Salmonella Infection in Emergency Medicine

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Background

Salmonella are gram-negative facultative intracellular anaerobes that cause a wide spectrum of disease. This spectrum can range from a gastroenteritis, enteric fever (caused by typhoid and paratyphoid serotypes), bacteremia, and focal infections, to a convalescent lifetime carrier state. The type of infection depends on the serotype of Salmonella and host factors. It maintains a broad host range and, for unknown reasons, results in different diseases in different hosts.



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Under a moderately high magnification of 8000X, this colorized scanning electron micrograph (SEM) revealed the presence of a small grouping of gram-ne....

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Although the taxonomy of Salmonella can be confusing, all salmonella serotypes are members of a single species, Salmonella enterica. More than 2600 serovars[2, 3, 1]  have been described, of which humans almost exclusively are infected by Salmonella enterica subspecies enterica serotypes Typhi, Typhimurium, and Choleraesuis worldwide.[4]  The name generally refers to where the serotype was isolated. In the United States, Salmonella serotype Enteritidis (2.6 per 100,000 population), Salmonella serotype Newport (1.4) and Typhimurium (1.3) account for nearly half of the human isolates.[5, 6]

Salmonellosis caused by Salmonella Enteritidis is the most common bacterial infectious cause of food-borne disease in the United States second to norovirus as the most common overall cause of foodborne disease outbreaks.[7, 8]  The World Health Organization (WHO) states Salmonella is one of the four most important causes of diarrhea worldwide.63 Ninety-five percent of cases of Salmonella infection are food-borne; however, the incidence of direct contact exposure with animal carriers is on the rise.[7]  Once infected, salmonellosis harbors a significant morbidity and mortality. One third of untreated patients experience complications and account for three fourths of deaths associated with salmonellosis.[4] Campylobacter and Salmonella are the most common bacterial pathogens found in stool cultures recovered from patients presenting with gastroenteritis or severe diarrhea.[2, 6]

Salmonella has a widespread distribution in the environment and certain host factors make humans particularly susceptible to infection. Its increasing antimicrobial resistance, prevalence, virulence, and adaptability are a challenge worldwide.

 

 

Pathophysiology

Salmonella infections most commonly begin with ingestion of bacteria in contaminated food or water. However, direct contact with animal and human carriers has been implicated. Reptile and amphibian carriers are the most commonly recognized sources of direct contact.[7]  Transmission may also occur from mother to fetus transplacentally.[9]  Studies involving healthy human volunteers required a median dose of 1 million bacteria to produce disease. However, point outbreaks suggest as few as 200 bacteria may produce nontyphoid gastroenteritis.[2]

Once the bacteria survive the acidic stomach, they colonize the intestine and translocate across the intestinal epithelium via three routes: (1) invasion of the enterocytes, (2) invasion of epithelial cells called M cells, and (3) through dendritic cells that intercalate epithelial cells. Interaction with the epithelium and resident cells promote a proinflammatory response to include cytokines, chemokines, neutrophils, macrophages, dendritic cells, and T and B cells. This inflammatory host response actually can benefit the intestinal pathogens and contribute to the nature and severity of the infection by establishing a competitive advantage against the native flora.[10]  Animal studies reveal that prolonged antibiotic use may disrupt this host susceptibility as well.[11]

After crossing this epithelial layer, the bacteria replicate in macrophages in Peyer’s patches, mesenteric lymph nodes, and the spleen. Once colonized, the bacteria then may potentially disseminate to the lungs, gallbladder, kidneys, or central nervous system. When transferring to a new host cell every 1-7 days, it is unknown how and why Salmonella escapes extracellular fluid containing antibodies.[12]  The nontyphoid species of Salmonella tend to produce a more localized response because they are believed to lack the human-specific virulence factors. However, the typhi serotype can develop the more invasive disease resulting in bacteremia. The severity of disease is related to the serotype, number of organisms, and host factors.

