A comparison of fluoroquinolones versus other antibiotics for treating enteric fever: meta-analysis

Abstract

Objectives: To review evidence supporting use of fluoroquinolones as first line agents over other antibiotics for treating typhoid and paratyphoid fever (enteric fever).

Design: Meta-analysis of randomised controlled trials.

Data sources: Cochrane Infectious Diseases Group specialised register, CENTRAL (issue 4, 2007), Medline (1966-2007), Embase (1974-2007), LILACS (1982-2007), selected conferences, reference lists, and ongoing trial register (November 2007). Review methods Trials comparing fluoroquinolones with chloramphenicol, cephalosporins, or azithromycin in culture-proven enteric fever were included. Two reviewers extracted data and assessed methodological quality. Odds ratios with 95% confidence intervals were estimated. Trials recruiting over 60% children were analysed separately from trials on adults. Primary outcomes studied were clinical failure, microbiological failure, and relapse.

Results: Twenty trials were included. Trials were small and often of limited methodological quality. Only 10 trials concealed allocation and only three were blinded. In trials on adults, fluoroquinolones were not significantly different from chloramphenicol for clinical failure (594 participants) or microbiological failure (n=378), but reduced clinical relapse (odds ratio 0.14 (95% confidence interval 0.04 to 0.50), n=467, 6 trials). Azithromycin and fluoroquinolones were comparable (n=152, 2 trials). Compared with ceftriaxone, fluoroquinolones reduced clinical failure (0.08 (0.01 to 0.45), n=120, 3 trials) but not microbiological failure or relapse. Compared with cefixime, fluoroquinolones reduced clinical failure (0.05 (0.01 to 0.24), n=238, 2 trials) and relapse (0.18 (0.03 to 0.91), n=218, 2 trials). In trials on children infected with nalidixic acid resistant strains, older fluoroquinolones (ofloxacin) produced more clinical failures than azithromycin (2.67 (1.16 to 6.11), n=125, 1 trial), but there were no differences with newer fluoroquinolones (gatifloxacin, n=285, 1 trial). Fluoroquinolones and cefixime were not significantly different (n=82, 1 trial).

Conclusions: In adults, fluoroquinolones may be better than chloramphenicol for preventing clinical relapse. Data were limited for other comparisons, particularly for children.

Fig 1 Studies evaluated at each stage of the meta-analysis. (*Supplementary search includes: reference lists, authors’ files, contacting experts, selected conference proceedings, on-going trial register. †See Cochrane review for further details or analyses. ‡Includes sample size <5, comparing different formulations/routes of same fluoroqinolone, not enough information presented in published report. §Trials contributing to more than 1 category counted only once.)

Fig 2 Forest plots for trials of fluoroquinolones versus chloramphenicol for treating enteric fever in adult inpatients. Details of studies reporting proportion of multidrug resistant and nalidixic acid resistant strains are in text. See Cochrane review for stratifications.

Fig 3 Forest plots for trials of fluoroquinolones versus cefixime for treating enteric fever in adult outpatients and inpatients. There were no relapses in either arm in Yu et al 1998. Pandit et al 2007 reported 2/87 v 6/51 relapses (odds ratio 0.18 (95% confidence interval 0.03 to 0.91). Details of studies reporting proportion of nalidixic acid resistant strains are in text.

Fig 4 Forest plots for trials of fluoroquinolones versus ceftriaxone for treating enteric fever in adult inpatients. Details of studies reporting proportion of nalidixic acid resistant strains are in text. See Cochrane review for stratifications.