Ciprofloxacin-Resistant Salmonella enterica Serotype Typhimurium, China

We characterized 44 Salmonella enterica serotype Typhimurium isolates from Tongji Hospital outpatients in Wuhan, China, May 2002–October 2005. All 31 ciprofloxacin-resistant isolates were also resistant to >8 other antimicrobial drugs and carried >2 mutations in GyrA and 1 mutation in ParC. Class 1 integrons were identified in 37 isolates.

. Although >2,500 serotypes have been reported, Salmonella enterica serotype Typhimurium is 1 of the leading serotypes causing salmonellosis worldwide (2). Fluoroquinolones such as ciprofl oxacin are strongly recommended for treatment of severe S. Typhimurium infections in adults (3).
In this study, we characterized all S. Typhimurium isolates recovered from May 2002 through October 2005 from outpatients of Tongji Hospital, Wuhan, China, a sentinel hospital in the National Center for Surveillance of Antimicrobial Resistance. During the time of this study, Tongji Hospital strictly followed the recommendation for treatment of severe S. Typhimurium infections.

The Study
We analyzed stool samples from outpatients who came to Tongji Hospital from the local community for treatment of diarrhea during the study period. A total of 44 S. Typhimurium isolates were recovered from the samples. S. Typhimurium was identifi ed by using standard biochemical tests and commercial typing antiserum (Statens Serum Institute, Copenhagen, Denmark) according to the manufacturer's instructions. MICs of 15 antimicrobial drugs (Table) were determined by using the broth-microdilution method; susceptibility to streptomycin was measured by using the disk-diffusion method as recommended by the Clinical and Laboratory Standards Institute (4). All isolates were further characterized by mutation analysis in the quinolone-resistance determining regions (QRDRs), pulsed-fi eld gel electrophoresis (PFGE), and screening for class I integrons and β-lactamase genes as previously described (5)(6)(7)(8).

Conclusions
We report a high incidence of fl uoroquinolone-resistant S. Typhimurium isolates from Tongji Hospital outpatients. The MIC variation for ciprofl oxacin differed 2-to 4-fold in isolates that had the same QRDR mutation profi le, which implies that other mechanisms might partially contribute to the resistance phenotype (online Appendix Figure). After PFGE analysis, S. Typhimurium isolates were grouped into 3 ciprofl oxacin-susceptible clusters and ciprofl oxacinresistant clusters. Similar distribution patterns have also been observed in isolates from Japan (9), which suggests a distinct genetic lineage for ciprofl oxacin-resistant isolates that have become dominant. Studies have reported that ciprofl oxacin-resistant S. Typhimurium isolates were usually resistant to multiple drugs (9,10). In this study, all ciprofl oxacin-resistant S. Typhimurium isolates were resistant to 8-11 additional antimicrobial drugs. Among the 32 isolates harboring OXA-30 enzyme in this study, only 5 with PFGE pattern F showed intermediate resistance to cefepime, which suggests different levels of OXA gene expression or the contribution of other unknown mechanisms.
The high incidence of quinonlone-resistant S. Typhimurium isolates in this study might be affected by several factors. First, patients infected by antimicrobial drug-resistant S. Typhimurium strains had higher rates of hospitalization than did patients infected by susceptible strains (11,12), and the isolates in this study were from a university-affi liated medical center that usually treats patients with severe illness. Second, US studies have estimated that half of outpatient antimicrobial drugs were inappropriately prescribed for conditions such as viral illness (13). In China, inappropriate prescriptions might be even more common because antimicrobial drug prescriptions in hospitals are a source of profi t. Although we do not have patient antimicrobial drug-use information, the easy access to antimicrobial drugs raises the possibility that outpatients might have taken fl uoroquinolones after the onset of the illness but before the collection of stool specimens. Third, because livestock products are a common source of salmonellosis, the dissemination of ciprofl oxacin-resistant S. Typhimurium might have been facilitated by the use of fl uoroquinolones in livestock production (2). Last, use of other antimicrobial drugs, such as ampicillin, gentamicin, or streptomycin, may also contribute to the spreading of fl uoroquinolone-resistant S. Typhimurium because all the ciprofl oxacin-resistant isolates were also resistant to 8-11 additional antimicrobial drugs.
Although fl uoroquinolone-resistant isolates were prevalent in Tongji Hospital, ciprofl oxacin is still empirically used to treat salmonellosis in adults, due partly to the absence of systematic surveillance programs to actively monitor antimicrobial drug resistance in Salmonella spp. Because local data on antimicrobial drug susceptibility are less available, we strongly recommend that hospitals and national and local health laboratories develop and maintain the capacity to perform Salmonella culture and in vitro susceptibility testing.

Ciprofl oxacin-Resistant S. Typhimurium, China
Dr Cui is a microbiologist in the National Center for Surveillance of Antimicrobial Resistance, the State Food and Drug Administration, Beijing, China. His professional interests include developing detection methods for bacterial pathogens, molecular epidemiology, and antimicrobial drug-resistance mechanisms of bacterial pathogens.