Salmonellosis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2] Jolanta Marszalek, M.D. [3]

Overview

The majority of cases of uncomplicated salmonellosis are self-limited and only require supportive care. Supportive therapy for salmonellosis includes elctrolyte replacement, rehydration, and adequate nutrition. Symptomatic treatment includes either Loperamide or Bismuth subsalicylate. Antimicrobial therapy is indicated in infants, elderly patients, immunocompromised patients, and patients with severe disease. Antimicrobial therapy for salmonellosis may include either Trimethoprim-sulfamethoxazole, fluoroquinolones, or Ceftriaxone.

Medical Therapy

Mild cases of salmonelloses usually resolve within 5 to 7 days. Patients with severe cases of the disease may require rehydration with intravenous fluids. Antibiotic treatment is not routinely recommended, unless the patient becomes severely dehydrated, belongs to one of the risk groups described below, or the infection reaches the blood stream.[1]

Salmonellosis commonly presents with unspecific gastrointestinal symptoms, such as diarrhea, fever, and abdominal pain. Antibiotic treatment of infectious diarrhea is considered controversial because:[2]

  • Symptoms may be caused by different types of enteric pathogens, what makes the initial treatment of severe cases often "empiric"
  • Antibiotic treatment of non-typhoidal salmonellosis prolongs shedding of the bacteria in feces

Supportive Therapy

Initial therapy of infectious diarrhea, irrespectively to the causative agent, should start with rehydration. Oral rehydration with a glucose and electrolyte solution is preferred, except in cases where the patient is severely dehydrated or comatose. [3]

Nutritional support should also be provided, particularly in children, where it was shown to improve outcomes. The use of the "BRAT diet" is also frequently recommended. This diet consists of bananas, rice, applesauce and toast, with avoidance of dairy products, due to the potential deficiency of lactase, following the gastrointestinal disturbance.[3][4]

Symptomatic Therapy

Although there is little evidence of the efficacy of most of the antidiarrheal agents on the marker, the following have demonstrated to be effective in controlled, randomized trials:[3][5]

  • Loperamide

Antimotility agent, with anti-secretory properties, able to inhibit intestinal peristalsis. Despite being an opiate, it does not have the potential of addiction, since it does not penetrate the nervous system.[6]

Loperamide should be avoided in patients with inflammatory or bloody diarrhea because of the relation between antimotility agents and prolonged fever in patients infected with Shigella and C. difficile (other potential causative agents of infectious diarrhea).[7]

  • Bismuth Subsalicylate

Bismuth subsalicylate may alleviate symptoms such as: nausea, diarrhea and abdominal pain.[8] It was also shown to decrease stool output in pediatric patients.[9]

Antibiotic Therapy

Indications

Antibiotics are not recommended for uncomplicated salmonellosis because they prolong shedding of the bacteria, typically do not alleviate the diarrhea, and have been associated with relapse.[3][10][11] Antibiotic therapy is only indicated for patients with severe cases of the disease, and for those with risk factors for extra-intestinal infection, after blood and fecal cultures have been obtained. Risk groups for the development of severe disease, and extra-intestinal manifestations include:[2][3][12]

Antibiotic treatment may be indicated in cases when rapid interruption of fecal shedding of the bacteria is required to avoid outbreaks in institutions.[13]

