Quinolone‐ResistantSalmonella typhiin Viet Nam: Molecular Basis of Resistance and Clinical Response to Treatment

Abstract

Nalidixic acid-resistant Salmonella typhi (NARST) was first isolated in Viet Nam in 1993. Analysis of the quinolone resistance-determining region of gyrA in 20 NARST isolates by polymerase chain reaction and single-stranded conformational polymorphism yielded two novel patterns: pattern II corresponding to a point mutation at nucleotide 87 Asp-->Gly (n = 17), and pattern III corresponding to a point mutation at nucleotide 83 Ser-->Phe (n = 3). In trials of short-course ofloxacin therapy for uncomplicated typhoid, 117 (78%) of 150 patients were infected with multidrug-resistant S. typhi, 18 (15%) of which were NARST. The median time to fever clearance was 156 hours (range, 30-366 hours) for patients infected with NARST and 84 hours (range, 12-378 hours) for those infected with nalidixic acid-susceptible strains (P < .001). Six (33.3%) of 18 NARST infections required retreatment, whereas 1 (0.8%) of 132 infections due to susceptible strains required retreatment (relative risk = 44; 95% confidence interval = 5.6-345; P < .0001). We recommend that short courses of quinolones not be used in patients infected with NARST.

High Level of Resistance to nalidixic acid in Salmonella enterica serovar Typhi in Central India

“…However, towards the end of last decade, treatment failures with ciprofloxacin have been reported due to infection with nalidixic acid resistant Salmonella Typhi which were found to be susceptible to ciprofloxacin in disc diffusion tests. These strains exhibited a higher minimum inhibitory concentration (MIC) of ciprofloxacin [3]. The present study was undertaken to assess the nalidixic acid resistant strains of Salmonella Typhi circulating in the central west part of the country.…”

Molecular Analysis of Fluoroquinolone-resistantSalmonellaParatyphi A Isolate, India

“…Paratyphi A, associated with chromosomally mediated reduced susceptibility to ciprofloxacin, has caused concern ( 4 ). Reduced susceptibility to fluoroquinolones results in a poor response of salmonellosis patients to treatment and may allow prolonged bacterial shedding ( 5 ). Rising resistance to fluoroquinolones is likely to be driving an increase in cases of paratyphoid fever in regions where fluoroquinolones are used empirically to treat enteric fever.…”

Current Trends in the Management of Typhoid Fever

“…However, patients infected with relatively quinolone-resistant S typhi strains (resistant to nalidixic acid and a minimal inhibitory ciprofloxacin concentration of 0.125 to 1 mg/dl) who receive shortcourse quinolone therapy (i.e. <5 days), may not demonstrate clinical recovery and could require repeated or alternative treatment [17]. Therefore, all S typhi isolates should be screened for nalidixic acid resistance and tested against a clinically appropriate quinolone.…”

“…Patients with nalidixic acid-resistant strains should be treated with higher doses of ciprofloxacin (i.e. 10 mg/kg twice daily for 10 days) or ofloxacin (10 to 15 mg/kg divided twice daily for 7 to 10 days) [17]. Third generation cephalosporins such as cefotaxime, ceftriaxone, and cefoperazone have been used successfully to treat typhoid fever, with courses as short as 3 days showing similar efficacy to the usual 10 to 14 days regimens [18,19].…”