Changes in antimicrobial susceptibility of Mycoplasma bovis isolates from Great Britain

Abstract

The UK has approximately 10 million cattle (Veterinary Medicines Directorate 2011), and each year approximately 1.9 million of these cattle are affected by respiratory disease. A disease that is often complex, caused by viruses and/or bacteria, with as many as one-third of these infected with the Mycoplasma bovis pathogen (Nicholas and Ayling 2003). The welfare and economic effects of clinical cases of M. bovis on farming are therefore substantial and costs may be even more when morbidity associated with respiratory infection is considered. Apart from respiratory disease, M. bovis is also associated with other clinical signs, including mastitis, arthritis, meningitis, infertility, abortion and keratoconjunctivitis (Nicholas and Ayling 2003). Elimination of M. bovis is difficult and treatment with antimicrobials often has limited effect unless animals are treated early in the course of disease. In recent years, as much as 11 tonnes per annum of active antimicrobials have been sold for use in the UK cattle antimicrobial products, which includes all intramammary products (Veterinary Medicines Directorate 2011). With no commercial vaccines available in Europe, although use of autogenous vaccines has shown some success (Nicholas and others 2006), it is important to effectively target antimicrobial treatment to ensure prudent use of antimicrobials and to reduce the development of antimicrobial resistance. Between 2004 and 2009, in vitro minimum inhibition concentration (MIC) data for 45 M. bovis isolates have been determined for up to 13 antimicrobials.

Mutations Associated with Decreased Susceptibility to Seven Antimicrobial Families in Field and Laboratory-Derived Mycoplasma bovis Strains

“…Macrolides have been used traditionally in the therapy of mycoplasmosis in cattle, but now these antibiotics are losing their efficiency against M. bovis in many countries (8,12,14,18). In the present study, the rapid evolution of macrolide and lincomycin resistance was observed in the in vitro-selected M. bovis mutants similarly to avian Mycoplasma species (20), presuming the small number of mutation events needed for the change of antibiotic susceptibility in these cases.…”

“…Tetracyclines, and particularly oxytetracycline, are generally used for the treatment of M. bovis-related diseases, but increasing resistance have been reported from Europe and other continents as well (7,14,18). The number of mutations in region Tet-1 was shown to correlate with the increase of MICs to tetracycline in M. bovis strains (13).…”

“…Although fluoroquinolones are considered to be effective agents in the therapy of bovine mycoplasmosis, strains with high MICs (Ն8 g/ml) have been reported from several countries (5,7,14,18). The development of resistance to the fluoroquinolones is usually due to target mutations in QRDRs of the genes encoding topoisomerases, but enhanced efflux of the drug by the overexpression of efflux pumps has also been described (6).…”

Alterations in the Quinolone Resistance-Determining Regions and Fluoroquinolone Resistance in Clinical Isolates and Laboratory-Derived Mutants of Mycoplasma bovis: Not All Genotypes May Be Equal

“…Three studies reported highly resistant isolates, with MICs of Ͼ8 g/ml, in the United Kingdom, Japan, and Belgium (9-11), while several others indicated a low to no increase in resistance, except for a few isolates, in Japan, the United States, and several European countries (6,(12)(13)(14)(15). Some of these studies involved isolates collected before 2005 (11, 13), but the majority referred to recent ones (6,9,10,12,14,15), suggesting a recent phenomenon. In the United Kingdom, a shift of resistance from an MIC 90 of 1 g/ml to one of 32 g/ml occurred during the last decade (9, 16).…”

“…Some of these studies involved isolates collected before 2005 (11,13), but the majority referred to recent ones (6,9,10,12,14,15), suggesting a recent phenomenon. In the United Kingdom, a shift of resistance from an MIC 90 of 1 g/ml to one of 32 g/ml occurred during the last decade (9,16). This significant increase over a relatively short period is indicative of highly efficient resistance mechanisms.…”