Akiba Masato, Nakaoka Yuji, Kida Muneyoshi, Ishioka Yukiko, Sameshima Toshiya, Yoshii Noriyo, Nakazawa Muneo, Uchida Ikuo, Terakado Nobuyuki
Safety Research Team, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba 305-0856, Japan.
J Antimicrob Chemother. 2007 Dec;60(6):1235-42. doi: 10.1093/jac/dkm402. Epub 2007 Oct 23.
We investigated the antimicrobial susceptibilities and resistance mechanisms of cattle-adapted Salmonella enterica serovar Dublin isolated in Japan in the past 30 years. This study is an example of evaluation of the impact of introduction of antimicrobials in veterinary medical practice on the selection of resistance in S. enterica.
The antimicrobial susceptibilities and prevalence of R-plasmids in Salmonella Dublin isolated in Japan from 1976 to 2005 were investigated. To evaluate the importance of gyrA mutation and active efflux, we derived the gyrA revertants and acrAB deletion mutants, and then compared with their parental strains the MICs of quinolone antimicrobials such as nalidixic acid, enrofloxacin, ofloxacin and ciprofloxacin.
Salmonella Dublin isolates with R-plasmids and resistance to more than three antimicrobials were predominant between 1981 and 1995. From the latter half of the 1990s to the present, Salmonella Dublin isolates without R-plasmids became dominant. The introduction of nalidixic acid into the veterinary field in the mid-1980s was followed by the emergence of nalidixic acid-resistant isolates, which are now predominant. We found only a single gyrA mutation (Asp-87-->Tyr) among the nalidixic acid-resistant isolates. Although the reduced susceptibilities to the fluoroquinolones were observed among the nalidixic acid-resistant isolates, none of the isolates was resistant to the fluoroquinolones used in this study. The MIC data for the fluoroquinolones differed up to 4-fold. Results of the susceptibility test using gyrA revertants and acrAB mutants suggest that the isolates with the gyrA mutation were selected by the use of nalidixic acid, and the AcrAB-TolC system accounts for the decreased fluoroquinolone susceptibilities.
These data suggest that the introduction of nalidixic acid in veterinary medicine seemed to affect the susceptibilities of Salmonella Dublin among the cattle population in Japan, whereas the introduction of enrofloxacin has not caused any additional effect. The prudent use of antimicrobials in the veterinary field should be continuously stressed.
我们调查了过去30年在日本分离出的适应牛的肠炎沙门氏菌都柏林血清型的抗菌药敏性及耐药机制。本研究是评估兽医学实践中引入抗菌药物对肠炎沙门氏菌耐药性选择影响的一个实例。
对1976年至2005年在日本分离出的都柏林沙门氏菌的抗菌药敏性及R质粒流行情况进行了调查。为评估gyrA突变和主动外排的重要性，我们构建了gyrA回复突变体和acrAB缺失突变体，然后将萘啶酸、恩诺沙星、氧氟沙星和环丙沙星等喹诺酮类抗菌药物对其亲本菌株和突变体的最低抑菌浓度（MIC）进行了比较。
1981年至1995年间，携带R质粒且对三种以上抗菌药物耐药的都柏林沙门氏菌分离株占主导地位。从20世纪90年代后半期至今，无R质粒的都柏林沙门氏菌分离株成为优势菌株。20世纪80年代中期萘啶酸引入兽医领域后，出现了对萘啶酸耐药的分离株，目前这些分离株占主导地位。在对萘啶酸耐药的分离株中，我们仅发现一个gyrA突变（Asp-87→Tyr）。尽管在对萘啶酸耐药的分离株中观察到对氟喹诺酮类药物的敏感性降低，但本研究中使用的氟喹诺酮类药物均未出现耐药菌株。氟喹诺酮类药物的MIC数据差异高达4倍。使用gyrA回复突变体和acrAB突变体进行药敏试验的结果表明，携带gyrA突变的分离株是因使用萘啶酸而被选择出来的，AcrAB-TolC系统导致了对氟喹诺酮类药物敏感性的降低。
这些数据表明，萘啶酸引入兽医学似乎影响了日本牛群中都柏林沙门氏菌的药敏性，而恩诺沙星的引入未产生任何额外影响。应持续强调在兽医领域谨慎使用抗菌药物。
