Mycoplasmas are small bacteria that lack a cell wall and certain metabolic pathways, both important target features for antibiotics. This is important to remember when choosing an antibiotic for their control or treatment. Mycoplasmas were often considered to have a limited survival time outside the host. However, some recent data show that animal Mycoplasma species can survive for variable periods outside the host, depending on the species, moisture, pH, presence of organic material and temperature.
Some species have been shown to survive for 50 to 150 days at 4oC in liquid media and from 7 to 14 days in dry conditions at 30oC. Recently M. synoviae was shown to survive for 9 days on synthetic materials (Abolnik et al., 2014). The presence of persistently infected populations (e.g. backyard and wild birds) ensures that the biosecurity of surrounding flocks is continually challenged. These are important reasons why Mycoplasma is still a major problem in the poultry industry. Secondly, antigenic variation and intracellular location of Mycoplasma spp. help the pathogen to evade the immune system, leading to chronically infected animals. Vaccines can only help, in the best-case scenario, to reduce production losses and clinical symptoms.
The current approaches for controlling avian Mycoplasma include continuous survelliance and quarantine measures, medication, vaccination and/or elimination of infected breeding flocks. To maintain Mycoplasma-free flocks it is important to use only negative replacements, use single age farms (isolated if possible), depopulate and disinfect between flocks, maintain good biosecurity and set up a monitoring program.
Elimination of a positive breeder flock is the surest way to eradicate the shed of M. gallisepticum or M. synoviae, but this is not always feasible. Positive flocks should be isolated as much as possible; the eggs and chicks should also be segregated. Once a flock is infected or vaccines are unable to control Mycoplasma, antibiotics are still required.
The clinical outcome of this antibiotic treatment depends on three crucial steps in the decision process of the veterinary surgeon:
- Selecting the correct antimicrobial, considering:
- known or suspected antimicrobial susceptibility of the pathogen
- ability of the antimicrobial to sufficiently reach the site of infection
- Other features
- Correct dosing and administration
1. Selecting the correct antimicrobial
The susceptibility of a pathogen can be based upon susceptibility testing, which is unfortunately rather complicated and time demanding for Mycoplasma spp.. For this reason, the clinical experience of the veterinarian, farm history and antibiotic susceptibility surveys (Table 1) are also of importance.
In addition to susceptibility, the antibiotic needs to reach sufficient concentrations in the respiratory tract and preferably also be present intracellularly (as Mycoplasmas are located intracellularly). Pharmasin® / Tylovet® (tylosin), Tilmovet® (tilmicosin) and Vetmulin® / Rodotium® (tiamulin) not only deliver high concentrations in the respiratory tract (Figure 1), but also show beneficial intracellular/extracellular ratios of up to 75.
2. Other features
Other features are also of importance when choosing the right antimicrobial to treat and control Mycoplasma. Some products are more suitable for layers (Pharmasin® / Tylovet®), whilst other are more suited for breeders (Vetmulin® / Rodotium®) or for use at start-up (Tilmovet®).
Pharmasin® / Tylovet®, for example, does not have any negative effect on water intake, is very safe and has no known incompatibilities. Moreover, Pharmasin® / Tylovet® has a zero-withdrawal time for eggs in the EU, which makes it ideal for the control and treatment of Mycoplasma spp. in layers.
Vetmulin® / Rodotium® is unique in that it ensures concentrations in the eggs remain above the MIC90 for both M. gallisepticum and M. synoviae for several days, which is why excellent results are achieved in the control of vertical transmission in breeder stocks in the field (Figure 2).
The slow elimination phase of Tilmovet® (Figure 1) results in prolonged continuous tissue concentrations, making it less dependent on variable feed and water intake. Some antibiotics are known to have a negative influence on immunity build-up, possibly interfering with vaccination response. However, the macrolide class of antibiotics and specifically Tilmovet® have been shown to have a positive effect, making the product ideal for start-up and for pullets.
3. Correct dosing and administration
Dosing should be done in grams per kilogram live bodyweight, independent of the application form. By doing so, misdosing will be avoided by considering the changing ratio of bodyweight / water or feed intake, which is especially important in fast growing birds such as broilers.
In addition to the dosage per kg bodyweight, the dosage regimen is also important. A daily dose can be administered in different ways, either continuously or as a pulse.
For time-dependent antimicrobials, such as Pharmasin® / Tylovet® (tylosin), Tilmovet® (tilmicosin) and Vetmulin® / Rodotium® (tiamulin), administration should be continuous over 24 hours for a sufficiently long period.
Mycoplasma efficacy studies with Pharmasin® / Tylovet®, Vetmulin® / Rodotium® and Tilmovet® indicate that therapeutic levels for a minimum of 5 days are appropriate. For this reason, a minimum treatment period of 5 days is recommended for Pharmasin® / Tylovet® and Vetmulin® / Rodotium® and of 3 days for Tilmovet® (Figure 1).
Depending on the risk of exposure, the treatment can be repeated every 4 weeks (low risk) up to every 2 weeks (high risk, like multi-age farms).
In the following example, the efficacy of Pharmasin® / Tylovet® for controlling Mycoplasma was tested at different dosing levels. Broilers (n=45) were kept in isolators and challenged with a M. gallisepticum isolate (Italy, 2012, MIC value < 0.015 μg/ml). The treated groups were given 35 and 100 mg tylosin/kg bodyweight respectively for 5 days, starting one day post-challenge. The control group was infected but did not receive treatment. Monitored parameters included clinical scoring of respiratory disease (Figure 3), macroscopic scoring of the respiratory tract, weight gain, mortality and M. gallisepticum recovery from the trachea, airsacs and lungs.
Both dosing levels were efficacious in protecting against the detrimental consequences of M. gallisepticum infection as indicated by the difference with the infected untreated control group.
Despite fine-tuning of management, vaccination schemes, feeding, housing and biosecurity meaures, animals can still become diseased. Therefore, antibiotics are, and will remain, essential for protecting animal health and welfare as well as the safe protection of food from animal origin. However, the responsible and wise use of antimicrobials is mandatory to safeguard the use of veterinary medicines in the long term. This means targeting the pathogen with the right product and administering it correctly.
One such major pathogen is Mycoplasma, for which Huvepharma can offer the right tools and the right advice based upon extensive field experience and product specific efficacy trials.
For more information on the correct use of our products, please contact: Wouter.firstname.lastname@example.org.