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Meta-Analysis
. 2011 Oct 5;2011(10):CD004530.
doi: 10.1002/14651858.CD004530.pub4.

Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever)

Emmanuel E Effa  1 , Zohra S Lassi, Julia A Critchley, Paul Garner, David Sinclair, Piero L Olliaro, Zulfiqar A Bhutta
Affiliations
Meta-Analysis

Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever)

Emmanuel E Effa et al. Cochrane Database Syst Rev. .

Abstract

Background: Typhoid and paratyphoid are febrile illnesses, due to a bacterial infection, which remain common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends the fluoroquinolone antibiotics in areas with known resistance to the older first-line antibiotics.

Objectives: To evaluate fluoroquinolone antibiotics for treating children and adults with enteric fever.

Search strategy: We searched The Cochrane Infectious Disease Group Specialized Register (February 2011); Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (2011, Issue 2); MEDLINE (1966 to February 2011); EMBASE (1974 to February 2011); and LILACS (1982 to February 2011). We also searched the metaRegister of Controlled Trials (mRCT) in February 2011.

Selection criteria: Randomized controlled trials examining fluoroquinolone antibiotics, in people with blood, stool or bone marrow culture-confirmed enteric fever.

Data collection and analysis: Two authors independently assessed the trial's methodological quality and extracted data. We calculated risk ratios (RR) for dichotomous data and mean difference for continuous data with 95% confidence intervals (CI).Comparative effectiveness has been interpreted in the context of; length of treatment, dose, year of study, known levels of antibiotic resistance, or proxy measures of resistance such as the failure rate in the comparator arm.

Main results: Twenty-six studies, involving 3033 patients, are included in this review.Fluoroquinolones versus older antibiotics (chloramphenicol, co-trimoxazole, amoxicillin and ampicillin)In one study from Pakistan in 2003-04, high clinical failure rates were seen with both chloramphenicol and co-trimoxazole, although resistance was not confirmed microbiologically. A seven-day course of either ciprofloxacin or ofloxacin were found to be superior. Older studies of these comparisons failed to show a difference (six trials, 361 participants).In small studies conducted almost two decades ago, the fluoroquinolones were demonstrated to have fewer clinical failures than ampicillin and amoxicillin (two trials, 90 participants, RR 0.11, 95% CI 0.02 to 0.57).Fluoroquinolones versus current second-line options (ceftriaxone, cefalexin, and azithromycin)The two studies comparing a seven day course of oral fluoroquinolones with three days of intravenous ceftriaxone were too small to detect important differences between antibiotics should they exist (two trials, 89 participants).In Pakistan in 2003-04, no clinical or microbiological failures were seen with seven days of either ciprofloxacin, ofloxacin or cefixime (one trial, 139 participants). In Nepal in 2005, gatifloxacin reduced clinical failure and relapse compared to cefixime, despite a high prevalence of NaR in the study population (one trial, 158 participants, RR 0.04, 95% CI 0.01 to 0.31).Compared to a seven day course of azithromycin, a seven day course of ofloxacin had a higher rate of clinical failures in populations with both multi-drug resistance (MDR) and nalidixic acid resistance (NaR) enteric fever in Vietnam in 1998-2002 (two trials, 213 participants, RR 2.20, 95% CI 1.23 to 3.94). However, a more recent study from Vietnam in 2004-05, detected no difference between gatifloxacin and azithromycin with both drugs performing well (one trial, 287 participants).

Authors' conclusions: Generally, fluoroquinolones performed well in treating typhoid, and maybe superior to alternatives in some settings. However, we were unable to draw firm general conclusions on comparative contemporary effectiveness given that resistance changes over time, and many studies were small. Policy makers and clinicians need to consider local resistance patterns in choosing a fluoroquinolone or alternative.There is some evidence that the newest fluoroquinolone, gatifloxacin, remains effective in some regions where resistance to older fluoroquinolones has developed. However, the different fluoroquinolones have not been compared directly in trials in these settings.

PubMed Disclaimer

Conflict of interest statement

None known. Professor ZA Bhutta has been part of trials of treatment for typhoid therapy in children, none of which involved fluoroquinolones.

