MILBEMYCIN OXIME RESISTANCE in veterinary parasites: heartworms

Milbemycin oxime is a macrocyclic lactone that was introduced in the 1980s for heartworm prevention and for the control of several gastrointestinal roundworms (e.g hookworms) and some mite species in dogs and cats.

The most relevant resistant species are:

See below for DETAILS.

There are reports on other parasites that have developed resistance to macrocyclic lactones, but so far, such cases remain restricted to limited regions and/or do not represent a global threat for domestic animals yet, and thus are not particularly analyzed in this article. Recommended measures to handle these cases are more or less the same as for the most critical ones: Rotation to chemical classes with different modes of action that remain effective and/or Integrated Pest Management. The following cases can be mentioned:

Milbemycin oxime is available mostly for oral administration in the form of tablets or chews, often in combination with other anthelmintics. It is not used in livestock or horses. Generic products are available.

Milbemycin oxime belongs to the chemical class of the macrocyclic lactones, together with several other compounds that are also used against veterinary parasites: abamectin, doramectin, eprinomectin, ivermectin, moxidectin, and selamectin.

It is a general rule that compounds that belong to the same chemical class show so-called cross-resistance among them, i.e., if a parasite develops resistance to one compound, it will be more or less resistant to other compounds of the same chemical class.

Parasites with resistance to milbemycin oxime

  • Heartworms (Dirofilaria immitis) in dogs

    • OCCURRENCE. Resistant cases on heartworm microfilariae to milbemycin oxime and other macrocyclic lactones have been repeatedly reported in the USA since the mid 2010s, mainly in the South and Southeast. This means that dogs treated with an approved preventative became infested with adult worms, i.e. that microfilariae in their blood were able to develop to adult worms. Basically all macrocyclic lactones are affected, (so-called cross-resistance) although different formulations (e.g. for oral, injectable or topical administration) may show different degrees of tolerance, and some may still be active, e.g. because the blood levels they achieve may be higher and/or last longer after a single administration. Little is now yet about how many dogs are affected by such resistance in the concerned regions.
    • OUTLOOK. Resistance will not disappear, as it always happened before with resistance. Since it has taken very long to appear (about 30 years) some specialists believe that spreading and strengthening may be relatively slow. Although no cases of heartworm resistance to ivermectin have been reported in cats so far, it's probably only a matter of time for this to happen in affected regions.
    • RECOMMENDED MEASURES. Compliance, i.e. strictly following the use recommendations are crucial, because incorrect use is the most frequent cause of product failure, and because chronic under-dosing may favor resistance development. Since heartworm microfilariae are transmitted by mosquitoes, exposure of dogs to mosquitoes should be diminished, either by avoiding places where mosquitoes are particularly abundant, or by reducing the chances of contact of the dogs with the mosquitoes (e.g. using mosquito nets, repellents, etc.).
    • ALTERNATIVE PARASITICIDES for ROTATION. Unfortunately there are no real chemical alternatives to macrocyclic lactones for the chemical prevention of heartworm microfilariae.

Where available, follow national or regional recommendations for delaying resistance development or for handling already confirmed cases.

If you want to learn more about resistance, read one of the following articles in this site:

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Parasiticides