Pathways of Salmonella Entry into the Bloodstream
Salmonella enters the bloodstream primarily through invasion of intestinal epithelial cells, followed by dissemination via macrophages, with nontyphoidal Salmonella strains having a special predilection for vascular tissue, particularly in patients with atherosclerotic disease. 1
Intestinal Invasion Process
Salmonella's journey from the gastrointestinal tract to the bloodstream follows a well-defined pathway:
Initial Intestinal Epithelial Invasion
- Salmonella penetrates the intestinal mucosa through specialized M cells overlying Peyer's patches
- The bacteria can also directly invade enterocytes using type III secretion systems
- This invasion is facilitated by bacterial virulence factors that manipulate host cell machinery 2
Survival Within Macrophages
- After crossing the epithelial barrier, Salmonella is engulfed by macrophages
- Instead of being destroyed, the bacteria survive and replicate within these phagocytic cells
- Salmonella uses pathogenicity islands and virulence factors to create a specialized niche within macrophages 3
Dissemination Through Lymphatics and Bloodstream
- Infected macrophages transport Salmonella to mesenteric lymph nodes
- From there, bacteria can enter the bloodstream via the thoracic duct
- Direct invasion of blood vessels can also occur, particularly in cases of severe infection 4
Risk Factors for Bloodstream Invasion
Several factors increase the likelihood of Salmonella bacteremia:
- Immunocompromised Status: HIV-infected individuals are at higher risk for Salmonella bacteremia 1
- Atherosclerotic Disease: Damaged endothelium in atherosclerotic plaques provides an attachment site for Salmonella 1
- Gastric Achlorhydria: Reduced stomach acid allows more bacteria to survive and reach the intestines 1
- Age: Both very young children and older adults are at increased risk 5
Specific Mechanisms for Different Salmonella Types
Nontyphoidal Salmonella (NTS)
- Primarily causes self-limiting gastroenteritis but can invade bloodstream in 5-10% of cases
- Approximately 25% of patients aged ≥50 years with Salmonella species bacteremia have an endovascular focus of infection 1
- S. enteritidis and S. choleraesuis have particular predilection for vascular tissue 1
Typhoidal Salmonella
- More frequently causes bacteremia than NTS strains
- Has evolved specific mechanisms to evade immune detection
- Can establish persistent infection in the gallbladder, leading to chronic carriage and recurrent bacteremia 4
Clinical Implications
The ability of Salmonella to invade the bloodstream has important clinical consequences:
- Endovascular Infections: Salmonella has a special predilection to infect vascular tissue, particularly in patients with atherosclerotic disease 1
- Mycotic Aneurysms: Nontyphoidal Salmonella strains account for 30-40% of mycotic aneurysms 1
- Vertebral Osteomyelitis: Lumbar spine osteomyelitis has been reported in up to one-third of patients with aortic mycotic aneurysms caused by Salmonella 1
Diagnostic Considerations
For patients with suspected Salmonella bacteremia:
- Blood cultures are essential and should be obtained before antimicrobial therapy 1
- Multiple blood cultures (2-3 sets) increase detection rates due to the low colony counts (0.3-1.0 CFU/mL) typically seen in Salmonella bacteremia 1
- Bone marrow culture may have higher sensitivity than blood culture for diagnosis of invasive nontyphoidal Salmonella infection 1
Prevention Strategies
To prevent Salmonella bloodstream infections:
- Proper food handling and thorough cooking to reduce exposure 6
- Handwashing after potential contact with fecal material 1
- Avoiding unprotected sexual practices that might result in fecal-oral exposure 1
- Particular vigilance in immunocompromised patients, including prompt evaluation of fever and diarrhea 1
Understanding these pathways is crucial for early identification and management of patients at risk for invasive Salmonella disease, particularly those with immunocompromise or vascular disease.