This patient most likely has systemic drug hypersensitivity syndrome, otherwise known as drug reaction with eosinophilia and systemic symptoms (DRESS). DRESS is a severe and potentially life-threatening type IV hypersensitivity reaction. Similar to most type IV reactions, onset of the syndrome is delayed, usually occurring 10 days to several weeks after the start of the causative medication. The most common medications that trigger this reaction are sulfonamide antibiotics, allopurinol, and anticonvulsants, but many others have been implicated. In DRESS, patients develop an exanthem rash on the face, trunk, and extremities, and they often have facial edema. Due to systemic inflammation, patients may have fever, lymphadenopathy, and, in severe reactions, hypotension. When these findings occur in a patient being treated with antibiotics, the systemic inflammatory nature of the reaction may make it difficult to differentiate between a response to an antimicrobial agent or inadequate control of the underlying infection, as in this patient. The treatment of DRESS is to stop the suspected medication immediately, switch to another medication that is unlikely to cross-react, and start systemic glucocorticoids, which can reduce systemic inflammation and lower the risk of end-organ damage.

Morbilliform (meaning measles-like) drug exanthems are the most common pattern of a cutaneous drug reaction. This reaction occurs in up to 8% of hospitalized patients and appears 5 to 15 days after exposure to the causative drug. The characteristic findings include erythematous papules coalescing into plaques, often with some pruritus, and no accompanying systemic symptoms. Facial edema, fever, and laboratory abnormalities are not expected.

Stevens-Johnson syndrome (SJS) is an inflammatory reaction with prominent skin findings that is more commonly triggered by medications than infections. Patients may also have flu-like symptoms, and these may precede the onset of the rash. SJS can be differentiated by the presence of mucosal erosions. Patients with SJS have two or more mucosal sites involved, associated with erythema, pain, and often bloody discharge, none of which this patient has. SJS also has different cutaneous findings including annular erythematous plaques that may have purpuric and eroded centers. These are found on the face, trunk, and extremities including the palms and soles, and involve no more than 10% of the body surface area.

Medications can cause a cutaneous or systemic vasculitis; however, the appearance of this patient's skin findings is not consistent with vasculitis. Purpuric or nonblanching erythematous macules, papules, or plaques are indicative of vasculitis.