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 1 Clinical failure.
1.2
1.2. Analysis
Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 2 Microbiological failure.
1.3
1.3. Analysis
Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 3 Relapse.
1.4
1.4. Analysis
Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 4 Convalescent faecal carriage.
1.5
1.5. Analysis
Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 5 Fever clearance time.
1.6
1.6. Analysis
Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 6 Duration of hospitalization.
1.7
1.7. Analysis
Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 7 Serious adverse events.
1.8
1.8. Analysis
Comparison 1 Fluoroquinolone versus chloramphenicol, Outcome 8 Non‐serious adverse events.
2.1
2.1. Analysis
Comparison 2 Fluoroquinolone versus co‐trimoxazole, Outcome 1 Clinical Failure.
2.2
2.2. Analysis
Comparison 2 Fluoroquinolone versus co‐trimoxazole, Outcome 2 Microbiological failure.
2.3
2.3. Analysis
Comparison 2 Fluoroquinolone versus co‐trimoxazole, Outcome 3 Relapse.
2.4
2.4. Analysis
Comparison 2 Fluoroquinolone versus co‐trimoxazole, Outcome 4 Convalescent faecal carriage.
2.5
2.5. Analysis
Comparison 2 Fluoroquinolone versus co‐trimoxazole, Outcome 5 Fever clearance time.
2.6
2.6. Analysis
Comparison 2 Fluoroquinolone versus co‐trimoxazole, Outcome 6 Non serious adverse events.
3.1
3.1. Analysis
Comparison 3 Fluroqunolone versus ampicillin/amoxicillin, Outcome 1 Clinical failure.
3.2
3.2. Analysis
Comparison 3 Fluroqunolone versus ampicillin/amoxicillin, Outcome 2 Microbiological failure.
3.3
3.3. Analysis
Comparison 3 Fluroqunolone versus ampicillin/amoxicillin, Outcome 3 Non‐serious adverse events.
4.1
4.1. Analysis
Comparison 4 Fluoroquinolone versus cefixime, Outcome 1 Clinical failure.
4.2
4.2. Analysis
Comparison 4 Fluoroquinolone versus cefixime, Outcome 2 Microbiological failure.
4.3
4.3. Analysis
Comparison 4 Fluoroquinolone versus cefixime, Outcome 3 Relapse.
4.4
4.4. Analysis
Comparison 4 Fluoroquinolone versus cefixime, Outcome 4 Convalescent faecal carriage.
4.5
4.5. Analysis
Comparison 4 Fluoroquinolone versus cefixime, Outcome 5 Fever clearance time.
4.6
4.6. Analysis
Comparison 4 Fluoroquinolone versus cefixime, Outcome 6 Duration of hospitalization.
4.7
4.7. Analysis
Comparison 4 Fluoroquinolone versus cefixime, Outcome 7 Serious adverse Events.
4.8
4.8. Analysis
Comparison 4 Fluoroquinolone versus cefixime, Outcome 8 Non‐serious adverse events.
5.1
5.1. Analysis
Comparison 5 Fluoroquinolone versus ceftriaxone, Outcome 1 Clinical failure.
5.2
5.2. Analysis
Comparison 5 Fluoroquinolone versus ceftriaxone, Outcome 2 Microbiological failure.
5.3
5.3. Analysis
Comparison 5 Fluoroquinolone versus ceftriaxone, Outcome 3 Relapse.
5.4
5.4. Analysis
Comparison 5 Fluoroquinolone versus ceftriaxone, Outcome 4 Convalescent faecal carriage.
5.5
5.5. Analysis
Comparison 5 Fluoroquinolone versus ceftriaxone, Outcome 5 Fever clearance time.
5.6
5.6. Analysis
Comparison 5 Fluoroquinolone versus ceftriaxone, Outcome 6 Non‐serious adverse events.
6.1
6.1. Analysis
Comparison 6 Fluoroquinolone versus azithromycin, Outcome 1 Clinical failure.
6.2
6.2. Analysis
Comparison 6 Fluoroquinolone versus azithromycin, Outcome 2 Microbiological failure.
6.3
6.3. Analysis
Comparison 6 Fluoroquinolone versus azithromycin, Outcome 3 Relapse.
6.4
6.4. Analysis
Comparison 6 Fluoroquinolone versus azithromycin, Outcome 4 Convalescent faecal carriage.
6.5
6.5. Analysis
Comparison 6 Fluoroquinolone versus azithromycin, Outcome 5 Fever clearance time.
6.6
6.6. Analysis
Comparison 6 Fluoroquinolone versus azithromycin, Outcome 6 Duration of Hospitalization.
6.7
6.7. Analysis
Comparison 6 Fluoroquinolone versus azithromycin, Outcome 7 Serious adverse events.
6.8
6.8. Analysis