Antimicrobial regimen

  • 1. Salmonellosis in immunocompetent hosts[14]
  • 1.1 Gastroenteritis
  • Antimicrobial therapy is usually not recommended for uncomplicated diarrheal illness.
  • 1.1.1 Indications for antimicrobial therapy
  • severedisease,
  • Age > 50 yrs
  • Prosthesis
  • Presence of valvular heart disease
  • Severe atherosclerosis
  • Cancer
  • Uremia
  • Immunosuppression
  • 1.1.2 Treatment regimens
  • Preferred regimen (1): TMP-SMX DS PO bid for 5-7 days
  • Preferred regimen (2): Ciprofloxacin 500 mg PO bid for 5-7 days
  • Preferred regimen (3): Ceftriaxone 2 g IV q24h for 5-7 days
  • 1.2 Typhoid fever[15]
  • 1.2.1 Uncomplicated typhoid
  • Preferred regimen (1) (fully susceptible): Fluoroquinolone (e.g., Ofloxacin 15 mg/kg PO qd for 5–7 days)
  • Preferred regimen (2) (multi drug-resistant): Fluoroquinolone (Ofloxacin 15 mg/kg PO qd for 5–7 days)
  • Preferred regimen (3) (quinolone-resistant): Azithromycin 8–10 mg/kg PO qd for 7 days
  • Preferred regimen (4) (quinolone-resistant): Fluoroquinolone 20 mg/kg PO qd for 10-14 days
  • Alternative regimen (1) (fully susceptible): Chloramphenicol 50–75 mg/kg PO qd for 14-21 days
  • Alternative regimen (2) (fully susceptible): Amoxicillin 75–100 mg/kg PO qd for 14 days
  • Alternative regimen (3) (fully susceptible): Trimethoprim–Sulfamethoxazole, 8 mg/kg (trimethoprim)– 40 mg/kg (sulfamethoxazole) PO qd for 14 days
  • Alternative regimen (4) (multi drug-resistant): Azithromycin 8–10 mg/kg PO for 7 days
  • Alternative regimen (5) (multi drug-resistant): Third-generation cephalosporin, e.g., Cefixime 20 mg/kg PO qd for 7-14 days
  • Alternative regimen (6) (quinolone-resistant): Third-generation cephalosporin, e.g., Cefixime 20 mg/kg PO qd for 7-14 days
  • 1.2.2 Severe typhoid
  • Preferred regimen (1) (fully susceptible): Fluoroquinolone (e.g., Ofloxacin 15 mg/kg IV qd for 10-14 days)
  • Preferred regimen (2) (multi drug-resistant): Fluoroquinolone (Ofloxacin 15 mg/kg IV qd for 10-14 days)
  • Preferred regimen (3) (quinolone-resistant): Ceftriaxone 60 mg/kg IV qd for 10-14 days
  • Preferred regimen (4) (quinolone-resistant): Cefotaxime 80 mg/kg IV qd for 10-14 days
  • Alternative regimen (1) (fully susceptible): Chloramphenicol 100 mg/kg PO qd for 14-21 days
  • Alternative regimen (2) (fully susceptible): Ampicillin 100 mg/kg PO qd for 14-21 days
  • Alternative regimen (3) (fully susceptible): Trimethoprim–Sulfamethoxazole, 8 mg/kg (trimethoprim)– 40 mg/kg (sulfamethoxazole) IV qd for 10-14 days
  • Alternative regimen (4) (multi drug-resistant): Ceftriaxone 60 mg/kg IV qd for 10-14 days
  • Alternative regimen (5) (multi drug-resistant): Cefotaxime 80 mg/kg IV qd for 10-14 days
  • Alternative regimen (6) (quinolone-resistant): Fluoroquinolone 20 mg/kg IV qd for 10-14 days
  • 1.3 Non-typhoid (serious infection)[16]
  • Preferred regimen (2): Cefotaxime 2 g IV q6-8h for 7-14 days
  • Preferred regimen (3): Ciprofloxacin 400 mg IV q12h for 7-14 days
  • 1.5 Vascular prosthesis infection[18]
  • 1.6 Osteomyelitis[19]
  • Preferred regimen (3): Ciprofloxacin 750 mg PO bid for ≥ 4 weeks
  • Preferred regimen (2): Cefotaxime 2 g IV q6-8h for 6 weeks
  • 1.8 Endocarditis[21]
  • Preferred regimen (2): Cefotaxime 2 g IV q6-8h for 6 weeks
  • 1.10 Carrier state[23]
  • Preferred regimen (1): Ciprofloxacin 500 mg PO bid for 4-6 weeks
  • Preferred regimen (2): TMP-SMX 1DS bid PO for 6 weeks
  • Preferred regimen (3): Amoxicillin 500 mg PO for 6 weeks
  • 2. Salmonellosis in immunocompromised hosts
  • 2.1 HIV and salmonellosis[24]
  • 2.1.1 Gastroenteritis
  • Preferred regimen: Ciprofloxacin 500-750 mg PO bid or 400 mg IV q12h, if susceptible
  • Alternative regimen (1): Levofloxacin 750 mg PO/IV q24h
  • Alternative regimen (2): Moxifloxacin 400 mg PO/IV q24h
  • Alternative regimen (3): TMP 160 mg AND SMX 800 mg PO/IV q12h
  • Alternative regimen (4): Ceftriaxone 1 g IV q24h
  • Alternative regimen (5): Cefotaxime 1 g IV q8h
  • Duration of treatment for gastroenteritis without bacteremia
  • If CD4 count ≥ 200 cells/μL: Duration of treatment is 7–14 days
  • If CD4 count < 200 cells/μL: Duration of treatment is 2–6 weeks
  • Duration of treatment for gastroenteritis with bacteremia
  • If CD4 count ≥ 200/μL: Duration of treatment is 14 days; longer duration if bacteremia persists or if the infection is complicated (e.g., if metastatic foci of infection are present)
  • If CD4 count < 200 cells/μL: Duration of treatment is 2–6 weeks
  • Note (1): Secondary prophylaxis should be considered for
  • Patients with recurrent Salmonella gastroenteritis with or without bacteremia
  • Patients with CD4 < 200 cells/μL with severe diarrhea


  • 1. Salmonella bacteremia treatment
  • 2.When the salmonellae are known to be susceptible

\====Recommended Agents==== For the cases where antibiotics are indicated, treatment should include one of the following:[3][26]

  • Trimethoprim-Sulfamethoxazole

Indicated for children, and when susceptibility is suspected

Children
5 mg/kg (trimethoprim) + 25 mg/kg (sulfamethoxazole) twice/day, during 3 days
Adults
160 mg (trimethoprim) + 800 mg (sulfamethoxazole) twice/day, during 3 days


