Identifying the mechanism underlying treatment failure for Salmonella Paratyphi A infection using next-generation sequencing – a case report

Abstract

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.

Extended drug-resistant Salmonella typhi osteomyelitis: a case report and literature review

“…He presented with backache and fevers and had failure of therapy with azithromycin. Patient responded well to ciprofloxacin and cefotaxime combination as evident by improvement in backache and decline of ESR [27].…”

Quinolones resistance in Salmonella spp. isolated from broilers and chickens’ carcasses under federal inspection

“…These percentages were like those found in this study. The presence of Salmonella strains resistant to quinolones in foods, especially those used for treatment in humans, such as nalidixic acid and ciprofloxacin, is worrying because when its use becomes necessary for the treatment of serious infections it can increase the risk of failure (Park et al 2019).…”

“…Although antimicrobials are not indicated in most cases of salmonellosis in humans, its use becomes necessary in severe cases of systemic infections (Boxstael et al 2012, WHO 2018. However, the antimicrobials' lack of susceptibility increases the risk of treatment failures (Park et al 2019).…”

Exploring the Impact of Probiotic Route of Administration on Its Protective Effects against Pathogenic Infection inGalleria mellonella

“…In this study, Escherichia coli Nissle 1917 (EcN1917), a commercialised and well-characterised therapeutic with over a century-long history of human use [8], was used as the model probiotic while Salmonella Typhimurium, a widespread gastrointestinal pathogen with increasing outbreaks of drug-resistant infections [9] was used to establish a gut infection of the larval model. This study demonstrated that the route of probiotic administration significantly impacts its protective effects and should be considered when screening for probiotics in G. mellonella .…”