van den Bogaard A E, Hazen M, Hoyer M, Oostenbach P, Stobberingh E E
Department of Medical Microbiology, University Maastricht, NL-6200 MD Maastricht, The Netherlands.
Antimicrob Agents Chemother. 2002 Jan;46(1):110-8. doi: 10.1128/AAC.46.1.110-118.2002.
A "plasmid-curing effect" of multiresistant Escherichia coli by flavophospholipol, an antibiotic used as an antimicrobial growth promoter (AMGP) in animal feeds, has been reported to occur in vitro and in vivo under experimental conditions. In this study, the effect of flavophospholipol under field conditions was studied. The prevalence and degree (proportion of resistant strains to the total numbers present per gram of feces) of resistance of indicator bacteria, E. coli and enterococci, was determined in fecal samples from three groups of pigs that were fed a commercial finisher feed without any AMGP. Group A was the negative control group without any AMGP, group B received the same feed with 9 mg of flavophospholipol/kg of feed (study group), and group C received the same feed with 15 mg of avoparcin/kg (positive control). Fecal samples from each pig were collected at the start and at the end of the study and assessed for the prevalence and degree of resistance against antibiotics commonly used either for therapy in pig medicine or as an AMGP. Before the start of the study, all pigs were colonized with multiresistant E. coli by mixing three resistant pig isolates through their feed after disturbance of the colonization resistance of the intestinal flora by a 3-day course of lincomycin and spectinomycin. At the end of the study, the overall prevalence and degree of resistance of E. coli in the fecal flora had increased significantly in groups A and C but remained at the same level as at the start of the study in group B. The prevalence of vancomycin resistance was 44 and 41% in groups A and B, respectively, but only very low numbers of vancomycin-resistant enterococci (VRE) per gram of feces were found. In the avoparcin-fed group, the prevalence was 72%, and in 57% of the samples, more than 50% of all enterococci present were vancomycin resistant. The prevalence of resistant Enterococcus faecalis increased only in the flavophospholipol-exposed group, from 23% before the start of the study to 43% at the end of the study. It was concluded that flavophospholipol effectively suppressed the augmentation and dissemination of multiresistant E. coli in the intestinal flora of fattening pigs. Avoparcin use strongly selected for VRE carriage and excretion. Therefore, as neither flavophospholipol nor any related molecule is used therapeutically, no cross-resistance with therapeutic antibiotics exists and no transmissible resistance has been shown; the major decrease in resistance in intestinal E. coli of flavophospholipol-fed animals seemed to outweigh the small increase in the risk of transfer of flavophospholipol-resistant E. faecalis from animals to humans via the food chain.
据报道，作为动物饲料中抗菌生长促进剂（AMGP）使用的抗生素黄霉素磷脂对多重耐药性大肠杆菌具有“质粒消除效应”，这种效应已在体外和实验条件下的体内观察到。在本研究中，对黄霉素磷脂在实际生产条件下的效果进行了研究。在三组喂食不含任何AMGP的商业育肥猪饲料的猪的粪便样本中，测定指示菌大肠杆菌和肠球菌的耐药性流行率和程度（耐药菌株占每克粪便中总菌数的比例）。A组为不含任何AMGP的阴性对照组，B组接受添加9毫克黄霉素磷脂/千克饲料的相同饲料（研究组），C组接受添加15毫克阿伏帕星/千克的相同饲料（阳性对照组）。在研究开始和结束时收集每头猪的粪便样本，并评估其对猪医学治疗中常用的抗生素或作为AMGP的抗生素的耐药性流行率和程度。在研究开始前，通过为期3天的林可霉素和壮观霉素疗程破坏肠道菌群的定植抗性后，将三种耐药猪分离株混入饲料中，使所有猪都被多重耐药性大肠杆菌定植。在研究结束时，A组和C组粪便菌群中大肠杆菌的总体耐药性流行率和程度显著增加，但B组仍保持在研究开始时的水平。A组和B组中万古霉素耐药性的流行率分别为44%和41%，但每克粪便中仅发现极少量的万古霉素耐药肠球菌（VRE）。在喂食阿伏帕星的组中，流行率为72%，在57%的样本中，所有肠球菌中有超过50%对万古霉素耐药。耐粪肠球菌的流行率仅在暴露于黄霉素磷脂的组中增加，从研究开始前的23%增加到研究结束时的43%。得出的结论是，黄霉素磷脂有效地抑制了育肥猪肠道菌群中多重耐药性大肠杆菌的增加和传播。使用阿伏帕星强烈选择了VRE的携带和排泄。因此，由于黄霉素磷脂及其任何相关分子均未用于治疗，不存在与治疗性抗生素的交叉耐药性，也未显示出可传播的耐药性；喂食黄霉素磷脂的动物肠道大肠杆菌耐药性的大幅下降似乎超过了通过食物链将耐黄霉素磷脂的粪肠球菌从动物传播给人类的风险的小幅增加。
