Our systematic review of studies estimated the length of hospital stay and associated treatment costs for patients with susceptible or antibiotic-resistant Salmonella Typhi, Paratyphi, and non-typhoidal Salmonella infections. Quantifying the impact on healthcare utilisation and costs through this systematic approach is critical for informing economic evaluations and policy decisions regarding interventions to curb Salmonella infections and antimicrobial resistance.
Patients with resistant Salmonella infections had significantly longer hospital stays across multiple studies, with an additional 0.5–2.2 days compared to susceptible infections. The direct hospitalisation costs were higher for resistant typhoidal Salmonella, with mean estimates being 71–103% higher than for susceptible infections in the same setting. Notably, extensively drug-resistant (XDR) typhoidal Salmonella was associated with a 103% cost increase versus multidrug-resistant (MDR) cases, highlighting the economic burden of highly resistant pathogens. Duration of fever varied across studies without clear patterns related to resistance.
The increased costs and hospital stays for resistant Salmonella infections are expected given that resistant infections require more time to clear than susceptible infections, as has been demonstrated for other pathogens (39–41). This could be explained by increased virulence of resistant Salmonella strains or antibiotic treatment failure. Duong et al. showed that changes to secondary or tertiary antimicrobials from the initial primary treatment were significantly correlated with prolonged hospitalisation (34).
We identified critical gaps in evidence from regions with high typhoid fever burden, including Sub-Saharan Africa, parts of Southeast Asia (e.g. Cambodia, Laos, Myanmar), and remaining Oceanic countries. Typhoid fever remains highly endemic in these settings, with a high disease burden. However, no studies from these high-burden areas were included in this review. The economic burden may differ in these understudied countries compared to the more extensively researched countries in South Asia, East Asia, Europe, and the Americas. Excluding the high-burden regions for Salmonella limits generalisability and underscores the need for more data on the health and economic burden of these infections. Better utilisation of routine healthcare records, including electronic health records where available, will help fill the gaps in data and evidence from high-burden regions for Salmonella.
Our study has limitations. First, the type and timing of antibiotic administration varied across studies. Some patients received antibiotics only after delayed periods, likely increasing hospital stay for reasons unrelated to resistance. Second, longer stays for resistant infections may also be influenced by other factors like timing of hospital presentation, antibiotic use before hospitalisation, and disease complications that were unaddressed. Third, the quality of evidence on length of hospital stay and costs varied across the included studies. Many studies were observational without control groups, limiting the ability to attribute outcomes to antibiotic resistance status. Fourth, while we pooled estimates across countries, healthcare costs can vary substantially across different healthcare systems and settings. We chose to combine estimates to gain a broader overview of the economic burden, and used random effects models along with GDP per capita quantiles to account for between-study heterogeneity and minimise differences in costs across countries. However, there remains uncertainty around applying cost estimates from one context to another. Future studies should aim to evaluate costs within specific countries and regions to gain a more localised understanding of the economic burden of antibiotic-resistant Salmonella infections.
Preventive measures for AMR in Salmonella infections include improvements in access to safe water, sanitation and hygiene (WASH) to block transmission pathways (42). Further, vaccines mitigate AMR by protecting both vaccine recipients and unvaccinated individuals (herd effect), as well as reducing antibiotic use associated with infections (43, 44). WHO recommends introducing and scaling up typhoid conjugate vaccines (TCV) alongside water, sanitation and hygiene (WASH) interventions in typhoid-endemic areas (45). Pakistan, Liberia, and Zimbabwe have included TCV in immunisation programs and campaigns (46). However, TCV introduction to other endemic regions has been delayed due to regulatory approvals, establishment of vaccination strategies, need for additional research, and funding constraints (47). Furthermore, vaccines are still lacking for Salmonella Paratyphi and NTS, although progress is being made to develop new vaccines (48, 49).
Assessing the value of vaccines, WASH improvements, and responsible antibiotic use requires contextual data on the health and economic burden of resistant Salmonella strains. Our systematic review addresses in part this evidence gap by generating estimates for length of hospital stay and associated treatment costs for patients with susceptible or antibiotic-resistant Salmonella Typhi, Paratyphi, and non-typhoidal Salmonella infections.
In conclusion, based on our systematic review and meta-analysis, we infer that resistant strains of Salmonella are associated with an increased economic burden in terms of increased hospitalisation costs and length of stay. However, there are remaining gaps in understanding the specific healthcare costs and extended durations of hospitalisation linked to antibiotic resistance in Salmonella infections, especially in areas endemic to typhoid such as sub-Saharan Africa and warrants future studies to address these evidence gaps.