Ciprofloxacin-resistant Salmonella Kentucky in Travelers

To the Editor: Ciprofloxacin is the treatment of choice of severe non-typhoidal Salmonella infections in adults. Resistance to ciprofloxacin has been found exceptionally in nonty-phoidal Salmonella enterica isolates and only in serotypes Typhimurium, Choleraesuis, and Schwarzengrund (1–8). Such isolates have been collected from humans and animals in Europe, Asia, and North America. We report the emergence of ciprofloxacin-resistant isolates of S. Kentucky since 2002 in French travelers returning from northeast and eastern Africa. From 2000 through 2005, 197 S. Kentucky isolates from humans (1 per patient) were serotyped, from 69,759 total S. enter-ica isolates serotyped at the French National Reference Centre for Salmonella. Antimicrobial drug susceptibility was determined for 186 isolates by the disk-diffusion method with 32 antimicrobial drugs, as previously described (9). Resistance to several drugs, amoxicillin (18%), gen-tamicin (16%), nalidixic acid (21%), sulfonamides (24%), and tetracycline (24%), has been observed from 2000 through 2005. A total of 17 (9%) ciprofloxacin-resistant S. Kentucky strains were isolated. A resistant isolate that was unty-pable by conventional serotyping (rough) but that had a pulsed-field gel electrophoresis (PFGE) profile associated with serotype Kentucky, was included in this study. Ciprofloxacin MIC levels in these isolates, determined by standard agar doubling dilution as previously described (2), were 4–16 mg/L. The first ciprofloxacin-resistant strain was isolated in December 2002 from a French tourist who had gastroenteritis during a Nile cruise in Egypt. In 2004 and 2005, 17 ciprofloxacin-resistant isolates were identified in unrelated adults who lived in different cities of France at different times of the year. The 16 patients we contacted acquired the infection during or immediately after travel to Egypt (10 patients), Kenya and Tanzania (3), or Sudan (1). In 2 cases, gastroenteritis occurred 2 months after travel to Egypt. None of the investigated cases were fatal or life-threatening. The 18 ciprofloxacin-resistant isolates (17 serotype Kentucky and 1 rough) displayed various susceptibility patterns, from single resistance to quinolones to multiple resistance (up to 9 antimicrobial agents). To identify mutations responsible for cipro-floxacin resistance, the quinolone resistance–determining regions (QRDRs) of gyrA, gyrB, parC, and parE were amplified by PCR and sequenced as described previously (3,9), except that different forward primers for gyrB (5′-TTATCGACGC-CGCGCGTGCGC-3′) and parE (5′-CGCGTAACTGCATCG-GGTTC-3′) were used. The 18 ciprofloxacin-resistant isolates had different double mutations in gyrA leading to amino acid substitutions, Ser83Phe and Asp87Gly (8 isolates), Ser83Phe and Asp87Asn (5), and Ser83Phe and Asp87Tyr (5), but had identical mutations in parC (resulting in …