Introduction
Typhoid fever, caused by Salmonella enterica serovar Typhi (S.Typhi), remains a global public health problem centred in devel-oping countries [1]. The emergence of multi-drug resistant (MDR)S. Typhi, with resistance to all first line drugs: (chloramphenicol,co-trimoxazole and ampicillin) led to the fluoroquinolones becom-ing the treatment of choice for enteric fever [2]. There is a clearrelationship between increasing fluoroquinolone MIC and outcomeduring fluoroquinolone treatment of typhoid fever. Therefore for clinical management, any increase in fluoroquinolone MIC needsto be detected [3]. No zone around a nalidixic acid 30 g disc hasbeen used as a screening test for isolates with a clinically rele-vant ciprofloxacin resistance; MIC of ≥0.125 mg/L with a sensitivityof 92.9% (248/267); and a specificity of 98.4% (540/549) [4]. Themost common mutation associated with reduced susceptibility tofluoroquinolones in S. Typhi is in the quinolone resistance deter-mining region of the GyrA sub-unit of DNA gyrase. This mutation,at amino acid 83, also confers resistance to nalidixic acid (NALR)and so nalidixic acid can be a marker for fluoroquinolone resis-tance where this mutation is the sole cause of resistance. Strainsof S. Typhi with decreased susceptibility to fluoroquinolones (e.g.ciprofloxacin (CIPI) MIC > 0.064 mg/L are now very common in India[3]. The reports of alternative mechanisms of fluoroquinolone resis-tance are increasing [5,6]. In response to this the CLSI has redefinedthe breakpoints for ciprofloxacin as ≤0.064 mg/L and ≥1 mg/L and ≥31 mm and ≤20 mm for susceptibility and resistance using MICand disc diffusion [7], and strains that are >0.064 mg/L and