Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever)

Emmanuel E Effa; Zohra S Lassi; Julia A Critchley; Paul Garner; David Sinclair; Piero L Olliaro; Zulfiqar A Bhutta

doi:10.1002/14651858.CD004530.pub4

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Figure 1

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 1 Clinical failure.

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Analysis 1.2

Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 2 Microbiological failure.

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Analysis 1.3

Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 3 Relapse.

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Analysis 1.4

Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 4 Convalescent faecal carriage.

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Analysis 1.5

Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 5 Fever clearance time.

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Analysis 1.6

Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 6 Duration of hospitalization.

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Analysis 1.7

Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 7 Serious adverse events.

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Analysis 1.8

Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 8 Non‐serious adverse events.

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Analysis 2.1

Comparison 2 Fluoroquinolone versus co‐trimoxazole, Outcome 1 Clinical Failure.

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Analysis 2.2

Comparison 2 Fluoroquinolone versus co‐trimoxazole, Outcome 2 Microbiological failure.

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Analysis 2.3

Comparison 2 Fluoroquinolone versus co‐trimoxazole, Outcome 3 Relapse.

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Analysis 2.4

Comparison 2 Fluoroquinolone versus co‐trimoxazole, Outcome 4 Convalescent faecal carriage.

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Analysis 2.5

Comparison 2 Fluoroquinolone versus co‐trimoxazole, Outcome 5 Fever clearance time.

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Analysis 2.6

Comparison 2 Fluoroquinolone versus co‐trimoxazole, Outcome 6 Non serious adverse events.

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Analysis 3.1

Comparison 3 Fluroqunolone versus ampicillin/amoxicillin, Outcome 1 Clinical failure.

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Analysis 3.2

Comparison 3 Fluroqunolone versus ampicillin/amoxicillin, Outcome 2 Microbiological failure.

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Analysis 3.3

Comparison 3 Fluroqunolone versus ampicillin/amoxicillin, Outcome 3 Non‐serious adverse events.

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Analysis 4.1

Comparison 4 Fluoroquinolone versus cefixime, Outcome 1 Clinical failure.

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Analysis 4.2

Comparison 4 Fluoroquinolone versus cefixime, Outcome 2 Microbiological failure.

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Analysis 4.3

Comparison 4 Fluoroquinolone versus cefixime, Outcome 3 Relapse.

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Analysis 4.4

Comparison 4 Fluoroquinolone versus cefixime, Outcome 4 Convalescent faecal carriage.

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Analysis 4.5

Comparison 4 Fluoroquinolone versus cefixime, Outcome 5 Fever clearance time.

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Analysis 4.6

Comparison 4 Fluoroquinolone versus cefixime, Outcome 6 Duration of hospitalization.

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Analysis 4.7

Comparison 4 Fluoroquinolone versus cefixime, Outcome 7 Serious adverse Events.

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Analysis 4.8

Comparison 4 Fluoroquinolone versus cefixime, Outcome 8 Non‐serious adverse events.

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Analysis 5.1

Comparison 5 Fluoroquinolone versus ceftriaxone, Outcome 1 Clinical failure.

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Analysis 5.2

Comparison 5 Fluoroquinolone versus ceftriaxone, Outcome 2 Microbiological failure.

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Analysis 5.3

Comparison 5 Fluoroquinolone versus ceftriaxone, Outcome 3 Relapse.

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Analysis 5.4

Comparison 5 Fluoroquinolone versus ceftriaxone, Outcome 4 Convalescent faecal carriage.

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Analysis 5.5

Comparison 5 Fluoroquinolone versus ceftriaxone, Outcome 5 Fever clearance time.

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Analysis 5.6

Comparison 5 Fluoroquinolone versus ceftriaxone, Outcome 6 Non‐serious adverse events.

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Analysis 6.1

Comparison 6 Fluoroquinolone versus azithromycin, Outcome 1 Clinical failure.

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Analysis 6.2

Comparison 6 Fluoroquinolone versus azithromycin, Outcome 2 Microbiological failure.

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Analysis 6.3

Comparison 6 Fluoroquinolone versus azithromycin, Outcome 3 Relapse.

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Analysis 6.4

Comparison 6 Fluoroquinolone versus azithromycin, Outcome 4 Convalescent faecal carriage.

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Analysis 6.5

Comparison 6 Fluoroquinolone versus azithromycin, Outcome 5 Fever clearance time.

