This study aimed to investigate the incidence, risk factors, and outcome of SBSI in South Sweden. The mean age- and sex-standardized incidence of SBSI during the study period was 1.0 (0.8–1.2) per 100,000 person years, and the incidence saw a slight decrease during the study period, with a noteworthy decrease during the COVID-19 pandemic in 2020. As around half of the SBSI cases in our study were travel-related, international travel likely influence the incidence of SBSI in Sweden. In our study, a declining trend was noted in the annual proportion of Salmonella infections associated with travel. However, the limited number of travel-related cases in our study prevents a robust assessment of the significance of this trend, and it should be noted that information on international travel was missing for more than one-fifth of the SBSI cases. Nonetheless, the diminishing trend observed in travel-related cases warrants further research investigating the epidemiological factors of Salmonella infections in the context of global travel patterns such as travel destination, specific serotypes associated with travel-related cases, and travel behavior.

In Sweden, infection with Salmonella is a notifiable disease, and data from the Public Health Agency of Sweden reveal a declining trend in the number of annual cases during the study period, including both BSI and enteric cases (https://www.folkhalsomyndigheten.se/the-public-health-agency-of-sweden). This further supports that the preventive work to reduce Salmonella-contaminated food by the Swedish Food Agency is successful.

A study from Denmark in 2006 found a higher mean incidence of 2.3 per 100,000 person-years, and the incidence steadily increased during the study period [10]. This could be explained by the fact that Denmark has a higher Salmonella incidence in general than Sweden [11].

Notably, these trends align with findings from several other studies, including research in the Netherlands (2012), a long-term study in Queensland, Australia (2007–2016), and a multinational population-based study spanning Australia, Finland, Canada, and Denmark (2000–2006), all of which reported increasing incidence rates [6, 12, 13]. Given the substantial regional variation in the incidence of Salmonella bacteremia, there is a compelling need for further research to comprehensively explore contributing factors. These may encompass travel behaviors, food practices, agricultural influences, and other pertinent variables, aligning with a One Health approach. We are not aware of any Salmonella outbreaks in our region during the study period. Overall, the incidence of SBSI in this study confirms that SBSI is a rare medical condition in our setting [3, 14].

The Salmonella strains included in this study exhibited low antimicrobial resistance towards antibiotics commonly used in healthcare. The highest rate of resistance was found for ciprofloxacin (17%), which is lower than what has been reported for the first-line antibiotic therapy with tetracycline, ampicillin, ceftriaxone, and ciprofloxacin from the USA (20%) and England (34%) [15, 16]. Higher rates of antimicrobial resistance have been reported from countries in South Asia, sub-Saharan Africa, and East Asia where Salmonella is endemic and antimicrobial resistance is a major concern [17, 18]. It should be noted that 1% of the strains included in our study were resistant to cefotaxime, which constitutes the first-line antibiotic for treating sepsis and suspected BSI in Sweden [19].

The 30- and 180-day mortality rates in this study were 3% and 9%, respectively, which are lower than those found in a 2006 study from Denmark, where the 30-day and 180-day mortality were 11% and 22%, respectively [10]. Studies in neighboring Denmark reported more cases of domestic Salmonella cases, which tend to have a worse prognosis compared to imported cases [5, 20, 21]. In our study the mortality rates, as well as the need for and duration of both hospitalization and intensive care, were significantly higher in patients with SBSI than in patients without BSI. This is not surprising but supports the fact that SBSI is a serious medical condition with substantial impact [22,23,24,25].

Patients with SBSI in this study exhibited a distinctive clinical presentation when compared to patients without BSI. Notably, they presented with fewer gastrointestinal symptoms, aligning with previous findings by Yen et al. [26], who concluded that the majority of adults with SBSI do not display symptoms of gastroenteritis. Furthermore, our observations indicated a statistically longer duration of symptoms (such as abdominal pain) and diarrhea among patients with BSI when compared to the control group. This finding corresponds with the research conducted by Bar-Meir et al. [27], who noted that children with SBSI experienced a more extended duration of symptoms in comparison to those with Salmonella gastroenteritis. It is worth noting, however, that the difference in the duration of symptoms and diarrhea, although statistically significant, may not be considered clinically significant, as it amounted to just one additional day. Additionally, the duration of symptoms remains highly contingent on when the patient seeks medical care and, consequently, when blood cultures are obtained during the course of the disease.