  • Fluoroquinolones
Adults
Ciprofloxacin - 500 mg PO twice/day, during 1 to 3 days
Norfloxacin - 400 mg PO twice/day, during 1 to 3 days
Levofloxacin - 500 mg PO once/day, during 1 to 3 days
Ofloxacin - 300 mg twice/day, during 1 to 3 days


  • Ceftriaxone
Children <12 years old
50-75 mg/kg body weight/day in 1 or 2 doses
Adults
100 mg/Kg body weight/day in 1 or 2 doses

For immunocompromised patients, the duration of the antibiotic treatment described above should be prolonged for 14 days, or longer in case of relapse.[26]

Multidrug Resistance

Some serovars of Salmonella enterica, particularly Typhimurium and Newport, are linked to more severe cases of salmonellosis and multi-drug resistance.[12]

Follow Up

Fecal cultures are not indicated for patient follow-up after uncomplicated cases of salmonellosis, irrespectively to the treatment administrated. The results tend to be intermittently positive for a long period of time, and do not show any utility in asymptomatic patients.[2][27]

References

  1. ↑ "Salmonella (non-typhoidal)".
  2. ↑ 2.0 2.1 2.2 Hohmann EL (2001). "Nontyphoidal salmonellosis". Clin Infect Dis. 32 (2): 263–9. doi:10.1086/318457. PMID 11170916.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Thielman NM, Guerrant RL (2004). "Clinical practice. Acute infectious diarrhea". N Engl J Med. 350 (1): 38–47. doi:10.1056/NEJMcp031534. PMID 14702426.
  4. ↑ "Managing Acute Gastroenteritis Among Children Oral Rehydration, Maintenance, and Nutritional Therapy".
  5. ↑ "Antidiarrheal Drug Products for Over-the-Counter Human Use; Amendment of Final Monograph".
  6. ↑ DuPont HL, Flores Sanchez J, Ericsson CD, Mendiola Gomez J, DuPont MW, Cruz Luna A; et al. (1990). "Comparative efficacy of loperamide hydrochloride and bismuth subsalicylate in the management of acute diarrhea". Am J Med. 88 (6A): 15S–19S. PMID 2192553.
  7. ↑ DuPont HL, Hornick RB (1973). "Adverse effect of lomotil therapy in shigellosis". JAMA. 226 (13): 1525–8. PMID 4587313.
  8. ↑ DuPont HL, Sullivan P, Pickering LK, Haynes G, Ackerman PB (1977). "Symptomatic treatment of diarrhea with bismuth subsalicylate among students attending a Mexican university". Gastroenterology. 73 (4 Pt 1): 715–8. PMID 330307.
  9. ↑ Figueroa-Quintanilla D, Salazar-Lindo E, Sack RB, León-Barúa R, Sarabia-Arce S, Campos-Sánchez M; et al. (1993). "A controlled trial of bismuth subsalicylate in infants with acute watery diarrheal disease". N Engl J Med. 328 (23): 1653–8. doi:10.1056/NEJM199306103282301. PMID 8487823.
  10. ↑ Wiström J, Jertborn M, Ekwall E, Norlin K, Söderquist B, Strömberg A; et al. (1992). "Empiric treatment of acute diarrheal disease with norfloxacin. A randomized, placebo-controlled study. Swedish Study Group". Ann Intern Med. 117 (3): 202–8. PMID 1616214.
  11. ↑ Neill MA, Opal SM, Heelan J, Giusti R, Cassidy JE, White R; et al. (1991). "Failure of ciprofloxacin to eradicate convalescent fecal excretion after acute salmonellosis: experience during an outbreak in health care workers". Ann Intern Med. 114 (3): 195–9. PMID 1898630.
  12. ↑ 12.0 12.1 Gal-Mor O, Boyle EC, Grassl GA (2014). "Same species, different diseases: how and why typhoidal and non-typhoidal Salmonella enterica serovars differ". Front Microbiol. 5: 391. doi:10.3389/fmicb.2014.00391. PMID 25136336.
  13. ↑ Lightfoot NF, Ahmad F, Cowden J (1990). "Management of institutional outbreaks of Salmonella gastroenteritis". J Antimicrob Chemother. 26 Suppl F: 37–46. PMID 2292544.
  14. ↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
  15. ↑ "TYPHOID FEVER".
  16. ↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
  17. ↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
  18. ↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
  19. ↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
  20. ↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
  21. ↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
  22. ↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
  23. ↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
  24. ↑ "Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents" (PDF).
  25. ↑ Goldman, Lee (2012). Goldman's Cecil Medicine, Twenty-Fourth Edition. Saunders, an imprint of Elsevier Inc. ISBN 978-1-4377-1604-7.
  26. ↑ 26.0 26.1 Guerrant RL, Van Gilder T, Steiner TS, Thielman NM, Slutsker L, Tauxe RV; et al. (2001). "Practice guidelines for the management of infectious diarrhea". Clin Infect Dis. 32 (3): 331–51. doi:10.1086/318514. PMID 11170940.
  27. ↑ Buchwald DS, Blaser MJ (1984). "A review of human salmonellosis: II. Duration of excretion following infection with nontyphi Salmonella". Rev Infect Dis. 6 (3): 345–56. PMID 6377442.

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