Implications for practice
Generally, fluoroquinolones performed well in the treating typhoid. Generally, fluoroquinolones performed well in the 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. In choosing any fluoroquinolone, clinicians need to take into account current, local resistance patterns.

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 head to head trials.

Implications for research
The re-emergence of chloramphenicol sensitive strains in some regions may suggest a similar trend for other first line drugs which had been abandoned following prevalent MDR. Trials may therefore focus on re-examining these relatively inexpensive alternatives in robust comparisons with fluoroquinolones in appropriate endemic populations.

Most of the studies were small . Given the importance of the study question, we would recommend multi-centred, adequately powered trials, with robust methods and analytical design. Given the nature of the disease and the importance of accurate diagnoses, we would recommend the development of robust diagnostic tests and gold standards for defining disease and resistance patterns, based on molecular methods if possible. Rapid diagnostic tests for diagnosing enteric fever should be made more widely available in endemic areas; this will ensure more efficient participant recruitment in trials and avoid the problem of syndromic treatment. In addition, it will reduce the widespread abuse of antibiotics, especially the use of fluoroquinolones for suspected typhoid fever.

Definitions of outcomes and their measurement should also be standardized to make more effective comparisons and adaptability across regions.


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