Hung-Jen Tang1, Chih-Cheng Lai2, Chi-Chung Chen3, Chun-Cheng Zhang4, Tzu-Chieh Weng4, Yu-Hsin Chiu5, Han-Siong Toh4, Shyh-Ren Chiang4, Wen-Liang Yu6, Wen-Chien Ko7, Yin-Ching Chuang8. 1. Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan. 2. Department of Intensive Care Medicine, Chi Mei Medical Center, Liou Ying, Tainan, Taiwan. 3. Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; Institute of Biotechnology, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan. 4. Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan. 5. Department of Medicine, Chi Mei Medical Center, Liou Ying, Tainan, Taiwan. 6. Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan. 7. Department of Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan. Electronic address: winston3415@gmail.com. 8. 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.
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.
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.
Authors: Wenzi Bi; Haiyang Liu; Rhys A Dunstan; Bin Li; Von Vergel L Torres; Jianming Cao; Lijiang Chen; Jonathan J Wilksch; Richard A Strugnell; Trevor Lithgow; Tieli Zhou Journal: Front Microbiol Date: 2017-06-30 Impact factor: 5.640