Pediatric Salmonella Infection 

Updated: Jun 10, 2016
Author: Archana Chatterjee, MD, PhD; Chief Editor: Russell W Steele, MD 

Overview

Background

Infections due to Salmonella species represent a major public health problem in many countries. In the United States, nontyphoidal Salmonella (NTS) is the most common pathogen implicated in food-borne gastroenteritis.[1] In most cases, NTS is a self-limiting disease that causes mild gastroenteritis; however, it can lead to a wide spectrum of complications including bacteremia, enterocolitis, and severe local infections such as meningitis and osteomyelitis.[2, 3, 4] Salmonella serotype typhi can cause serious and prolonged bacteremic illness referred to as enteric fever or typhoid fever.[5]

Pathophysiology

The extension of the disease to various organs depends on the serotype, the size of the inoculum, and the status of the host. If large enough numbers of bacteria are ingested, they can survive in the normally lethal acidic pH of the stomach. Once ingested, Salmonella can gain access to the small intestine, producing diffuse mucosal inflammation, edema, and microabscesses. Generally, most NTS do not extend beyond the lamina propria and lymphatics of the gut. Exceptions include Salmonellacholeraesuis and Salmonelladublin, which can cause bacteremia with little intestinal involvement.[6] In individuals with S. typhi, areas of intestinal necrosis can ulcerate and result in perforation. In addition, this mucosal penetration allows uptake into the draining lymph nodes, contributing to blood stream infections (BSI) and subsequent invasion of the liver, spleen, and bone marrow. This process explains the delayed onset of symptoms in S.typhi.[7]

Epidemiology

Frequency

United States

NTS caused an estimated 11% of the 9.4 million food-borne illnesses in the United States, second to norovirus. From 2006-2008, NTS was the leading cause of food-borne illnesses that resulted in hospitalization and death.[8] . Approximately 400 cases of typhoid fever are reported per year. Most of cases are a result of foreign travel, either US citizens traveling to developing countries or foreign travelers to the United States. Most cases are from travel to India or Pakistan.[9] However, over the last 10 years, US travelers to Asia, Africa, and Latin America have been especially at risk.[10]

The preliminary data from the Foodborne Diseases Active Surveillance Network (FoodNet) of the Centers for Disease Control and Prevention's (CDC's) Emerging Infections Program for 2011 revealed a steady increase in the reported incidence of Salmonella infections in the 10 US states in which active, population-based surveillance is performed.[11]

A study by Walters et al investigated turtle-associated salmonellosis outbreaks occurring in 2011-2013. The study identified 8 outbreaks totaling 473 cases from 41 states, Washington DC, and Puerto Rico. The median patient age was 4 years; 45% percent were Hispanic; and 28% were hospitalized. The study added that in the week preceding illness, 68% of case-patients reported turtle exposure and among these, 88% described small turtles.[12]

International

The past 2 decades have seen an increase in the incidence of NTS in Europe and North America.[13] A report from the GeoSentinel Surveillance Network revealed enteric fever as the leading cause of vaccine-preventable disease in international travelers.[14] Typhoid fever is endemic in many developing areas of the world, with incidence rates estimated to be 40-50 cases per 1,000,000 population in Pakistan and India.[15] Five Asian countries are considered to be endemic for typhoid: China, India, Indonesia, Pakistan, and Vietnam.[5] However, the CDC has removed 26 countries in Eastern Europe and the Middle East from the most current recommendations for typhoid vaccination.[15, 16] Annually, the World Health Organization (WHO) estimates 16-33 million cases of typhoid fever worldwide and 500,000-600,000 deaths.

