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Salmonella enterica serovar typhi, is endemic in India. Since 1990′s Fluoroquinolones (ciprofloxacin, ofloxacin) had been effective for multidrug resistant (MDR) strains, resistant to Ampicillin, Chloramphenical and Co-trimoxazole (ACCo). Presently however, many isolates of Salmonella, MDR and non-MDR show delayed response to ciprofloxacin [1, 2]. In UK, decreased sensitivity to ciprofloxacin increased from 2.7% in 1995 to 23% in 1999 . An increase in Minimum Inhibitory Concentration (MIC) of ciprofloxacin (0.004-0.0039 mg/L in 1990 to 0.19-0.2 mg/L in 2003) has also been noted in India . This is attributed to point-mutation in quinolone resistance determining region (QRDR) of topoisomerase gene, gyrA in Salmonella and leads to simultaneous resistance against nalidixic acid, a non-fluorinated narrow-spectrum quinolone . Resistance to 30 μg nalidixic acid disc (zone diam < 13mm) is a simple laboratory indication of low-level susceptibility/resistance to ciprofloxacin . Recent reports from India show nalidixic acid resistant salmonella (NARST) even among non-MDR salmonella strains [2, 4]. At our institute in Pune, we carried out MIC to ciprofloxacin for 21 isolates of S typhi from different parts of the country known to be resistant to nalidixic acid (MIC > 128 mg/L). Disk strengths and zone interpretations were in accordance with National Committee for Clinical Laboratory Standards (NCCLS). Out of 21 strains, 14 were known MDR isolates and 7 were sensitive strains. MIC for ciprofloxacin was raised in all, being 0.5 mg/L in 16 isolates (9MDR strains) and 1.0 mg/L in 5 isolates (all MDR strainsand all 7 sensitive strains). An MIC of >0.125 mg/L of ciprofloxacin has been associated with poor clinical response in several studies [1, 2, 4, 5]. These stains will either respond poorly or inappreciably to ciprofloxacin in-vivo, even if found sensitive invitro using 5 μg ciprofloxacin disc . The current NCCLS breakpoints may have to be reevaluated for Salmonellae [3, 5]. These strains respond well to ceftriaxone or azithromycin [1, 2, 4]. Laboratories should look for nalidixic acid resistance in Salmonella isolates as a surrogate marker of decreased fluoroquinolone susceptibility and alert the physician. A blood culture is a must before starting any antibiotic in suspected enteric fever so that diagnosis is confirmed and the strain made available to the laboratory for further characterization.