Table 3.
Summary of published literature reporting azithromycin hypersensitivity.
| Reaction | Time of Onset # | Demographics | Dosage Form | Concomitant Agents | Allergy Evaluation/Confirmation | Prior Sensitization | Notes |
|---|---|---|---|---|---|---|---|
| TEN [95] | NR | n = 4, <18 y/o and gender NR | PO | Y (IBU) | N | N | |
| EM [95] | NR | n = 4, <18 y/o and gender NR | PO | Y (IBU) | N | N | |
| SJS [95] | NR | n = 4, <18 y/o and gender NR | PO | Y (IBU) | N | N | |
| SJS [95] | NR | <18 y/o and gender NR | PO | N | N | N | |
| Anaphylaxis [100] | 2 h | 68 y/o F | PO | N | Y (SPT+, IDT+) | Y (C, 1 day prior urticaria and dyspnea) | Cross reactivity with C and A. Desensitized with C. |
| IR [104] | <1 h | n = 6, NR | PO | NR | Y (n = 4 ST+) | NR | |
| NIR [104] | 1–3 h | n = 13, NR | PO | NR | Y (n = 5 ST+, 8 ST−) | NR | |
| Toxic pustuloderma [107] | 16 h | 34 y/o F | PO | N | N | N | |
| Angioedema [108] | NR | NR | NR | NR | N | NR | |
| MPE [109] | 7 days | 20 y/o M | PO | N | N | N | Coinfected with mononucleosis |
| AMS, fever, generalized rash, and hepatitis [110] | 5 days | 79 y/o M | PO | Y (atenolol, benazepril, clonidine, ASA) | N | NR | |
| MPE [111] | <1 day | 19 y/o M | PO | N | N | N | Coinfected with mononucleosis |
| Mild pruritus [112] | NR | n = 135, NR | PO | NR | N | NR | |
| Severe pruritus [112] | NR | n = 19, NR | PO | NR | N | NR | |
| Rash [112] | NR | n = 6, NR | PO | NR | N | NR | |
| LCV [113] | 3 days | 8 mo. M | PO | NR | N | NS | |
| SJS [114] | 3 days | 5 y/o M | PO | N | N | N | |
| FDE [16] | 6 yrs | n = 2, 40 y/o M and 44 y/o M | TOP | N | Y (PT+) | N | Occupational exposure |
| EM [115] | NR | NR | NR | NR | N | N | |
| SJS [116] | 10 days | 62 y/o F | PO | NR | N | N | |
| CD [17] | 3 mo-4 yrs | >18 y/o, gender NR | TOP | NR | Y (n = 4, PT+) | N | Occupational Exposure |
| LABD [117] | 3 days | 54 y/o M | PO | N | N | N | |
| MPR DRESS Myocarditis [118] |
H 7 days 2 mo. |
48 y/o M | PO | NR | N | N | Skin and heart biopsy proven |
| CD [18] | 28 days | 39 y/o M | TOP | NR | Y (A, PT +; C, PT−) | N | No cross reactivity with A and C. Occupational Exposure |
| CD [119] | 21 days | 76 y/o F | OPTH | Y (tobramycin/dexamethasone) | Y (PT+) | N | No cross-reactivity with A and C |
| DRESS [120] | 5 days | 8 y/o M | PO | N | N | N | |
| Anaphylaxis [121] | 2 days | 8 y/o, gender NR | IV | NR | Y (SPT+, IDT+) | NR | |
| Anaphylaxis [121] | 2 days | 9 y/o, gender NR | PO | NR | Y (SPT+, IDT+) | Y (C, 1 yr prior same reaction) | Cross reactivity with A and C. |
| Anaphylaxis [121] | 1 day | 7 y/o, gender NR | PO | NR | Y (SPT−, IDT+) | Unknown | |
| MPE [122] | 2 days | 23 y/o M | PO | N | N | N | Coinfected mononucleosis |
| CD [123] | NR | 85 y/o F | OPTH | N | Y (A, PT +; C and E PT−) | Y (A, 1 yr prior no reaction) | No cross reactivity with A, C, E. |
| DRESS [124] | 7 days | 44 y/o M | PO | Y (promethazine, dextromethorphan) | N | N | |
| AGEP [125] | 2 days | 18 y/o F | PO | N | N | N | |
| FDE [126] | <24 h | 35 y/o M | PO | N | Y (DPT+) | Y (A, same reaction ~12 mo. apart) | |
| SJS [127] | 1 day | 58 y/o M | PO | Y (atenolol, atorvastatin, famotidine, prednisone, hydroxyzine) | N | N | |
| AGEP [128] | 1 day | 71 y/o F | PO | NR | Y (A, PT−, DPT+; E PT−; C PT− and C DPT−) | NR | No cross reactivity with A, C, E. |
| DRESS [129] | 4 days | 1.4 yrs M | PO | Y (pranlukast) | N | N | |
| FDE [130] | 1 day | 50 y/o F | PO | N | Y (A, same reaction 2 yrs prior) | ||
| SJS [131] | 1 day | 6 y/o M | PO | Y (cefmetazole) | N | N |
Abbreviations: ACDR = acute cutaneous drug reaction¤; ADR = adverse drug reaction; AGEP = acute generalized exanthematous pustulosis; APAP = acetaminophen; ASA = aspirin; A = azithromycin; C = clarithromycin; CD = contact dermatitis; DR = delayed reaction; DPT = drug provocation test; DRESS = Drug reaction with eosinophilia and systemic symptoms syndrome; E = erythromycin; EM = erythema multiforme; ER = extended release; ETH = ethambutol; F = female; FDX = fidaxomicin; HRT = leukocyte histamine release test; HSP = Henoch- Schönlein Purpura; h = hour(s); HCTZ = hydrochlorothiazide; HIV = human immunodeficiency virus; IBU = ibuprofen; IDT = intradermal test; Ig E = immunoglobulin E; IM = intramuscular; IR = immediate reaction (<1 hr); LABD = Linear Immunoglobulin A Bullous Dermatosis; LCV = leukocytoclastic vasculitis; LTT = lymphocyte transformation test; MAS = multiple allergy sensitivity; MDT = mast cell degranulation test; min= minutes; mo = months; MMIT = macrophage migration inhibitory test; MPE= maculopapular exanthema; MPR = maculopapular rash; N = no; NIR= nonimmediate reaction (1–72 h); NR= not reported; NTG = nitroglycerin; opth = ophthalmic; PT = patch test; R = roxithromycin; RIF = rifampin; RFB = rifabutin; S = spiramycin; SJS = Steven’s Johnson syndrome; SOB = shortness of breath; SPT = skin prick test; ST = scratch test; TEN = toxic epidermal necrolysis; TMP/SMX= trimethoprim/sulfamethoxazole; top = topical; wks = weeks; Y = yes; yrs = years; y/o = years old. * Exact time course unknown as awoke with FDE. # Time of onset means time when symptoms began to occur either during macrolide therapy or after completion of macrolide therapy. ACDR defined as allergic reaction, adverse drug reaction, pruritis, general swelling, local or general redness, erythema, rash, urticaria, or other skin disease. π Review was meant to include azithromycin, clarithromycin, erythromycin, and fidaxomicin; however, there is a chance these data include excluded macrolides since the type of macrolides reported were not fully specified