Eggs and poultry are the most common sources of infection.[7, 13]  Ingestion of contaminated water, milk, milk products, beef, fruit, vegetables, and dairy products also are common sources. Potential sources of infection for infants with Salmonella are exposure to reptiles, riding in a shopping cart next to meat or poultry, or consuming liquid infant formula.[14]  Outbreaks have been associated with contaminated frozen potpies, puffed vegetable snacks, and exposure to turtles.[3]  More recently, multistate human outbreaks have been seen in contaminated dry dog food and peanut butter products.[15, 16]

Reservoirs of the bacteria include humans, poultry, swine, cattle, rodents, and pets such as iguanas, tortoises, turtles, terrapins, chicks, dogs, and cats. Up to 90% of reptiles and amphibians harbor Salmonella in their gastrointestinal tracts and 6% of nontyphoid disease is related to direct contact with these animals.[7]

Fecal-oral transmission from person to person in areas with poor sanitation and contaminated or nonchlorinated water is the route for enteric or typhoid fever. Humans are the only known carriers of Salmonella typhi.[7]

Individual susceptibility to Salmonella infection increases with extremes of age, immunodeficiency states, prior antibiotic use, neoplastic disease, achlorhydria or antacid use, recent bowel surgery, and malnutrition.

 

 

Epidemiology

Frequency

United States

Prevalence estimates vary secondary to inconsistent diagnosis and reporting techniques. It is estimated that only 3% of Salmonella infections are laboratory confirmed and reported to the Centers for Disease Control and Prevention (CDC). However, an estimated 1.4 million people in the United States are infected with nontyphoid Salmonella annually at a cost of $365 million in direct medical costs.[17]

The overall incidence of Salmonella infection has not changed much compared to 2016-2018 due to a decreased incidence for Typhimurium (13%) with an increase in Infantis (69%).[5, 6]  The true burden of nontyphoid Salmonella in the United States is calculated to be 520 cases per 100,000 compared with 17.1 cases per 100,000 of laboratory-confirmed cases annually, taking into account approximately 38.6 cases of nontyphoid Salmonella for each culture-confirmed case.[18, 19]  The reported 2019 culture-confirmed incidence is 17.1 cases per 100,000.[5, 6]

Additionally, an estimated 500 people are infected with typhoid Salmonella annually.[7]  Most cases of documented typhoid disease in the United States are related to foreign travel to developing nations such as India (30%), Pakistan (13%), Mexico (12%), Bangladesh (8%), Philippines (8%), and Haiti (5%).[7]

International

Fully industrialized nations report frequencies of gastroenteritis similar to that of the United States. However, worldwide estimates of nontyphoid Salmonella range from 200 million to 1.3 billion, with an estimated death toll of 3 million each year.[20]

The serovars responsible for typhoid or enteric fever, typhi and paratyphi, that cause systemic illness lead to an estimated 21.7 million cases and 217,000 deaths worldwide, of which paratyphoid fever accounts for 5.4 million cases.[21]  Salmonella Typhi is estimated to outweigh Salmonella Paratyphi by a ratio of about 4:1 in endemic countries.[22]  Compared with tourists, travelers visiting friends or relatives in developing nations exhibit a much higher incidence of typhoid or enteric fever.[7]  Eighty percent of the total typhoid fever cases and deaths occur in Asia; the rest mainly occur in Africa and Latin America.[23]

Salmonella is identified as a major cause of invasive bacterial febrile illness across sub-Saharan Africa, with a high prevalence of resistance against first-line antimicrobials in both S typhi and invasive nontyphoidal Salmonella.[24]

Mortality/Morbidity

Twenty percent of patients require hospitalization, with an estimated death rate of 0.6%.[19]  Infection with drug-resistant nontyphoid Salmonella and Salmonella typhi increase the likelihood of hospitalization and death.[19]

Invasive nontyphoid Salmonella infection occurs in about 5% of cases in Israel[19]  and is responsible for 400-600 deaths in the United States each year.[7]  Mortality for nontyphoid Salmonella is reported to be as high as 60% in African patients with HIV.[25]  Mycotic abdominal aortic aneurysms are more common in immunocompromised and HIV patients.

