Institutional outbreak involving multiple clades of IMP-producing Enterobacter cloacae complex sequence type 78 at a cancer center in Tokyo, Japan

• Published in: BMC infectious diseases 2021-03, Vol.21 (1), p.289-289, Article 289
• Main Authors: Harada, Sohei, Aoki, Kotaro, Ohkushi, Daisuke, Okamoto, Koh, Takehana, Kazumi, Akatsuchi, Tomomi, Ida, Keito, Shoji, Daigo, Ishii, Yoshikazu, Doi, Yohei, Moriya, Kyoji, Hayama, Brian
• Format: Article
• Language: English
• Subjects: Aged; Amides; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; Bacterial Proteins - genetics; beta-Lactamases - genetics; Cancer therapies; Carbapenems; Carbapenems - pharmacology; Carbapenems - therapeutic use; Causes of; Chemotherapy; Conjugation; Cross infection; Disease Outbreaks; E coli; Enterobacter; Enterobacter - drug effects; Enterobacter - genetics; Enterobacter - isolation & purification; Enterobacter cloacae; Enterobacter cloacae - drug effects; Enterobacter cloacae - genetics; Enterobacter cloacae - isolation & purification; Enterobacter cloacae complex; Enterobacterales; Enterobacteriaceae; Enterobacteriaceae infections; Enterobacteriaceae Infections - diagnosis; Enterobacteriaceae Infections - drug therapy; Enterobacteriaceae Infections - epidemiology; Enterobacteriaceae Infections - microbiology; Enzymes; Epidemics; Epidemiology; Female; Gene sequencing; Genetic aspects; Genomes; Health facilities; Hospitalization; Hospitals; Humans; Identification and classification; IMP-type carbapenemase; Infections; Infectious diseases; Integrons - genetics; Japan; Japan - epidemiology; Laboratories; Lactose; Male; Medical records; Medical research; Microbial Sensitivity Tests; Multidrug resistance; Multilocus Sequence Typing; Nosocomial infection; Nosocomial infections; Nucleotide sequence; Nucleotides; Outbreak; Outbreaks; Patients; Phenotypes; Plasmids; Plasmids - genetics; Polymorphism; Single nucleotide polymorphism analysis; Single-nucleotide polymorphism; Surgery; Surveillance; Whole Genome Sequencing; β-Lactam antibiotics
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-021-05952-9

Information about the clinical and microbiological characteristics of IMP-producing Enterobacterales has been limited. Here, we describe an institutional outbreak of IMP-producing Enterobacter cloacae complex (ECC) involving multiple clades of ECC sequence type (ST) 78 strains. Antimicrobial susceptibility testing, whole-genome sequencing, and conjugation experiments of 18 IMP-producing ECC strains isolated during four-year study period were performed. Species and subspecies were determined by average nucleotide identity analysis and clonal relatedness of the isolates was analyzed with multilocus sequence typing and core-genome single nucleotide polymorphism (SNP) analysis. Relevant clinical information was extracted from medical records. Fourteen of 18 IMP-producing ECC isolates were determined as Enterobacter hormaechei ST78. Sixteen isolates, including 13 isolates belonging to ST78, carried bla in In316-like class 1 integron and also carried IncHI2 plasmids. Conjugation experiments were successful for 12 isolates carrying bla on IncHI2 plasmids and for an isolate carrying bla on an IncL/M plasmid. Although isolation of ST78 strains was clustered in a 14-months period suggesting nosocomial transmission, these strains were subdivided into three clades by SNP analysis: clade A (n = 10), clade B (n = 1), clade C (n = 3). A part of clonal relatedness was unexpected by the epidemiological information at the time of isolation of the strains. Most of the IMP-producing ECC strains were susceptible to non-β-lactam antibiotics and had relatively low minimum inhibitory concentrations to carbapenems (≤4 μg/mL). Five of six infections caused by IMP-producing ECC were treated successfully. Whole-genome sequencing analysis revealed the outbreak was caused by three different clades of ST78 strains, where patients had favorable treatment outcome of the infections compared with that caused by Enterobacterales producing other carbapenemases, possibly due to their non-multidrug-resistant phenotype.