新一代驱虫抗生素—莫西菌素

莫西菌素同伊维菌素一样 ,是一种目前广泛用于兽医临床的广谱、高效、新型大环内酯类驱虫抗生素 ,是美贝霉素家族中的一员。由于其独特的理化性质 ,在国外 ,已被广泛用于治疗奶牛、猪等动物体内外寄生虫病。文章对莫西菌素的理化特性、作用机制、药动学、制剂、药效、耐药性、毒性、残留等进行了较详细地综述 ,同时也介绍了减少耐药性产生的一些方法 ,为该药能在国内应用提供第一手资料 ,以求为兽医临床用药提供参考     

Evaluation of the chemoprophylactic efficacy of 10% long acting injectable moxidectin against gastrointestinal nematode infections in calves in Belgium

The chemoprophylactic efficacy of a single dose of the 10% long acting (LA) injectable formulation of moxidectin on nematode infections in calves, was evaluated. Two similar groups of 11 female, first grazing season Holstein calves were turned out in early May on separate plots of a single, naturally infected pasture. Until 56 days post-treatment (pt), the percentage reduction in faecal egg output was 100%, remaining above 90% during the entire trial, except for day 126 pt. More than 90% of the larvae in the treated group were identified as Cooperia until 140 days after treatment and more than 70% during the rest of the trial, whereas in the control group Cooperia was the most abundant species until day 84 pt and Ostertagia from 126 days pt onwards. The reduction in faecal egg output in the treated group was reflected in the mean pepsinogen levels being below the pathogenic threshold at the end of the grazing season (1.8 units of tysrosine (U tyr)) and the absence of diarrhoea during the second half of the grazing season. In the control group pepsinogen levels remained high (mean: 5.5 U tyr) and prolonged diarrhoea occurred in the second half of the grazing season. Furthermore, the weight gain for the treated group at the end of the grazing season was 41.9 kg higher than for the control group. At necropsy, the reduction in O. ostertagi worm burden in the treated group was 97.5% compared to the control group, while the reduction in C. oncophora worm burden was 57%. An additional benefit of the long acting parasitological control, was reduced pasture contamination.     

Echocardiographic quantification of Dirofilaria immitis in experimentally infected cats

The safety of heartworm preventives in heartworm-positive cats has traditionally been evaluated using adult Dirofilaria immitis removed from infected dogs and surgically implanted into the cats. An alternate study model uses infective larvae to establish adult infections in cats. Unfortunately, the number of adult worms resulting from the latter method varies widely from none to more than 30, both unacceptable for studies of natural heartworm infection and for studies evaluating product safety in heartworm-infected cats. We sought to determine infection severity in experimental infections via echocardiography to reduce the chances of enrolling uninfected and heavily infected cats into a study. Eighty adult cats were each inoculated with 60 infective D. immitis larvae and maintained for 8 months to allow for the development of adult worms. Antigen and antibody testing, as well as echocardiographic imaging, were performed to confirm and estimate adult worm burdens. Approximately 8 and 12 months post-infection, echocardiographic examination was performed to confirm and enumerate adult D. immitis populations in the cardiovascular system. Worm burdens were stratified as 0, 1-3, 4-11, and > 11 adults, with 0 being considered uninfected and more than 11 considered too heavily infected to be relevant for anthelmintic studies. Cats with clinically relevant infections (1-10 adults) subsequently received multiple treatments with the investigational drug, and worm burdens were confirmed by necropsy 30 days following the final treatment. Worm burden estimated with echocardiography correlated well, but not precisely, with post-mortem counts (p < 0.001, r2 = 0.67). Echocardiography under-, over-, and exactly estimated heartworm burden 53%, 27%, and 22% of the time, respectively. Although the correct category (0-4) was determined by echocardiography in only 54% of cats, positive cats were distinguished from negative cats 88% of the time and the heaviest infections (> 11) were correctly categorized 95% of the time. Both false negative and false positive results were observed. We conclude that echocardiography is useful for detecting mature experimental heartworm infections, identifying cats that have rejected mature infection, and detecting very heavy heartworm burdens, but it is only moderately accurate in classifying lesser burdens. While echocardiography cannot be relied upon to consistently determine the exact heartworm burden in experimentally infected cats, it is useful in stratifying worm burdens for anthelmintic safety studies.     

