副猪嗜血杆菌对喹诺酮类药物流行病学临界值的建立

Establishment of the Epidemiological Cut-off Values of Haemophilus parasuis for Quinolones

为了解副猪嗜血杆菌对喹诺酮类药物的耐药现状,制定副猪嗜血杆菌对喹诺酮类药物的流行病学临界值,本试验根据CLSI-VET中规定的方法,对ScienceDirect、PubMed、中国知网等数据库中副猪嗜血杆菌对喹诺酮药物的耐药数据进行收集,共收集到605株环丙沙星、74株氧氟沙星、322株左氧氟沙星、211株达氟沙星、276株萘啶酸、143株洛美沙星、638株恩诺沙星及262株马波沙星的最小抑菌浓度数据,进行数据修正后利用统计软件ECOFFinder进行整理拟合,得出MIC拟合直方分布图,确定了副猪嗜血杆菌对8种喹诺酮类药物的流行病学临界值和耐药率。8种药物中可用于兽医临床使用的药物为达氟沙星、恩诺沙星、马波沙星、环丙沙星;萘啶酸作为第1代喹诺酮抗菌药,已基本退出市场;另外3种药物不可用于兽医临床。通过调查研究得出副猪嗜血杆菌对氧氟沙星、萘啶酸、洛美沙星、左氧氟沙星、环丙沙星、达氟沙星、马波沙星、恩诺沙星药物的流行病学临界值分别为8、4、4、0.25、0.25、0.0625、0.0625和0.03125μg/mL,说明目前野生型副猪嗜血杆菌对环丙沙星、达氟沙星、马波沙星和恩诺沙星这4种兽医临床可用药敏感性较高,临床推荐使用。文章得出的数据在国际交流频繁的时代普遍适用,在国内外缺乏相应药效学折点和临床折点时可作为敏感和耐药的判定标准,并为进一步制定临床折点,指导临床用药、延长喹诺酮药物的临床使用寿命奠定了基础。

In order to better understand the current situation of drug resistance of Haemophilus parasuis(Hps)to quinolones and establish the epidemiological cut-off values(ECOFFs)of Hps to quinolones,this test was done according to the method specified in the CLSI-VET.By searching from databases such as ScienceDirect,PubMed,CNKI and others,the MICs of 605 strains of ciprofloxacin,74 strains of ofloxacin,322 strains of levofloxacin,211 strains of danofloxacin,276 strains of nalidixic acid,143 strains of lomefloxacin,638 strains of enrofloxacin and 262 strains of mabofloxacin were collected and corrected.Then the statistical software ECOFFinder was used to fit the data,draw the nonlinear regression of MIC distribution and determine the ECOFFs and drug resistance rates of Hps to 8 quinolones.Among the 8 drugs,the drugs that could only be used for veterinary clinical use were danofloxacin,enrofloxacin,marbofloxacin and ciprofloxacin.As the first generation quinolone antibacterial,nalidixic acid had been withdrawn from the market.And the other three drugs should not be used in the veterinary clinic.The result of the experiment was that the ECOFFs of Hps to ofloxacin,nalidixic acid,lomefloxacin,levofloxacin,ciprofloxacin,danofloxacin,marbofloxacin and enrofloxacin were 8,4,4,0.25,0.25,0.625,0.625 and 0.03125μg/mL,respectively.It showed that wild type strains of Hps had high sensitivity to ciprofloxacin,danofloxacin,marbofloxacin and enrofloxacin which were available in veterinary clinic and it’s recommended to use them in veterinary clinical use.However,the drug resistance rate of these four drugs was also high,indicating that the existence of drug-resistant strains was serious.The data concluded in this paper was applicable in the era of frequent international exchanges and could be used as the criterion of sensitivity and resistance when there was no corresponding pharmacodynamics and clinical breaking point at home and abroad.And it also laid a foundation for further establishing clinical breaking point,guiding clinical medication and prolonging the clinical service life of quinolones.