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Analysis 6.6

Comparison 6 Fluoroquinolone versus azithromycin, Outcome 6 Duration of Hospitalization.

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Analysis 6.7

Comparison 6 Fluoroquinolone versus azithromycin, Outcome 7 Serious adverse events.

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Analysis 6.8

Comparison 6 Fluoroquinolone versus azithromycin, Outcome 8 Non‐serious adverse events.

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Analysis 7.1

Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 1 Clinical failure.

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Analysis 7.2

Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 2 Microbiological failure.

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Analysis 7.3

Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 3 Relapse.

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Analysis 7.4

Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 4 Convalecsent faecal carriage.

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Analysis 7.5

Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 5 Fever clearance time.

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Analysis 7.6

Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 6 Duration of hospitalization.

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Analysis 7.7

Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 7 Serious adverse events.

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Analysis 7.8

Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 8 Non‐serious adverse events.

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Analysis 8.1

Comparison 8 Fluoroquinolone 3 days vs 5 days, Outcome 1 Relapse.

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Analysis 8.2

Comparison 8 Fluoroquinolone 3 days vs 5 days, Outcome 2 Fever Clearance time.

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Analysis 8.3

Comparison 8 Fluoroquinolone 3 days vs 5 days, Outcome 3 Non‐serious adverse events.

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Analysis 9.1

Comparison 9 Fluoroquinolone 5 days vs 7 days, Outcome 1 Microbiological Failure.

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Analysis 9.2

Comparison 9 Fluoroquinolone 5 days vs 7 days, Outcome 2 Relapse.

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Analysis 9.3

Comparison 9 Fluoroquinolone 5 days vs 7 days, Outcome 3 Fever clearance time.

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Analysis 9.4

Comparison 9 Fluoroquinolone 5 days vs 7 days, Outcome 4 Non‐serious adverse events.

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Analysis 10.1

Comparison 10 Fluoroquinolone 7 days vs 10 days, Outcome 1 Microbiological failure.

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Analysis 10.2

Comparison 10 Fluoroquinolone 7 days vs 10 days, Outcome 2 Relapse.

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Analysis 11.1

Comparison 11 Gatifloxacin (OD for 7 days) vs chloramphenicol (QDS for 14 days), Outcome 1 All outcomes.

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Analysis 12.1

Comparison 12 Fluoroquinolone 10 days vs 14 days, Outcome 1 Relapse.

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Analysis 12.2

Comparison 12 Fluoroquinolone 10 days vs 14 days, Outcome 2 Fever clearance time.

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Analysis 12.3

Comparison 12 Fluoroquinolone 10 days vs 14 days, Outcome 3 Non‐serious adverse events.

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Analysis 13.1

Comparison 13 Gatifloxacin (OD for 7 days) vs cefixime (BD for 7 days), Outcome 1 All outcomes.

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Analysis 14.1

Comparison 14 Gatifloxacin (OD for 7 days) vs azithromycin (OD for 7 days), Outcome 1 All outcomes.

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Comparison 1. Fluoroquinolone versus chloramphenicol

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical failure Show forest plot	8		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Ciprofloxacin versus chloramphenicol	4	293	Risk Ratio (M‐H, Fixed, 95% CI)	0.24 [0.07, 0.82]
1.2 Ofloxacin versus chloramphenicol	4	249	Risk Ratio (M‐H, Fixed, 95% CI)	0.15 [0.03, 0.64]
1.3 Pefloxacin versus chloramphenicol	2	126	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 Gatifloxacin versus chloramphenicol	1	352	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.32, 1.96]
2 Microbiological failure Show forest plot	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Ciprofloxacin versus chloramphenicol	2	142	Risk Ratio (M‐H, Random, 95% CI)	0.05 [0.00, 0.81]
2.2 Ofloxacin versus chloramphenicol	3	199	Risk Ratio (M‐H, Random, 95% CI)	0.16 [0.02, 1.07]
2.3 Pefloxacin versus chloramphenicol	2	126	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.4 Gatifloxacin versus chloramphenicol	1	352	Risk Ratio (M‐H, Random, 95% CI)	4.94 [0.24, 102.24]
3 Relapse Show forest plot	6		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Ciprofloxacin versus chloramphenicol	4	292	Risk Ratio (M‐H, Fixed, 95% CI)	0.15 [0.02, 1.15]
3.2 Ofloxacin versus chloramphenicol	2	149	Risk Ratio (M‐H, Fixed, 95% CI)	0.14 [0.01, 2.65]
3.3 Pefloxacin versus chloramphenicol	2	126	Risk Ratio (M‐H, Fixed, 95% CI)	0.15 [0.02, 1.21]
3.4 Gatifloxacin versus chloramphenicol	1	352	Risk Ratio (M‐H, Fixed, 95% CI)	0.56 [0.17, 1.90]
4 Convalescent faecal carriage Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 Ciprofloxacin versus chloramphenicol	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.16 [0.01, 2.89]
4.2 Ofloxacin versus chloramphenicol	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.01, 1.98]
4.3 Pefloxacin versus chloramphenicol	2	126	Risk Ratio (M‐H, Fixed, 95% CI)	0.13 [0.02, 1.01]
4.4 Gatifloxacin versus chloramphenicol	1	273	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.01, 7.82]
5 Fever clearance time Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

