AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

First described in 1880 and cultured in 1884, salmonellae are motile, gram-negative, rod-shaped bacteria of the family Enterobacteriaceae. Named after Daniel E. Salmon, the pathologist who first isolated the organism from porcine intestine, salmonellae are common in the gastrointestinal tracts of mammals, reptiles, birds, and insects.

As with the closely related bacterium Escherichia coli, salmonellae are potential enteric pathogens and a leading cause of bacterial food-borne illness. Additionally, salmonellae have been implicated in a spectrum of other diseases, including enteric or typhoid fever (primarily Salmonella typhi and Salmonella paratyphi), bacteremia, endovascular infections, focal infections (eg, osteomyelitis), and enterocolitis (typically Salmonella typhimurium, Salmonella enteritidis, and Salmonella heidelberg).

All salmonellae are grouped into a single overarching species. This species, Salmonella choleraesuis, is divided into 7 subgroups based on DNA homology and host range. Most of the salmonellae that are pathogenic in humans belong to a single subgroup (subgroup I). Additionally, each of the salmonellae can be serotyped according to their particular complement of somatic O, surface Vi, and flagellar H antigens. Presently, more than 2,300 Salmonella serovars exist.

Salmonellae can be isolated in the microbiology laboratory using a number of low-selective media (MacConkey agar, deoxycholate agar), intermediate-selective media (Salmonella-Shigella [SS] agar, Hektoen [HE] agar), and highly selective media (selenite agar with brilliant green). Individual isolates can then be distinguished by serotyping, bacteriophage typing, and genotyping.

Pathophysiology

The transmission of salmonellae to a susceptible host usually occurs by consumption of contaminated foods. The most common sources of salmonellae are beef, poultry, and eggs. In one recent estimate, consumption of egg shell fragments contaminated with Salmonella enterica serovar Enteritidis was responsible for approximately 182,060 cases of enteritis in the United States in the year 2000. Improperly prepared fruits, vegetables, dairy products, and shellfish have also been implicated as sources of Salmonella. Moreover, human-to-human and animal-to-human transmission can occur. For example, amphibian and reptile exposure is associated with approximately 74,000 Salmonella infections annually in the United States. Recently, cats have also been implicated as a potential reservoir.

Although the infectious dose varies among strains, a large inoculum is thought to be necessary to overcome stomach acidity and to compete with normal intestinal flora. Large inocula are also associated with higher rates of illness and shorter incubation periods. However, lower infectious doses may be adequate to cause infection if these organisms are co-ingested with foods that rapidly transit the stomach (eg, liquids) or that raise gastric pH (eg, cheese, milk), if antacids are used concomitantly, or if these organisms are ingested by individuals with impaired immune systems.

After ingestion, infection with salmonellae is characterized by attachment of the bacteria by fimbriae or pili to cells lining the intestinal lumen. Salmonellae selectively attach to specialized epithelial cells (M cells) of the Peyer patches. The bacteria are then internalized by receptor-mediated endocytosis and transported within phagosomes to the lamina propria, where they are released. Once there, salmonellae induce an influx of macrophages (typhoidal strains) or neutrophils (nontyphoidal strains). Although nontyphoid salmonellae generally precipitate a localized response, S typhi and other especially virulent strains invade deeper tissues via lymphatics and capillaries and elicit a major immune response.

Virulence factors of salmonellae are complex and encoded both on the organism's chromosome and on large (34-120 kd) plasmids. Some areas of active investigation include the means by which salmonellae attach to and invade the intestine, survive within phagosomes, effect a massive efflux of electrolytes and water into the intestinal lumen, and develop drug resistance. Several Salmonella pathogenicity islands have been identified that mediate uptake of the bacteria into epithelial cells (type III secretion system [TTSS]), nonphagocytic cell invasion (Salmonella pathogenicity-island 1 [SPI-1]), and survival and replication within macrophages (Salmonella pathogenicity-island 2 [SPI-2], phoP/phoQ).

The severity of illness in individuals infected with salmonellae is determined not only by the virulence factors of the infecting strain but by host properties as well. For example, individuals at the extremes of age (ie, people who are very young or very old) are at an increased risk for bacteremia. Similarly, systemic lupus erythematosus, malignancies, and immune deficiency are also associated with increased risk of bacteremia.