The case fatality rate (CFR) in immunocompetent individuals for nontyphoid Salmonella is estimated to be 0.0003-0.003%. However, recent studies have shown that the invasive CFR is estimated to be as high as 37% in Kenyan adults, 47% in Malawian adults, and 12% in African children.[26]

Treated typhoid cases have a 2% mortality rate with a 15% relapse rate.[4]  A significant number of typhoid patients become chronic asymptomatic carriers and can shed high numbers of bacteria in the stool for a lifetime without obvious symptoms.[25]  Depending on the serotype, roughly 1% of adults and 5% of children excrete organisms for greater than a year.[27]

Age

Attack rates are highest in persons younger than 20 years or older than 70 years. The highest rate is found in infants (130 isolates/100,000). One quarter to one third of pediatric typhoid patients are younger than 5 years, of which 6-21% are younger than 2 years.[23]

The clinical appearance of the disease varies in children, especially among very young children.[28]

Neonates are at a greater risk for fecal-oral transmission secondary to relative decreased stomach acidity and buffering of ingested breastmilk and formula.

Invasive Salmonella infection is most prevalent among infants in the United States.[29]

Additional links to nontyphoid Salmonella infection in children include powdered formula, pet ownership, and recent antibiotic use.[30]

Elderly persons are at a relative greater risk for infection secondary to chronic underlying illness and weakened immunity. Nursing home residents have a particularly higher risk. The case-fatality rate (CFR) is estimated at 1.3% for nontyphoid Salmonella among those aged 50 years or older.

Prognosis

Nontyphoid Salmonella is generally self-limiting. Most patients are treated on an outpatient basis. Extremes of age and an immunocompromised state increase morbidity and mortality.

Typhoid Salmonella generally requires treatment. Mortality rate for treated cases is 2%, whereas complications occur in 30% of untreated cases.[4]  Morbidity and mortality increase with drug-resistant S typhi.[19]

Patient Education

Emphasize good hand-washing, thorough cleaning of cooking utensils, appropriate food preparation techniques, and adequate cooking temperature for killing the bacteria.

History

Obtain the patient's dietary history. Inquire about potential restaurant sources, food preparation techniques, and exposure to potentially contaminated or nonchlorinated water sources. Note: In the United States, half of Salmonella outbreaks occur in restaurant settings.[31]

Obtain the patient's travel history. Typhoid fever increasingly is associated with international travel to developing nations.

Determine if other patient contacts have similar illnesses, food ingestions, or animal contacts.

Salmonella syndromes can be divided into gastroenteritis, enteric fever, bacteremia, localized infection, and a chronic carrier state.

Gastroenteritis

Incidence is highest during May through October in temperate climates.[2]

An incubation period of 8-48 hours after the ingestion of contaminated food or water is typical, with reported incubation periods of up to 6-14 days.[32]

Symptoms are acute onset of fever and chills, nausea and vomiting, abdominal cramping, and diarrhea.

If a fever is present, it generally abides in 72 hours.

Diarrhea usually is self-limited, lasting 3-7 days and may be grossly bloody. Diarrhea lasting more than 10 days suggests another diagnosis.[2]

Enteric (typhoid) fever

Enteric fever should be considered when a febrile person (with or without diarrhea) has traveled to an endemic area, has consumed food prepared by individuals with recent exposure, or has laboratory exposure.[33]

The incubation period of enteric (typhoid) fever is 5-21 days.

Transmission generally is from contaminated water or animal products or contact with an infected person or carrier.

The initial prodrome lasting 7-10 days includes headache, cough, diaphoresis, anorexia, weakness, sore throat, malaise, abdominal pain, and constipation or "pea soup" diarrhea. Abdominal pain is present in 20-40% of patients.[2] Constipation is found in 10-38% of patients.[2]

These prodromal symptoms typically plateau as the fever increases in a stepwise fashion peaking in the second week of illness.

After the prodrome, splenomegaly, abdominal distention and pain, relative bradycardia, rash, meningismus, and mental confusion may occur. It may disseminate to lungs, gallbladder, kidneys, or CNS.

Untreated patients experience either complications or resolution by the fourth week. Intestinal perforation occurs in 3-10% of patients.[2] Other complications include endocarditis, pericarditis, pneumonitis, orchitis, and focal abscess.

Bacteremia

Bacteremia occurs in about 5% of patients and  typically occurs in immunocompromised patients, infants, and older adults..

Prolonged or recurrent fevers may occur.

Focal infections may occur.

Mycotic abdominal aortic aneurysm may occur.

Localized infection

Localized infection occurs in 5-10% of persons with bacteremia.[2]

The endocardium, arteries, CNS (more commonly in infants), lungs, bones, joints, muscles, soft tissues, reticuloendothelial system, kidneys, and genital regions are documented sites of extraintestinal infection.

