A patient treated with hydroxyurea had a lower extremity ulcer that was found infected with Pseudomonas aeruginosa. Drug discontinuation and ceftazidime treatment did not initially lead to resolution due to misidentification of inducible betalactamases expressed by the organism and subsequent clinical failure of the cephalosporin in eradicating infection. These class C enzymes may be strongly induced after betalactam exposure and confer resistance to penicillins, cephalosporins, betalactamase inhibitors but not to carbapenems. Though hydroxyurea represents a major cause of essential thrombocythemia-related ulcers, lesion infections by difficult-to-treat organisms should be eradicated to promote wound healing.