AgResearch Grasslands, Private Bag 11008, Palmerston North 4442, New Zealand.
Vet Parasitol. 2012 May 4;186(1-2):93-100. doi: 10.1016/j.vetpar.2011.11.050. Epub 2011 Nov 20.
Since 2009 two new classes of anthelmintics have been registered for use in sheep in New Zealand. This raises challenging questions about how such new actives should be used, not only to minimise the development of resistance to them, thereby ensuring their availability as effective treatments for as long as possible, but also to minimise the further development of resistance to the other anthelmintic classes. One strategy which appears to offer considerable potential for slowing the development of resistance is the use of combinations of different anthelmintic classes, although this approach remains contentious in some countries. The potential benefit of using anthelmintics in combination is particularly relevant to two recently released anthelmintic compounds because one, monepantel, is presently only available as a single active product while the other, derquantel, is only available in combination with abamectin. A simulation modelling approach was used to investigate the potential benefits of using anthelmintics in combination. The rate at which resistance develops to a new 'active' when used alone was compared to an equivalent compound used in combination with a second compound from an alternative class (in this case, abamectin), when various levels of resistance occur to the second active. In addition, the potential of a new active to reduce further development of resistance to the second compound in the combination was evaluated. Finally, the use of combinations as compared to sequential or rotational use patterns, in the presence of side resistance between two actives was investigated. The modelling simulations suggest a significant advantage to both compounds when they are used in combination, especially if both initially have high efficacy. The development of resistance to the new active was delayed, although to a lesser extent, even when the efficacy of the second active in the combination was only 50%. Under a 'low-refugia' management environment resistance to all actives developed more rapidly, and the advantage of using actives in combination was reduced. When used in conjunction with other resistance management strategies, a combination containing a new active prevented further development of resistance to the older class. Using actives in combination was superior to using them individually either sequentially or in rotation, even in the presence of side-resistance between the two anthelmintic classes.
自 2009 年以来，新西兰已注册了两类新的驱虫药用于绵羊。这就提出了一个具有挑战性的问题，即如何使用这些新药，不仅要尽量减少对它们的耐药性发展，从而确保它们在尽可能长的时间内作为有效的治疗药物，还要尽量减少对其他驱虫药类别的耐药性进一步发展。一种似乎具有很大潜力的减缓耐药性发展的策略是使用不同驱虫药类别的组合，尽管在一些国家，这种方法仍存在争议。联合使用驱虫药的潜在好处对于最近发布的两种驱虫化合物特别重要，因为一种叫做莫能菌素的药物目前仅作为单一活性产品供应，而另一种叫做双羟萘酸噻嘧啶的药物仅与阿维菌素联合供应。采用模拟建模方法研究了联合使用驱虫药的潜在好处。当一种新的“活性”药物单独使用时，与等效的化合物与第二种来自不同类别（在这种情况下是阿维菌素）的化合物联合使用时，对第二种活性的耐药性发生的各种水平进行了比较。此外，评估了新活性物质对组合中第二种化合物的进一步耐药性发展的潜力。最后，研究了在两种活性物质之间存在侧耐药性的情况下，与顺序或轮换使用模式相比，联合使用的潜力。模型模拟表明，这两种化合物联合使用时都有明显的优势，尤其是当它们最初都具有高疗效时。即使组合中第二种活性的疗效仅为 50%，对新活性的耐药性发展也会延迟，但程度较小。在“低避难所”管理环境下，所有活性物质的耐药性发展得更快，联合使用活性物质的优势降低。当与其他耐药性管理策略结合使用时，含有新活性物质的组合可防止对旧类别的耐药性进一步发展。与单独使用或顺序或轮换使用相比，联合使用活性物质甚至在两种驱虫药类别之间存在侧耐药性的情况下，效果也更好。
