Nontyphoidal salmonellae are gram-negative bacteria that primarily cause gastroenteritis, bacteremia, and focal infection. Symptoms may be diarrhea, high fever with prostration, or symptoms of focal infection. Diagnosis is by cultures of blood, stool, or site specimens. Treatment, when indicated, is with trimethoprim/sulfamethoxazole, ciprofloxacin, azithromycin, or ceftriaxone with surgery for abscesses, vascular lesions, and bone and joint infections.
(See also Overview of Salmonella Infections.)
Nontyphoidal Salmonella infections are common and remain a significant public health problem in the United States. Many serotypes of Salmonella have been given names and are referred to informally as if they were separate species even though they are not. Most nontyphoidal Salmonella infections are caused by S. enterica subspecies enterica serotype Enteritidis, S. Typhimurium, S. Newport, S. Heidelberg, and S. Javiana.
Human disease occurs by direct and indirect contact with numerous species of infected animals, the foodstuffs derived from them, and their excreta. Contaminated meat, poultry, raw milk, eggs, egg products, and water are common sources of Salmonella. Other reported sources include infected pet turtles and reptiles, carmine red dye, and contaminated marijuana.
Risk factors
Subtotal gastrectomy, achlorhydria (or ingestion of antacids), hemolytic conditions (eg, sickle cell anemia, Oroya fever, malaria), bartonellosis, splenectomy, louse-borne relapsing fever, cirrhosis, leukemia, lymphoma, and HIV infection are all risk factors for Salmonella infection.
Diseases caused by nontyphoidal Salmonella species
Each Salmonella serotype can cause any or all of the clinical syndromes described below, although given serotypes tend to produce specific syndromes. Enteric fever, for instance, is caused by S. Paratyphi types A, B, and C.
An asymptomatic carrier state may also occur. However, carriers are rare and do not seem to play a major role in large outbreaks of nontyphoidal gastroenteritis. Persistent shedding of organisms can occur in the stool for years with nontyphoidal Salmonella infections (1).
Reference
1. Foster N, Tang Y, Berchieri A, Geng S, Jiao X, Barrow P. Revisiting Persistent Salmonella Infection and the Carrier State: What Do We Know?. Pathogens. 2021;10(10):1299. Published 2021 Oct 9. doi:10.3390/pathogens10101299
Symptoms and Signs of Nontyphoidal Salmonella Infections
Salmonella infection may manifest as
Enteric fever
Focal disease
Gastroenteritis usually starts 12 to 48 hours after ingestion of organisms, with nausea and cramping abdominal pain followed by diarrhea, fever, and sometimes vomiting. Usually, the stool is watery but may be a pastelike semisolid. Rarely, mucus or blood is present. The disease is usually mild, lasting 1 to 4 days. Occasionally, a more severe, protracted illness occurs. About 10 to 30% of adults develop reactive arthritis weeks to months after diarrhea stops. Reactive arthritis causes pain and swelling, usually in the hips, knees, and Achilles tendon.
Enteric fever is a term often used interchangeably with typhoid fever. Enteric fever typically refers to a form of typhoid caused by nontyphoidal Salmonella infections caused by S. enterica subspecies; it is characterized by fever, prostration, and septicemia.
Bacteremia is relatively uncommon in patients with gastroenteritis, except in infants (who also can have meningitis) and older adults. However, S. Choleraesuis, S. Typhimurium, and S. Heidelberg, among others, can cause a sustained and frequently lethal bacteremic syndrome lasting ≥ 1 week, with prolonged fever, headache, malaise, and chills but rarely diarrhea. Sustained bacteremia suggests endovascular infection, such endocarditis or infection of an abdominal aortic aneurysm, which can occur as a complication of Salmonella bacteremia. Patients may have recurrent episodes of bacteremia or other invasive infections (eg, infectious arthritis) due to Salmonella. Bacteremia is more likely to occur in patients who are immunologically compromised (eg, those with HIV/AIDS) and in patients with a hemolytic condition (eg, sickle cell anemia, malaria, Oroya fever), who are also more likely to develop a focal infection, such as infectious arthritis, osteomyelitis, pneumonia, endarteritis (eg, infected aortic aneurysm), endocarditis, urinary tract infection, cholangitis, or meningitis. Recurrent or multiple episodes of Salmonella infection in a patient without other risk factors should prompt HIV testing.
Photo courtesy of Dr. Thomas F. Sellers, Emory University, via the Public Health Image Library of the Centers for Disease Control and Prevention.
