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Symposium Marks Official Launch of ZUPREVO 4%

by 5m Editor
17 July 2012, at 12:49pm

BELGIUM - MSD Animal Health (known as Merck Animal health in the USA and Canada) formally launched ZUPREVO® 4% (tildipirosin) injectable solution for pigs in all EU markets at a recent veterinary symposium held in Bruges (Belgium). ZUPREVO is indicated for the treatment of swine respiratory disease (SRD) associated with Bordetella bronchiseptica, Actinobacillus pleuropneumoniae, Pasteurella multocida and Haemophilus parasuis.

The single-dose antibiotic works quickly and is long acting, yet it features a short, 9-day withholding period before slaughter due to its favorable human food safety profile.

The symposium marked the official European launch of ZUPREVO following the product’s successful introduction late last year in France, Germany, Italy and Portugal. It has since been licensed for use in Belgium, Bulgaria, Czech Republic, Denmark, Hungary, Poland, Slovakia and Spain. ZUPREVO is expected to become available in more EU countries in the second half of 2012.

Next evolution

The new-generation macrolide antimicrobial has a unique structure that provides several therapeutic advantages, according to MSD Animal Health veterinarians speaking at the seminar, which was held in conjunction with the European Symposium for Porcine Health Management.

“Tildipirosin represents the next evolution of macrolide antimicrobials,” said Monika Menge, DVM, preclinical development manager at MSD Animal Health, Schwabenheim (Germany). She noted that the product’s development by MSD Animal Health culminated an exhaustive search of more than 100,000 molecules for a better SRD therapeutic intended exclusively for veterinary use. The active ingredient of ZUPREVO, tildipirosin, is the only 16- membered ring macrolide for livestock with three amine groups. “Each of these structural features is significant and together they yield treatment advantages,” Dr Menge said.

It is believed that the three positively charged amine groups enhance tidipirosin’s ability to penetrate the bacterial outer cell wall compared to molecules with a lower charge. In addition, the structure of tildipirosin, especially the size of the central lactone ring, prevents the molecule from being pumped out of the bacterial cell, a process that can render macrolides inactive because they need to be inside the bacterial cell to have any antimicrobial effect, she continued. The third important structural feature of tildipirosin are its two piperidine rings, which are uniquely located and block the “peptide exit tunnel” of the bacterial cell’s ribosome, Menge explained. Bacteria need to synthesize proteins and peptides in order to survive and to proliferate. By inhibiting ribosomal protein synthesis, tildipirosin is able to provide excellent antibacterial activity against bacteria associated with SRD.

Fast absorption

Ivo Petersen, DVM, a clinical research manager at MSD Animal Health in Schwabenheim (Germany), said that one of ZUPREVO’s main advantages is the quick absorption of its active ingredient, tildipirosin, which reaches peak plasma concentrations in just 23 minutes. The antibiotic exhibits lung and bronchial fluid concentrations above the minimum inhibitory concentration (MIC) for most SRD pathogens. “The high concentrations of tildipirosin achieved in lung tissue and bronchial fluid far exceed those in blood plasma,” Petersen said. “Once in lung tissue, tildipirosin persists for at least 14 days at or above 1 μg/mL."

Only one dose of ZUPREVO (1 mL/10 kg or 22 lbs) given by IM injection is needed to achieve clinical efficacy and the maximum dose volume is 5 mL per injection site. ”ZUPREVO minimizes labor requirements as well as stress on animals, and the dose volume is ideal for treating smaller pigs,” Petersen said. ZUPREVO has also been shown to be highly syringeable, even at low temperatures, and has been demonstrated safe for use in swine.

Field experience

Stephan von Berg, DVM, swine technical manager at MSD Animal Health, said that initial field experience in Germany has demonstrated the benefits of treating SRD with ZUPREVO. A controlled trial was conducted on a farm where nursery pigs were exhibiting severe respiratory infections, swollen joints and increased mortality. Post-mortem diagnosis had revealed H. parasuis infection with serotypes 1, 5 and 6. Three strategies were tried and compared: Some piglets were vaccinated with a combined Mycoplasma hyopneumoniae plus H. parasuis vaccine, some were treated with tulathromycin and a third group was treated with ZUPREVO. A fourth, untreated group served as a control. “Vaccination had no impact on mortality and tulathromycin had to be re-administered due to recurring respiratory disease. In contrast, one treatment with ZUPREVO significantly reduced mortality”, he reported.

Similar results were obtained during an 18-day controlled trial in Spain, which compared ZUPREVO with tulathromycin, said Jesús Bollo, DVM, swine technical manager at MSD Animal Health in Madrid (Spain). “ZUPREVO was safe and effective for the early treatment of an acute outbreak of Glässer’s disease (H. parasuis) that occurred at weaning or shortly after weaning,” he reported. Furthermore, there were statistically significant improvements compared to untreated controls that were not achieved with tulathromycin. ZUPREVO also demonstrated an excellent duration of activity. “The total mortality and the percentage of pigs that had to be culled were lowest with ZUPREVO,” he said (Table 1).

Table 1.Trial summary: End of 18 days and 45 days post-injection trial (weaning – nursery)
Treatment% dyspnea after 18 days% depression after 18 days% mortality after 18 days% culled after 18 days% mortality + culled after 18 days% mortality after 45 days
ZUPREVO 2.52 5.04 3.36 5.04 8.40 3.36
Tulathromycin 4.42 7.96 2.65 7.96 10.62 3.54
Control 9.09 11.36 10.91 11.36 22.27 13.51

Dr Bollo cited another trial from Spain where ZUPREVO or tulathromycin were used to treat pigs with SRD due to co-infection with H. parasuis and P. multocida. Both treatments reduced the severity of the disease, but ZUPREVO yielded the best results. For instance, pigs treated with ZUPREVO during the nursery period (28-60 days of age) gained 26 grams a day more compared to the tulathromycin group. “Swine producers will find that ZUPREVO is efficacious, safe for use, convenient and that it will provide a good return on their investment,” Dr Bollo predicted.

Prevent economic losses

Raul Berro, DVM, global marketing director for swine at MSD Animal Health, pointed out that SRD is a prevalent cause of nursery pig and grower/finisher deaths. “Without proper treatment, SRD results in serious economic losses due to high mortality and in pigs that survive, there is lower feed efficiency, a high cull rate, higher treatment costs as well as increased days to market. Although vaccines for SRD can help control respiratory infection, their use is sometimes compromised by timing, the availability of appropriate vaccines and insufficient management practices,” he said.

To help prevent SRD outbreaks, producers should minimize stress on animals and avoid mixing of animals from various sources. “One should institute antimicrobial therapy when animals are present with bacterial infections. Select the most effective therapy and one that has good tissue penetration and pharmacokinetic characteristics. If the specific bacteria are not identified, use a broad-spectrum antimicrobial,” Dr Berro added.

For more information about ZUPREVO for swine, veterinarians should contact their MSD Animal Health representative or visit www.msd-animal-health.com.

Further Reading

Find out more information on the diseases mentioned here by clicking here.