The treatment of multidrug-resistant and nalidixic acid-resistant typhoid fever in Viet Nam.
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.
Parry
Christopher M
CM
Oxford University Wellcome Trust Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam. cmparry@liv.ac.uk
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use; D002511:Cephalosporins / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D024841:Fluoroquinolones / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D009268:Nalidixic Acid / Q000627:therapeutic use*; D016896:Treatment Outcome; D014435:Typhoid Fever / Q000188:drug therapy* / Q000453:epidemiology; D014744:Vietnam / Q000453:epidemiology
D000890:Anti-Infective Agents; D002511:Cephalosporins; D024841:Fluoroquinolones; D009268:Nalidixic Acid; D017963:Azithromycin