Multidrug-resistant (MDR) Salmonella Typhi (resistant to
chloramphenicol,
ampicillin, and
trimethoprim-
sulphamethoxazole) and isolates with reduced susceptibility to
fluoroquinolones (indicated by resistance to
nalidixic acid, NaR) have caused epidemics and become endemic in southern Viet Nam during the 1990s. Short courses of
ofloxacin have proved acceptable for treating MDR/
NaS isolates of S. Typhi (
ofloxacin MIC90 = 0.06 mg/l) causing uncomplicated disease.
Ofloxacin (10-15 mg/kg/d) given for 2, 3, or 5 d cured >90% of patients with an average
fever clearance time (FCT) of 4 d. Less than 3% of patients relapsed or had a positive post-treatment stool culture. In contrast, the response of NaR isolates (
ofloxacin MIC90 = 0.5 mg/l) to such regimens is poor. For example,
ofloxacin (20 mg/kg/d) given for 7 d cured only 75% of patients, with an FCT of 7 d, and 19% of patients had positive post-treatment faecal cultures. Currently available alternatives for NaR
infections include
ceftriaxone,
cefixime, and
azithromycin. These antimicrobials are reasonably effective but expensive. New, effective, and affordable regimens are needed to treat these NaR
infections. Short courses of the new generation
fluoroquinolones or combinations of the available antimicrobials are possible options.