Mortality/Morbidity

Enteric infections account for significant morbidity and mortality in young children (aged 1-4 y). Morbidity and mortality rates are highest in infants (most dangerous in infants < 3 mo with bacteremia), elderly patients, and patients with sickle cell disease, acquired immunodeficiency syndrome (AIDS), neoplasms, or other immunosuppressive conditions.[5, 17, 18] Substantial differences in outcomes have been noted based on varying serotypes.[19]

Race

The incidence of infection for all serotyped NTS is almost twice as high in blacks and Latinos, Salmonella typhimurium is the most common pathogen.[20]

Sex

No sex differences are noted.[20]

Age

Attack rates are highest in persons younger than 5 years or older than 70 years.[20, 5]

 

Presentation

History

Carefully obtain the patient's history to determine any potential sources of Salmonella and to help determine if the correct diagnosis has been made.

  • General history

    • Inquire about any recent travel abroad.

    • Inquire about possible animal exposures, including contact with pet iguanas, turtles, tortoises, or other reptiles.

    • Inquire whether any family members have current or recent gastroenteritis.

    • Inquire whether any recent outbreaks have occurred in the community.

  • Salmonella gastroenteritis

    • The incubation period of Salmonella gastroenteritis is 6-72 hours.

    • In most cases, children have cramping abdominal pain, nausea, vomiting, and loose watery stools.

    • Stools may be bloody; however, this is not as common as in infection with Shigella.

    • Fever, which rarely exceeds 39°C, occurs in approximately one half of infected patients.

    • Symptoms usually resolve spontaneously in 2-7 days.

  • Enteric fever (typhoid fever)

    • Enteric fever is caused by S. typhi and several other Salmonella serotypes.

    • The incubation period for enteric fever is 3-60 days, but symptoms typically occur in 1-2 weeks.

    • Patients may present with high fever, which rises in a steplike fashion.

    • Other symptoms include anorexia, abdominal pain, malaise, myalgias, headache, cough, diarrhea or constipation, and delirium.

Physical

Physical findings may include the following:

  • Salmonella gastroenteritis

    • Upon physical examination, patients may have signs of dehydration, such as delayed capillary refill, sunken eyes, dry mucous membranes, or tachycardia.

    • Patients may have tenderness to palpation on abdominal examination, which sometimes can be difficult to differentiate from appendicitis.

    • Rectal examination may reveal heme-positive stools, gross blood, or mucoid stools.

  • Enteric fever (typhoid fever)

    • A typical finding of enteric fever is relative bradycardia for the height of the fever.

    • Hepatosplenomegaly may be found on examination.

    • Patients with enteric fever may develop rose spots; these spots are blanching pink papules most commonly found on the anterior thorax. They usually fade about 3-4 days after appearance, are 2-4 mm in diameter, and occur in groups of 5-20.

Causes

Salmonella organisms are gram-negative rod-shaped bacilli in the family Enterobacteriaceae. All Salmonella organisms are to be considered a single species (Salmonella enterica) because of their close relationship by DNA hybridization studies.[7]

Differences in lipopolysaccharide (LPS) and flagellar structure generate the antigenic variation that is reflected in the more than 2500 known serotypes that cause human disease.

Nontyphoidal Salmonella (NTS) serotypes are divided into O-antigen groups A through E. Since 1997, Salmonellaenteritidis (D), S. typhimurium (B), and Salmonella newport (C2) account for about half of the culture-confirmed Salmonella isolates. The principal reservoirs for NTS organisms are poultry, livestock, reptiles, and pets. The mode of transmission is ingestion of foods of animal origin, including poultry, red meats, unpasteurized dairy products, and eggs that have been contaminated by infected animals or an infected human.[5, 21]

Recent Salmonella outbreaks have been attributed to commercially produced items, such as peanut butter, frozen pot pies, puffed vegetable snacks, and dry dog food.[22, 23, 24, 25, 26] Contact with infected reptiles, such as iguanas, pet turtles and tortoises, and ingestion of contaminated water are other modes of transmission.

