> Table of Contents > Salmonella Infection
Salmonella Infection
Justin Thomas Ertle, BS, MD
Marie L. Borum, MD, EdD, MPH
image BASICS
DESCRIPTION
  • Infection caused by any serotype of the bacterial genus Salmonella, a gram-negative anaerobic bacillus
  • Nontyphoidal Salmonella typically causes gastroenteritis via foodborne infection and sporadic outbreaks. Less commonly causes infection outside the gastrointestinal tract
Clinical syndromes
  • Enteric fever (see “Typhoid Fever”)
  • Nontyphoidal gastroenteritis
    • Chronic carrier state (> 1 year)
  • Nontyphoidal invasive disease
    • Bacteremia
      • Endovascular complications
      • Localized infection outside GI tract
Geriatric Considerations
Patients >65 years old have increased risk of developing invasive disease with bacteremia and endovascular complications due to comorbidities (atherosclerotic endovascular lesions, prostheses, etc.) that increase risk of seeding (1).
Pediatric Considerations
Neonates (<3 months) are more susceptible to invasive disease and complications (1).
EPIDEMIOLOGY
Incidence
  • Global incidence of nontyphoidal Salmonella enteritidis estimated to be 93.8 million per year in 2009 (2).
    • Wide variation by region from 40 to 3,980 estimated cases per 100,000 in 2009 (2)
  • Global incidence of invasive nontyphoidal Salmonella infection estimated to be 2.1 to 6.5 million in 2010 (2).
    • Wide variation by region from 0.8 to 227 estimated cases per 100,000 in 2010 (2)
  • Most commonly identified foodborne illness in the United States and a common cause of traveler's diarrhea (3)
  • Second most common bacteria isolated from stool cultures in diarrheal illness (following Campylobacter) in the United States (3)
  • Highest incidence in children <5 years old
  • Hospitalization rates higher in patients >50 years old
  • Peak frequency: July to November
ETIOLOGY AND PATHOPHYSIOLOGY
  • Salmonella enterica
    • Most pathogenic species in humans
    • 2,500 different serotypes
Etiology
  • ˜95% of cases are foodborne (3).
  • Majority of the other 5% of cases are due to direct or indirect fecal-oral contact with animals or human carriers.
  • Iatrogenic contamination (e.g., blood transfusion, endoscopy) is possible, although rare.
Pathophysiology
  • Typical infectious dose in immunocompetent patients is ingestion of one million bacteria (3).
  • Bacteria ingested invade the distal ileal and proximal colonic mucosa to produce an inflammatory and cytotoxic response.
  • Bacteria can enter the mesenteric lymphatic system and then into systemic circulation to cause disseminated/invasive disease.
RISK FACTORS
  • Recent travel
  • Consumption of undercooked meat, egg, or unpasteurized dairy products. Nonanimal products have also been implicated in outbreaks.
  • Contact with live reptiles or poultry.
  • Contact with human carrier who has Salmonella fecal shedding.
  • Impaired gastric acidity: H2 receptor blockers, antacids, proton pump inhibitors (PPIs), gastrectomy, achlorhydria, pernicious anemia, infants
  • Recent antibiotic use
  • Reticuloendothelial blockade: sickle cell disease, malaria, bartonellosis
  • Immunosuppression: HIV, diabetes, corticosteroid or other immunosuppressant use, chemotherapy
  • Iron overload, chronic granulomatous disease
  • Age <5 years or >50 years
GENERAL PREVENTION
  • Proper hygiene in production, transport, and storage of food (e.g., refrigeration during food storage and thoroughly cooking food prior to consumption)
  • Control of animal reservoirs: Avoid contact with high-risk animals, animal feces, and polluted waters.
  • Hand hygiene
  • CDC Web site (http://www.cdc.gov/salmonella/) tracks outbreaks
COMMONLY ASSOCIATED CONDITIONS
  • Gastroenteritis
  • Bacteremia: immunocompromised patients or those with underlying medical conditions (e.g., cholelithiasis, prostheses)
  • Osteomyelitis: higher incidence in sickle cell disease
  • Abscesses: higher incidence with malignant tumors
  • Reactive arthritis
image DIAGNOSIS
PHYSICAL EXAM
  • Fever (1)[A]
  • Evidence of hypovolemia (1)[C]
  • Abdominal tenderness (1)[C]
  • Heme-positive stool in some patients (1)[C]
  • Hepatosplenomegaly in some patients (3)[C]
DIFFERENTIAL DIAGNOSIS
  • Viral gastroenteritis
  • Bacterial enteritis due to other organisms
  • Pseudomembranous colitis
  • Inflammatory bowel disease
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Gastroenteritis
    • Stool culture for Salmonella, Escherichia coli, Shigella, and Campylobacter (1)[C]
    • Indications for stool culture include:
      • Severe diarrhea (≥6 loose stools daily) (1)[C]
      • Diarrhea >1 week in duration (1)[C]
      • Fever (1)[C]
      • Diarrhea containing blood or mucous (1)[C]
      • Multiple cases suggesting an outbreak (1)[C]
    • Fecal leukocytes: positive
  • Bacteremia
    • Blood cultures (1)[C]
    • Stool cultures: may also be positive (1)[C]
  • Endovascular infection
    • Consider angiography in patients >50 years of age with bacteremia if aortic or vascular source is suspected (4)[A].
