title: The role of doxycycline in the therapy of multidrug-resistant E. coli - an in vitro study.
abstract: This study assessed the in vitro antibacterial activity of combinations of amikacin and doxycycline or tigecycline against multidrug-resistant E. coli isolates. Twenty-four different pulsotypes, including 10 extended-spectrum β-lactamase (ESBL)-, 10 carbapenem-resistant, 2 New Delhi Metallo-beta-lactamase (NDM)- and 2 Klebsiella pneumoniae carbapenemase (KPC)-E. coli isolates were collected. All 24 isolates were susceptible to amikacin and tigecycline. Only 30% of ESBL and 50% of carbapenem-resistant E. coli were susceptible to doxycycline. Both of the NDM-E. coli had a MIC of 64 μg/ml. The checkerboard method showed that for the ESBL- and carbapenem-resistant E. coli, the synergistic effects of amikacin/doxycycline were 80% and 90%, respectively. For the two KPC- and two NDM-E. coli, the FIC index of amikacin/doxycycline were 0.5/0.375 and 0.5/0.281, respectively. For the ESBL- and carbapenem-resistant E. coli isolates, the combinations of amikacin and doxycycline exhibited synergistic activities against 80%, and 80% and 10% vs 60%, and 80% and 10% of the isolates at concentrations of 1x, 1/2x and 1/4xMIC, respectively. The synergistic effect seems to be similar for doxycycline and tigecycline based combinations with amikacin. In conclusion, the antibacterial activity of doxycycline can be enhanced by the addition of amikacin and is observed against most multidrug-resistant E. coli isolates.
authors.affiliation: Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Lai
authors.affiliation: Department of Medical Research; Chi Mei Medical Center; Tainan, Taiwan.
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Health and Nutrition, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Huang
authors.affiliation: Department of Medical Research; Chi Mei Medical Center; Tainan, Taiwan.|Department of Internal Medicine; Chi Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: Yin-Ching
authors.initials: YC
authors.lastname: Chuang
authors.affiliation: Department of Health and Nutrition, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.|Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Tang
mesh_terms: D000583:Amikacin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004318:Doxycycline / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects*; D066298:In Vitro Techniques; D008911:Minocycline / Q000031:analogs & derivatives / Q000494:pharmacology; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D000583:Amikacin; D008911:Minocycline; D004318:Doxycycline