title: Fatal sepsis caused by multidrug-resistant Bacteroides fragilis, harboring a cfiA gene and an upstream insertion sequence element, in Japan.
abstract: Here, we report a case of fatal sepsis resulting from an intra-abdominal infection caused by a Bacteroides fragilis strain containing a CfiA4 metallo-β-lactamase and an upstream insertion sequence (IS) element. Meropenem was used as empiric therapy for septic shock as a result of the intra-abdominal infection, although two rounds of carbapenem treatment had been administered previously. B. fragilis was isolated from two anaerobic blood culture bottles 4 days after the onset of septic shock. Susceptibility testing revealed that the isolate was non-susceptible to all tested agents except metronidazole and tigecycline. The isolate gave a positive result in ethylenediaminetetraacetic acid and carbapenem inactivation tests, but a negative result in a double-disk synergy test using sodium mercaptoacetate. Next-generation whole-genome sequencing indicated the presence of the cfiA4, emrG and emrF genes. PCR indicated the presence of an IS element upstream of the cifA4 gene. Although carbapenem-resistant B. fragilis isolates have previously been reported, clinical sepsis by this organism is considered rare. In Japan, as in most countries worldwide, routine susceptibility testing and the detection of metallo-β-lactamases is not carried out in anaerobic organisms, including B. fragilis. The emergence of carbapenem resistance during therapy should be monitored, as B. fragilis strains containing the cfiA gene show decreased sensitivity during carbapenem therapy. Therefore, susceptibility testing and appropriate antibiotic stewardship are required in cases of anaerobic bacterial infections.
authors.affiliation: Department of Infection Prevention and Control, Tokyo Medical University Hospital, Tokyo, Japan. Electronic address: task300@tokyo-med.ac.jp.
authors.forename: Itaru
authors.initials: I
authors.lastname: Nakamura
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo, Japan. Electronic address: koh.aoki27@gmail.com.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Aoki
authors.affiliation: Department of Infection Prevention and Control, Tokyo Medical University Hospital, Tokyo, Japan. Electronic address: yuuuuuri_miura@yahoo.co.jp.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Miura
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo, Japan. Electronic address: tetsuo.yamaguchi@med.toho-u.ac.jp.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Microbiology, Tokyo Medical University, Tokyo, Japan. Electronic address: tetsu@sc4.so-net.ne.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D001442:Bacteroides Infections / Q000175:diagnosis* / Q000382:microbiology / Q000473:pathology; D001441:Bacteroides fragilis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D000071997:Blood Culture; D004251:DNA Transposable Elements; D024901:Drug Resistance, Multiple, Bacterial; D017809:Fatal Outcome; D005260:Female; D016680:Genome, Bacterial; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D059413:Intraabdominal Infections / Q000150:complications; D007564:Japan; D008826:Microbial Sensitivity Tests; D018805:Sepsis / Q000175:diagnosis* / Q000382:microbiology / Q000473:pathology; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D001618:beta-Lactamases; C063912:carbapenemase
keywords: Bacteroides fragilis; Carbapenem; Insertion element; Treatment failure; cfiA