Chronic carrier state

Chronic carrier state is defined as Salmonella in the stool or urine for greater than 1 year.

A chronic carrier state has been identified in 2.2% of patients with reported nontyphoid Salmonella, ​lasting 30 days to 8.3 years.[34]

A chronic carrier state occurs in 1-4% of patients with untreated typhoid Salmonella.

SalmonellaTyphi and SalmonellaParatyphi A are able to survive for protracted periods in the gallbladder and kidney in otherwise healthy people, resulting in long term fecal shedding.[23, 35]

Chronic SalmonellaTyphi carrier state is found to be a risk factor for carcinoma of the gall bladder.[36]

Repetitive exposure to non-Typhoidal Salmonella increases risk for colon cancer.[37]

Physical

Physical findings of salmonellosis can vary depending on the clinical syndrome, serotype, and patient’s immune status. However, the physical findings in gastroenteritis, enteric (typhoid) fever, and bacteremia frequently overlap.

The chronic carrier state is asymptomatic and occurs in about 1-6% infected with Salmonella Typhi.

Gastroenteritis

Fevers (temperature 38-39°C) are common.

Physical signs of dehydration may be found.

Stool examination findings can be negative to grossly bloody.

Diffuse nonfocal abdominal tenderness commonly is present.

In rare cases, Salmonella infection mimics inflammatory bowel disease or pseudoappendicitis.[2]

Enteric or typhoid fever

A stepwise increase in temperature that plateaus in the second week at 39-40°C may be noted.

Cervical adenopathy may occur.

Relative bradycardia occurs in fewer than 50% of cases.

Abdominal examination may reveal distention with pain on deep palpation.

Hepatosplenomegaly is found in 50% of patients.[2]

A rose spot rash that typically occurs in the second week of disease is seen in 30% of patients. This rash is described as a faint salmon-colored 2-3 mm papule lesion located primarily on the trunk that fades with pressure.

Findings of meningismus may appear after the early prodrome.

Bacteremia

Bacteremia usually is associated with a prolonged or recurrent fever.

Generally, it is associated with a localized infection.

It may be a part of a mixed Salmonella infection.[2]

Causes

Currently, more than 2600 serotypes of Salmonellaenterica have been identified.[10, 20]  Although clinical manifestations of each overlap, typhi and paratyphi, tend to cause enteric or typhoid fever and the more invasive form of the disease, whereas most others cause a self-limited form of gastroenteritis.

Complications

Complications of Salmonella infection may include the following:

Laboratory Studies

Serologic testing

Serologic testing for Salmonella lacks overall sensitivity and specificity and varies with the stage of infection.[4, 39]

Complete blood cell count

Anemia is a result of blood loss and inflammation.

The white blood cell (WBC) count in enteric or typhoid fever often is low.

Leukocytosis is common in the first 10 days in children and may result from bacteremia, localized infection, bowel perforation, or other extraintestinal complications.

Reversible thrombocytopenia may occur.

Liver function tests

Liver function tests may be mildly elevated. Elevated alanine aminotransferase level (>70 IU/L) can be seen in enteric fever.[40]

Disseminated intravascular coagulopathy

A reversible form of a mild disseminated intravascular coagulopathy (DIC) may occur.

Cultures

The diagnosis of Salmonella infection is based on isolation of the infecting organism.

Stool culture results can take 3-7 days. Three to 10 grams collected over several days are preferred.[27] Due to the time involved with stool culture detection, treatment decisions should be based on the patient’s presentation. Rapid testing technologies, such as polymerase chain reaction (PCR), have not yet been proven feasible.[41] . However, experimental detection methods such as phagomagnetic immunoassay have obtained good selectivity and sensitivity.[42]

Culture sensitivity decreases after the first week of illness and antibiotic therapy.[4, 39]

Bone marrow evaluation is considered the criterion standard for enteric fever and has a sensitivity of 90% but is rarely performed. Bone marrow aspirates have approximately 10 times the concentration of viable organisms versus blood and continue to have high sensitivity with prior antimicrobial treatment and regardless of duration of disease.[35]

Blood culture results in enteric fever are positive in 50-70% of cases and often are considered a practical first choice.

