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 Aslam, 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 or complicated forms of the disease are treated with either Ceftriaxone, Cefotaxime, or a fluoroquinolone.

Medical therapy

Antimicrobial therapy is recommended for all patients who develop typhoid fever. Adults and children suffering from typhoid fever require different courses of treatment.

Adults

• The mainstay of therapy in adults is the administration of fluoroquinolones due to rapid response rate.
• Other agents used due to emerging resistance to fluoroquinolones are third-generation cephalosorins and Azithromycin.

Fluoroquinolones

• Mainstay of therapy in regions which demonstrates antibiotic susceptiblity to fluoroquinolones
• Bactericidial; concentrates intracellularly and in bile
• Early defervescence (less than 4 days)
• Cure rate of 96 percent
• Relapse and carrier state of less than 2 percent

Third-generation cephalosporins

• First-line agent in adults with fluoroquinolone resistance
• Main agents include ceftriaxone, cefixime, cefotaxime, and cefoperazone
• Defervescence averages one week
• Cure rate of 95 percent
• Relapse and carrier rate of less than 3 percent

Azithromycin

• First-line agent in adults with fluoroquinolone or third-generation cephalsporin resistance
• Excellent intracellular concentration
• Defervescence of 4 to 6 days
• Cure rate of 95 percent
• Relapse and carrier rate of less than 3 percent

Children

• The mainstay of therapy for children in United States is third-generation cephaloporins due to suspected skeletal and tendinous side effects of fluoroquinolones in children.
• First-line treatment for children in endemic areas is fluoroquinolones, especially in children with severe typhoid illness.
• Other drugs that may be used for the treatment of typhoid fever in children include chlorampanicol, ampicillin, and trimethoprim sulfamethoxazole, depending on antibiotic susceptibility.

Pregnancy

• Beta-lactam antibiotics and fluoroquinolones are considered safe to use during pregnancy.

Chronic carrier state

• Fluoroquinolones may be considered the ideal therapy for chronic carrier state, in which patients show antibiotic sensitivity to fluoroquinolones.

Relapse

• Instances of relapse are treated in the same way as an initial infection.
• Optimal therapy depends on antibiotic susceptibility.

Resistance

• Antibiotics such as ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole have commonly been used to treat typhoid fever in developed countries. However, due to resistance to these antibiotics in highly endemic areas, these are no longer used as travelers have become infected with the resistant strains.
• Typhoid that is resistant to these antibacterial agents is known as multidrug-resistant typhoid (MDR typhoid).
• Ciprofloxacin resistance is an increasing problem, especially in the Indian subcontinent and other parts of Southeast Asia, including Pakistan, Bangladesh, Thailand, and Vietnam.
• Current recommendations for testing antibiotic susceptibility of fluoroquinolone indicate that isolates should be tested simultaneously against ciprofloxacin (CIP) and nalidixic acid (NAL). Isolates that are sensitive to both CIP and NAL should be reported as "sensitive to ciprofloxacin," while isolates that are 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.

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