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Chronic soft tissue wound infections due to multidrug-resistant bacteria are a clinical challenge. Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), aminoglycoside-resistant Escherichia coli and Pseudomonas aeruginosa are examples of several problematic pathogens. A multipronged clinical approach is necessary for resolution of these chronic infections and a good medical outcome.The final article in this series summarizes the advances in the management of serious wound infections in horses, with the focus on wounds involving soft tissues. The previous articles focused on wounds involving joints and other synovial structures and wounds involving bone.Wound infections can be a considerable challenge in this era of multidrug-resistant bacteria. A number of more common equine wound pathogens that can be challenging to treat are as follows:Methicillin-resistant Staphylococcus aureus and S. epidermidisVancomycin-resistant Enterococcus spp.Heteroresistant vancomycin-intermediate S. aureusPenicillin-resistant Actinobacillus spp.Aminoglycoside-resistant Escherichia coliPseudomonas aeruginosa strains that are resistant to most commonly used antibioticsResistance is now recognized in equine isolates for vancomycin and imipenem—drugs that were reserved for documented multidrug-resistant pathogens. Thus a carefully planned strategy of surgical debridement and ancillary treatments are needed to achieve wound healing.