PCR sensitivity on blood is 84.5% and is as high as 95% when performed in the first 5 days.[39]

PCR evaluations on urine and feces are 69% and 47% sensitive, respectively.[39]

Real-time PCR assay for the specific identification of S Typhi and S Paratyphi A, B, And C with a 2-hour turnaround has shown high reliability[43] ;  however, per a 2017 review, the accuracy of the Salmonella Typi or Parathyphi A rapid diagnostic tests (RDTs) is unclear.[44]

Duodenal string culture is an additional option.[35]

Three serially collected urine samples for suspected enteric fever patients have reported sensitivities of 92% and specificities of 71%.[35]

Antibody assays commonly are used to detect nontyphoid Salmonella in veterinary and food sectors, but this has not extended to standardized testing in human salmonellosis.[45]

Imaging Studies

A focused ultrasonographic examination, CT scan, or MRI should be performed if an extraintestinal manifestation is of concern. This should include muscle/soft tissue, hepatobiliary, spleen, urinary, genital, vascular, and bone.

An acute abdominal series for free air under the diaphragm may be needed to rule out intestinal perforation.

A CT scan of the brain should be performed if central nervous system complications arise (more commonly in neonates).

Procedures

A rectal examination is needed to assess for bleeding. A blood transfusion rarely is required.

Prehospital Care

Perform a standard evaluation of airway, breathing, and circulation.

Provide intravenous fluids if signs or symptoms of dehydration are present.

Emergency Department Care

Perform a standard evaluation of airway, breathing, and circulation.

Treat with rehydration and electrolyte replacement via oral or intravenous solutions for an uncomplicated gastroenteritis.

Transfusions should be based on hemoglobin and hematocrit levels.

Symptomatically manage pain, nausea, vomiting, and diarrhea.

Antibiotics are indicated for infants aged up to 2 months, elderly patients, immunocompromised patients, those with a history of sickle cell disease or prosthetic grafts, or patients who have extraintestinal findings.

Consultations

Admission may be required if the patient exhibits unstable vital signs, harbors significant risk factors, is younger than 2 months or is elderly, is immunocompromised, or shows signs or symptoms of an extraintestinal manifestation.

Appropriate specialty consultation for specific extraintestinal manifestations is indicated.

Arrange for follow-up care on an outpatient basis with the patient’s primary care physician if discharged from the emergency department.

Prevention

Proper hygiene and food storage

Infection rates decrease in parallel with introduction of municipal water treatment, pasteurization of dairy products, and exclusion of human feces from food production.[46]

Keep raw meat and poultry away from unprepared foods.

Clean surfaces, utensils, and hands after contact with raw foods. Commonly used disinfectants have limited efficacy on mature Salmonellaenterica biofilm strains in food processing environments.[47]

Myrtle leaves oil has shown promise as an alternative disinfectant.[48]

The Food and Drug Administration (FDA) published a rule allowing irradiation of fresh iceberg lettuce and spinach as well as piloting an advanced border screening program in August 2008.

Avoid eating raw or undercooked eggs. Salmonella can withstand temperatures as high as 194o F (90o C) for 50 minutes.[16]

Studies note an increased concern for acquired resistance of Salmonella serovars against acids, in low-water activity foods (powders, flours, dried fruits, spices, oily foods, and nuts) and biofilm formation on surfaces.[49]

Vaccine for enteric or typhoid fever

Current multidose oral live attenuated Ty21a vaccine (5 years) or single-dose Vi capsular polysaccharide parental vaccine (2 years) has an efficacy of 50-80%.[7] Newer conjugate Vi vaccines may offer increased and longer protection against SalmonellaTypi[22]

Capsules licensed for ≥6 years, while parental licensed ≥2 years in the United States

Antibody and cell-mediated immunity responses occur after infection and immunization with live oral vaccines but may not be specific to the infecting organism[35]

Trials are underway for a single-dose oral vaccine to include an oral DNA vaccine.[25, 50]

Current vaccines do provide any significant protection against the SalmonellaParatyphi strain.[22]

Immunity against typhoid after infection or vaccination is only temporary.[21]

A new WHO prequalified typhoid conjugate vaccine (TCV) that can be administered to infants as young as six months provides high and prolonged immunity wtih 79-95% efficacy.[51]

Other measures

Animal reservoirs and flies should be controlled.