5.1 Ciprofloxacin versus chloramphenicol	2	147	Mean Difference (IV, Fixed, 95% CI)	‐62.46 [‐75.52, ‐49.39]
5.2 Ofloxacin versus chloramphenicol	2	140	Mean Difference (IV, Fixed, 95% CI)	‐75.85 [‐88.52, ‐63.17]
6 Duration of hospitalization Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

6.1 Ciprofloxacin versus chloramphenicol	1	55	Mean Difference (IV, Fixed, 95% CI)	‐0.40 [‐1.63, 0.83]
6.2 Ofloxacin versus chloramphenicol	1	50	Mean Difference (IV, Fixed, 95% CI)	‐9.9 [‐11.42, ‐8.38]
7 Serious adverse events Show forest plot	3	203	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.18, 5.52]

7.1 Ciprofloxacin versus chloramphenicol	2	153	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.18, 5.52]
7.2 Ofloxacin versus chloramphenicol	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Non‐serious adverse events Show forest plot	8	1410	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.61, 0.94]

8.1 Ciprofloxacin versus chloramphenicol	4	253	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.61, 1.64]
8.2 Ofloxacin versus chloramphenicol	4	207	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.60, 1.87]
8.3 Pefloxacin versus chloramphenicol	2	106	Risk Ratio (M‐H, Fixed, 95% CI)	1.32 [0.69, 2.52]
8.4 Gatifloxacin versus chloramphenicol	1	844	Risk Ratio (M‐H, Fixed, 95% CI)	0.58 [0.44, 0.78]

Comparison 1. Fluoroquinolone versus chloramphenicol

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Comparison 2. Fluoroquinolone versus co‐trimoxazole

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical Failure Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Ciprofloxacin versus co‐trimoxazole	2	132	Risk Ratio (M‐H, Fixed, 95% CI)	0.06 [0.01, 0.43]
1.2 Ofloxacin versus co‐trimoxazole	1	89	Risk Ratio (M‐H, Fixed, 95% CI)	0.04 [0.00, 0.59]
1.3 Pefloxacin versus co‐trimoxazole	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Microbiological failure Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Ciprofloxacin versus co‐trimoxazole	2	132	Risk Ratio (M‐H, Fixed, 95% CI)	0.06 [0.01, 0.43]
2.2 Ofloxacin versus co‐trimoxazole	1	89	Risk Ratio (M‐H, Fixed, 95% CI)	0.04 [0.00, 0.59]
2.3 Pefloxacin versus co‐trimoxazole	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Relapse Show forest plot	1	181	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

3.1 Ciprofloxacin versus co‐trimoxazole	1	92	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Ofloxacin versus co‐trimoxazole	1	89	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Convalescent faecal carriage Show forest plot	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

5 Fever clearance time Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

5.1 ciprofloxacin versus co‐trimoxazole	1	92	Mean Difference (IV, Fixed, 95% CI)	‐84.0 [‐99.72, ‐68.28]
5.2 Ofloxacin versus co‐trimoxazole	1	92	Mean Difference (IV, Fixed, 95% CI)	‐96.0 [‐115.64, ‐76.36]
6 Non serious adverse events Show forest plot	3	219	Risk Ratio (M‐H, Fixed, 95% CI)	0.70 [0.46, 1.08]