  • Local infections
    • Wound culture
    • Consider CT or MRI for soft tissue or bone infections (3)[C].
  • Chronic carrier state
    • Stool culture positive for > 1 year (3)[C]
    • Urine culture may be positive in chronic carriers.
Follow-Up Tests & Special Considerations
  • Diarrhea lasting > 10 days should prompt investigation for other causes.
  • Asymptomatic excretion of Salmonella may occur for weeks after infection; follow-up fecal cultures are generally not indicated for patients with uncomplicated gastroenteritis (3,4)[C].
  • Follow-up blood cultures are suggested for patients with bacteremia (3)[C].
Test Interpretation
Intestinal biopsies (if taken) may show mucosal ulceration, hemorrhage, and necrosis seen on along with reticuloendothelial hypertrophy/hyperplasia.
image TREATMENT
  • Treatment for nonsevere nontyphoidal Salmonella gastroenteritis in immunocompetent patients is supportive. The illness is typically self-limited. There is no proven benefit to treatment of mild disease. Treatment can suppress the host immunologic, and higher rates of relapse have been reported (1)[C],(5)[A].
  • Consider antibiotics in immunocompetent hosts with severe diarrhea, high fever, or in those requiring hospitalization (1)[C].
  • Some patients are at increased risk of bacteremia and benefit from antibiotics:
    • Infants <3 months of age (1)[C]
    • Persons >50 years old especially >65 years old (1,3)[C]
    • Patients with hemoglobinopathies, atherosclerotic lesions, and prosthetic valves, grafts, or joints or any immunosuppressed state (1,3)[C],(4)[A]
  • Chronic carriage of nontyphoidal Salmonella
    • 4 to 6 weeks of antimicrobial therapy
    • Prophylactic therapy in immunocompromised patients (4)[A]
P.937

GENERAL MEASURES
  • Hydration and electrolyte replacement
  • Hand washing and barrier precautions for inpatients
  • Avoid antimotility drugs in patients with fever or dysentery. Antimotility drugs may increase contact time of the enteropathogen in the gut mucosa (1)[C].
MEDICATION
First Line
  • Gastroenteritis, uncomplicated: No specific medications are necessary. Supportive care (1)[A]
  • Gastroenteritis, complicated (due to illness severity or host risk factors such as immunocompromise)
    • Adults (treat for 14 days if immunocompromised)
      • Levofloxacin (or other fluoroquinolone) 500 mg/day PO for 7 to 10 days (1)[C]; or
      • Trimethoprim-sulfamethoxazole: 160/800 mg PO BID for 7 to 10 days or
      • Amoxicillin: 500 mg PO TID for 7 to 10 days or
      • Ceftriaxone: 1 to 2 g/day IV for 7 to 10 days or
      • Azithromycin: 500 mg/day PO for 7 days (1)[C]
    • Children
      • Ceftriaxone: 100 mg/kg/day IV or IM in 2 equally divided doses for 7 to 10 days (1)[C]; or
      • Azithromycin: 20 mg/kg/day PO daily for 7 days (1)[C]
    • HIV patients
      • Increased duration of antimicrobial therapy and/or zidovudine may decrease relapse (4)[C].
  • Bacteremia: Due to resistance trends, treat lifethreatening infections in adults with a fluoroquinolone and a 3rd-generation cephalosporin until susceptibilities are determined (4)[A].
    • Adults
      • Ciprofloxacin (or other fluoroquinolone): 400 mg IV BID for 10 to 14 days; plus
      • Ceftriaxone: 1 to 2 g/day IV for 10 to 14 days; or
      • Cefotaxime: 2 g IV q8h for 10 to 14 days
    • Children
      • Ampicillin: 200 mg/kg/day in 4 divided doses for 10 to 14 days; or
      • Trimethoprim-sulfamethoxazole: 8 to 12 mg/kg/day of trimethoprim component in 2 divided doses for 10 to 14 days; or
      • Ceftriaxone: 50 to 75 mg/kg/day (max 1 g) once per day for 10 to 14 days
  • Localized infection (e.g., septic arthritis, osteomyelitis, cholangitis, and pneumonia)
    • Same treatment as for bacteremia
    • In sustained bacteremia, prolonged local infection, or immunocompromised patients, give antibiotics PO for 4 to 6 weeks (4)[A].
  • Chronic carrier state (shedding > 1 year duration)
    • Amoxicillin: 1 g PO TID for 12 weeks; or
    • Trimethoprim-sulfamethoxazole 160 mg/800 mg PO BID for 12 weeks; or
    • Ciprofloxacin: 500 mg PO BID for 4 weeks, or
    • Levofloxacin 500 mg/day for 4 weeks; or
    • Norfloxacin 400 mg PO BID for 4 weeks if gallstones are present.