Comparison 6 Fluoroquinolone versus azithromycin, Outcome 8 Non‐serious adverse events.
7.1
7.1. Analysis
Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 1 Clinical failure.
7.2
7.2. Analysis
Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 2 Microbiological failure.
7.3
7.3. Analysis
Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 3 Relapse.
7.4
7.4. Analysis
Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 4 Convalecsent faecal carriage.
7.5
7.5. Analysis
Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 5 Fever clearance time.
7.6
7.6. Analysis
Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 6 Duration of hospitalization.
7.7
7.7. Analysis
Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 7 Serious adverse events.
7.8
7.8. Analysis
Comparison 7 Fluoroquinolone 2 days vs 3 days, Outcome 8 Non‐serious adverse events.
8.1
8.1. Analysis
Comparison 8 Fluoroquinolone 3 days vs 5 days, Outcome 1 Relapse.
8.2
8.2. Analysis
Comparison 8 Fluoroquinolone 3 days vs 5 days, Outcome 2 Fever Clearance time.
8.3
8.3. Analysis
Comparison 8 Fluoroquinolone 3 days vs 5 days, Outcome 3 Non‐serious adverse events.
9.1
9.1. Analysis
Comparison 9 Fluoroquinolone 5 days vs 7 days, Outcome 1 Microbiological Failure.
9.2
9.2. Analysis
Comparison 9 Fluoroquinolone 5 days vs 7 days, Outcome 2 Relapse.
9.3
9.3. Analysis
Comparison 9 Fluoroquinolone 5 days vs 7 days, Outcome 3 Fever clearance time.
9.4
9.4. Analysis
Comparison 9 Fluoroquinolone 5 days vs 7 days, Outcome 4 Non‐serious adverse events.
10.1
10.1. Analysis
Comparison 10 Fluoroquinolone 7 days vs 10 days, Outcome 1 Microbiological failure.
10.2
10.2. Analysis
Comparison 10 Fluoroquinolone 7 days vs 10 days, Outcome 2 Relapse.
11.1
11.1. Analysis
Comparison 11 Gatifloxacin (OD for 7 days) vs chloramphenicol (QDS for 14 days), Outcome 1 All outcomes.
12.1
12.1. Analysis
Comparison 12 Fluoroquinolone 10 days vs 14 days, Outcome 1 Relapse.
12.2
12.2. Analysis
Comparison 12 Fluoroquinolone 10 days vs 14 days, Outcome 2 Fever clearance time.
12.3
12.3. Analysis
Comparison 12 Fluoroquinolone 10 days vs 14 days, Outcome 3 Non‐serious adverse events.
13.1
13.1. Analysis
Comparison 13 Gatifloxacin (OD for 7 days) vs cefixime (BD for 7 days), Outcome 1 All outcomes.
14.1
14.1. Analysis
Comparison 14 Gatifloxacin (OD for 7 days) vs azithromycin (OD for 7 days), Outcome 1 All outcomes.
See this image and copyright information in PMC

Update of

References

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Smith 1994 VNM {published data only}
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References to studies awaiting assessment

Bran 1991 {published data only}
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Flores 1991 {published data only}
    1. Flores GR. Pharmacological treatment of typhoid fever: A comparative study of ciprofloxacin versus trimethoprim‐sulfamethoxazole [Tratamiento farmacológico del paciente con fiebre tifoidea: estudio comparativo entre ciprofloxacina y trimetoprim‐sulfametoxazol]. Investigacion Medica International 1991;17(4):185‐8.
Quintero 1988 {published data only}
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Weng 1996 {published data only}
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Xiao 1991 {published data only}
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Yu 1998 {published data only}
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References to ongoing studies

ISRCTN66534807 {unpublished data only}
    1. ISRCTN66534807. A randomised clinical trial of Azithromycin versus Ofloxacin in the treatment of adults with uncomplicated typhoid fever at Mahosot Hospital, Vientiane, Lao People's Democratic Republic (PDR). www.controlled‐trials.com/ISRCTN66534807.

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