Clinical and microbiological characterization of Salmonella spp. isolates from patients treated in a university hospital in South America between 2012–2021: a cohort study

An absence of information about the patterns of Salmonellosis in Latin America has been identified and an imperative need has arisen to generate population and clinical studies to evaluate disease dynamics, mortality and risk factors for severe disease [11, 19]. This study contributes to the generation of knowledge about clinical patterns, resistance, mortality and related factors in the region, in addition to providing a basis that can be used in future monitoring of the disease.

Although it was found an apparent low prevalence of salmonellosis with respect to the total number of health consultations in our hospital, 4% of the patients attended with this condition died. In addition, in patients with other associated conditions, such as bacteremia, infections by ESBL species, or neoplasms, mortality rises significantly to a proportion close to 10%. This situation is compounded by an increase in the rates of resistance to the first-line antibiotics commonly used for the treatment of the disease. According to these findings, salmonellosis remains a public health problem, especially for populations with vulnerable health conditions. Strengthening prevention policies, improving access to diagnostic tools in low-income countries, and promoting the responsible use of antibiotics in the treatment of infectious diseases should be a public health priority.

It was identified a similar proportion of Salmonella cases in children and adults, and in women and men. Previous studies have already reported that there are no significant differences in the proportion of cases by sex [20]; however, it is usually described that Salmonella spp. affects more children than adults and usually occurs in immunocompromised patients [21]. One of the conditions that may explain our high proportion of adults with Salmonellosis is the fact that our clinic receives a significant number of patients with malignant diseases, transplant recipients and/or immunosuppressed patients.

Consistent with what has been identified in previous studies [22], the most frequent symptoms of salmonellosis were diarrhea, fever, emesis and dehydration. Remarkably, one in five children aged 15 years or younger had respiratory symptoms, while abdominal pain occurred more frequently in patients older than 15 years. When identifying this type of symptomatology, especially in the context of foodborne disease outbreaks, it is important to suspect Salmonella spp. infections and to ask about risk factors such as not using a cutting board specifically for raw meat, consuming raw/undercooked meat or eggs, or the recent use of antibiotics [23].

If salmonellosis is suspected, the corresponding study and empirical management of the cases should be initiated according to the severity and diagnostic suspicion. Antimicrobial agents are not recommended for the treatment of non-severe NTS diarrhea in healthy adults or children; however, their use is indicated for persons with evidence of sepsis, extraintestinal infection, populations with bacteremia or risk of bacteremia, and patients with disseminated disease. Antibiotics such as ampicillin, amoxicillin, azithromycin, fluoroquinolones, 3rd and 4th generation cephalosporins or carbapenems can be used according to the conditions of the patients [24]. In our study, more than 70% of the patients received empirical antibiotic therapy. This can be explained by the fact that, being a highly complex institution, it is more likely to find patients with more severe conditions and greater underlying comorbidities, which is also supported by the fact that nearly 80% of the patients required in-hospital management.

Most of Salmonella spp. infections in which the species was identified in our population corresponded to NTS, with an approximate ratio of 9:1 respect to Salmonella typhi isolates. This is consistent with a high NTS prevalence described in food in Latin American studies, which ranged from 0.005% to 93.3%. Contrarily, previous reports of studies conducted in the old world have described a case distribution of 27.07% of NTS and 72.93% of Salmonella typhi [25]. The finding of a higher prevalence of NTS in our population is of special interest considering that the proportion of antimicrobial resistant isolates was higher in NTS than in Salmonella typhi.

Mortality in the group older than 15 years was found to be slightly higher than in the group aged 15 years or younger, although these differences did not reach statistical significance (5.4% vs. 2.8%; p 0.13). In a recently published systematic review with meta-analysis, no studies were found evaluating mortality by NTS in the Americas region in areas other than the United States that recorded higher mortality in people older than 15 years than that estimated in younger people (21% [16.6–25.7] vs. 12% [9–15.4%]) [11].

We hypothesize that the reason why our mortality was considerably lower than that estimated in that study may be because, being a highly complex institution, there may have been greater clinical suspicion, facilitating timely diagnosis. In addition, with greater opportunity for access to early antibiotic therapy directed against the infecting agent, compared to centers of lower complexity. Despite this, we found that mortality occurred mainly in vulnerable groups such as those with hematological malignancy, bacteremia and ICU requirement, so it is necessary to strengthen surveillance and therapeutic measures in these vulnerable groups. A recent study performed in oncologic patients with NTS infections found that salmonellosis produced more severe disease [26]. Although we did not find statistically significant associations in the multivariate model of hematological malignancy with mortality, we did find a higher proportion of deaths in that group. This may be due to lack of power due to poor representation of these subgroups in our cohort. Future studies with larger sample sizes are required to obtain better estimates.

One of the most important problems evidenced by our research is the increase in antibiotic resistance in recent years, which represents a threat to public health in our communities. According to our study, the most prevalent resistance phenotypes in Salmonella spp. are against ciprofloxacin, ceftriaxone, ampicillin/sulbactam and ampicillin, with a sustained increase in the resistance rates to these antibiotics in addition to cefepime. Some factors that could explain this increase are the indiscriminate use of self-formulated antibiotics, incomplete treatments by the patients, the use of broad-spectrum antibiotics in livestock and poultry, the use of chemicals such as triclosan, among others [27, 28].

Our findings are consistent with reports from the Centers for Disease Control and Prevention (CDC) indicating an increasing prevalence of antibiotic-resistant NTS infections, with resistance rates to any antibiotic reaching close to 20% in 2017 [29]. However, we observed a strikingly low proportion of ciprofloxacin-resistant Salmonella typhi samples in our population (less than 1%), despite that up to 74% of S. typhi strains were non-susceptible to this antibiotic in the CDC report. Instead, the highest resistance profiles were against TMP/SMX and ceftriaxone, with a high proportion of ESBL in our population. Notably, resistance to ceftriaxone was estimated to reach 60% in NTS. A previous study evaluating the geographic distribution and trends of typhoid fever disease in Colombia, based on data from the National Institute of Health, reported 836 isolates over a 3-year period, with a mortality rate of 0.74% and 84.3% of S. typhi sensitive to all antimicrobials. In agreement with our findings, in the INS study, resistance to ciprofloxacin was only 2% of the isolates [30].

Some of the limitations of this study are its retrospective nature, the use of medical records as a secondary source of information that in some cases may not contain all the information regarding the conditions of the patients at the time of infection, the lack of long-term follow-up of infected patients, the low availability of isolates serotyped for salmonella, and the selection and information biases inherent to this type of observational research. In addition, since the Salmonella cultures were performed according to medical criteria, it is possible that some cases of salmonellosis that consulted at Fundación Valle de Lili were not identified by our study. Also, it is necessary to consider the possibility of a beta error, as the “n” in some analysis performed was low. Among the strengths are the number of patients enrolled, the efforts to ensure better data quality through double validation and structured data entry in electronic case report formats, the use of standardized definitions and trained personnel for the identification of information in the clinical history, and the fact of discriminating the analysis by clinical groups of interest and by age, which can be a source of confusion in less robust analyses.