Table 4. . Controlled and noncontrolled trials on monotherapy and combination therapy for typhoid fever.
| Antibiotics | No. of patients (n) | Study type (duration of the study)/location | Dose/duration of therapy (days) | Fever defervescence (days) | Clinical/microbiological failure (%) | Relapse (%) | Fecal carriage (%) | Ref. |
|---|---|---|---|---|---|---|---|---|
| Azithromycin vs ceftriaxone (IV; short course therapy) | 108 (children) | Prospective study (2000)/Egypt | Azithromycin 10 mg/kg per day for 7 days 2.5 g per day for 7 days |
Azithromycin – 4.1 Ceftriaxone – 3.9 |
Clinical failure: Azithromycin – 0 Ceftriaxone – 19 Microbiological failure: Azithromycin – 0 Ceftriaxone – 3 |
Azithromycin – 0 Ceftriaxone – 13 | NA | [65] |
| Azithromycin vs ceftriaxone (IV; short course therapy) | 149 | Prospective study (2004)/Egypt | Azithromycin 20 mg/kg per day for 5 days 2.5 g per day for 5 days |
Azithromycin – 4.5 Ceftriaxone – 3.6 |
Clinical failure: Azithromycin – 6 Ceftriaxone – 3 Microbiological failure: Azithromycin – 3 Ceftriaxone – 3 |
Azithromycin – 0 Ceftriaxone – 17 | NA | [66] |
| Azithromycin | 117 (children) | Open-labeled noncomparative study (2011)/India | Azithromycin – 20 mg/kg per day for 6 days | 3.45 |
Clinical failure: Azithromycin – 6 Microbiological failure: Azithromycin – 15.5 |
NA | NA | [67] |
| Azithromycin vs ofloxacin | 40 (adult) | Prospective (2012)/India | Ofloxacin – 200 mg orally twice daily for 7 days Azithromycin – 1 g on day 1 and then 500 mg daily from days 2–6 |
Ofloxain – 3.68 Azithromycin – 3.65 |
Clinical failure: Ofloxacin–10 Azithromycin – 0 |
No relapse | 0 | [68] |
| Ofloxacin vs cefixime |
82 (children) | Randomized open trial (1995–1996)/Vietnam | Ofloxacin – 10 mg/kg per day for 5 days Cefixime – 20 mg/kg per day for 7 days |
Ofloxacin – 4.4 Cefixime – 8.5 |
Clinical failure: Ofloxacin – 3 Cefixime – 25 |
Ofloxacin – 0 Cefixime – 3 |
Ofloxacin – 0 Cefixime – 3 | [69] |
| Ofloxacin | 235 | Randomized open study/Vietnam | Ofloxacin (10 mg/kg per day) – 2 days Ofloxacin (10 mg/kg per day) – 3 days | 2-day group: 3.8 3-day group: 4.2 |
Clinical failure: 2-day group: 13.5 3-day group: 7.5 Microbiological failure: 2-day group: 4 3-day group: 1 |
2-day group: 2 3-day group: 2 |
NA | [70] |
| Chloramphenicol vs ofloxacin | 50 | Randomized open study/Laos | Chloramphenicol (50 mg/kg per day) for 14 days Ofloxacin (15 mg/kg per day) – 3 days |
Chloramphenicol – 3.7 Ofloxacin – 2.2 |
Clinical failure: Chloramphenicol – 1% |
NA | NA | [71] |
| Ofloxacin vs azithromycin | 88 | Randomized control study/Nepal | Azithromycin (20 mg/kg per day) for 5 days Ofloxacin – (8 mg/kg per day) for 5 days |
Ofloxacin – 7 Azithromycin – 5 |
Clinical failure: Ofloxacin – 13.6 Azithromycin – 4.5 Microbiological failure: Ofloxacin – 4.5 Azithromycin – 0 |
Ofloxacin – 4.5 Azithromycin – 0 | Ofloxacin – 41 Azithromycin – 0 | [72] |
| Ofloxacin, azithromycin, ofloxacin/azithromycin | 187 | Randomized control study (1998–2002)/Vietnam | Ofloxacin – 20 mg/kg per day for 7 days Azithromycin – 10 mg/kg per day for 7 days Ofloxacin (15 mg/kg per day)/azithromycin (10 mg/kg per day) |
Ofloxacin – 8.2 Azithromycin – 5.8 Ofloxacin/azithromycin – 7.1 |
Clinical failure: Ofloxacin – 12.3 Azithromycin – 18.8 Ofloxacin/azithromycin – 6.4 Microbiological failure: Ofloxacin – 1.6 Azithromycin – 0 Ofloxacin/azithromycin - 1.6 (patient experienced microbiologcal failure) |
Relapse was not seen in patients treated with ofloxacin or azithromycin or ofloxacin/azithromycin | Ofloxacin – 19.4 Azithromycin – 1.6 Ofloxacin/azithromycin – 6.5 |
[73] |
| Gatifloxacin vs azithromycin | 287 | RCT/Vietnam | Gatifloxacin (10 mg/kg per day) for 7 days Azithromycin (20 mg/kg per day) for 7 days |
Gatifloxacin – 4.4 Azithromycin – 4.4 | Clinical failure: Gatifloxacin – 4.3 Azithromycin – 4.2 Microbiological failure: Gatifloxacin – 1.4 Azithromycin – 2.2 | Gatifloxacin – 2.9 Azithromycin – 0 | Gatifloxacin – 0.7 Azithromycin – 0 | [46] |
| Gatifloxacin vs cefixime | 390 | RCT/Nepal | Gatifloxacin (10 mg/kg per day) for 7 days Cefixime (20 mg/kg per day) for 7 days | Gatifloxacin – 3.8 Cefixime – 5.7 |
Clinical failure: Gatifloxacin – 1 Cefixime – 27 |
Gatifloxacin – 0.9 Cefixime – 3 | NA | [48] |
| Gatifloxacin vs chloramphenicol | 844 | RCT/Nepal | Gatifloxacin (10 mg/kg per day) for 7 days Chloramphenicol (75 mg/kg per day) for 14 days |
Clinical failure: Gatifloxacin – 7 Chloramphenicol – 8 Microbiological failure: Gatifloxacin – 1 Chloramphenicol – 0 | Gatifloxacin – 2 Chloramphenicol – 4 | NA | [74] | |
| Gatifloxacin vs ofloxacin | 627 | RCT/Nepal | Gatifloxacin (10 mg/kg per day) for 7 days Ofloxacin (10 mg/kg per day) for 7 days |
Gatifloxacin – 3.3 Ofloxacin – 4.7 | Clinical failure: Gatifloxacin – 5 Ofloxacin – 7 Microbiological failure: None |
Gatifloxacin – 5 Ofloxacin – 6 | NA | [75] |
| Gatifloxacin vs ceftriaxone | 239 | RCT/Nepal | Gatifloxacin (10 mg/kg per day) for 7 days Ceftriaxone (2 g per day) for 7 days |
Gatifloxacin – 2.43 Ceftriaxone – 2.93 |
Gatifloxacin – 15 Ceftriaxone – 16 | NA | NA | [76] |
| Azithromycin–ceftriaxone combination | 25 | Prospective study (2014–2015)/India | Ceftriaxone (IV) – 2 g daily for 14 days Azithromycin – 500 mg daily for the first 7 days |
4.8 | Clinical and microbiological failure: 4 | No relapse | NA | [77] |
IV: Intravenous; NA: Not available; RCT: Randomized clinical trial.