Frequency

United States

In 1997, the estimated annual incidence of salmonellosis was 13.8 cases per 100,000 people; however, most cases are unreported, and the true incidence may be much higher. Although the incidence is greatest among children, outbreaks are common among individuals who are institutionalized and residents of nursing homes. Far fewer cases of typhoid fever occur each year (0.2 per 100,000 people), and these are increasingly associated with travel to developing countries (currently 72% of cases).

International

In many countries, the incidence of salmonellosis has markedly increased; however, a paucity of good surveillance data exists. An estimated 12-33 million cases of typhoid fever occur globally each year, and the disease is endemic in many developing countries of the Indian subcontinent, South and Central America, and Africa. Outbreaks of typhoid fever have also occurred amidst the recent social upheaval of Eastern Europe.

Mortality/Morbidity

Infection with nontyphoidal salmonellae typically produces a self-limiting gastroenteritis, and dehydrated patients occasionally require hospitalization. Still, death rarely occurs. For example, the mortality rate associated with S enteritidis outbreaks in the United States from 1985-1991 was 0.4%. Case-fatality rates were 70 times higher in nursing homes and hospitals. Mortality rates from typhoid fever are similarly low in the United States (<1%), but mortality rates of 10-30% have been reported in certain Asian and African countries. Between 1996 and 1999, an estimated 1.4 million nontyphoid Salmonella infections occurred in the United States, with an estimated 15,000 hospitalizations and 400 deaths annually. A related study during the same period found that 22% of people infected with nontyphoid Salmonella required hospitalization, with an annual incidence of 0.08 deaths per 100,000 population.

• Although uncommon, extraintestinal complications of salmonellosis caused by seeding of bacteria to other organs are associated with increased mortality rates. Such complications include endocarditis and arterial infections, cholecystitis, hepatic and splenic abscesses, urinary tract infections, pneumonia or empyema, meningitis, septic arthritis, and osteomyelitis.
• Resistance to quinolone antibiotics has also been associated with a 3.15-fold increased risk of invasiveness or death with infection by S typhimurium.

Race

The disease has no predilection for a particular race.

Sex

The disease has no predilection for either sex.

Age

The incidence of salmonellosis in the United States is greatest among children younger than 5 years (61.8 per 100,000 people), with a peak among those younger than 1 year. Infants and people older than 60 years are most susceptible and tend to have more severe infections. In one 4-year surveillance study, 47% of people hospitalized with nontyphoid Salmonella infections were older than 60 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Salmonella infections typically produce 1 of 3 distinct syndromes: gastroenteritis, typhoid (enteric) fever, or focal disease.

• Infection with nontyphoidal salmonellae usually causes enterocolitis similar to that caused by other bacterial enteric pathogens.
• Nausea, vomiting, and diarrhea occur within 6-48 hours after ingestion of contaminated food or drink.
• In most cases, stools are loose and bloodless. Salmonellae may rarely cause large-volume choleralike diarrhea or may be associated with tenesmus.
• • The diarrhea is typically self-limiting and resolves within 3-7 days.
  • While an initial transient diarrhea may occur, established infections with S typhi or S paratyphi are associated with abdominal pain and either constipation (~40%) or recurrent diarrhea (~40%).
• Fever, abdominal cramping, chills, headache, and myalgia are common.
• • Fever usually resolves within 48 hours.
  • Enteric fever (typically caused by S typhi or S paratyphi) is generally an acute illness manifested by fever, headache, and abdominal symptoms and should be considered in travelers returning from tropical and subtropical areas.
• Focal disease is variable and defined by the site of infection.

Physical

Patients with Salmonella gastroenteritis typically have a self-limiting fever (38-39°C) within 48 hours of ingestion. A prolonged persistent fever (4-8 wk in untreated individuals) that increases daily (as high as 41°C) suggests typhoid fever. Nontyphoidal gastroenteritis is generally limited to diarrhea, although typhoid (enteric) fever may present with both gastrointestinal and skin manifestations (ie, rose spots). The following organ systems may be involved with Salmonella infection:

• Gastrointestinal: Salmonella infections typically cause nonbloody loose stool or watery diarrhea. Abdominal tenderness (~50%) and mild hepatosplenomegaly (~50%) are both common in patients with typhoid fever.
• Cardiovascular: Salmonella infections (commonly S typhimurium or S choleraesuis) may produce arterial infections or endocarditis.
• Pulmonary: Salmonella pneumonia or empyema is rare in the absence of comorbid illnesses such as underlying lung disease, malignancy, diabetes, sickle cell anemia, or alcohol abuse.
• Genitourinary: Individuals with urolithiasis or structural abnormalities or individuals who are undergoing immunosuppressive therapy are predisposed to Salmonella urinary tract infections.
• Neurologic: Salmonella meningitis may rarely occur, typically in infants and young children.
• Skeletal: Infection with salmonellae may cause septic arthritis and osteomyelitis. The latter affects the long bones and typically occurs in patients with sickle cell disease.
• Integument: Enteric fever may be associated with pink, blanchable, slightly raised macules (rose spots) on the chest and abdomen.

Causes

• In 1994, the 10 most frequently isolated Salmonella strains causing human disease were reported to the US Centers for Disease Control and Prevention as the following:
• • S enteritidis (26.1%)
  • S typhimurium (22.1%)
  • S enteritidis heidelberg (4.8%)
  • Salmonella enteritidis newport (4.3%)
  • Salmonella hadar (2.7%)
  • Salmonella enteritidis agona (2.0%)
  • Salmonella enteritidis montevideo (1.7%)
  • Salmonella oranienburg (1.6%)
  • Salmonella muenchen (1.5%)
  • Salmonella enteritidis thompson (1.5%)

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Ingestion of preformed toxins (eg, staphylococci, botulin, bacilli)

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Bacteriology
• • Freshly passed stool is the preferred specimen for the isolation of nontyphoidal Salmonella species. Various selective media are routinely used, including MacConkey agar, eosin-methylene blue (EMB) agar, HE agar, SS agar, and xylose-lysine-deoxycholate (XLD) agar.
  • In cases of typhoid fever, S typhi or S paratyphi may be isolated from stool, urine, or rose spot biopsy and from gastric or intestinal secretions, although blood and bone marrow aspirates have the highest yields.
  • Salmonella species may be differentiated by conventional biochemical assays, phage typing, and serological typing.
• Hematology: Although the white blood cell count is usually within reference ranges, approximately one fourth of patients with typhoid fever are leukopenic, neutropenic, or anemic.

Other Tests

• Specialized laboratories may use phage typing, plasmid analysis, ribotyping, pulsed field gel electrophoresis, and polymerase chain reaction when diagnosing salmonellosis.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Salmonella gastroenteritis is usually a self-limiting disease. Direct therapy at fluid and electrolyte replacement. Because antibiotics do not appear to shorten the duration of symptoms and actually prolong the duration of convalescent carriage, they are not routinely used to treat uncomplicated nontyphoidal Salmonella gastroenteritis. Current recommendations are that antibiotics should be reserved for patients with severe disease or patients who are at a high risk of invasive disease.

Historically, recommended oral regimens for the treatment of typhoid fever included ampicillin, trimethoprim-sulfamethoxazole, or chloramphenicol. However, emerging drug resistance has limited the usefulness of these antibiotics. Presently, quinolone, macrolide, and third-generation cephalosporin antibiotics are preferred for empiric therapy. However, resistance to these drugs has also been reported.

• Although still uncommon in the United States, resistance to quinolone antibiotics among typhoidal and nontyphoidal salmonellae is increasingly common elsewhere. In one 22-year surveillance study in Spain, the prevalence of nalidixic acid resistance increased almost 80-fold to 38.5%.
• In a recent review of US data from the National Antimicrobial Resistance Monitoring System, 58% of S typhimurium isolated between 1997 and 1998 were resistant to at least one antibiotic, and 3 multidrug-resistant strains (resistant to 5 or more antibiotics) accounted for 74% of isolates.

Surgical Care

Typhoid fever may occasionally be complicated by intestinal perforation or hemorrhage, cholecystitis, endocarditis, arteritis, osteomyelitis, or soft tissue abscess formation, necessitating surgical intervention. Moreover, long-term carriage with S typhi (usually with the gallbladder as the reservoir) may necessitate cholecystectomy.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals or pharmacotherapy are to eradicate infection, reduce morbidity, and prevent complications.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Deterrence/Prevention

• The mode of Salmonella transmission is primarily oral. Disease prevention consequently includes proper sanitation and hygiene as well as the avoidance of insufficiently cooked or mishandled food.