牛、羊奶中莫昔克丁残留高效液相色谱荧光检测方法的建立

建立了适用于牛、羊奶样品中莫昔克丁残留的高效液相色谱荧光检测方法。以乙腈为提取液,C18固相萃取柱净化,并用N-甲基咪唑-乙腈(1+1,V/V)和三氟乙酸酐-乙腈(1+2,V/V)进行衍生化。乙腈+水(90+10,V/V)为流动相,荧光法定量。经测定,该方法对牛、羊奶中莫昔克丁的检测限为2 μg/kg,定量限为5 μg/kg。空白牛、羊奶中标准品莫昔克丁添加量分别为5、20、40和80 μg/kg时,牛奶中莫昔克丁平均回收率范围为75.5%～110%,其批内变异系数小于738%,批间变异系数小于7.87%;羊奶中莫昔克丁平均回收率范围为77.5%～95.6%,其批内变异系数小于5.06%,批间变异系数小于5.92%。该方法准确性强、灵敏度高,适用于牛、羊奶中莫昔克丁的快速检测。     

液相色谱-三重四极杆/线性离子阱复合质谱技术检测牛奶中莫昔克丁残留

建立了牛奶中莫昔克丁残留检测的液相色谱-三重四极杆/线性离子阱复合质谱技术(LC-QTRAP)。样品用乙腈提取后,用C18固相萃取柱净化,上机测试。液相色谱条件:色谱柱为BEH C18(50 mm×2.1 mm,1.7μm),流动相为0.1%甲酸水溶液+0.1%甲酸乙腈溶液,梯度洗脱,流速为0.4 mL/min,柱温为30℃,进样量为5μL。质谱条件:电喷雾正离子源(ESI~+),采用多反应监测-信息依赖扫描-增强子离子扫描(MRM-IDA-EPI)方式采集。结果表明:在牛奶中,莫昔克丁在1～80 ng/mL基质匹配标准溶液浓度范围内均呈现良好的线性关系,相关系数(R~2)大于0.990,定量限为2μg/kg。牛奶中莫昔克丁在2、40和80μg/kg三个添加浓度平均回收率都在60%～120%之间,批内、批间RSD均小于15%。该方法简便快捷、定性准确、灵敏度高,回收率和精密度满足残留检测要求。     

Resistance to moxidectin and abamectin in naturally acquired Ostertagia circumcincta infections in sheep

AIM: To investigate the occurrence of resistance to macrocylic lactone (ML) anthelmintics by Ostertagia circumcincta in lambs on a sheep and cattle property in the North Island of New Zea- land.

METHODS: Thirty lambs were randomly allocated to one of five equal-sized groups, consisting of an untreated control and four treatment groups. The treatments, which were administered at the manufacturer's recommended dose rates, included oral moxidectin, oral abamectin (both at 0.2 mg/kg), an albendazole-levamisole combination, and an albendazole-levamisole-ivermectin combination. Post mortem worm counts were undertaken 7 days after treatment to determine the efficacy of each anthelmintic.

RESULTS: The albendazole-levamisole and albendazole-levam-isole-ivermectin combinations both reduced O. circumcincta burdens to zero whereas for moxidectin and abamectin efficacies of only 72% and 29%, respectively, were recorded.

CONCLUSIONS: These results clearly demonstrated the occurrence of resistance to MLs by O. circumcincta. Although this is not the first occasion where resistance to this anthelmintic family has been detected in this parasite in sheep in New Zealand, it is the first instance that resistance to either moxidectin or abamectin has been reported.     

