The OXA-β-lactamases (OXA from oxacillinases) were among the earliest β-lactamases discovered; however, these molecular class D β-lactamases were originally relatively rare and always plasmid mediated. They had a substrate profile that was restricted to penicilins. Some, however, were able to develop resistance to cephalosporins. For example, isolates of Acinetobacter baumannii that were resistant to the carbapenems manifested by plasmid-encoded β-lactamases (OXA-23, OXA-40, and OXA-58) in the 1980s. They were categorized as OXA enzymes based on their sequence similarity to earlier OXA-β-lactamases.
It was soon found that each A. baumannii strain possessed a chromosomally encoded OXA-β-lactamase (OXA-51-like), some of which possessed resistance to carbapenems. Similarly, Acinetobacter species closely related to A. baumannii also possessed their own chromosomally encoded OXA-β-lactamases; some could be transferred to A. baumannii, and they formed the basis of transferable carbapenem resistance in that species. In some cases, carbapenem-resistant OXA-β-lactamases (OXA-48) were transferred to Enterobacteriaceae and became a significant cause of carbapenem resistance there.