title: Comparison of the risk of acquiring in vitro resistance to doripenem and tazobactam/piperacillin by CTX-M-15-producing Escherichia coli.
abstract: To compare the risk of acquiring in vitro resistance between doripenem and tazobactam/piperacillin by CTX-M-15-producing Escherichia coli, the in vitro frequency of resistance was determined. Four strains carrying multiple β-lactamases such as blaOXA-1 or blaCTX-M-27 as well as blaCTX-M-15 and blaTEM-1 were used. No resistant colonies appeared on doripenem-containing plates, whereas resistant colonies were obtained from three of four test strains against tazobactam/piperacillin using agar plate containing 8- to 16-fold MIC of each drug. These three acquired tazobactam/piperacillin-resistant strains were not cross-resistant to doripenem, and they showed 1.9- to 3.1-fold higher piperacillin-hydrolysis activity compared to those of each parent strain. The change of each β-lactamase mRNA expression measured by real-time PCR varied among three resistant strains. One of three tazobactam/piperacillin-resistant strains with less susceptibility to ceftazidime overexpressed both blaCTX-M-15 and blaTEM-1, and the other two strains showed higher mRNA expression of either blaTEM-1 or blaOXA-1. These results demonstrate that multiple β-lactamases carried by CTX-M-15-producing E. coli contributed to the resistance to tazobactam/piperacillin. On the other hand, these resistant strains maintained susceptibility to doripenem. The risk of acquiring in vitro resistance to doripenem by CTX-M-15-producing E. coli seems to be lower than that to tazobactam/piperacillin.
authors: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Toyonaka, Osaka 561-0825, Japan. Electronic address: tsukasa.horiyama@shionogi.co.jp.
authors: Tsukasa
authors: T
authors: Horiyama
authors: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Toyonaka, Osaka 561-0825, Japan.
authors: Sachi
authors: S
authors: Kanazawa
authors: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Toyonaka, Osaka 561-0825, Japan.
authors: Takafumi
authors: T
authors: Hara
authors: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Toyonaka, Osaka 561-0825, Japan.
authors: Masaaki
authors: M
authors: Izawa
authors: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Toyonaka, Osaka 561-0825, Japan.
authors: Takafumi
authors: T
authors: Sato
authors: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Toyonaka, Osaka 561-0825, Japan.
authors: Takahiro
authors: T
authors: Yamaguchi
authors: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Toyonaka, Osaka 561-0825, Japan.
authors: Masakatsu
authors: M
authors: Tsuji
authors: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Toyonaka, Osaka 561-0825, Japan.
authors: Hideki
authors: H
authors: Maki
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000378:metabolism / Q000494:pharmacology*; D015169:Colony Count, Microbial; D000077726:Doripenem; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics; D006868:Hydrolysis; D008826:Microbial Sensitivity Tests; D059645:Mutation Rate; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D010878:Piperacillin / Q000378:metabolism / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D029968:Escherichia coli Proteins; D012333:RNA, Messenger; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D000077726:Doripenem; C477098:CTX-M-27, E coli; C473109:beta-lactamase CTX-M-15; C039404:beta-lactamase OXA-2; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1; D010878:Piperacillin
keywords: CTX-M-15; Escherichia coli; In vitro resistance frequency; OXA-1; TEM-1