Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever).
BACKGROUND
Fluoroquinolones are recommended as first-line therapy for typhoid and paratyphoid fever (enteric fever), but how they compare with other antibiotics and different fluoroquinolones is unclear.


OBJECTIVE
To evaluate fluoroquinolone antibiotics for treating enteric fever in children and adults compared with other antibiotics, different fluoroquinolones, and different durations of fluoroquinolone treatment.


METHODS
In November 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 4), MEDLINE, EMBASE, LILACS, mRCT, conference proceedings, and reference lists.


METHODS
Randomized controlled trials of fluoroquinolones in people with blood or bone marrow culture-confirmed enteric fever.


METHODS
Two authors independently assessed the trials' methodological quality and extracted data. We calculated odds ratios (OR) for dichotomous data with 95% confidence intervals (CI). We analysed trials with greater than 60% children separately from trials of mostly adults.


RESULTS
Of 38 included trials, 22 had unclear allocation concealment and 34 did not use blinding. Four trials included exclusively children, seven had both adults and children, and three studied outpatients.
Among primary outcomes (clinical failure, microbiological failure, and relapse), compared with chloramphenicol, fluoroquinolones were not statistically significantly different for clinical failure (594 participants) or microbiological failure (378 participants), but they reduced clinical relapse (OR 0.14, 95% CI 0.04 to 0.50; 467 participants, 6 trials). We detected no statistically significant difference versus co-trimoxazole (82 participants, 2 trials) or azithromycin (152 participants, 2 trials). Fluoroquinolones reduced clinical failure compared with ceftriaxone (OR 0.08, 95% CI 0.01 to 0.45; 120 participants, 3 trials), but not microbiological failure or relapse. Versus cefixime, fluoroquinolones reduced clinical failure (OR 0.05, 95% CI 0.01 to 0.24; 238 participants; 2 trials) and relapse (OR 0.18, 95% CI 0.03 to 0.91; 218 participants, 2 trials).
In children with high proportions of nalidixic acid-resistant strains, older fluoroquinolones increased clinical failures compared with azithromycin (OR 2.67, 95% CI 1.16 to 6.11; 125 participants, 1 trial), with no differences using newer fluoroquinolones (285 participants, 1 trial). Fluoroquinolones and cefixime were not statistically significantly different (82 participants, 1 trial). Trials comparing different durations of fluoroquinolone treatment were not statistically significantly different (889 participants, 9 trials). Norfloxacin had more clinical failures than other fluoroquinolones (417 participants, 5 trials).


CONCLUSIONS
Trials were small and methodological quality varied. In adults, fluoroquinolones may be better for reducing clinical relapse rates compared to chloramphenicol. Data are limited for other comparisons, particularly in children.
Department of Paediatrics & Child Health, Aga Khan University Hospital, Stadium Road, PO Box 3500, Karachi, Pakistan, 74800. zulfiqar.bhutta@aku.edu
Durrane
D
Thaver
Anita Km
AK
Zaidi
Julia A
JA
Critchley
Asma
A
Azmatullah
Syed Ali
SA
Madni
Zulfiqar A
ZA
Bhutta
D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D024841:Fluoroquinolones / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009643:Norfloxacin / Q000627:therapeutic use; D010284:Paratyphoid Fever / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014435:Typhoid Fever / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D009643:Norfloxacin