Individuals with diarrhea who attend or work in childcare centers, healthcare facilities, food service, or recreational water venues should follow local outbreak reporting and infection-control procedures.[33]

Long-Term Monitoring

Follow-up treatment with the patient's primary care physician is highly recommended.

Worsening symptoms warrant a return visit to the ED.

Reduced osmolarity oral rehydration solution (ORS) is recommended for mild to moderate dehydration, whereas breastfeeding should be continued in infants.

Antibiotic treatment for a chronic carrier in coordination with the patient’s primary care physician may be indicated. Asymptomatic carriage occurs on average for about 5 weeks, with prolonged duration existing in children younger than 5 years.[52]

Patients with HIV infection who achieve a short-term response to combination antiretroviral therapy (cART) have a lower risk for recurrent nontyphoid Salmonella bacteremia.[53]

Probiotic preparations may be offered and have shown antagonistic properties against Salmonella.[54]

Consider zinc supplementation in children aged 6 months to 5 years who reside in countries with a high prevalence of zinc deficiency or who are malnourished.

Reassessment of fluid and electrolyte balance, nutritional status, and antimicrobial therapy for patients with persistent symptoms is strongly recommended.

Medication Summary

Antibiotics, antidiarrheals, and glucocorticoids are used to treat symptoms and/or documented Salmonella infection.

Ciprofloxacin (Cipro)

Clinical Context:  Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, S epidermidis, and most gram-negative organisms but has no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. Is effective in treatment of long-term carriers of S typhi.

Chloramphenicol

Clinical Context:  Acts by inhibiting bacterial protein synthesis. Binds reversibly to the 50S subunit of bacterial 70S ribosome and prevents attachment of the amino acid-containing end of the aminoacyl-tran to acceptor site on ribosome. Active in vitro against a wide variety of bacteria, including gram-positive, gram-negative, aerobic, and anaerobic organisms. Well-absorbed from GI tract and metabolized in the liver, where it is inactivated by conjugation with glucuronic acid and then excreted by the kidneys. Oral form is not available in the United States.

Trimethoprim and sulfamethoxazole (Bactrim)

Clinical Context:  Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.

Ceftriaxone (Rocephin)

Clinical Context:  Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.

Azithromycin (Zithromax)

Clinical Context:  Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.

Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

Treats mild-to-moderate microbial infections.

Amoxicillin (Amoxil, Biomox, Polymox, and Wymox)

Clinical Context:  Interferes with synthesis of cell wall mucopeptides during active multiplication resulting in bactericidal activity against susceptible bacteria.

Ampicillin (Principen)

Clinical Context:  Broad-spectrum penicillin. Interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.

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

Cefpodoxime (Vantin)

Clinical Context:  Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins; bacteria eventually lyse because of ongoing activity of cell wall autolytic enzymes while cell wall assembly is arrested.

Bactericidal activity is against gram-positive and gram-negative bacteria.

Cefotaxime (Claforan)

Clinical Context:  Third-generation cephalosporin with broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. Arrests bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins, which in turn inhibits bacterial growth. Used for septicemia and treatment of gynecologic infections caused by susceptible organisms.

Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms.

Cefixime (Suprax)

Clinical Context:  Third-generation oral cephalosporin with broad activity against gram-negative bacteria. By binding to one or more of the penicillin-binding proteins, it arrests bacterial cell wall synthesis and inhibits bacterial growth.

Class Summary

Antibiotic

Nontyphoid Salmonella gastroenteritis is generally self-limited. In a systematic review, 12 trials showed no significant change in the overall length of the illness or the related symptoms in otherwise healthy children and adults treated with a course of antibiotics for nontyphoid Salmonella disease. Antibiotics tend to increase adverse effects, prolong Salmonella detection in stools, and do not shorten the duration of gastrointestinal symptoms.[55, 56]

The intracellular nature of nontyphoid Salmonella protects against extracellular antibiotics and promotes relapse; however, antibiotic treatment should be considered on a case-by-case basis to include patients with severe symptoms.[57] Antibiotics are currently indicated for infants aged up to 2 months, elderly patients, immunocompromised patients, those with a history of sickle cell disease or prosthetic grafts, patients who have extraintestinal findings, or patients with signs of sepsis. Treatment of at-risk patients should last 2-5 days or until the patient is afebrile.[4]

Traditional first-line antibiotic medications include ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole.  Salmonella infections are more commonly treated with ampicillin, fluoroquinolones such as ciprofloxacin and levofloxacin, third-generation cephalosporins such as ceftriaxone, and marcolides.