6.1 Ciprofloxacin versus co‐trimoxazole	2	110	Risk Ratio (M‐H, Fixed, 95% CI)	0.62 [0.34, 1.12]
6.2 Ofloxacin versus co‐trimoxazole	1	67	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.46, 1.83]
6.3 Pefloxacin versus co‐trimoxazole	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.56 [0.14, 2.21]

Comparison 2. Fluoroquinolone versus co‐trimoxazole

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Comparison 3. Fluroqunolone versus ampicillin/amoxicillin

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical failure Show forest plot	2	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.02, 0.57]

1.1 Ofloxacin versus ampicillin	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.09 [0.01, 1.54]
1.2 Ofloxacin versus amoxicillin	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.13 [0.02, 0.93]
2 Microbiological failure Show forest plot	2	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.13 [0.03, 0.68]

2.1 Ofloxacin versus ampicillin/amoxicillin	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.14 [0.01, 2.60]
2.2 Ofloxacin versus amoxicillin	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.13 [0.02, 0.93]
3 Non‐serious adverse events Show forest plot	2	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.12, 0.93]

3.1 Ofloxacin versus amoxicillin	2	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.12, 0.93]

Comparison 3. Fluroqunolone versus ampicillin/amoxicillin

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Comparison 4. Fluoroquinolone versus cefixime

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical failure Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Ciprofloxacin versus cefixime	1	94	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Ofloxacin versus cefixime	2	173	Risk Ratio (M‐H, Fixed, 95% CI)	0.14 [0.02, 1.11]
1.3 Gatifloxacin versus cefixime	1	158	Risk Ratio (M‐H, Fixed, 95% CI)	0.04 [0.01, 0.31]
2 Microbiological failure Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Ciprofloxacin versus cefixime	1	94	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Ofloxacin versus cefixime	2	173	Risk Ratio (M‐H, Fixed, 95% CI)	0.23 [0.01, 4.66]
2.3 Gatifloxacin versus cefixime	1	158	Risk Ratio (M‐H, Fixed, 95% CI)	0.27 [0.01, 6.43]
3 Relapse Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Ciprofloxacin versus cefixime	1	94	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Ofloxacin versus cefixime	2	131	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 7.72]
3.3 Gatifloxacin versus cefixime	1	138	Risk Ratio (M‐H, Fixed, 95% CI)	0.20 [0.04, 0.93]
4 Convalescent faecal carriage Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 Gatifloxacin versus cefixime	1	147	Risk Ratio (M‐H, Fixed, 95% CI)	0.27 [0.01, 6.40]
5 Fever clearance time Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

5.1 Ciprofloxacin versus cefixime	1	94	Mean Difference (IV, Fixed, 95% CI)	‐12.00 [‐24.42, 0.42]
5.2 Ofloxacin versus cefixime	1	91	Mean Difference (IV, Fixed, 95% CI)	‐24.0 [‐41.46, ‐6.54]
6 Duration of hospitalization Show forest plot	1	81	Mean Difference (IV, Fixed, 95% CI)	‐3.0 [‐4.53, ‐1.47]

6.1 Ofloxacin versus cefixime	1	81	Mean Difference (IV, Fixed, 95% CI)	‐3.0 [‐4.53, ‐1.47]
7 Serious adverse Events Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 Ofloxacin versus cefixime	1	82	Risk Ratio (M‐H, Fixed, 95% CI)	3.46 [0.15, 82.56]
7.2 Gatifloxacin versus cefixime	1	169	Risk Ratio (M‐H, Fixed, 95% CI)	1.67 [0.15, 18.11]
8 Non‐serious adverse events Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 Ciprofloxacin versus cefixime	1	94	Risk Ratio (M‐H, Fixed, 95% CI)	1.57 [0.83, 2.95]
8.2 Ofloxacin versus cefixime	1	91	Risk Ratio (M‐H, Fixed, 95% CI)	1.70 [0.83, 3.49]
8.3 Gatifloxacin versus cefixime	1	169	Risk Ratio (M‐H, Fixed, 95% CI)	20.92 [2.90, 150.90]