S. typhi (D) is the species known to cause enteric fever (typhoid fever). S. typhi is found only in humans. In the United States, typhoid fever is usually caused by foreign travel to countries with contaminated food and drinking water or by ingestion of food contaminated by a chronic carrier.[5] Travelers visiting friends and relatives in typhoid-endemic countries may be at more risk than tourists because of a lack of precautionary measures.[27] Historically, Salmonella paratyphi (A) has been the cause of a smaller proportion of the cases of enteric fever.[28] However, China and India have experienced a substantial increase in enteric fever caused by S.paratyphi (A).[29]

Excess antibiotic use in the prior year has been associated with a higher incidence of NTS. Disruption of the microflora of the gut has been offered as a possible cause; however, an alternate explanation may be that these individuals are a more medically fragile group, requiring more antibiotics and, in general, are more susceptible to illness.[30]

 

DDx

 

Workup

Laboratory Studies

The following tests are indicated in Salmonella infection:

  • CBC count with differential

    • CBC count is often 10,000-15,000/μ L in simple gastroenteritis.

    • Patients with enteric fever commonly have anemia, thrombocytopenia, or neutropenia, although a shift to more immature forms can be seen on the differential count.

  • Cultures

    • Isolation of Salmonella from cultures of stool, blood, urine, or bone marrow is diagnostic (see the image below).

      Under a moderately-high magnification of 8000X, th Under a moderately-high magnification of 8000X, this colorized scanning electron micrograph (SEM) revealed the presence of a small grouping of gram-negative Salmonella typhimurium bacteria that had been isolated from a pure culture. Image courtesy of the Centers for Disease Control and Prevention, Bette Jensen, and Janice Haney Carr.
    • Cultures of rose spots and/or bone marrow aspirate may be positive in enteric fever even when stool culture findings are negative for Salmonella.

  • Stool examination: Stool may be Hemoccult positive and may have positive findings for fecal polymorphonuclear cells.

  • Chemistry

    • Electrolyte tests may reveal metabolic acidosis or other abnormalities consistent with dehydration.

    • Patients with enteric fever may have mild hepatitis.

  • Serologic tests: Tests for Salmonella agglutinins (febrile agglutinins, Widal test) may suggest infection with S. typhi; however, they are not recommended because of the number of false-positive and false-negative results.

Imaging Studies

Imaging studies are not necessary for most patients with simple gastroenteritis and enteric fever without any severe complications.

Consider chest radiography if pneumonia is suggested as the result of bacteremia. Perform abdominal radiography if the patient presents with peritoneal signs on physical examination. Consider intestinal perforation as a complication of enteric fever.

Perform a bone scan if osteomyelitis is considered as a complication of bacteremia. MRI, which is more sensitive, is preferred to evaluate osteomyelitis.

 

Treatment

Medical Care

Aspects of treatment in Salmonella infection include the following:

  • Salmonella gastroenteritis

    • For uncomplicated gastroenteritis caused by nontyphoidal Salmonella species, antimicrobial therapy is not indicated because it does not shorten the duration of illness and may prolong the duration of fecal excretion.

    • Treatment involves monitoring hydration status and intravenous (IV) therapy to correct electrolyte imbalance or restore intravascular volume.

    • Antidiarrheal agents may actually prolong GI transit time and the illness.

    • Antimicrobial agents and hospital admission may be recommended in Salmonella gastroenteritis in infants younger than 3 months, infants younger than 12 months with temperatures of more than 39°C and unknown blood culture results, and patients with hemoglobinopathies, human immunodeficiency virus (HIV) infection or other causes of immunosuppression, neoplasms, or chronic GI illnesses.

    • The recommended antibiotics for individuals at high risk for invasive disease include ampicillin, amoxicillin, and trimethoprim-sulfamethoxazole (TMP-SMZ). In areas with multidrug resistance, cefotaxime or ceftriaxone are recommended.

  • Treatment of invasive Salmonella disease (bacteremia, extraintestinal manifestations)

    • Empiric antimicrobial therapy should include a broad-spectrum cephalosporin (cefotaxime or ceftriaxone). Once susceptibilities are available, narrower-spectrum therapy includes ampicillin, amoxicillin, as well as broader-spectrum agents such as chloramphenicol, TMP-SMZ, or a fluoroquinolone.

    • A 14-day course of antibiotics is recommended for patients with bacteremia.

