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

Area of Science:

• Microbiology
• Genomics
• Antimicrobial Resistance

Background:

• Diphtheria, a severe respiratory illness caused by toxigenic Corynebacterium diphtheriae, has seen recognized erythromycin resistance.
• However, β-lactam antibiotic resistance in toxigenic strains remained undescribed until this study.

Observation:

• A case of fatal respiratory diphtheria involved toxigenic C. diphtheriae BQ11, exhibiting high-level resistance to penicillin, cephalosporins, and β-lactam/β-lactamase inhibitors.
• Genomic analysis identified a novel transposon encoding Pbp2c, a penicillin-binding protein conferring resistance to penicillin and cephalosporins.

Findings:

• Exposure to meropenem induced high-level resistance in C. diphtheriae BQ11 through transposon amplification.
• This demonstrates a novel mechanism of inducible carbapenem resistance linked to mobile genetic elements.

Implications:

• This inducible resistance mechanism, where initially susceptible isolates become resistant upon repeated exposure, poses a significant threat.
• It could lead to clinical treatment failure in patients with C. diphtheriae infections and necessitates careful monitoring of antibiotic susceptibility.