Typhoid fever and paratyphoid fever (also collectively known as enteric fever) are severe systemic illnesses characterized by sustained fever and generalized symptoms.
The infections are transmitted through fecal-oral route and are caused by the bacterium Salmonella typhi or Salmonella paratyphi A, B, or C. Together, they cause an estimated 26 million infections and 200,000 deaths every year, with high numbers originating from parts of South Asia.
An increased prevalence of antibiotic resistance has been found with first line treatments using oral amoxicillin, chloramphenicol and trimethoprim-sulfamethoxazole. This has led to a new generation of antibiotics known as fluoroquinolones to curb the new resistant species.
Gatifloxacin was previously released in 1999, but was withdrawn after concerns about its side effect of causing unstable blood sugar levels was published in 2006 by the New England Journal of Medicine.
Led by Dr. Amit Arjyal in Nepal, researchers from the Wellcome Trust Major Overseas Programme at the Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam, together with researchers at the Oxford University Clinical Research Unit–Patan Academy of Health Sciences, Kathmandu, Nepal, ran an open-label randomized superiority trial, investigating the efficacy and side effects of a new fluoroquinolone, gatifloxacin, against chloramphenicol.
In this trial, the team discovered that gatifloxacin was not inferior to chloramphenicol in rates of treatment failure and had similar fever clearance time. There was also neither a difference in rates of positive stool cultures at the 1 and 6 month mark nor any difference in relapse rates.
The results of this trial was published in Lancet Infectious Diseases. The researchers identified several advantages of using gatifloxacin over chloramphenicol. There were fewer side effects associated with gatifloxacin such as anorexia, nausea, dizziness and diarrhea. Gatifloxacin required less frequent administration for a shorter duration compared to chloramphenicol (1 time a day for 7 days, versus 4 times a day for 14 days). It also cost less than chloramphenicol, at . Finally, chloramphenicol-resistant strains may be susceptible to gatifloxacin.
However, gatifloxacin use resulted in elevated sugar levels in elderly patients, which returned to normal after the treatment was concluded. Hence, the researchers submitted a recommendation to the World Health Organization that gatifloxacin be used in young populations with a low risk of diabetes. The drug is also currently in Phase III trials for the treatment of mycobacterium tuberculosis