Comparison 4. Fluoroquinolone versus cefixime

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Comparison 5. Fluoroquinolone versus ceftriaxone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical failure Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Ciprofloxacin versus ceftriaxone	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.08 [0.01, 1.41]
1.2 Ofloxacin versus ceftriaxone	1	47	Risk Ratio (M‐H, Fixed, 95% CI)	0.09 [0.01, 1.46]
2 Microbiological failure Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Ciprofloxacin versus ceftriaxone	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Ofloxacin versus ceftriaxone	1	47	Risk Ratio (M‐H, Fixed, 95% CI)	0.38 [0.02, 8.80]
3 Relapse Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Ciprofloxacin versus ceftriaxone	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.37 [0.02, 8.48]
3.2 Ofloxacin versus ceftriaxone	1	23	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.02, 8.04]
4 Convalescent faecal carriage Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 Ciprofloxacin versus ceftriaxone	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.37 [0.02, 8.48]
5 Fever clearance time Show forest plot	1	47	Mean Difference (IV, Fixed, 95% CI)	‐113.00 [‐150.67, ‐79.33]

5.1 Ofloxacin versus ceftriaxone	1	47	Mean Difference (IV, Fixed, 95% CI)	‐113.00 [‐150.67, ‐79.33]
6 Non‐serious adverse events Show forest plot	1	47	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.06, 5.85]

6.1 Ofloxacin versus ceftriaxone	1	47	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.06, 5.85]

Comparison 5. Fluoroquinolone versus ceftriaxone

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Comparison 6. Fluoroquinolone versus azithromycin

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical failure Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Ciprofloxacin versus azithromycin	1	64	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Ofloxacin versus azithromycin	2	213	Risk Ratio (M‐H, Fixed, 95% CI)	2.20 [1.23, 3.94]
1.3 Gatifloxacin versus azithromycin	1	287	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.32, 2.96]
2 Microbiological failure Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Ciprofloxacin versus azithromycin	1	64	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Ofloxacin versus azithromycin	2	213	Risk Ratio (M‐H, Fixed, 95% CI)	1.32 [0.30, 5.76]
2.3 Gatifloxacin versus azithromycin	1	285	Risk Ratio (M‐H, Fixed, 95% CI)	0.64 [0.11, 3.79]
3 Relapse Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Ciprofloxacin versus azithromycin	1	64	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Ofloxacin versus azithromycin	2	163	Risk Ratio (M‐H, Fixed, 95% CI)	6.11 [0.31, 119.33]
3.3 Gatifloxacin versus azithromycin	1	264	Risk Ratio (M‐H, Fixed, 95% CI)	0.12 [0.01, 2.20]
4 Convalescent faecal carriage Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 Ciprofloxacin versus azithromycin	1	64	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 Ofloxacin versus azithromycin	2	193	Risk Ratio (M‐H, Fixed, 95% CI)	13.52 [2.64, 69.36]
4.3 Gatifloxacin versus azithromycin	1	268	Risk Ratio (M‐H, Fixed, 95% CI)	2.87 [0.12, 69.82]
5 Fever clearance time Show forest plot	3		Mean Difference (IV, Random, 95% CI)	Subtotals only

5.1 Ciprofloxacin versus azithromycin	1	64	Mean Difference (IV, Random, 95% CI)	‐12.0 [‐24.39, 0.39]
5.2 Ofloxacin versus azithromycin	2	213	Mean Difference (IV, Random, 95% CI)	30.41 [‐22.12, 82.93]
6 Duration of Hospitalization Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

6.1 Ofloxacin versus azithromycin	2	213	Mean Difference (IV, Fixed, 95% CI)	1.01 [0.19, 1.83]
7 Serious adverse events Show forest plot	1	88	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.06, 15.49]

7.1 Ofloxacin versus azithromycin	1	88	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.06, 15.49]
8 Non‐serious adverse events Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 Ciprofloxacin versus azithromycin	1	64	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [0.73, 1.99]
8.2 Ofloxacin versus azithromycin	2	213	Risk Ratio (M‐H, Fixed, 95% CI)	0.56 [0.27, 1.16]
8.3 Gatifloxain versus azithromycin	1	287	Risk Ratio (M‐H, Fixed, 95% CI)	1.96 [0.18, 21.36]

Comparison 6. Fluoroquinolone versus azithromycin

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Comparison 7. Fluoroquinolone 2 days vs 3 days

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical failure Show forest plot	3	396	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.54, 2.53]

