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Identifying the mechanism underlying treatment failure for Salmonella Paratyphi A infection using next-generation
Hye-Ran Park1, Dong-Min Kim2, Na-Ra Yun1
1Department of Internal Medicine, College of Medicine, Chosun University, 588 Seosuk-dong, Dong-gu, Gwangju, 501-717, Republic of Korea.
Background:
Salmonella is a notorious pathogen that causes gastroenteritis in humans and the emergence of resistance to third-generation cephalosporins and azithromycin have raised concern. There has been rare case of Salmonella Paratyphi A infection accompanied by spondylitis. Here, we report a case of initial antibiotic treatment failure in a Korean man with Salmonella Paratyphi A infection and conducted next-generation sequencing (NGS) to determine the cause of failure of initial treatment for Salmonella Paratyphi A infection.
Case Presentation:
A 70-year-old man was admitted to Chosun University Hospital with reported consistent low back pain with a history of having 5 days of chills and fever in another hospital a month ago. He was administered ceftriaxone (2 g daily) for 18 days including initial treatment to cover Salmonella enterica. The antimicrobial susceptibility test using MIC plate, found that the identified organism was resistant to ciprofloxacin and nalidixic acid. Moreover, the Salmonella Paratyphi A isolates were found to have an MIC > 16 mg/L for azithromycin, as he had resistance to both azithromycin and nalidixic acid, the treatment was switched to a combination of ciprofloxacin and cefotaxime. We carried out next-generation sequencing (NGS) to determine the cause of failure of initial treatment for Salmonella Paratyphi A infection. NGS showed that the amino acid substitution GyrA S83F and the expression of multiple RNA-family efflux pumps led to a high-level resistance to quinolone. No genes related to ceftriaxone resistance, such as CTX-M, CMY-2, or other extended-spectrum beta-lactamases were identified in Salmonella enterica Paratyphi A using NGS. The GyrA S83F mutation and the expression of multiple RNA-family efflux pumps may have contributed to the treatment failure of ceftriaxone, even though the MIC of the isolate to ceftriaxone was less than 1.
Conclusion:
This case involved a Salmonella Paratyphi A infection accompanied by spondylitis. To our knowledge, this is the first report to elucidate the mechanism underlying antimicrobial resistance using NGS.
Insights
This study reports a rare case of Salmonella Paratyphi A infection with spondylitis in a Korean man. Next-generation sequencing revealed genetic mutations and efflux pumps causing multidrug resistance, explaining initial antibiotic treatment failure.
Area of Science:
- Infectious Diseases
- Genomics
- Antimicrobial Resistance
Background:
- Salmonella infections, including Salmonella Paratyphi A, pose a significant public health threat due to increasing antimicrobial resistance.
- The emergence of resistance to third-generation cephalosporins and azithromycin is a growing concern.
- Co-infection of Salmonella Paratyphi A with spondylitis is rare.
Observation:
- A 70-year-old Korean man presented with Salmonella Paratyphi A infection and spondylitis, experiencing initial antibiotic treatment failure.
- Antimicrobial susceptibility testing revealed resistance to ciprofloxacin, nalidixic acid, and azithromycin.
- Next-generation sequencing (NGS) was employed to investigate the underlying mechanisms of resistance.
Findings:
- NGS identified the GyrA S83F amino acid substitution and the expression of multiple RNA-family efflux pumps, conferring high-level quinolone resistance.
- No genes associated with ceftriaxone resistance (e.g., CTX-M, CMY-2) were detected in the Salmonella Paratyphi A isolates.
- The identified genetic mutations and efflux pumps are implicated in the treatment failure, despite a low minimum inhibitory concentration (MIC) for ceftriaxone.
Implications:
- This case highlights the utility of NGS in elucidating complex antimicrobial resistance mechanisms in Salmonella.
- Understanding these mechanisms is crucial for guiding effective treatment strategies for multidrug-resistant Salmonella infections.
- The findings contribute to the limited knowledge on Salmonella Paratyphi A resistance, particularly in conjunction with spondylitis.
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