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

Abstract

Abstract Background 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. Methods 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. Results Fourteen of 18 IMP-producing ECC isolates were determined as Enterobacter hormaechei ST78. Sixteen isolates, including 13 isolates belonging to ST78, carried bla IMP-1 in In316-like class 1 integron and also carried IncHI2 plasmids. Conjugation experiments were successful for 12 isolates carrying bla IMP-1 on IncHI2 plasmids and for an isolate carrying bla IMP-11 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. Conclusions 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.

Keywords

• Enterobacter cloacae complex
• IMP-type carbapenemase
• Outbreak
• Whole-genome sequencing
• Single nucleotide polymorphism analysis