Drug desensitization enables essential treatment in patients with drug hypersensitivity when alternatives are unavailable. We describe an 81-year-old woman with chronic renal failure and malignancies who developed a Klebsiella pneumoniae infection. She had a remote, unconfirmed history of a penicillin-associated adverse reaction and experienced an immediate hypersensitivity reaction to meropenem. Given her age and comorbidities, direct 12-step meropenem desensitization was performed without prior testing. During the final step, urticaria occurred but was controlled, and therapy was completed after adding an intermediate step. The patient tolerated the full dose without further reaction. This case illustrates the safety and effectiveness of individualized meropenem desensitization in high-risk elderly patients.