Salmonella Infection in Emergency Medicine Medication

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

Class Summary

Nontyphoid Salmonella gastroenteritis is generally self-limited. In a Cochrane Database of Systematic Reviews article, 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 and prolong Salmonella detection in stools.^[28]

However, antibiotic treatment should be considered on a case-by-case basis to include patients with severe symptoms.^[29] Antibiotics are currently indicated for infants up to 2 months of age, elderly, immunocompromised, those with a history of sickle cell disease or prosthetic grafts, or patients who have extraintestinal findings. Treatment of those 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. In 2004, the prevalence of resistance among nontyphoid Salmonella isolates was 2.6% for quinolones and 3.4% for third-generation cephalosporins.^[30]

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.^[31] Ampicillin and amoxicillin have been the classic treatment of choice in pregnancy patients and neonates.^[16]

Salmonella antibiotic resistance is a global concern that includes multidrug resistant strains.^[15] Overuse, misuse, inappropriate antibiotic prescribing practices, and patient poor compliance lead to a continued increase in multidrug-resistant typhoid fever.^[20] Traditional first-line antibiotic medications include ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. Resistance to these first-line antibiotics defines multidrug resistance in S enterica.^[32] Despite the increase in ciprofloxacin resistance in typhoid and paratyphoid, it is still considered the drug of choice by many physicians. However, in the case of treatment failures, a third-generation cephalosporin and macrolide are good alternatives.^[33] The reemergence of chloramphenicol-sensitive strains in prior resistant organisms points towards the concept of antibiotic recycling.^[16]

Outbreaks show that a connection may exist between antimicrobial drug treatment and the risk of disease from Salmonella.^[34] A mouse model has shown enhanced ability of Salmonella to translocate the intestinal tract more easily in the presence of antibiotics.^[8]

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.^[16]

Fluoroquinolone resistance is an important factor in Salmonellatyphi and was reported by the CDC to be 41.8% in 2004. Trimethoprim-sulfamethoxazole and chloramphenicol have a 13.2% prevalence of resistance in Salmonella typhi, while ampicillin, streptomycin, and sulfisoxazole are 11.8%.^[30]

In a Cochrane Database of Systematic Reviews article, 38 trials showed a reduced clinical relapse rate using fluoroquinolones versus chloramphenicol. However, this same review was not statistically significant for clinical failure or microbiological failure and was limited for other comparisons including children.^[35] Additionally, because nalidixic acid resistance is no longer a reliable method for detecting decreased ciprofloxacin susceptibility, international in vitro studies suggest that gatifloxacin may be more active than ciprofloxacin in these isolates.^[36]

Ciprofloxacin (Cipro)

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

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)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.

Ceftriaxone (Rocephin)

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)

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)

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

Ampicillin (Principen)

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)

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)

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)

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.

Note: After a period of inavailability, oral Cefixime is again FDA-approved in tablet and suspension forms. However, at the time of writing, tablets remain unavailable in this country. Wyeth Pharmaceuticals (Collegeville, Pennsylvania) discontinued manufacturing cefixime (Suprax®) in the United States. In October 2002, the company ceased marketing cefixime tablets (200 mg and 400 mg) because of depletion of company inventory. Wyeth's patent for cefixime expired on November 10, 2002.

Class Summary

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

Loperamide (Imodium)

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)

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

Dexamethasone (Decadron)

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