Fatal Respiratory Diphtheria Caused by ß-Lactam-Resistant Corynebacterium diphtheriae.

Autor:	Forde BM; School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia.; Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Australia.; Australian Centre for Ecogenomics, University of Queensland, Brisbane, Australia., Henderson A; University of Queensland Centre For Clinical Research, Brisbane, Australia.; Infection Management Services, Princess Alexandra Hospital, Brisbane, Australia., Playford EG; Infection Management Services, Princess Alexandra Hospital, Brisbane, Australia.; School of Medicine, University of Queensland, Brisbane, Australia., Looke D; Infection Management Services, Princess Alexandra Hospital, Brisbane, Australia.; School of Medicine, University of Queensland, Brisbane, Australia., Henderson BC; Infection Management Services, Princess Alexandra Hospital, Brisbane, Australia., Watson C; Infection Management Services, Princess Alexandra Hospital, Brisbane, Australia., Steen JA; Institute for Molecular Biosciences, University of Queensland, Brisbane, Australia., Sidjabat HE; Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Australia.; University of Queensland Centre For Clinical Research, Brisbane, Australia., Laurie G; Intensive Care Unit, Princess Alexandra Hospital, Brisbane, Australia., Muttaiyah S; Department of Microbiology, Pathology Queensland, Brisbane, Australia., Nimmo GR; Department of Microbiology, Pathology Queensland, Brisbane, Australia., Lampe G; Department of Anatomical Pathology, Pathology Queensland, Brisbane, Australia., Smith H; Public Health Microbiology, Forensic and Scientific Services, Queensland Health, Brisbane, Australia., Jennison AV; Public Health Microbiology, Forensic and Scientific Services, Queensland Health, Brisbane, Australia., McCall B; Metro South Public Health Unit, Metro South Health, Brisbane, Australia., Carroll H; Communicable Diseases Branch, Prevention Division, Department of Health, Queensland Health, Brisbane, Australia., Cooper MA; Institute for Molecular Biosciences, University of Queensland, Brisbane, Australia., Paterson DL; Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Australia.; University of Queensland Centre For Clinical Research, Brisbane, Australia., Beatson SA; School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia.; Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, Australia.; Australian Centre for Ecogenomics, University of Queensland, Brisbane, Australia.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2021 Dec 06; Vol. 73 (11), pp. e4531-e4538.
DOI:	10.1093/cid/ciaa1147
Abstrakt:	Background: Diphtheria is a potentially fatal respiratory disease caused by toxigenic Corynebacterium diphtheriae. Although resistance to erythromycin has been recognized, β-lactam resistance in toxigenic diphtheria has not been described. Here, we report a case of fatal respiratory diphtheria caused by toxigenic C. diphtheriae resistant to penicillin and all other β-lactam antibiotics, and describe a novel mechanism of inducible carbapenem resistance associated with the acquisition of a mobile resistance element. Methods: Long-read whole-genome sequencing was performed using Pacific Biosciences Single Molecule Real-Time sequencing to determine the genome sequence of C. diphtheriae BQ11 and the mechanism of β-lactam resistance. To investigate the phenotypic inducibility of meropenem resistance, short-read sequencing was performed using an Illumina NextSeq500 sequencer on the strain both with and without exposure to meropenem. Results: BQ11 demonstrated high-level resistance to penicillin (benzylpenicillin minimum inhibitory concentration [MIC] ≥ 256 μg/ml), β-lactam/β-lactamase inhibitors and cephalosporins (amoxicillin/clavulanic acid MIC ≥ 256 μg/mL; ceftriaxone MIC ≥ 8 μg/L). Genomic analysis of BQ11 identified acquisition of a novel transposon carrying the penicillin-binding protein (PBP) Pbp2c, responsible for resistance to penicillin and cephalosporins. When strain BQ11 was exposed to meropenem, selective pressure drove amplification of the transposon in a tandem array and led to a corresponding change from a low-level to a high-level meropenem-resistant phenotype. Conclusions: We have identified a novel mechanism of inducible antibiotic resistance whereby isolates that appear to be carbapenem susceptible on initial testing can develop in vivo resistance to carbapenems with repeated exposure. This phenomenon could have significant implications for the treatment of C. diphtheriae infection, and may lead to clinical failure. (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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