How Do You Treat Invasive Salmonella Infections?

Patient Presentation
A 16-year-old female came to the emergency room with a 36 hour history of diarrhea and emesis.
She had been on a school trip in Europe and during the day she was leaving to return to the United States had 2 bouts of diarrhea, one of which was accompanied by emesis.
During the flight back, she had more diarrhea and emesis. She then had to drive home 4 hours.
At home she was taken to the emergency room where she was given intravenous fluids for dehydration.
As she was being discharged she began to have a fever so she was admitted for further evaluation.
Additional history revealed that the diarrhea did not contain blood or mucous and was described as watery. The emesis occurred usually around the time of the diarrhea.
She could not remember how many episodes she had had, but did state that she had not eaten or drunk anything since being in Europe.
She complained of crampy abdominal pain around the episodes, and nausea inbetween them.
The past medical history and family history were non-contributory.
The review of systems was negative for fever, chills, cough, upper respiratory symptoms, dysuria, or rashes.
The social history revealed that she had traveled to several countries, had swum in a lake, and had eaten mainly eggs, rice and vegetables as she was a vegetarian.
Several other students on the trip had been ill with diarrhea of short duration 3 days before her symptoms began.
The pertinent physical exam at admission showed a tired, ill-appearing female with a temperature of 38.5 degrees Celsius.
She had mild left lower quadrant tenderness with deep palpation without guarding. The rest of the examination was negative.
The work-up was begun and included an abdominal radiograph and laboratory testing.
Over the next 2-3 hours as the testing was being completed, her temperature increased to 40.3 degrees Celsius and she complained of neck and back pain.
On repeat physical examination, she had a non-specific confluent red flat rash over her neck and upper shoulders. She complained of pain with flexion of her neck and legs at the hips.
She had no abdominal tenderness at that time.
The patient was begun on ceftriaxone intravenously and a lumbar puncture was performed which had a normal glucose, protein and cell count.
As this was occurring her previous testing became available and showed hemoglobin of 13.2 g/dl, hematocrit of 37%, white blood cell count of 9.0 x 1000/mm2 with 900 neutrophils, 4140 bands, 1700 lymphocytes and 180 reactive lymphocytes.
The C-reactive protein was 28.2 mg/dl and the erythrocyte sedimentation rate was 27 mm/hour.
She continued to be febrile from 38-39.5 degrees Celsius over the next 10-12 hours, but her rash disappeared as did her neck and back pain.
At this time, she became afebrile but began to complain of left lower quadrant pain again that now radiated to her umbilicus.
The radiologic evaluation of an abdominal CT showed a non-inflamed appendix but with an appendicolith, a small amount of fluid in the pelvis and thickened bowel walls.
Surgical consultation was obtained who took the adolescent to the operating room for an elective appendectomy due to the presence of the appendicolith and exploration.
The appendix was normal with no abscess or perforation but the surgeons noted that the patient had an extremely inflamed colon.
The patient continued to clinically improve on the ceftriaxone without fever, with 3-4 episodes of non-bloody, non-mucous diarrhea per day. On day 3, as she was being readied for discharge on home ceftriaxone, she began to have bloody diarrhea.
Her initial stool culture was also now growing Salmonella, which was subsequently identified as Salmonella enteritidis confirming the diagnosis of enteric fever.
She received a total of 10 days of ceftriaxone and at followup her diarrhea had resolved. Repeat stool cultures were negative.
The airline, state public health department and the U.S. Centers for Disease Control were also contacted at various points during her illness to provide appropriate information to protect the public’s health.

Figure 66 – Axial computed tomography image of the lower
abdomen obtained with intravenous, oral, and rectal contrast reveals
the cecum to be filled with liquid stool, a small appendicolith in
the appendix medial to the cecum without evidence of appendicitis and
mild thickening of the wall of the descending colon consistent with

Salmonella is a highly contagious organism causing an estimated 17 million cases of typhoid fever and 600,000 deaths yearly worldwide.
It causes a spectrum of illness. Most commonly it causes gastroenteritis with diarrhea, abdominal cramps and fever.
Bacteremia may be intermittent or continuous
Focal infections such as meningitis or osteomyelitis occur in up to 10% of patients with bacteremia.

