Salmonella Infection in Emergency Medicine Medication: Antibiotics, Antidiarrheals, Glucocorticoids (2024)

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. ^{[50, 51]}

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. ^[52] 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. ^[3]

Salmonella infections are commonly treated with fluoroquinolones or third-generation cephalosporins, such as ciprofloxacin and ceftriaxone.

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. ^[3] 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. ^[53] Ampicillin and amoxicillin have been the classic treatment of choice in pregnancy patients and neonates. ^[22]

Salmonella antibiotic resistance is a global concern that includes multidrug resistant strains. ^[20] Overuse, misuse, inappropriate antibiotic prescribing practices, and patient poor compliance lead to a continued increase in multidrug-resistant typhoid fever. ^[24] 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. ^[54] 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. ^[55]

The prevalence of resistance among nontyphoid Salmonella isolates was 3.4% for third-generation cephalosporins in 2004, ^[56] and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) reported 6% ciprofloxacin resistance in 2015. Fluoroquinolone-resistant Salmonella is listed by the WHO as a priority pathogen for which new antibiotics are needed as of 2017. ^[57] Patients with antimicrobial-resistant nontyphoidal strains more commonly developed blood stream infections and were admitted to the hospital more often. ^[58] The reemergence of chloramphenicol-sensitive strains in prior resistant organisms points towards the concept of antibiotic recycling. ^[20]

In a systematic review, 38 trials showed a reduced clinical relapse rate using fluoroquinolones versus chloramphenicol. ^[59]

Outbreaks show that a connection may exist between antimicrobial drug treatment and the risk of disease from Salmonella. ^[59] A mouse model has shown enhanced ability of Salmonella to translocate the intestinal tract more easily in the presence of antibiotics. ^[12]

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. ^[22] Zinc and probiotic supplements have been shown to reduce the severity and duration of diarrhea. ^[59]

Ciprofloxacin (Cipro)

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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

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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)

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Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.

Ceftriaxone (Rocephin)

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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)

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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)

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

Ampicillin (Principen)

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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)

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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)

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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)

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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.