Atividade in vitro da tildipirosina contra cepas clínicas de haemophilus parasuis

Abstract

The pork production chain is one of the most important sectors in Brazil and it is continuously in progress in order to get high development, updating and global recognition. The respiratory diseases of swine are considered a high animal health challenge for industrial pig farms since they can be highly transmissible within a production unit. Amongst the pathogens related to the swine respiratory complex, Haemophilus parasuis has emerged as one of the most important and it affects piglets mainly in the nursery phases producing important economic losses for the industry. Vaccination stands out as the main form of prevent Glässer’s disease (GD), but the current commercial vaccines do not guarantee protective cross-immunity due to the high phenotypic variability of the clinical strains of H. parasuis. Consequently, protection failures occur especially when the farm is infected with a serovar different from those contained in the vaccine. Thus, the use of antimicrobials to treat diseased animals is essential, as is the surveillance of the susceptibility profile of the antibiotics used for this purpose, due to the continuous appearance of resistant strains, which makes it difficult to predict the efficacy of any molecule without prior evaluation. Tildipirosin is a last generation macrolide that has been recently used in pigs in Brazil, and its chemical structure is aimed at hindering the emergence of bacterial resistance. Due to the importance of continuous evaluation of antibiotics against bacteria able to trigger diseases in pigs, here, we have evaluated the susceptibility profile of 100 clinical strains of H. parasuis to tildipirosin. All strains included in this study were isolated from pigs with Glässer's disease. From the total, 58 strains were isolated from systemic sites (joints, peritoneum, pericardium and brain) and 42 were recovered from lung tissue. Each strain represents an individual clinical case of GD. The tildipirosin susceptibility test was carried out using the broth microdilution technique, evaluating the minimum inhibitory concentration (MIC) of the product (0.03 - 256 μg / ml). Our results demonstrate that in general the clinical strains of H. parasuis are susceptible to tildipirosin, with MIC50 and MIC90 of 0.25 and 32 μg / ml, respectively. The tildipirosin susceptibility analysis relative to the sample isolation site showed that the strains from systemic sites presented a MIC50 (0.25 μg/ml) higher than those observed in strains of pulmonary origin (0.12 μg/ml). Taking into account the maximum tissue concentration of tildipirosin after parenteral administration of the therapeutic dose (4 mg / kg) of the commercial product Zuprevo® (MSD, Brazil), 72% of the strains could be potentially affected. A small dose adjustment taking into consideration the MICs values could increase the breadth of the efficacy of the product. However, it would not be sufficient to treat 8% of the strains, which have been shown to be highly resistant to the tildipirosin. In summary, our results indicate that tildipirosin may be recommended for the clinical treatment of pigs suffering Glässer's disease, however, because of the presence of strains already resistant to the antibiotic, the MIC test should be periodically used to (i) determine the therapeutic dos e and (ii) monitoring the H. parasuis susceptibility profile to tildipirosin.