Importantly, our study revealed a noteworthy clinical distinction between SBSI and non-BSI cases. We observed that the presence of diarrhea significantly decreases the risk of developing BSI. In practical terms, this suggests that patients presenting with diarrhea as their primary symptom may not necessarily require antibiotic treatment. Conversely, individuals with invasive Salmonella infections tend to present with a more severe clinical profile that includes signs of sepsis, underlining the importance of distinguishing between these clinical presentations to guide appropriate treatment decisions, when Salmonella infections are suspected and managed. While our study was conducted in a specific geographic area, the association between symptoms of gastroenteritis and decreased risk of BSI aligns with findings from other disparate epidemiological profiles, suggesting that these findings could be generalized to other settings [28].

This finding holds critical clinical importance when faced with management of suspected Salmonella infections. When considering whether to initiate antibiotic treatment, the presence of gastroenteritis symptoms may suggest refraining from treatment, especially in patients without other signs of severity.

Regarding PPI treatment, other studies have found an association between PPI treatment and non-typhoidal salmonellosis [29,30,31,32,33], as well as other causes of gastroenteritis [34]. To the best of our knowledge, however, there are no studies exploring the risk of SBSI and the use of PPIs. In our study, there was statistically significant less PPI treatment in the SBSI cohort compared to non-BSI cases, an association that did not remain when only adults were analyzed. We are unable to explain this association, and more research is needed in this area to investigate this further.

In our study, we did not find that age was a risk factor for SBSI. Prior studies have found that higher age is a risk factor for invasive infection [6, 10, 12, 16, 35, 36]. Also, some studies have identified a higher risk of developing invasive infection in infants [25, 35, 37]. In contrast to many other studies, this study found no significant risk increase for male sex and SBSI [6, 12, 16, 25, 35].

Furthermore, patients with SBSI had significantly higher leukocyte counts and alanine transaminase and lactate levels. Although again the differences are small and may not be clinically relevant, the finding is consistent with previous published research [27, 38].

Both comorbidities and immunosuppression have previously been identified as plausible risk factors for SBSI in other studies [16, 22, 27, 39,40,41]. Although significant in the univariate analysis, we did not associate comorbidities and immunosuppression with SBSI.

International travel was common in both patients with SBSI and controls. We did not find that international travel was associated with an increased risk of SBSI, which contradicts the findings of the study by Koch et al. [5] in Denmark 2011. As the domestic cases of Salmonella are low in Sweden compared to many countries, international travel likely impacts both BSI and non-BSI Salmonella cases.

Risk factors such as age, sex, comorbidities, immunosuppression, and international travel have thus been identified as risk factors of SBSI in other studies, but not in ours. This could be due to the different populations studied, the use of different definitions of these variables, and the relatively few SBSI cases included in our study.

We refrained from investigating differences in risk factors and clinical presentation of typhoidal versus non-typhoidal Salmonella as the number of typhoidal SBSI cases was very low.

One of the strengths of this study is that it is population-based, including all BSI in the region, with data from one microbiological lab including all ten hospitals in Skåne, South Sweden. We standardized incidence rates to age and gender to enable comparisons with other populations. We did not select individuals for the control group but included all patients with Salmonella in feces with a concurrent negative blood culture, and the control group was twice as large as the group of cases. Moreover, there was no selection based on age, as the study included both children and adults. We did not exclude patients from the group of cases nor the control group. In Sweden, all individuals have a unique personal number which makes it easy to link information from medical records, laboratory results, and microbiological findings to each individual, which is another strength of this study. In addition, the study started in 2012, when MALDI-TOF was established in clinical routine use at the clinical microbiology laboratory, improving the differentiation between bacterial species.

Our study has some limitations. A major limitation is that overall, a substantial number of patients with Salmonella detected in their stool samples did not undergo blood culture during the study period. Out of the 2732 patients included with positive cultures/PCR from blood or stool only 448 (16%) were cultured from blood, potentially missing a vast number of SBSI. This limitation potentially underestimated the number of BSI cases included in the study and could hence impact our analyses of risk factors. It is plausible that younger, healthier individuals seeking primary care for gastroenteritis were less likely to undergo blood culture, potentially introducing bias into the risk factor analysis. Also, not every variable was available from the medical records for every individual in the study. For some variables, there were considerable missing data, which is a common limitation of retrospective studies. These variables included some symptoms that were not accounted for, not all blood tests were taken, and most notably there was no record of international travel in more than a fifth of SBSI cases. The substantial missing data in these areas may have implications for the comprehensiveness and accuracy of our analyses and findings. Another limitation is the rather modest number of study participants, even if there were no patients excluded and we included all patients with at least one positive blood culture. In addition, 44% of the control group had received antibiotic treatment prior to blood culture, which could make their blood cultures false negative.

It is important to monitor the incidence, trends, and resistance patterns of SBSI, to provide a basis for recommendations for empirical antibiotics and to oversee preventive measures. To fully investigate the prevalence and burden of invasive Salmonella infection, more patients with suspected Salmonella need to be blood cultured.