Enteric or typhoid fever is best treated with antibiotics for 5-7 days for uncomplicated cases and up to 10-14 days for a severe infection.[4] Bacteremia and focal infections may require antibiotics for up to 4-6 weeks depending on the site of infection and serotype of Salmonella. Specific surgical intervention is often necessary in conjunction with antibiotic management. Chronic Salmonella carriers require 1-3 months of oral antibiotics depending on the serotype, susceptibility, and antibiotic used.

Some evidence suggests that fluoroquinolones may be used in children with infections that are difficult to treat. When treating children and pregnant women, note that treatment with fluoroquinolones should be carefully weighed against the possibility of damaging developing cartilage.[58] Ampicillin and amoxicillin have been the classic treatment of choice in pregnancy patients and neonates.[23]

Salmonella antibiotic resistance is a global concern that includes multidrug resistant strains.[21]  Resistance is exhibiting an escalating trend of 20-30% per decade. 63 Overuse, misuse, inappropriate antibiotic prescribing practices, and patient poor compliance lead to a continued increase in multidrug-resistant typhoid fever.[25] Traditional first-line antibiotic medications include ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole.

Overall global Salmonella Typhi resistance to chloramphenicol, trimethoprim-sulfamethoxazole, and ampicillin is 25.9%, 37.9%, and 38.8%, respectively, per a recent global literature review.  Additionally, 35% were found to be multidrug resistant (MDR), defined as resistance to all three medications while 64.7% were nalidixic acid (discontinued in the United States) resistant and 15.0% were ciprofloxacin resistant. Ceftriaxone and azithromycin were found to exhibit 1.3% and 4.5% resistance, respectively.  Some regions such as Pakistan (2.6%) exhibit extensive drug resistance (XDR), which is defined as resistance to MDR plus fluoroquinolone and third-generation cephalosporin.[59] Despite the increase in ciprofloxacin resistance in typhoid and paratyphoid, it is still considered the drug of choice by many physicians. In the case of treatment failures, a third-generation cephalosporin and macrolide are good alternatives.[60]  

The prevalence of resistance among nontyphoid Salmonella isolates was 1.1%- 3.4% for third-generation cephalosporins in 2004 to 2021,[61]  65  The European Committee on Antimicrobial Susceptibility Testing (EUCAST) reported 6% ciprofloxacin resistance in 2015 and the annual collection of Antimicrobial Resistance (AMR) found 22.6% ciprofloxacin resistance for S. enteritidis in 2021. 65. Fluoroquinolone-resistant Salmonella is listed by the WHO as a priority pathogen for which new antibiotics are needed as of 2017.[62] Patients with antimicrobial-resistant nontyphoidal strains more commonly developed blood stream infections and were admitted to the hospital more often.[63] The reemergence of chloramphenicol-sensitive strains in prior resistant organisms points towards the concept of antibiotic recycling.[21]

In a systematic review, 38 trials showed a reduced clinical relapse rate using fluoroquinolones versus chloramphenicol.[64]

Outbreaks show that a connection may exist between antimicrobial drug treatment and the risk of disease from Salmonella.[64] A mouse model has shown enhanced ability of Salmonella to translocate the intestinal tract more easily in the presence of antibiotics.[13]

Subsequently, stool and blood cultures and sensitivities are important, as susceptibilities not only vary depending on region of the world but also locally. In developing countries such as India, ciprofloxacin continues to be the mainstay of treatment, even though the incidence of resistant strains is increasing.[23] Zinc and probiotic supplements have been shown to reduce the severity and duration of diarrhea.[64]  The Food and Agriculture Organization (FAO)/WHO regulations state probiotics can be used as a therapeutic or prophylactic agent, which can affect the growth and virulence of Salmonella. 63

Loperamide (Imodium)

Clinical Context:  Acts on intestinal muscles to inhibit peristalsis and slow intestinal motility. Prolongs movement of electrolytes and fluid through bowel and increases viscosity and loss of fluids and electrolytes. Available as 2-mg tablets and 1-mg/5-mL liquid.