    • Patients with localized infection, such as osteomyelitis or an abscess, or patients with bacteremia and HIV infections should receive 4-6 weeks of therapy.

    • For Salmonella meningitis, ceftriaxone or cefotaxime is recommended for 4 weeks or longer.

  • Enteric fever caused by S. typhi infection

    • For S. typhi infection, initial empiric therapy with ceftriaxone is recommended due to widespread resistance. If susceptible, chloramphenicol, ampicillin, or TMP-SMZ may be used. Duration of therapy should be 14 days.

    • In severe infection, parenteral therapy is indicated.

    • Use antipyretics with caution or not at all because they may cause precipitous drops in temperature and shock. Fever may last 5-7 days, even with appropriate therapy.

    • Relapse is common (≤ 15%), and patients must be re-treated.

    • A short course of high dose-corticosteroids may be involved in treatment of patients with life-threatening neurologic complications of enteric fever.

    • High-dose ampicillin or high-dose amoxicillin plus probenecid for 4-6 weeks has cured many chronic carriers. Ciprofloxacin is the drug of choice for adult carriers.[5]

  • Multidrug resistance

    • As many as 40% of nontyphoidal Salmonella (NTS) isolates in the United States are multidrug resistant, with increasing resistance to all Salmonella strains worldwide.[7] In particular parts of the world (ie, India, Pakistan, Egypt), multiply antibiotic-resistant strains of S. typhi are reported. Travelers from these regions should be treated with a 7-day to 10-day course of ceftriaxone or 5-day to 7-day course of ciprofloxacin or ofloxacin.

    • Decreased ciprofloxacin susceptibility and ceftriaxone resistance has been reported in developing countries.[31, 32, 33, 34]

Surgical Care

Cholecystectomy may be curative in carriers with chronic gallbladder disease. Focal abscesses may require drainage.[7]

Consultations

Consider consultation with a pediatric infectious disease specialist if the appropriate antibiotic for treatment or the length of treatment are questioned in patients with documented Salmonella infection. Consider surgical consultation for patients with enteric fever who appear to have complications such as intestinal perforation, splenic rupture, or pancreatitis.

Diet

Restrict initial oral intake to electrolyte solutions, such as Pedialyte or clear liquids. Add solid foods only when the diarrhea appears to be improving and dehydration is not present. Initially, children can be started on a BRAT diet (ie, bananas, rice, applesauce, toast) and then slowly advanced to a regular diet as tolerated.

 

Medication

Medication Summary

In most simple gastroenteritis, antibiotics are not necessary and, in fact, can prolong the duration of illness.

Antibiotics

Class Summary

Patients who are susceptible to invasive disease, those with invasive Salmonella, and those with enteric fever require treatment with antimicrobials.

Amoxicillin (Amoxil, Polymox, Trimox)

Interferes with cell wall synthesis. High-dose amoxicillin can be used if treatment with parenteral therapy not necessary.

Ampicillin (Marcillin, Omnipen, Polycillin, Principen)

Demonstrated effectiveness in treatment of gastroenteritis, invasive disease, and enteric fever.

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad gram-negative coverage and CNS penetration. Ceftriaxone or cefotaxime is considered DOC for Salmonella meningitis.

Cefotaxime (Claforan)

Third-generation cephalosporin. Cefotaxime or ceftriaxone considered DOC for treatment of Salmonella meningitis.

Chloramphenicol (Chloromycetin)

Considered by many to be DOC for treatment of enteric fever. PO chloramphenicol no longer available in United States.

Trimethoprim-sulfamethoxazole (TMP-SMZ, Septra, Bactrim)

Sulfonamide derivative. Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.

Ciprofloxacin (Cipro)

Quinolone antibiotic considered DOC for adult chronic carriers with S. typhi infection.

Glucocorticoids

Class Summary

Glucocorticoids have been demonstrated to have some benefit in patients with severe neurologic complications of enteric fever.

Dexamethasone (Decadron)

Demonstrated some potential benefits in patients with obtundation, shock, stupor, or coma from enteric fever.

