synergistic effect was barely evident following 1/4× MIC combinations. There was no antagonism in any of the combination regimens. Conclusion: Enhanced activity was noted following treatment with doxycycline combined with gentamicin or amikacin against KPC-producing K. pneumoniae isolates, warranting further in vitro and animal investigations before clinical application.

AB - Background/Purpose: In vitro studies of the combination of an aminoglycoside with tigecycline or doxycycline against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates are rarely published. The goal of this study was to evaluate the antibacterial activity of the combination regimens. Methods: Thirteen genetically different KPC-producing K. pneumoniae isolates were randomly selected. Drug concentrations of amikacin, gentamicin, tigecycline, and doxycycline were adjusted to 1-, 1/2-, and 1/4-fold of respective minimum inhibitory concentrations (MICs). Each drug alone or the combinations of amikacin or gentamicin with tigecycline or doxycycline were tested by combination studies. Results: Treatment with the 1× MIC concentration in combinations of amikacin or gentamicin and tigecycline or doxycycline for 24 hours resulted in bactericidal activity of 84-100% in the isolates. Treatment with 1/2× MIC combinations resulted in synergism of 69-100% in the isolates. Notably, doxycycline plus gentamicin or amikacin was synergistic for all tested isolates. However, bactericidal or synergistic effect was barely evident following 1/4× MIC combinations. There was no antagonism in any of the combination regimens. Conclusion: Enhanced activity was noted following treatment with doxycycline combined with gentamicin or amikacin against KPC-producing K. pneumoniae isolates, warranting further in vitro and animal investigations before clinical application.

KW - Aminoglycoside

KW - Doxycycline

KW - KPC

KW - Synergism

KW - Tigecycline

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