Complications

• Cardiovascular - Endocarditis, pericarditis, valve perforation, and arteritis
• CNS - Meningitis, ventriculitis, and abscess
• Pulmonary - Pneumonia, abscess, empyema, and bronchopleural fistula
• Bone/joints - Osteomyelitis and septic arthritis
• Hepatobiliary - Hepatic abscess, cholecystitis, and peritonitis
• Splenic - Abscess
• Urinary - Cystitis, pyelonephritis, and renal abscess
• Genital - Ovarian abscess, testicular abscess, prostatitis, and epididymitis
• Soft tissue - Abscess

Prognosis

• Nontyphoidal salmonellosis is generally self-limiting, with symptoms typically lasting no longer than 3-7 days.
• Patients occasionally require hospitalization, but death is rare ( <1%).
• After resolution of symptoms, the mean duration of fecal shedding of Salmonella is 4-5 weeks, depending on the strain.
• In the absence of risk factors for severe disease, limit treatment to symptomatic care and fluid and electrolyte repletion. Indeed, some studies suggest that antibiotics actually prolong the carrier state.
• In the preantibiotic era, approximately 15% of patients with typhoid fever died. More recently, mortality rates as high as 30% have been reported in certain developing countries. The mortality rate for patients with typhoid fever who are appropriately treated is less than 1%.

Patient Education

• Because salmonellae are ubiquitous, their eradication is unlikely. Consequently, a mainstay of disease prevention and control is public education.
• Because transmission primarily occurs through ingestion of contaminated foods, inform people about the importance of sanitary food handling, proper food preparation, and personal hygiene.
• Notably, the emergence of drug-resistant salmonellae illustrates the importance of responsible antibiotic use in medicine and animal husbandry.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Although generally self-limiting, salmonellosis may be severe in patients who are debilitated, immunocompromised, or at the extremes of age. Failure to correctly diagnose and treat these individuals could result in adverse outcomes.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Aserkoff B, Bennett JV. Effect of antibiotic therapy in acute salmonellosis on the fecal excretion of salmonellae. N Engl J Med. Sep 18 1969;281(12):636-40. [Medline].
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• Hsu RB, Chen RJ, Chu SH. Risk factors for recurrent bacteremia in adult patients with nontyphoid salmonellosis. Am J Med Sci. Dec 2004;328(6):315-8. [Medline].
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• Mermin J, Hutwagner L, Vugia D, et al. Reptiles, amphibians, and human Salmonella infection: a population-based, case-control study. Clin Infect Dis. Apr 15 2004;38 Suppl 3:S253-61. [Medline].
• Mermin JH, Townes JM, Gerber M, et al. Typhoid fever in the United States, 1985-1994: changing risks of international travel and increasing antimicrobial resistance. Arch Intern Med. Mar 23 1998;158(6):633-8. [Medline].
• Miller SI, Pegues DA. Salmonella species, including Salmonella typhi. In: Mandell, et al, ed. Principles and Practices of Infectious Diseases. 5th ed. 2000;2:2344-62.
• Nelson JD, Kusmiesz H, Jackson LH, Woodman E. Treatment of Salmonella gastroenteritis with ampicillin, amoxicillin, or placebo. Pediatrics. Jun 1980;65(6):1125-30. [Medline].
• Rabatsky-Ehr T, Whichard J, Rossiter S, et al. Multidrug-resistant strains of Salmonella enterica Typhimurium, United States, 1997-1998. Emerg Infect Dis. May 2004;10(5):795-801. [Medline].
• Schroeder CM, Naugle AL, Schlosser WD, et al. Estimate of illnesses from Salmonella enteritidis in eggs, United States, 2000. Emerg Infect Dis. Jan 2005;11(1):113-5. [Medline].
• Van Immerseel F, Pasmans F, De Buck J, et al. Cats as a risk for transmission of antimicrobial drug-resistant Salmonella. Emerg Infect Dis. Dec 2004;10(12):2169-74. [Medline].
• Voetsch AC, Van Gilder TJ, Angulo FJ, et al. FoodNet estimate of the burden of illness caused by nontyphoidal Salmonella infections in the United States. Clin Infect Dis. Apr 15 2004;38 Suppl 3:S127-34. [Medline].
• Weinberger M, Andorn N, Agmon V, et al. Blood invasiveness of Salmonella enterica as a function of age and serotype. Epidemiol Infect. Dec 2004;132(6):1023-8. [Medline].

Article Last Updated: Aug 1, 2005