2 Microbiological failure Show forest plot	2	296	Risk Ratio (M‐H, Fixed, 95% CI)	1.94 [0.44, 8.47]

3 Relapse Show forest plot	3	312	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.14, 2.97]

4 Convalecsent faecal carriage Show forest plot	2	262	Risk Ratio (M‐H, Fixed, 95% CI)	0.31 [0.01, 7.45]

5 Fever clearance time Show forest plot	3	396	Mean Difference (IV, Fixed, 95% CI)	‐5.41 [‐14.59, 3.78]

6 Duration of hospitalization Show forest plot	3	396	Mean Difference (IV, Fixed, 95% CI)	‐0.33 [‐0.73, 0.06]

7 Serious adverse events Show forest plot	3	396	Risk Ratio (M‐H, Fixed, 95% CI)	2.40 [0.22, 26.08]

8 Non‐serious adverse events Show forest plot	2	296	Risk Ratio (M‐H, Fixed, 95% CI)	0.18 [0.01, 3.61]

Comparison 7. Fluoroquinolone 2 days vs 3 days

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Comparison 8. Fluoroquinolone 3 days vs 5 days

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Relapse Show forest plot	1	154	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.01, 7.65]

2 Fever Clearance time Show forest plot	1	195	Mean Difference (IV, Fixed, 95% CI)	‐12.0 [‐18.07, ‐5.93]

3 Non‐serious adverse events Show forest plot	1	425	Risk Ratio (M‐H, Fixed, 95% CI)	1.73 [0.74, 4.03]

Comparison 8. Fluoroquinolone 3 days vs 5 days

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Comparison 9. Fluoroquinolone 5 days vs 7 days

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Microbiological Failure Show forest plot	1	46	Risk Ratio (M‐H, Fixed, 95% CI)	3.26 [0.14, 76.10]

2 Relapse Show forest plot	1	46	Risk Ratio (M‐H, Fixed, 95% CI)	3.26 [0.14, 76.10]

3 Fever clearance time Show forest plot	1	46	Mean Difference (IV, Fixed, 95% CI)	‐7.20 [‐7.78, ‐6.62]

4 Non‐serious adverse events Show forest plot	1	46	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.21, 3.25]

Comparison 9. Fluoroquinolone 5 days vs 7 days

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Comparison 10. Fluoroquinolone 7 days vs 10 days

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Microbiological failure Show forest plot	1	30	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

2 Relapse Show forest plot	1	30	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 10. Fluoroquinolone 7 days vs 10 days

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Comparison 11. Gatifloxacin (OD for 7 days) vs chloramphenicol (QDS for 14 days)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All outcomes Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 Clinical failure (need for rescue medication or persistence of fever until day 10)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Microbiological failure (blood culture +ve on day 8)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Relapse (reappearance of culture confirmed or syndromic enteric fever on days 11 to 31)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 Convalescent faecal carriage	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.5 Serious adverse events	0		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.6 Other adverse events (selected gastrointestinal adverse events)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 11. Gatifloxacin (OD for 7 days) vs chloramphenicol (QDS for 14 days)

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Comparison 12. Fluoroquinolone 10 days vs 14 days

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Relapse Show forest plot	1	69	Risk Ratio (M‐H, Fixed, 95% CI)	0.19 [0.01, 3.91]

2 Fever clearance time Show forest plot	1	69	Mean Difference (IV, Fixed, 95% CI)	‐16.80 [‐42.65, 9.05]

3 Non‐serious adverse events Show forest plot	1	69	Risk Ratio (M‐H, Fixed, 95% CI)	0.43 [0.15, 1.27]

Comparison 12. Fluoroquinolone 10 days vs 14 days

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Comparison 13. Gatifloxacin (OD for 7 days) vs cefixime (BD for 7 days)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All outcomes Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 Clinical failure (need for rescue medication or persistence of fever until day 7)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Relapse (fever plus +ve blood culture within 1 month of successful treatment)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Microbiological failure (blood culture +ve on day 10)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 Serious adverse events	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.5 Other adverse events (may be incompletely reported)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 13. Gatifloxacin (OD for 7 days) vs cefixime (BD for 7 days)

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Comparison 14. Gatifloxacin (OD for 7 days) vs azithromycin (OD for 7 days)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All outcomes Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 Clinical failure (need for rescue medication of persistence of fever until day 10)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Relapse (symptoms and signs of typhoid fever within 1 month of successful treatment)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Microbiological failure (blood culture +ve on day 7 to 9)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 Convalescent faecal carriage	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.5 Serious adverse events	0		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.6 Other adverse events (may be incompletely reported)	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 14. Gatifloxacin (OD for 7 days) vs azithromycin (OD for 7 days)

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