 

Follow-up

Further Outpatient Care

Monitor patient's hydration status as an outpatient. Admission is warranted if the patient has signs and/or symptoms of dehydration. Monitor patients treated for enteric fever for possibility of relapse. Follow up on all blood cultures if the patient is being treated as an outpatient. Monitor for postinfectious functional GI disorders, such as irritable bowel syndrome.[35]

Further Inpatient Care

If admission is necessary in patients with Salmonella infection, monitor the patient's hydration and electrolyte levels, continue intravenous (IV) or oral (PO) antibiotics as needed, and observe for and appropriately treat complications of Salmonella.[36]

Deterrence/Prevention

Good personal hygiene, handwashing, and appropriate sanitary practices deter spread of the disease. Standard precautions and contact precautions must be used during the entire hospitalization of patients, especially for children who are in diapers or who are incontinent.

A study of 123 children with laboratory-confirmed Salmonella infections and 139 control children who had not experienced symptoms of GI illness during the month prior to the interviews concluded that after adjusting for race and household income, Salmonella infections were significantly associated with attendance of a daycare center, contact with cats, and contact with reptiles during the 3 days prior to the onset of illness.[37] Thus, exposure to environmental sources may play an important role in sporadic infections with Salmonella.

For patients hospitalized with S. typhi infection, precautions must be continued until results of 3 stool cultures are negative 48 hours after stopping antibiotic therapy.[5]

No vaccination is available for nontyphoidal Salmonella (NTS). Typhoid vaccination can help reduce the incidence of typhoid fever (50-75% efficacy). Although vaccinations enhance resistance to infection with S. typhi, immunity is overcome by a large bacterial inoculum. Immunization is recommended for the following individuals: (1) those who travel to an endemic area, (2) those with intimate exposure to an individual known to be a carrier of typhoid fever, (3) laboratory workers with frequent contact with S. typhi, and (4) individuals living in typhoid-endemic areas outside the United States.[5]

Two vaccinations are available in the United States. PO Ty21a vaccine is a live attenuated vaccination that can be given to children aged 6 years or older. Vaccination should be completed at least 1 week before exposure. A booster dose is recommended after 5 years in the case of continuous or repeated exposure. Vi capsular polysaccharide vaccine can be given to patients aged 2 years or older and consists of one intramuscular injection at least 2 weeks before exposure. A booster is recommended in 2 years.[5, 7]

Complications

Complications of Salmonella infection include the following:

  • Nontyphoidal salmonellosis

    • Bacteremia

    • Meningitis

    • Pneumonia

    • Endocarditis/pericarditis

    • Osteomyelitis (most common in patients with sickle cell anemia)

    • Hepatic/splenic abscess

  • Typhoid fever (enteric fever)

    • Intestinal perforation and severe hemorrhage (occurs in 1-10% of children)

    • Toxic encephalopathy and cerebral thrombosis

    • Hepatitis, pancreatitis, arthritis, and myocarditis

Prognosis

Prognosis varies, as follows:

  • Nontyphoidal salmonellosis

    • Prognosis of patients with simple gastroenteritis is excellent except for very young infants or patients with debilitating diseases.

    • The prognosis for Salmonella meningitis or endocarditis is poor.

  • Typhoid fever (enteric fever)

    • Therapy with antibiotics has decreased the mortality rate to 1%; however, prognosis depends on the extent of complications from the disease.

    • Relapse is common after therapy for enteric fever.

  • Chronic carrier state: Patients who continue to shed bacteria for more than 1 year (approximately 1% of patients) are considered chronic carriers.

  • NTS bacteremia: Increased mortality may be associated with a higher magnitude of NTS bacteremia.[38]

Patient Education

Good personal hygiene and hand washing are essential for all people involved in food handling. All medical personnel must also use standard precautions when treating patients with Salmonella to avoid patient-to-patient transmission.

For excellent patient education resources, see eMedicineHealth's patient education article Foreign Travel and the Centers for Disease Control and Prevention Web site.