What is the microbiology and treatment of Salmonella infections?

Microbiology of Salmonella

Bacterial Characteristics

Salmonella is a gram-negative, motile, non-sporulating, facultative anaerobic bacillus belonging to the family Enterobacteriaceae. 1

• The organism was first identified in 1884 and comprises more than 2,500 serotypes of Salmonella enterica, though fewer than 100 serotypes cause human infections 1
• Salmonella is a broad-spectrum pathogen that inhibits bacterial protein synthesis by interfering with the transfer of activated amino acids from soluble RNA to ribosomes 2
• The bacterium exerts mainly a bacteriostatic effect in vitro on a wide range of gram-negative and gram-positive bacteria 2

Classification and Serotypes

The clinically relevant serotypes fall into two major categories:

Typhoidal Salmonella

• S. enterica serovar Typhi (S. Typhi) and S. enterica serovars Paratyphi A, B, and C cause enteric (typhoid) fever 3, 1
• These serotypes are human-restricted pathogens with humans serving as the only natural host and reservoir 4
• Typhoid fever is characterized by sustained fever, headache, lethargy, malaise, abdominal pain, hepatosplenomegaly, and stupor, with diarrhea being an uncommon feature 3

Nontyphoidal Salmonella (NTS)

• Common serotypes include S. Typhimurium and S. Enteritidis, which cause gastroenteritis 3
• Animals (including pets) serve as the primary reservoir for NTS 4
• NTS typically causes self-limited gastroenteritis in immunocompetent hosts but can cause invasive disease in vulnerable populations 4

Transmission and Epidemiology

Transmission occurs through direct contact with infected persons or indirect contact via contaminated food and water. 1

• In the United States, Salmonella is a common agent for foodborne infections, with outbreaks most commonly associated with agricultural products 4
• Poultry and poultry products are primary contributors, followed by beef, pork, fish, and non-animal-derived foods such as fruits and vegetables 5
• Sexual activity with potential for fecal-oral exposure increases risk, especially for Shigella and Campylobacter, though this applies to enteric pathogens generally 3
• During 2004-2009,68% of patients with S. Typhi and 50% with S. Paratyphi reported travel history 3

Pathogenesis and Virulence Factors

Salmonella evades host defenses through multiple mechanisms including adhesion to epithelial cells and survival within host cells, mediated by virulence plasmids and genes clustered in Salmonella pathogenicity islands (SPIs). 6

• Acquisition of enteric bacterial infections is facilitated by HIV-associated gastric achlorhydria, treatment with gastric acid-suppressing agents, and HIV-associated alterations in mucosal immunity 3
• Bacterial flagellins from Salmonella can directly activate signaling pathways in intestinal epithelial cells, triggering inflammation 7
• The pathogen can cause intestinal perforation, typically in the ileum or jejunum during typhoid fever, usually occurring in the third week of disease 7

Clinical Syndromes

In Immunocompetent Hosts

• Self-limited gastroenteritis is the most common presentation 3
• Symptoms include abdominal pain, fever, and diarrhea due to inflammatory response in affected intestinal segments 7
• Bloody diarrhea can occur, indicating significant colonic inflammation 7

In Immunocompromised Hosts

The risk for severe illness increases dramatically with the degree of immunosuppression, with HIV-infected adults having 20-100 fold higher incidence rates compared to the general population. 3, 7

Three major clinical syndromes occur in immunocompromised patients:

• Self-limited gastroenteritis 3
• More severe and prolonged diarrheal disease with fever, bloody diarrhea, weight loss, and possible bacteremia 3
• Septicemia with extraintestinal involvement, with or without concurrent gastrointestinal illness 3

Recurrent Salmonella septicemia constitutes an AIDS-defining illness and may require chronic suppressive therapy. 3

Antimicrobial Resistance

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has become a major global concern, with plasmid-mediated resistance genes enabling resistance to broad-spectrum antibiotics. 6, 5

• Multidrug resistance (resistance to ≥3 drugs) is more common in pediatric patients compared to adults 8
• Among isolates with single drug resistance in Northwestern India, 81% were resistant to chloramphenicol 8
• The development of antimicrobial resistance during therapy, often associated with clinical deterioration or relapse, can occur in HIV-infected persons 3
• Increasing resistance to first-line agents (ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol) is being reported from Southeast Asia, Africa, and Latin America 4, 8

Diagnosis

Diagnosis is established through stool cultures and blood cultures, with blood cultures being essential for any patient with diarrhea and fever due to the high rate of bacteremia. 3, 7

• In HIV-infected patients with advanced disease, blood cultures should be obtained from any patient with diarrhea and fever due to high bacteremia rates 3
• Endoscopy may reveal ulcerations in the colon similar to those seen with other forms of colitis 3, 7
• Bacteriology studies to determine causative organisms and their susceptibility to ampicillin should be performed, though therapy may be instituted prior to susceptibility testing results 9

Treatment Principles

Nontyphoidal Salmonella

Antibiotic treatment is NOT recommended for mild to moderate gastroenteritis in immunocompetent adults or children over 1 year of age, as antibiotics may prolong shedding and are not indicated for most Salmonella infections. 3, 4

Exceptions requiring antimicrobial therapy include:

• Infants <3-6 months of age 3, 4
• Adults >50 years of age 10
• Immunocompromised hosts 10
• Patients with prosthetic devices or valvular heart disease 10
• Those with severe atherosclerosis, malignancy, or uremia 10

Treatment options for invasive disease:

• Fluoroquinolones or third-generation cephalosporins based on local susceptibility patterns 3
• In cases of osteomyelitis, aortitis, or septic arthritis, combination of antibiotics and surgical treatment may be required 3
• Immunosuppressive therapy should be temporarily withheld until resolution of active infection 3

Typhoid Fever

For acute typhoid fever, fluoroquinolones (ciprofloxacin 500-750 mg PO twice daily for 7-14 days) are first-line therapy in adults, while third-generation cephalosporins are preferred for children and in areas with quinolone resistance. 10

• Chloramphenicol is indicated for acute infections caused by S. typhi, with treatment at therapeutic levels for 8-10 days after the patient becomes afebrile to lessen relapse possibility 2
• Azithromycin may be considered as an alternative, particularly in quinolone-resistant areas 10
• For severe or complicated disease, consider combination therapy initially (ceftriaxone plus ciprofloxacin) for multidrug-resistant strains 10
• All isolates from Northwestern India were susceptible to ciprofloxacin and ceftriaxone 8

Chronic Carriers

Asymptomatic chronic carriers of S. Typhi should be treated with fluoroquinolones to reduce transmission risk, particularly if working in food service, healthcare, childcare, or eldercare settings. 10

• Serial stool cultures using traditional culture methods are required for clearance documentation before return to high-risk work settings 10

Prevention and Control

Scrupulous handwashing after potential contact with human feces, after handling animals, before food preparation, and before eating is the cornerstone of prevention. 3, 7

Additional preventive measures:

• Avoid consumption of raw or undercooked eggs, poultry, meat, and seafood 7
• Avoid unprotected sex practices that might result in oral exposure to feces 3
• Two typhoid vaccines are licensed in the United States (Ty21a oral live attenuated vaccine and Vi polysaccharide parenteral vaccine) providing 50-80% protection 10
• Vaccines should be administered to travelers to endemic areas, household contacts of chronic carriers, and laboratory personnel with S. Typhi exposure 10
• All S. Typhi infections must be reported to state, territorial, or local health departments with submission of isolates to enable outbreak detection 10