Predictive efficacy of nalidixic acid resistance as a marker of fluoroquinolone resistance in Salmonella enterica var Typhi.

BACKGROUND AND OBJECTIVES Resistance in Salmonella enterica var Typhi (S. Typhi) to chloramphenicol, amoxicillin and co-trimoxazole has posed a challenge to treatment of typhoid fever. Ciprofloxacin has been the empirical therapy of choice, but the recent increase in minimum inhibitory concentration (MIC) to ciprofloxacin in S. Typhi, not detectable by disc diffusion (DD) tests, may result in delayed response and serious complications. Nalidixic acid (NA) resistance has been used as an indirect evidence of increased ciprofloxacin MIC in S. Typhi. We evaluated the predictive value of NA resistance for fluoroquinolone resistance in clinical isolates of S. Typhi. METHODS A total of 70 clinical isolates of S. Typhi were tested for antimicrobial susceptibility according to the National Committee for Clinical Laboratory Standards (NCCLS) method. MIC to fluoroquinolones was carried out by the agar dilution method. RESULTS Thirteen (18.6 %) isolates were resistant to amoxicillin, chloramphenicol and cotrimoxazole; all were sensitive to ciprofloxacin and cefotaxime. Fifty (71.4%) were resistant to NA. Nineteen (27.1 %) isolates were resistant to ciprofloxacin by MIC tests. The MIC for ciprofloxacin was 0.03-4 microg/ml for NA(S) and 0.25-4 microg/ml for NA(R) isolates. NA susceptibility showed a predictive value of 95 per cent for ciprofloxacin susceptibility while NA resistance had a predictive value of 36 per cent for ciprofloxacin resistance. Thirty isolates studied were sensitive to gatifloxacin; MIC values were 0.03-0.5 microg/ml for NA(S) and 0.25-0.5 microg/ml for NA(R) isolates. INTERPRETATION AND CONCLUSION NA susceptibility was a good marker for fluoroquinolone susceptibility but NA resistance had a poor predictive value for ciprofloxacin resistance. NA resistant isolates should be tested for ciprofloxacin MIC before deciding a change in therapeutic regimen. Higher MIC for gatifloxacin was also noticed in NA resistant isolates.