title: Extended-spectrum cephalosporins and the inoculum effect in tests with CTX-M-type extended-spectrum β-lactamase-producing Escherichia coli: potential clinical implications of the revised CLSI interpretive criteria.
abstract: Based on the new recommendations of the Clinical and Laboratory Standards Institute (CLSI), the revised cephalosporin breakpoints may result in many CTX-M-producing Escherichia coli being reported as susceptible to ceftazidime. We determined the activity of ceftazidime and other parenteral β-lactam agents in standard- and high-inoculum minimum inhibitory concentration (MIC) tests against CTX-M-producing E. coli isolates. Antimicrobial susceptibility was determined using a broth microdilution MIC method with inocula that differed 100-fold in density. An inoculum effect was defined as an eight-fold or greater increase in MIC on testing with the higher inoculum. When the revised CLSI ceftazidime breakpoint of 4 μg/mL was applied, 34 (34.3%) of the 99 CTX-M-producers tested were susceptible. More specifically, for 42 CTX-M-14-producing E. coli isolates, 32 (76.2%) were susceptible at 4 μg/mL. Cefotaxime, ceftazidime, cefepime and piperacillin/tazobactam were found to be associated with inoculum effects in 100% of the evaluable tests for extended-spectrum β-lactamase-producing E. coli isolates. The MIC(50) (MIC required to inhibit 50% of isolates) of ceftazidime was 16 μg/mL in the standard-inoculum tests and >512 μg/mL in the high-inoculum tests. In the high-inoculum tests including isolates encoding CTX-M-14, ceftazidime was dramatically affected, with susceptibility decreasing from 82.1% of isolates inhibited at 4 μg/mL in the standard-inoculum tests to 0% at high inoculum. Although further studies may demonstrate that ceftazidime has a role in the treatment of infections caused by these organisms, we suggest that until more data become available, clinicians should be cautious about treating serious CTX-M-producing E. coli infections with ceftazidime or cefepime.
authors.affiliation: Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-ro 81, Gangnam-gu, Seoul 135-710, Republic of Korea. Electronic address: collacin@hotmail.com.
authors.forename: Cheol-In
authors.initials: CI
authors.lastname: Kang
authors.affiliation: Asia Pacific Foundation for Infectious Diseases (APFID), Seoul, Republic of Korea.
authors.forename: Min Kyeong
authors.initials: MK
authors.lastname: Cha
authors.affiliation: Asia Pacific Foundation for Infectious Diseases (APFID), Seoul, Republic of Korea.
authors.forename: So Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Division of Infectious Diseases, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea.
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Wi
authors.affiliation: Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-ro 81, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Doo Ryeon
authors.initials: DR
authors.lastname: Chung
authors.affiliation: Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-ro 81, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Kyong Ran
authors.initials: KR
authors.lastname: Peck
authors.affiliation: Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Nam Yong
authors.initials: NY
authors.lastname: Lee
authors.affiliation: Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-ro 81, Gangnam-gu, Seoul 135-710, Republic of Korea; Asia Pacific Foundation for Infectious Diseases (APFID), Seoul, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Song
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D058491:Bacterial Load; D002511:Cephalosporins / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods / Q000592:standards; D015203:Reproducibility of Results; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D001618:beta-Lactamases
keywords: CTX-M; Cephalosporin; Escherichia coli; Inoculum effect