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Microbiology and Pathogenesis
Salmonellae are facultatively anaerobic gram-negative bacilli that cause infection when between 200 and 106 organisms are ingested.
- Conditions that reduce gastric acidity or intestinal integrity increase susceptibility to infection.
- Organisms penetrate the small-intestinal mucus layer and traverse the intestinal epithelium through M cells overlying Peyer’s patches.
- S. Typhi and S. Paratyphi survive within macrophages, then disseminate throughout the body via lymphatics, and ultimately colonize reticuloendothelial tissues.
- Nontyphoidal salmonellae most commonly cause gastroenteritis, invading the large- and small-intestinal mucosa and resulting in massive PMN infiltration (as opposed to the mononuclear-cell infiltration seen with typhoid fever).
Epidemiology and Clinical Manifestations
Depending on the specific species, salmonellosis results in typhoid fever or gastroenteritis.
- Typhoid (enteric) fever: Typhoid fever is a systemic disease characterized by fever and abdominal pain and caused by dissemination of S. Typhi or S. Paratyphi, for which humans are the only hosts.
- Disease results from ingestion of food or water contaminated by chronic carriers and is rare in developed nations. Worldwide, there are ∼21–27 million cases, with 200,000–600,000 deaths annually.
- After an incubation period of 5–21 days, prolonged fever (>75% of cases), headache (80%), chills (35–45%), anorexia (55%), and abdominal pain (30–40%) are common. Other signs and symptoms may include sweating, cough, malaise, arthralgias, nausea, vomiting, and diarrhea—or, less often, constipation.
- Physical findings include rose spots (a faint, salmon-colored, blanching, maculopapular rash), hepatosplenomegaly, epistaxis, and relative bradycardia.
- Intestinal perforation and/or GI hemorrhage can occur in the third and fourth weeks of illness; neurologic manifestations (e.g., meningitis, Guillain-Barré syndrome) occur in 2–40% of pts.
- Long-term Salmonella carriage (i.e., for >1 year) in urine or stool develops in 2–5% of pts.
- Nontyphoidal salmonellosis (NTS): Most commonly caused by S. Typhimurium or S. Enteritidis, NTS typically presents within 6–48 h of exposure as gastroenteritis (nausea, vomiting, nonbloody diarrhea, abdominal cramping, and fever) that lasts 3–7 days.
- In the United States, NTS causes ∼12 million illnesses annually.
- Disease is acquired from multiple animal reservoirs. The main mode of transmission is via contaminated food products, such as eggs (S. Enteritidis), poultry, undercooked meat, dairy products, manufactured or processed foods, and fresh produce. Infection is also acquired during exposure to pets, especially reptiles.
- Stool cultures remain positive for 4–5 weeks and—in rare cases of chronic carriage—for >1 year.
- Bacteremia, usually due to S. Choleraesuis and S. Dublin, develops in 8% of pts; of these pts, 5–10% develop localized infections (e.g., hepatosplenic abscesses, meningitis, pneumonia, osteomyelitis).
- Reactive arthritis can follow Salmonella gastroenteritis, particularly in persons with the HLA-B27 histocompatibility antigen.
Positive cultures of blood, stool, or other specimens are required for diagnosis.
- Typhoid fever: A fluoroquinolone (e.g., ciprofloxacin, 500 mg PO bid for 5–7 days) is most effective against susceptible organisms.
- Enteric fever in regions with a high prevalence of reduced ciprofloxacin susceptibility and ciprofloxacin resistance (e.g., India, Nepal, and some locales in Africa) should be empirically treated with ceftriaxone (2 g/d IV for 10–14 days), azithromycin (1 g/d PO for 5 days), or high-dose ciprofloxacin (750 mg PO bid or 400 mg IV q8h for 10–14 days; only for isolates with reduced susceptibility to ciprofloxacin).
- Dexamethasone may be of benefit in severe cases.
- NTS: Antibiotic treatment is not recommended in most cases as it does not shorten the duration of symptoms and is associated with increased rates of relapse, a prolonged carrier state, and adverse drug reactions.
- Antibiotic treatment may be required for infants ≤3 months of age; pts >50 years of age with suspected atherosclerosis; pts with immunosuppression; pts with cardiac, valvular, or endovascular abnormalities; and pts with significant joint disease.
- Fluoroquinolones or third-generation cephalosporins are given for 3–7 days or until defervescence (if the pt is immunocompetent) or for 1–2 weeks (if the pt is immunocompromised).
- HIV-infected pts are at high risk for Salmonella bacteremia and should receive 4 weeks of oral fluoroquinolone therapy after 1–2 weeks of IV treatment. In cases of relapse, long-term suppression with a fluoroquinolone or TMP-SMX should be considered.
- Pts with endovascular infections or endocarditis should receive 6 weeks of treatment with a third-generation cephalosporin.