液相色谱串联质谱检测动物源性食品中莫西丁克残留

[目的]建立动物源性食品中莫西丁克残留的检测方法。[方法]首先对样品净化方法和试验参数进行了优化。利用乙腈对样品中莫西丁克进行提取,利用分散型固相萃取净化莫西丁克,利用液相色谱串联质谱测定动物源性食品中莫西丁克的含量。[结果]最佳质谱条件为：离子源温度300℃、喷雾针压力15 Psi、干燥气流速6 L/min。在此条件下,子离子峰的响应值最高。该方法的检测限为0.005 mg/kg,当在添加浓度0.005～0.02 mg/kg时,回收率为81.08%～113.72%,RSD为4.21%～9.69%。[结论]该方法步骤简单、可操作性强、有机溶剂用量少、成本低、杂质干扰少,有良好的精密度及较低的方法检测低限,适于动物源性食品中莫西丁克的快速测定。     

Evaluation of the persistent activity of moxidectin (10%) long-acting (LA) injectable formulation against Dictyocaulus viviparus, Haemonchus placei, Trichostrongylus axei and Oesophagostomum radiatum infections in cattle

Two controlled studies were conducted to evaluate the persistent efficacy of moxidectin (10%) long-acting (LA) injectable formulation against Dictyocaulus viviparus, Haemonchus placei, Trichostrongylus axei and Oesophagostomum radiatum in cattle. The moxidectin LA injectable formulation was administered as a single subcutaneous injection into the proximal third of the ear at a dose rate of 0.01 ml/kg BW to provide 1.0 mg moxidectin/kg BW. The product had persistent efficacy of >90% against D. viviparus, H. placei and Oe. radiatum for at least 150 days post-treatment and against T. axei for at least 90 days post-treatment.     

Effects of drug residues in the faeces of cattle treated with injectable formulations of ivermectin and moxidectin on larvae of the bush fly, Musca vetustissima and the house fly, Musca domestica

Objective: To assess the toxicity of residues of ivermectin and moxidectin in cattle faeces collected at intervals after treatment.
Design: Replicated bioassays of faeces using larvae of the bush fly, Musca vetustissima and the house fly, Musca domestica .
Animals: Two groups of five Murray Grey x Aberdeen Angus steers were treated with injectable formulations of ivermectin and moxidectin respectively. A third group was used as an untreated control.
Procedure: Newly emerged fly larvae were reared in the dung of treated animals.
Results: Drug residues in faeces collected 3 to 35 days after treatment with an injectable formulation of moxidectin had no significant effect on the survival of larvae of M vetustissima . Similarly, faeces dropped up to seven days after treatment caused no significant reduction in larval survival in M domestica . In day 2 dung, residues of moxidectin delayed development of M vetustissima larvae, but had no effect on their survival. In contrast, ivermectin-treated steers, produced dung that inhibited larval development of both M vetustissima and M domestica for 7 to 14 days after treatment. Significant reductions in survival of M vetustissima larvae occurred in dung collected on days 21 and 28 after treatment, but by day 35 survival did not differ from that in control dung.
Conclusion: Excreted faecal residues of moxidectin are relatively innocuous to larvae of both M vetustissima and M domestica . Those of ivermectin inhibit survival for 7 to 14 days after treatment and are likely to have adverse effects on non-target organisms.     

Therapeutic and persistent efficacy of moxidectin 1% nonaqueous injectable formulation against natural and experimentally induced lung and gastrointestinal nematodes in cattle

Four controlled trials were conducted to evaluate the therapeutic and persistent efficacy of a new moxidectin formulation (moxidectin 1% nonaqueous injectable) against nematode parasites in cattle. This injectable moxidectin formulation, given as a single subcutaneous injection at a dose rate of 0.02 ml/kg BW to provide 0.2 mg moxidectin/kg BW, was highly efficacious (>90–100%) against larval and/or adult stages of many species of nematodes in cattle including, Dictyocaulus viviparus, Ostertagia spp., Trichostrongylus axei, Haemonchus placei, Trichostrongylus colubriformis, Cooperia spp., Nematodirus helvetianus, Strongyloides papillosus, Oesophagostomum radiatum and Trichuris spp. This formulation had persistent efficacy of >90% against D. viviparus for at least 6 weeks post-treatment, H. placei and Oe. radiatum for 5 weeks post-treatment, and Ostertagia spp. and T. axei for 2 weeks post-treatment.