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Hypersensitivity reactions to macrolides, aminoglycosides, tetracyclines, clindamycin, and metronidazole

Roland Solensky, MD
Section Editor
N Franklin Adkinson, Jr, MD
Deputy Editor
Anna M Feldweg, MD


This topic will review hypersensitivity (allergic) reactions to macrolides, aminoglycosides, tetracyclines, clindamycin, and metronidazole. Hypersensitivity reactions to other antibiotic classes, namely beta-lactams, sulfonamides, fluoroquinolones, and vancomycin, are discussed separately. (See "Penicillin allergy: Immediate reactions" and "Cephalosporin allergy: Clinical manifestations and diagnosis" and "Sulfonamide allergy in HIV-uninfected patients" and "Hypersensitivity reactions to fluoroquinolones" and "Vancomycin hypersensitivity".)


The antimicrobial groups discussed in this review cause hypersensitivity reactions relatively infrequently compared with penicillins, cephalosporins, sulfonamides, and fluoroquinolones [1,2].

Types of hypersensitivity reactions — Hypersensitivity reactions, or allergic reactions, are immunologic reactions to a drug. There are many types of hypersensitivity reactions, which are broadly divided into immediate and delayed reactions, based upon the time between the first administered dose and the appearance of signs or symptoms [3]:

Immediate reactions are defined as reactions that begin within one hour of the first administered dose. In reality, symptoms and signs may appear up to one to two hours later if the drug was taken orally or with food or other medications that slow absorption. The most common signs and symptoms of immediate reactions are urticaria (picture 1 and picture 2), pruritus, flushing, angioedema of the face, extremities, or laryngeal tissues (leading to throat tightness with stridor, or rarely, asphyxiation), wheezing, nausea, abdominal cramping or diarrhea, and/or hypotension or shock. Immediate reactions can be caused by the formation of immunoglobulin E (IgE) to the causative drug, which can then activate mast cells and basophils in the presence of the drug. Some drugs can cause immediate reactions by directly or indirectly activating mast cells and basophils, without the presence of drug-specific IgE. Immediate-type skin testing is used to evaluate immediate reactions. (See 'Allergy evaluation' below.)

Delayed reactions begin later than one hour (and sometimes days) after the first dose. Many different reaction types are classified as delayed. The most common are maculopapular or morbilliform exanthems (picture 3 and picture 4). There is a lack of consensus about how best to evaluate patients with past maculopapular exanthems. Some allergy experts perform intradermal skin testing that is interpreted 24 to 72 hours after placement, with erythema and induration representing a positive reaction. Others only perform graded challenges to diagnose such reactions, which is the most common approach in the United States.

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Literature review current through: Nov 2017. | This topic last updated: Jan 22, 2016.
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