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The increasing prevalence of infectious diseases caused by drug- and multidrug-resistant pathogenic bacteria in companion animals (dogs, cats, horses), particularly in veterinary hospitals, is a worrisome development. Regarding companion animals, currently the four clinically most important groups of multidrug-resistant pathogenic bacteria are methicillin-resistant Staphylococcus (S.) aureus (MRSA), methicillin-resistant S. pseudintermedius (MRSP), Extended-ß-lactamase-producing (ESBL) Enterobacteriaceae and multidrug-resistant Acinetobacter (A.) baumannii. Infections caused by these bacteria are often associated with clinical settings and involve mostly wound, skin, ear or urinary tract infections. S. pseudintermedius is a typical cause of canine skin infections and until recently regarded as being host-specific. However, the epidemic spread of MRSP together with the changing socio-cultural interaction between companion animals and humans has already resulted in human cases of MRSP infections. Just the opposite development was observed with MRSA. Here, typical hospital-associated (HA) genotypes originating from humans spread into companion animals, now being a substantial cause of disease. In both cases, typical non-zoonotic bacteria turned into zoonotic agents. These findings are just the tip of the iceberg when it comes to the influence of antimicrobial drug usage and multidrug-resistance in speeding up microbial evolution. Concerted action is urgently needed to slow down these processes.