Revisit of Fluoroquinolone and Azithromycin susceptibility breakpoints for Salmonella enterica serovar Typhi


Surojit Das, Ujjwayini Ray, & Shanta Dutta


In recent years, increase in occurrence of fluoroquinolone (FQ) resistant S. Typhi isolates caused considerable inconvenience in selecting appropriate antimicrobials for treatment of typhoid. The World Health Organization (WHO) recommends azithromycin for empirical treatment option of uncomplicated typhoid. The CLSI 2015 updated the breakpoints of disk diffusion (DD) and minimum inhibitory concentration (MIC) results of FQs and azithromycin for S. Typhi, but DD breakpoints of ofloxacin and levofloxacin were not included. In this study, the inhibition zone diameters and MICs of nalidixic acid, ciprofloxacin, ofloxacin, levofloxacin and azithromycin were determined in S. Typhi Kolkata isolates (n=146) for 16 years period (1998 to 2013) and the data was compared with the available CLSI breakpoints. Very major error (VME) and major error (ME) of FQs were not observed in the study isolates, but the minor error (mE) of ciprofloxacin (15.8%) and ME of azithromycin (3.5%) exceeded the acceptable limit. A positive correlation between MICs of FQ and mutations in quinolone resistance-determining region (QRDR) showed reliability of MIC results to determine FQ susceptibility of S. Typhi (n=74). Isolates showing decreased ciprofloxacin susceptibility (MIC 0.125-0.5µg/ml) were likely to have at least one mutation in the QRDR region. The results on DD breakpoints of ofloxacin (resistant, ≤15mm; intermediate, 16 to 24mm and susceptible, ≥25mm) and levofloxacin (resistant, ≤18mm; intermediate, 19 to 27mm and susceptible, ≥28mm) corroborated with earlier studies. In view of the emerging FQs and azithromycin resistant S. Typhi isolates, DD and MIC breakpoints of those antimicrobials should be revisited routinely.

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