Diphenoxylate and atropine (Lomotil)

Clinical Context:  Drug combination that consists of diphenoxylate, which is a constipating meperidine congener, and atropine to discourage abuse. Inhibits excessive GI propulsion and motility. Supplied as diphenoxylate 2.5 mg and atropine 0.025 mg per tablet or per 5 mL of liquid.

Class Summary

These agents may prolong the course of the disease. If used, they should be used sparingly. 

Dexamethasone (Decadron)

Clinical Context:  Used in the treatment of various inflammatory diseases. Decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Class Summary

These agents may be indicated in patients with severe enteric or typhoid fever or significant complications such as CNS manifestations or DIC.

What is Salmonella infection?What is the pathophysiology of Salmonella infection?What are the most common sources of Salmonella infection?What are the natural reservoirs of Salmonella bacteria?How is Salmonella infection transmitted person to person?Which patient groups have increase susceptibility to Salmonella infection?What is the prevalence of Salmonella infection in the US?What is the global prevalence of Salmonella infection?What is the mortality and morbidity associated with Salmonella infections?Which age groups have the highest prevalence of Salmonella infections?What is the prognosis of Salmonella infection?What should be included in patient education about Salmonella infection?What is the focus of the clinical history for the diagnosis of Salmonella infection?Which clinical history findings are characteristic of Salmonella gastroenteritis?Which clinical history findings are characteristic of Salmonella enteric (typhoid) fever?Which clinical history findings are characteristic of bacteremia due to Salmonella infection?What is the prevalence of extraintestinal Salmonella infection?Which clinical history findings are characteristic of a Salmonella infection chronic carrier state?Which physical findings are characteristic of Salmonella infection?Which physical findings are characteristic of gastroenteritis due to Salmonella infection?Which physical findings are characteristic of enteric (typhoid) fever due to Salmonella infection?Which physical findings are characteristic of bacteremia due to Salmonella infection?What are causes of Salmonella infection?What are the possible complications of Salmonella infection?What are the differential diagnoses for Salmonella Infection in Emergency Medicine?What is the role of serologic testing in the workup of Salmonella infection?Which complete blood cell count findings suggest Salmonella infection?Which liver function test findings suggest Salmonella infection?Which coagulation findings suggest Salmonella infection?What is the role of cultures in the diagnosis of Salmonella infections?What is the role of imaging studies in the workup of Salmonella infections?What is the role of a rectal exam in the workup of Salmonella infections?What is included in prehospital care of Salmonella infection?What is included in the emergency department (ED) care of Salmonella infection?Which specialist consultations are beneficial to patients with Salmonella infection?How is Salmonella infection prevented?What is the role of vaccines in the prevention of Salmonella infection?What are public health measures to prevent Salmonella infection?What is included in long-term monitoring Salmonella infection?Which medications are used for treatment of Salmonella infection?Which medications in the drug class Glucocorticoids are used in the treatment of Salmonella Infection in Emergency Medicine?Which medications in the drug class Antidiarrheals are used in the treatment of Salmonella Infection in Emergency Medicine?Which medications in the drug class Antibiotics are used in the treatment of Salmonella Infection in Emergency Medicine?

Author

Michael D Owens, DO, MPH, FACEP, FAAEM, Assistant Professor of Military/Emergency Medicine, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor, Eastern Virginia Medical School: Clinical Faculty, Emergency Medicine Residency, Naval Medical Center Portsmouth; Consulting Staff, Department of Emergency Medicine, Chesapeake Emergency Physicians, Inc, Chesapeake Regional Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Jeter (Jay) Pritchard Taylor, III, MD, Assistant Professor, Department of Surgery, University of South Carolina School of Medicine; Attending Physician / Clinical Instructor, Compliance Officer, Department of Emergency Medicine, Prisma Health Richland Hospital

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Employed contractor - Chief Editor for Medscape.

Additional Contributors

Dirk A Warren, MD, Emergency Medicine Resident, Naval Medical Center Portsmouth

Disclosure: Nothing to disclose.

Mark Louden, MD, Assistant Professor of Clinical Medicine, Division of Emergency Medicine, Department of Medicine, University of Miami, Leonard M Miller School of Medicine

Disclosure: Nothing to disclose.

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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.

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.