title: In vitro reduction of antibacterial activity of tigecycline against multidrug-resistant Acinetobacter baumannii with host stress hormone norepinephrine.
abstract: The host stress hormone norepinephrine (NE), also called noradrenaline, is reported to augment bacterial growth and pathogenicity, but few studies have focused on the effect of NE on the activity of antimicrobials. The aim of this study was to clarify whether NE affects antimicrobial activity against multidrug-resistant Acinetobacter baumannii (MDR-AB). Time-kill studies of tigecycline (TIG) and colistin (COL) against MDR-AB as well as assays for factors contributing to antibiotic resistance were performed using MDR-AB clinical strains both in the presence and absence of 10 µM NE. In addition, expression of three efflux pump genes (adeB, adeJ and adeG) in the presence and absence of NE was analysed by quantitative reverse transcription PCR. Viable bacterial cell counts in TIG-supplemented medium containing NE were significantly increased compared with those in medium without NE. In contrast, NE had little influence on viable bacterial cell counts in the presence of COL. NE-supplemented medium resulted in an ca. 2 log increase in growth and in bacterial cell numbers adhering on polyurethane, silicone and polyvinylchloride surfaces. Amounts of biofilm in the presence of NE were ca. 3-fold higher than without NE. Expression of the adeG gene was upregulated 4-6-fold in the presence of NE. In conclusion, NE augmented factors contributing to antibiotic resistance and markedly reduced the in vitro antibacterial activity of TIG against MDR-AB. These findings suggest that NE treatment may contribute to the failure of TIG therapy in patients with MDR-AB infections.
authors.affiliation: Department of Emergency & Critical Care Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan; Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Inaba
authors.affiliation: Department of Emergency & Critical Care Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Matsuda
authors.affiliation: Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Banno
authors.affiliation: Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Wanchun
authors.initials: W
authors.lastname: Jin
authors.affiliation: Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Wachino
authors.affiliation: Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. Electronic address: yarakawa@med.nagoya-u.ac.jp.
authors.forename: Yoshichika
authors.initials: Y
authors.lastname: Arakawa
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion; D058491:Bacterial Load; D018441:Biofilms / Q000254:growth & development; D003091:Colistin / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D004336:Drug Antagonism; D005260:Female; D020869:Gene Expression Profiling; D005798:Genes, Bacterial; D006801:Humans; D008297:Male; D050296:Microbial Viability / Q000187:drug effects; D008875:Middle Aged; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000078304:Tigecycline; D013997:Time Factors
chemical_list: D000316:Adrenergic alpha-Agonists; D000900:Anti-Bacterial Agents; D003470:Culture Media; D000078304:Tigecycline; D008911:Minocycline; D009638:Norepinephrine; D003091:Colistin
keywords: AdeFGH; Adhesion; Biofilm; Multidrug-resistant Acinetobacter baumannii; Norepinephrine; Tigecycline resistance