Editor's Note: As the global issue of antimicrobial resistance intensifies, newly emerging resistant bacterial strains pose a significant threat to public health. At the 34th European Congress of Clinical Microbiology and Infectious Diseases (ESCMID Global 2024), a study by Professor Ning Shen's team from Peking University Third Hospital (Abstract No.: E0451) focused on the resistance issues of cefiderocol, a drug not yet marketed in China. The study identified that cefiderocol can induce resistance and amplification of the blaSHV-12 gene in vitro. Long-read sequencing technology demonstrated its potential for rapid and accurate detection of resistance gene amplification, offering a new tool for future resistance research.Full Resistance and Dynamic Host-Adapted Heterogeneous Resistance to Cefiderocol in ST11 Type Klebsiella pneumoniae Caused by blaSHV-12 Gene Amplification (Abstract No.: E0451)
Objective
Although cefiderocol (FDC) is not yet marketed in China, pan-drug-resistant highly virulent Klebsiella pneumoniae (PDR-hvKp) resistant to FDC have already been identified. This study performed FDC susceptibility tests on clinical Kp isolates to investigate the prevalence and mechanisms of FDC resistance in these isolates.
Methods
The study retrospectively included 151 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates to assess their sensitivity to FDC. Seven isolates with the blaSHV-12 gene from two patients were subjected to whole-genome sequencing. Phenotypic assessments including drug sensitivity, virulence, blaSHV-12 expression, and fitness costs were conducted, and qPCR and long-read sequencing were used to further explore the amplification of blaSHV-12.
Results
Of the 151 CRKP isolates tested, a lower resistance to FDC was observed (MIC50/MIC90 = 1/4 mg/L). Among the seven PDR-hvKP isolates, two showed resistance to FDC (MIC = 32 mg/L). The two FDC-resistant isolates carried 6 and 15 copies of blaSHV-12 on IncR/IncFII plasmids, respectively. Four FDC-sensitive isolates carried only one copy of blaSHV-12, and one sensitive isolate carried three copies. The blaSHV-12 genes were located within the same 7.3 kb fragment flanked by IS26, increasing blaSHV-12 expression and causing FDC resistance, without any fitness cost.
Moreover, the study found that cefiderocol (FDC) can induce resistance and amplification of the blaSHV-12 gene in vitro and can reverse this process during serial passaging.
Conclusion
The amplification of blaSHV-12 and the resulting heterogeneous resistance within the host are significant concerns for the appropriate use of antimicrobial agents. Long-read sequencing may be the preferred method for rapidly and accurately detecting resistance gene amplification.
References
Chao Liu, Juan Yi, Ming Lu, et al. Dynamic within-host cefiderocol heteroresistance caused by blaSHV-12 amplification in pandrug-resistant and hypervirulent Klebsiella pneumoniae sequence type 11. ESCMID Global 2024; ePoster E0451.
Professor Ning Shen
- Chief Physician, Professor, PhD Supervisor
- Vice President of Peking University Third Hospital
Positions
- Director of the Infection Disease Center
- Deputy Director of Respiratory and Critical Care Medicine
- Vice Leader of the Infection Group of the Chinese Medical Association’s Respiratory Diseases Branch
- Vice Chair of the Foreign Affairs Working Committee of the Chinese Medical Doctor Association Respiratory Physicians Branch
- Vice Chair of the Critical Care Committee of the Chinese Women Physicians Association
- Executive Member of the Respiratory Committee of the Chinese Women Physicians Association
- Executive Member of the Respiratory Endoscopy and Intervention Branch of the Beijing Medical Association
- Member of the Infection Diseases Committee of the Chinese Medical Education Association
- Associate Editor of The Clinical Respiratory Journal
- Editorial Board Member of the Chinese Journal of Tuberculosis and Respiratory Diseases
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