Larry K Kociolek1,2, Egon A Ozer2, Dale N Gerding3,4, David W Hecht3,5, Sameer J Patel1,2, Alan R Hauser2. 1. Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago Ave, Chicago, IL 60611, USA. 2. Northwestern University Feinberg School of Medicine, 320 E. Superior St, Chicago, IL 60611, USA. 3. Loyola University Chicago Stritch School of Medicine, 2160 S. 1st Ave, Maywood, IL 60153, USA. 4. Edward Hines, Jr. Veterans Administration Hospital, 5000 S. 5th Ave, Hines, IL 60141, USA. 5. Loyola University Medical Center, 2160 S. 1st Ave, Maywood, IL 60153, USA.
Abstract
Background: Clostridium difficile strain DH/NAP11/106, a relatively antibiotic-susceptible strain, is now the most common cause of C. difficile infection (CDI) among adults in the USA. Objectives: To identify mechanisms underlying the evolution and transmission of an MDR DH/NAP11/106 clone. Methods: WGS (Illumina MiSeq), restriction endonuclease analysis (REA) and antibiotic susceptibility testing were performed on 134 C. difficile isolates collected from paediatric patients with CDI over a 2 year period. Results: Thirty-one of 134 (23%) isolates were REA group DH. Pairwise single-nucleotide variant (SNV) analyses identified a DH clone causing seven instances of CDI in two patients. During the 337 days between the first and second CDI, Patient 1 (P1) received 313 days of antibiotic therapy. Clindamycin and rifaximin resistance, and reduced vancomycin susceptibility (MIC 0.5-2 mg/L), were newly identified in the relapsed isolate. This MDR clone was transmitted to Patient 2 (P2) while P1 and P2 received care in adjacent private rooms. P1 and P2 each developed two additional CDI relapses. Comparative genomics analyses demonstrated SNVs in multiple antibiotic resistance genes, including rpoB (rifaximin resistance), gyrB and a gene encoding PBP; gyrB and PBP mutations did not consistently confer a resistance phenotype. The clone also acquired a 46 000 bp genomic element, likely a conjugative plasmid, which contained ermB (clindamycin resistance). The element shared 99% identity with the genomic sequence of Faecalibacterium prausnitzii, an enteric commensal. Conclusions: These data highlight the emergence of MDR in C. difficile strain DH/NAP11/106 through multiple independent mechanisms probably as a consequence of profound antibiotic pressure.
Background: Clostridium difficile strain DH/NAP11/106, a relatively antibiotic-susceptible strain, is now the most common cause of C. difficileinfection (CDI) among adults in the USA. Objectives: To identify mechanisms underlying the evolution and transmission of an MDR DH/NAP11/106 clone. Methods: WGS (Illumina MiSeq), restriction endonuclease analysis (REA) and antibiotic susceptibility testing were performed on 134 C. difficile isolates collected from paediatric patients with CDI over a 2 year period. Results: Thirty-one of 134 (23%) isolates were REA group DH. Pairwise single-nucleotide variant (SNV) analyses identified a DH clone causing seven instances of CDI in two patients. During the 337 days between the first and second CDI, Patient 1 (P1) received 313 days of antibiotic therapy. Clindamycin and rifaximin resistance, and reduced vancomycin susceptibility (MIC 0.5-2 mg/L), were newly identified in the relapsed isolate. This MDR clone was transmitted to Patient 2 (P2) while P1 and P2 received care in adjacent private rooms. P1 and P2 each developed two additional CDI relapses. Comparative genomics analyses demonstrated SNVs in multiple antibiotic resistance genes, including rpoB (rifaximin resistance), gyrB and a gene encoding PBP; gyrB and PBP mutations did not consistently confer a resistance phenotype. The clone also acquired a 46 000 bp genomic element, likely a conjugative plasmid, which contained ermB (clindamycin resistance). The element shared 99% identity with the genomic sequence of Faecalibacterium prausnitzii, an enteric commensal. Conclusions: These data highlight the emergence of MDR in C. difficile strain DH/NAP11/106 through multiple independent mechanisms probably as a consequence of profound antibiotic pressure.
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Authors: Kate E Dingle; Xavier Didelot; T Phuong Quan; David W Eyre; Nicole Stoesser; Tanya Golubchik; Rosalind M Harding; Daniel J Wilson; David Griffiths; Alison Vaughan; John M Finney; David H Wyllie; Sarah J Oakley; Warren N Fawley; Jane Freeman; Kirsti Morris; Jessica Martin; Philip Howard; Sherwood Gorbach; Ellie J C Goldstein; Diane M Citron; Susan Hopkins; Russell Hope; Alan P Johnson; Mark H Wilcox; Timothy E A Peto; A Sarah Walker; Derrick W Crook Journal: Lancet Infect Dis Date: 2017-01-25 Impact factor: 71.421