title: Colistin-sparing regimens against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae isolates: Combination of tigecycline or doxycycline and gentamicin or amikacin.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Tang
authors.affiliation: Department of Intensive Care Medicine, Chi Mei Medical Center, Liou Ying, Tainan, Taiwan.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Lai
authors.affiliation: Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; Institute of Biotechnology, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan.
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Zhang
authors.affiliation: Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Tzu-Chieh
authors.initials: TC
authors.lastname: Weng
authors.affiliation: Department of Medicine, Chi Mei Medical Center, Liou Ying, Tainan, Taiwan.
authors.forename: Yu-Hsin
authors.initials: YH
authors.lastname: Chiu
authors.affiliation: Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Han-Siong
authors.initials: HS
authors.lastname: Toh
authors.affiliation: Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Shyh-Ren
authors.initials: SR
authors.lastname: Chiang
authors.affiliation: Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Yu
authors.affiliation: Department of Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan. Electronic address: winston3415@gmail.com.
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Ko
authors.affiliation: Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; Department of Medicine, Chi Mei Medical Center, Liou Ying, Tainan, Taiwan. Electronic address: chuangkenneth@hotmail.com.
authors.forename: Yin-Ching
authors.initials: YC
authors.lastname: Chuang
mesh_terms: D000583:Amikacin / Q000494:pharmacology; D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D003091:Colistin / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000235:genetics; D004318:Doxycycline / Q000494:pharmacology; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D004357:Drug Synergism; D005838:Genotype; D005839:Gentamicins / Q000494:pharmacology; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D008826:Microbial Sensitivity Tests; D000078304:Tigecycline / Q000494:pharmacology; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004338:Drug Combinations; D005839:Gentamicins; D000078304:Tigecycline; D000583:Amikacin; D001618:beta-Lactamases; C063912:carbapenemase; D004318:Doxycycline; D003091:Colistin
keywords: KPC; aminoglycoside; doxycycline; synergism; tigecycline