para>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 enteriditis 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
DIAGNOSIS
HISTORY
- Salmonella infections are typically asymptomatic or result in mild, self-limited gastroenteritis (1)[C].
- Exposure history: travel; contact with infected human, reptile, or poultry; improper food preparation
- Host factors: age, immune status, other risk factors
- Symptoms typically begin 12 to 72 hours after ingestion and resolve within 4 to 10 days (4)[A].
- Acute uncomplicated illness
- Sudden onset of nausea, vomiting, diarrhea (1)[C]
- Abdominal cramping (1)[C]
- Headache (1)[C]
- Myalgias (1)[C]
- Fever (1)[C]
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. ‚
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]
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 life-threatening 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.
ALERT
Antimicrobial resistance
‚
- 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.
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 self-limited and have an excellent prognosis.
- Increased mortality is seen in the young (<3 months), elderly (>65 years), and immunocompromised (1,2 and 3).
- Increased mortality is seen with bacteremia and other invasive infections (2,5).
- Mortality is increased in multidrug-resistant strains (5).
COMPLICATIONS
Toxic megacolon, hypovolemic shock, metastatic abscess formation, endocarditis, infectious endarteritis, meningitis, septic arthritis, reactive arthritis, osteomyelitis, pneumonia, appendicitis, cholecystitis (1,3,4) ‚
REFERENCES
11 DuPont ‚ HL. Clinical practice. Bacterial diarrhea. N Engl J Med. 2009;361(16):1560 " “1569.22 Ao ‚ TT, Feasey ‚ NA, Gordon ‚ MA, et al. Global burden of invasive nontyphoidal Salmonella disease, 2010. Emerg Infect Dis. 2015;21(6).33 Crum-Cianflone ‚ NF. Salmonellosis and the gastrointestinal tract: more than just peanut butter. Curr Gastroenterol Rep. 2008;10(4):424 " “431.44 Hohmann ‚ EL. Nontyphoidal salmonellosis. Clin Infect Dis. 2001;32(2):263 " “269.55 Onwuezobe ‚ IA, Oshun ‚ PO, Odigwe ‚ CC. Antimicrobials for treating symptomatic non-typhoidal Salmonella infection. Cochrane Database Syst Rev. 2012;(11):CD001167.66 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
- 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
Gastroenteritis; Typhoid Fever ‚
CODES
ICD10
- A02.9 Salmonella infection, unspecified
- A02.0 Salmonella enteritis
- A02.1 Salmonella sepsis
- A02.8 Other specified salmonella infections
- A02.21 Salmonella meningitis
- A02.22 Salmonella pneumonia
- A02.23 Salmonella arthritis
- A02.24 Salmonella osteomyelitis
- A02.25 Salmonella pyelonephritis
- A02.29 Salmonella with other localized infection
ICD9
- 003.9 Salmonella infection, unspecified
- 003.0 Salmonella gastroenteritis
- 003.1 Salmonella septicemia
- 003.8 Other specified salmonella infections
- 003.21 Salmonella meningitis
- 003.22 Salmonella pneumonia
- 003.23 Salmonella arthritis
- 003.24 Salmonella osteomyelitis
- 003.29 Other localized salmonella infections
- 003.20 Localized salmonella infection, unspecified
SNOMED
- 302231008 Salmonella infection (disorder)
- 42338000 Salmonella gastroenteritis (disorder)
- 449083008 Sepsis due to Salmonella (disorder)
- 402962004 Salmonella infection with skin involvement (disorder)
- 170485005 Salmonella carrier (finding)
- 77645007 Salmonella meningitis (disorder)
CLINICAL PEARLS
- 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.