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Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever)

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Abstract

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.

Objectives

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

Search 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.

Selection criteria

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

Data collection and analysis

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.

Main 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. ADULTS: 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). CHILDREN: 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).

Authors' 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.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

Not enough sound evidence for using fluoroquinolones in typhoid and paratyphoid fever compared with the standard antibiotics

The potentially fatal typhoid and paratyphoid fevers are caused by bacterial infection that begins in the small intestine (enteric fever). Transmission occurs through contaminated food and water, and there are areas where these diseases are endemic, such as Asia, Africa, and South and Central America. People often relapse or become carriers. Chloramphenicol has been the standard treatment, but the bacteria are becoming resistant. A new group of drugs, the fluoroquinolones, are being tried, but the review of trials found there were insufficient numbers of participants in the trials, which were also of varying quality, to be able to give recommendations with any degree of certainty, especially for children.