Typhoid fever medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2] Aysha Anwar, M.B.B.S[3]

Overview

The mainstay of therapy for typhoid fever is antimicrobial therapy. Patients with uncomplicated typhoid fever are treated with either Azithromycin or a fluoroquinolone whereas patients with severe disease are treated with either Ceftriaxone, Cefotaxime, or a fluoroquinolone.

Medical therapy

• Antimicrobial therapy is recommended among all patients who develop typhoid fever.
• Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and floroquinolones, have been commonly used to treat typhoid fever in developed countries. However, due to extensive resistance to these antibiotics in highly endemic areas these are no longer used due to travelers getting infected with the resistant strains.
• The main stay of therapy due to resistance to these strains is use of floroquinolone,third generation cephalosorins and azithromycin.

Floroquinolones

• Floroquinolones have been used successfully for typhoid fever for long periods of time due to rapid response rate.
• They are still used as main stay of treatment in the regions susceptible to this drug
• Cure rate, 96 percent
• Relapse and carrier state, less than 2 percent.

Resistance

• Resistance to ampicillin, chloramphenicol,and trimethoprim-sulfamethoxazole is common, and these agents have not been used as first line treatment now for almost 20 years.
• Typhoid that is resistant to these agents is known as multidrug-resistant typhoid (MDR typhoid).
• Ciprofloxacin resistance is an increasing problem, especially in the Indian subcontinent and Southeast Asia so its not being used as first line for treating suspected typhoid originating in India, Pakistan, Bangladesh, Thailand or Vietnam.
• For these patients, the recommended first line treatment is ceftriaxone.
• Current recommendations for testing antibiotic susceptibility of floroquinolone are that isolates should be tested simultaneously against ciprofloxacin (CIP) and against nalidixic acid (NAL), and that isolates that are sensitive to both CIP and NAL should be reported as "sensitive to ciprofloxacin", but that isolates testing sensitive to CIP but not to NAL should be reported as "reduced sensitivity to ciprofloxacin". However, an analysis of 271 isolates showed that around 18% of isolates with a reduced susceptibility to ciprofloxacin (MIC 0.125–1.0 mg/l) would not be picked up by this method. It not certain how this problem can be solved, because most laboratories around the world (including the West) are dependent disc testing and cannot test for MICs.

Antimicrobial regimen

• Typhoid fever

• 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

• 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. Uncomplicated typhoid fever

• 1.1 Fully sensitive

• Preferred regimen (1): Ofloxacin 15 mg/kg/day for 5-7 days

• Preferred regimen (2): Ciprofloxacin 15 mg/kg/day for 5-7 days
• Alternative regimen (1): Chloramphenicol 50-75 mg/kg/day for 14-21 days
• Alternative regimen (2): Amoxicillin 75-100 mg/kg/day for 14 days
• Alternative regimen (3): TMP-SMX 8-40 mg/kg/day for 14 days

• 1.2 Multidrug resistance

• Preferred regimen (1): Fluoroquinolone 15 mg/kg/day for 5-7 days

• Preferred regimen (2): Cefixime 15-20 mg/kg/day for 7-14 days
• Alternative regimen (1): Azithromycin 8-10 mg/kg/day for 7 days
• Alternative regimen (2): Cefixime 15-20 mg/kg/day for 7-14 days

• 1.3 Quinolone resistance

• Preferred regimen (1): Azithromycin 8-10 mg/kg/day for 7 days

• Preferred regimen (2): Ceftriaxone 75 mg/kg/day for 10-14 days
• Alternative regimen: Cefixime 20 mg/kg/day for 7-14 days

• 2. Severe typhoid fever

• 2.1 Fully sensitive

• Preferred regimen: Ofloxacin 15 mg/kg/day for 10-14 days
• Alternative regimen (1): Chloramphenicol 100 mg/kg/day for 14-21 days
• Alternative regimen (2): Amoxicillin 100 mg/kg/day for 14 days
• Alternative regimen (3): TMP-SMX 8-40 mg/kg/day for 14 days

• 2.2 Multidrug resistant

• Preferred regimen: Fluoroquinolone 15 mg/kg/day for 10-14 days
• Alternative regimen (1): Ceftriaxone 60 mg/kg/day for 10-14 days
• Alternative regimen (2): Cefotaxime 80 mg/kg/day for 10-14 days

• 2.3 Quinolone resistant

• Preferred regimen (1): Ceftriaxone 60 mg/kg/day for 10-14 days

• Preferred regimen (2): Cefotaxime 80 mg/kg/day for 10-14 days
• Alternative regimen: Fluoroquinolone 20 mg/kg/day for 7-14 days