YouTube video by ScienceAlert

and objectivesAzithromycin is a critical oral treatment for typhoid fever caused by Salmonella enterica serovar Typhi (Salmonella Typhi), since XDR has rendered other first-line treatment options ineffective. Azithromycin resistance conferred by amino acid changes in AcrB, an AcrAB-TolC efflux pump component, represents an emerging public health concern. Leveraging phenotypic and genotypic data from U.S. Salmonella Typhi surveillance systems, this study describes the prevalence, phenotype and genomic epidemiology of Salmonella Typhi with AcrB mutations in U.S. patients since the first detection in 2015.MethodsAST and WGS data of >3000 Salmonella Typhi isolates were used to identify all cases with an AcrB mutation in the United States (2015–2025). We calculated annual prevalence and MIC ranges. Phylogenetic analysis was used to contextualize U.S. cases of Salmonella Typhi with an AcrB mutation within all globally reported cases.ResultsWhile the prevalence of AcrB mutations in the United States is low (1.5%), it has risen significantly in recent years, from 0.2% in 2016–2022 to 2.2% in 2023–2025. This increase is predominantly driven by clonal expansion of existing strains circulating in South Asia. AcrB mutations do not reliably confer resistance to azithromycin (MIC ≥ 32 mg/L), complicating clinical interpretation.ConclusionsThe prevalence of AcrB mutations in Salmonella Typhi is increasing in the United States, and likely globally, given that U.S. data function as an informal proxy for regions without routine surveillance infrastructure. Clinical outcomes data are needed to inform Salmonella Typhi treatment guidelines and potentially amend clinical breakpoints for azithromycin.

This is a global problem.

A review and meta-analysis finds Salmonella Typhi and Paratyphi samples from human infections in Pakistan were highly resistant to first-line and other commonly used antibiotics.

Typhoid fever, caused by Salmonella Typhi, is evolving extensive drug resistance, making treatment challenging. Researchers found a rise in XDR Typhi strains resistant to frontline and newer...

Typhoid fever burdens low- and middle-income countries, especially children. Despite being curable, it now resists first-line antibiotics. This study aims to understand antimicrobial resistance patterns associated with multidrug-resistant (MDR) and extensively drug-resistant (XDR) typhoid fever cases in Pakistan.MethodsWe conducted a retrospective review of blood culture–confirmed typhoid cases from 5 large laboratory networks in Pakistan over a period of 3 years (2017–2019). Data were analyzed for 464 956 blood culture specimens, of which Typhi and Paratyphi were isolated in 23 924 (5%) of all blood cultures done.ResultsSindh had the highest proportion of S. Typhi cases (72%) of all positive cases, followed by Punjab with 46.9%. The 5–14-years age group had the highest proportion of S. Typhi (MDR: 46.1%; XDR: 44.2%), followed by the 2–4-years age group (MDR: 27%; XDR: 26.2%). XDR isolates of S. Typhi were found in 57%. Most S. Typhi isolates were resistant to ampicillin (79.8%), chloramphenicol (80.8%), cefixime (64.6%), ciprofloxacin (66.4%), ceftriaxone (63.3%), and co-trimoxazole (80.2%). Most S. Paratyphi isolates were responsive to antibiotics, ampicillin (97.2%), chloramphenicol (98.6%), cefixime (99.5%), ceftriaxone (99.5%), and co-trimoxazole (98.7%). Resistance to ciprofloxacin was 85.9%. Both S. Typhi and S. Paratyphi were susceptible to azithromycin and imipenem, whereas 99.8% of S. Typhi and 100% of S. Paratyphi were sensitive to meropenem.ConclusionsIncreased prevalence of culture-confirmed XDR S. Typhi cases was observed in 2019 as compared with 2017, presumably due to the outbreak of XDR in Sindh.

Typhoid fever burdens low- and middle-income countries, especially children. Despite being curable, it now resists first-line antibiotics. This study aims to understand antimicrobial resistance patterns associated with multi-drug resistant (MDR) and extensively drug resistant (XDR) typhoid fever cases in Pakistan.MethodsWe conducted a retrospective review of blood culture confirmed typhoid cases from five large laboratory networks of Pakistan over a period of 3 years (2017-2019). Data was analyzed for 464,956 blood cultures specimens, of which Typhi or Paratyphi were isolated in 23,924 (5%) of all blood cultures done.ResultsSindh had the highest proportion of S. Typhi cases (72%) of all positive cases, followed by Punjab with 46.9%. 5-14 year age-group had highest proportion of S.Typhi (MDR: 46.1%, XDR: 44.2%), followed by 2-4 year age-group (MDR: 27%, XDR: 26.2%). XDR isolates of S.typhi were 57%. Most S. Typhi isolates were resistant to ampicillin (79.8%), chloramphenicol (80.8%), cefixime (64.6%), ciprofloxacin (66.4%), ceftriaxone (63.3%), and cotrimoxazole (80.2%). Most S. Paratyphi isolates were responsive to antibiotics, ampicillin (97.2%), chloramphenicol (98.6%), cefixime (99.5%), ceftriaxone (99.5%), and co-trimoxazole (98.7%). Resistance to ciprofloxacin was 85.9%. Both S. typhi and S. Paratyphi were susceptible to azithromycin and imipenem, whereas 99.8% of S. typhi and 100% of S. Paratyphi were sensitive to meropenem.ConclusionIncreased prevalence of culture-confirmed XDR S.Typhi cases was observed in 2019 as compared to 2017, presumably due to the outbreak of XDR in Sindh.

Despite having plagued humans for millennia, typhoid fever is rarely considered a threat in developed countries today.