Enteric fever is caused by Salmonella typhi and other Salmonella serotypes when there is a protracted bacterial illness.
It may begin gradually with constitutional symptoms (i.e. anorexia, headache, lethargy and malaise), fever, abdominal tenderness and pain, hepatosplenomegaly, and mental status changes. Diarrhea is common and may or may not be bloody.

The transmission is mainly through food such as poultry, beef eggs and dairy products. Other food contaminated from humans may also transmit Salmonella such as vegetables, fruits and bakery products.
Other transmission routes include contaminated water and contact with amphibians and reptiles.
The incubation period for gastroenteritis is shorter usually 12-36 hours with a range of 6 -72 hours. The incubation period for enteric fever is longer; usual period is 7-14 days with a range of 3-60 days.

Salmonella has more than 2,640 serotypes. Human disease causing organisms are classified according to their O-antigen group (A-E).
In the US about 50% of all Salmonella is caused by Salmonella typhimurium (B), Salmonella enteritidis (D) and Salmonella Newport (E).
Salmonella typhi is a D serotype.

A carrier state is not uncommon with 45% of children < 5 years old and 5% of older children and adults being still excreting organisms in their stool 12 weeks later.
At one year, 1% of patients still excrete organisms.
Unfortunately instead of eliminating carriage, antibiotics tend to increase the carrier state. Enteric fever patients (~15%) may relapse requiring re-treatment.

Learning Point
Patients with localized invasive disease are initially treated with an expanded-spectrum cephalosporin such as cefotaxime or ceftriaxone. Once susceptibility results become available, ampicillin, ceftriaxone or cefotaxime for susceptible strains lasting at least 4 weeks in duration is recommended.
This should be increased to 6 weeks for meningitis. Localized disease means patients with abscess, meningitis, osteomyelitis, or patients with HIV and bacteremia.

For patients with invasive, nonfocal infections (e.g. bacteremia or enteric fever) the administration route, drug choice, and duration are based on the strain susceptibility, clinical response, host and site of infection.
A minimum 10-14 days of antibiotics is recommended. Salmonella typhi can be multidrug-resistant, and empiric treatment with an expanded-spectrum cephalosporin, azithromycin or fluoroquinolone may be necessary.

Chronic carriage of Salmonella typhi in children may be treated with high-dose parenteral ampicillin or high-dose oral amoxicillin with probenecid. Ciprofloxacin is recommended for adults.
Cholecystectomy is sometimes indicated for adult patients where gallstones contribute to the carrier state.

Questions for Further Discussion
1. What are the indications for corticosteroid use in patients with Salmonella?
2. What are the indications for typhoid vaccine use?
3. What commonly prescribed travel medication needs to be administered after oral typhoid vaccine because of potential interactions?
4. What percentage of patients with Salmonella get enteric fever?

Related Cases

To Learn More
To view pediatric review articles on ther topic from the past year check PubMed.

Information prescriptions for patients can be found at MedlinePlus for these topics: Salmonella Infections and Food Contamination and Poisoning.

To view current news articles on ther topic check Google News.

To view images related to ther topic check Google Images.

Graham SM.
Salmonellosis in children in developing and developed countries and populations.
Curr Opin Infect Dis. 2002 Oct;15(5):507-12.

American Academy of Pediatrics. Salmonella, In Pickering LD, Baker CJ, Long SS, McMillan JA, eds. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2006;579-584.

Linam WM, Gerber MA.
Changing epidemiology and prevention of Salmonella infections.
Pediatr Infect Dis J. 2007 Aug;26(8):7.

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Interpersonal and Communication Skills

    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Systems Based Practice
    23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

    August 25, 2008