  • Strains resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole have been reported (6)[B].
  • Fluoroquinolone resistance is increasing, perhaps due to increasing use in livestock (6)[B].
  • Extended-spectrum cephalosporin resistance has been reported with increasing frequency (6)[B].
Second Line
  • Aztreonam is an alternative agent that may be useful in patients with multiple allergies or organisms with unusual resistance patterns (4)[A].
  • Fluoroquinolones are now routinely given to children for 5 to 7 days in areas of the world where multidrug-resistant Salmonella typhi is common (4)[A].
SURGERY/OTHER PROCEDURES
  • Surgical excision and drainage for infected tissue sites, followed by a minimum of 2 weeks of antibiotic therapy (4)[A]
  • If biliary tract disease is present, a preoperative 10- to 14-day course of parenteral antibiotics is recommended prior to cholecystectomy.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Asymptomatic shedding of Salmonella may occur for weeks after infection. Follow-up fecal cultures are generally not indicated for patients with uncomplicated gastroenteritis. Requirements may differ during a Salmonella outbreak (4)[A].
  • Criteria may vary by state and local regulations. Some public health departments require negative stool cultures for health workers and food handlers prior to returning to work. Shedding may last 4 to 8 weeks (4)[A].
  • Serotyping of isolates can be performed at public health laboratories.
DIET
Easily digestible foods (1)[C]
PATIENT EDUCATION
  • Meticulous hand hygiene; caution handling raw meat, poultry, and eggs
  • Fruits and vegetables should be thoroughly washed prior to consumption.
  • Thoroughly cooking meats eliminates Salmonella.
  • Caution when handling animals with high fecal carriage rates
  • www.cdc.gov/salmonella/general/prevention.html
PROGNOSIS
  • Most cases of Salmonella gastroenteritis are selflimited and have an excellent prognosis.
  • Increased mortality is seen in the young (<3 months), elderly (>65 years), and immunocompromised (1,2,3).
  • Increased mortality is seen with bacteremia and other invasive infections (2,5).
  • Mortality is increased in multidrug-resistant strains (5).
REFERENCES
1. DuPont HL. Clinical practice. Bacterial diarrhea. N Engl J Med. 2009;361(16):1560-1569.
2. Ao TT, Feasey NA, Gordon MA, et al. Global burden of invasive nontyphoidal Salmonella disease, 2010. Emerg Infect Dis. 2015;21(6).
3. Crum-Cianflone NF. Salmonellosis and the gastrointestinal tract: more than just peanut butter. Curr Gastroenterol Rep. 2008;10(4):424-431.
4. Hohmann EL. Nontyphoidal salmonellosis. Clin Infect Dis. 2001;32(2):263-269.
5. Onwuezobe IA, Oshun PO, Odigwe CC. Antimicrobials for treating symptomatic non-typhoidal Salmonella infection. Cochrane Database Syst Rev. 2012;(11):CD001167.
6. Crump JA, Medalla FM, Joyce KW, et al. Antimicrobial resistance among invasive nontyphoidal Salmonella enterica isolates in the United States: National Antimicrobial Resistance Monitoring System, 1996 to 2007. Antimicrob Agents Chemother. 2011;55(3):1148-1154.
Additional Reading
&NA;
  • Chen HM, Wang Y, Su LH, et al. Nontyphoid Salmonella infection: microbiology, clinical features, and antimicrobial therapy. Pediatr Neonatol. 2013;54(3):147-152.
  • Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis. 2001;32(3):331-351.
  • Hurley D, McCusker MP, Fanning S, et al. Salmonella-host interactions—modulation of the host innate immune system. Front Immunol. 2014;5:481.
  • Lee MB, Greig JD. A review of nosocomial Salmonella outbreaks: infection control interventions found effective. Public Health. 2013;127(3):199-206.
  • Odey F, Okomo U, Oyo-Ita A. Vaccines for preventing invasive salmonella infections in people with sickle cell disease. Cochrane Database Syst Rev. 2015;(6): CD006975.
See Also
&NA;
Gastroenteritis; Typhoid Fever
Codes
&NA;
ICD10
  • A02.9 Salmonella infection, unspecified
  • A02.0 Salmonella enteritis
  • A02.1 Salmonella sepsis
Clinical Pearls
&NA;
  • Nontyphoidal Salmonella infection is typically a foodborne infection associated with a self-limited gastroenteritis.
  • Clinical syndromes include gastroenteritis, bacteremia, endovascular infection, localized infection outside the GI tract, and a chronic carrier state.
  • Those at greatest risk of complications from Salmonella infection include the young, the elderly, and immunocompromised patients.
  • Uncomplicated gastroenteritis in healthy patients can be treated with supportive care.
  • Antibiotics should be used in infants, the elderly, immunocompromised patients, and for invasive infections such as bacteremia outside the GI tract.