Focal Salmonella infection can occur with or without sustained bacteremia, causing pain in or referred from the involved organ—the gastrointestinal tract (liver, gallbladder, appendix), endothelial surfaces (eg, atherosclerotic plaques, ileofemoral or aortic aneurysms, heart valves), pericardium, meninges, lungs, joints, bones, genitourinary tract, or soft tissues. Preexisting solid tumors are occasionally seeded and develop abscesses that may, in turn, become a source of Salmonella bacteremia. S. Choleraesuis and S. Typhimurium are the most common causes of focal infection.
Diagnosis of Nontyphoidal Salmonella Infections
Cultures
Diagnosis of nontyphoidal Salmonella infections is by isolating the organism from stool or another infected site. In bacteremic and focal forms, blood cultures are positive, but stool cultures may be negative.
Antibiotic resistance has become a problem with both S. Typhi and nontyphoidal Salmonella, so antimicrobial susceptibility testing is important.
In patients with gastroenteritis, Salmonella can be detected on multiplex nucleic acid testing panels, but these do not provide antibiotic resistance testing. Stool specimens stained with methylene blue often show white blood cells, indicating inflammatory colitis.
Patients at high risk (eg, older nursing home residents, infants, and patients with hemoglobinopathies, HIV infection, or other immunocompromising conditions) should be evaluated for complications (eg, typically blood culture and cerebrospinal fluid testing in infants).
Treatment of Nontyphoidal Salmonella Infections
Supportive care
Antibiotics for patients at high risk of invasive disease and patients with systemic or focal infections
Sometimes surgery
Uncomplicated gastroenteritis due to nontyphoidal Salmonella infection is treated symptomatically with oral or IV fluids (see treatment of gastroenteritis).
Antibiotics do not hasten resolution of gastroenteritis, may prolong excretion of the organism, and are unwarranted in uncomplicated cases. However, in older nursing home residents, infants, and patients with hemoglobinopathies, HIV infection, or other immunocompromising conditions, increased mortality dictates treatment with antibiotics. Acceptable antibiotics include the following:
TMP/SMX orally for children
Ciprofloxacin orally for adults
Azithromycin orally for adults
Ceftriaxone IV for adults
Extraintestinal focal infections occur in 5 to 10% of patients with Salmonella bacteremia (1), necessitating additional evaluation and longer courses of antibiotics.
Pearls & Pitfalls
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Patients who are not immunocompromised should be treated for 3 to 5 days; patients who have HIV/AIDS or other severely immunocompromising conditions may require prolonged suppression to prevent relapses.
Systemic or focal disease should be treated with antibiotic doses as for typhoid fever. Sustained bacteremia is generally treated for 4 to 6 weeks.
Abscesses should be drained surgically. At least 4 weeks of antibiotic therapy should follow surgery.
Infected aneurysms and heart valves and bone or joint infections usually require surgical intervention and prolonged courses of antibiotics.
The prognosis is usually good, unless severe underlying disease is present. Case fatality rates resulting from endocarditis and endarteritis are high.
Carriers
Asymptomatic carriage is usually self-limited, and antibiotic treatment is rarely required. In unusual cases (eg, in food handlers or health care workers), eradication may be attempted with oral ciprofloxacin for 1 month. Follow-up stool cultures should be obtained in the weeks after antibiotic administration to document elimination of Salmonella.
Treatment reference
1. Mandal BK, Brennand J. Bacteraemia in salmonellosis: a 15 year retrospective study from a regional infectious diseases unit. BMJ. 1988;297:1242–1243. PMID: 3145067
Prevention of Nontyphoidal Salmonella Infections
Preventing contamination of foodstuffs by infected animals and humans is paramount. Preventive measures for travelers also apply to most other enteric infections.
Case reporting is essential.
Key Points
Nontyphoidal Salmonella infections are common and result from direct and indirect contact with numerous species of infected animals, the foodstuffs derived from them, and their excreta.
Clinical syndromes include gastroenteritis, enteric fever, and focal infections; bacteremia occasionally occurs.
Diagnose using cultures.
For uncomplicated gastroenteritis, antibiotics are unnecessary; they do not hasten resolution and may prolong excretion of the organism.
Treat high-risk patients (eg, older nursing home residents, infants, patients with hemoglobinopathies, HIV infection, or other immunocompromising conditions) with antibiotics, such as ciprofloxacin, azithromycin, ceftriaxone, or trimethoprim/sulfamethoxazole (TMP/SMX).
An asymptomatic carrier state may occur, but carriers do not play a major role in outbreaks, and treatment with antibiotics is rarely indicated.
