Update on the Management of Antibiotic Allergy

Abstract

Drug allergy to antibiotics may occur in the form of immediate or non-immediate (delayed) hypersensitivity reactions. Immediate reactions are usually IgE-mediated whereas non-immediate hypersensitivity reactions are usually non-IgE or T-cell mediated. The clinical manifestations of antibiotic allergy may be cutaneous, organ-specific (e.g., blood dyscracias, hepatitis, interstitial nephritis), systemic (e.g., anaphylaxis, drug induced hypersensitivity syndrome) or various combinations of these. Severe cutaneous adverse reactions manifesting as Stevens Johnson syndrome or toxic epidermal necrolysis (TEN) may be potentially life-threatening. The management of antibiotic allergy begins with the identification of the putative antibiotic from a detailed and accurate drug history, complemented by validated in-vivo and in-vitro allergological tests. This will facilitate avoidance of the putative antibiotic through patient education, use of drug alert cards, and electronic medical records with in-built drug allergy/adverse drug reaction prescription and dispensing checks. Knowledge of the evidence for specific antibiotic cross-reactivities is also important in patient education. Apart from withdrawal of the putative antibiotic, immunomodulatory agents like high-dose intravenous immunoglobulins may have a role in TEN. Drug desensitization where the benefits outweigh the risks, and where no alternative antibiotics can be used for various reasons, may be considered in certain situations. Allergological issues pertaining to electronic drug allergy alerts, computerized physician prescriptions and decision support systems, and antibiotic de-escalation in antimicrobial stewardship programmes are also discussed.

Drug-Hypersensitivity Syndrome: Diagnosis and Treatment

“…The lymphocyte transformation test tends to test positive in maculopapular exanthemas, bullous exanthema, acute generalized exanthematous pustulosis, and DRESS, but rarely in TEN, cytopenias, and vasculitis. 21 Drug provocation tests may also be useful in diagnosing the drug allergy. 19 …”

“…For milder cases, systemic corticosteroids dosed at 0.5 to 1 mg/kg/day and tapered over 6 to 8 weeks are recommended; for SJS, 1 mg/kg/day of prednisolone or 1 to 2 mg/kg/day of methylprednisolone is recommended. 21 Steroid therapy for TEN is reported as both controversial and no longer recommended; if used, it should be within the first 48 hours of treatment because of the increased risk of septic complications with an anti-inflammatory agent. Strict control of blood glucose levels is needed for patients with history of diabetes or on corticosteroids.…”

Allergy to Antibiotics in Children: Who Is to Blame and What to Do?

“…Visceral involvement is prognostically unfavorable; mortality may reach 30% [54][55][56][57]. Toxic epidermal necrolysis (Lyell's syndrome) is a severe toxicoallergic reaction with fever, formation of bubbles, epidermal rejection on more than 30% of body surface and visceral lesion [58]. The highest mortality is observed at Lyell's syndrome (40-80%, according to different authors) [54][55][56][57].…”

“…One of the key points of treating severe forms of drug allergy is as fast as possible withdrawal of the causative drug. Further management tactics for patients with severe allergic syndromes depends on the syndrome [58]. Thus, it is advisable to prescribe systemic glucocorticoids in the dosage of 1-2 mg/kg per day within the first 72 hours of Stevens-Johnson syndrome as soon as possible, whereas prescription of systemic glucocorticoids at Lyell's syndrome is not advisable: there has been a sufficient number of cases where risk exceeded benefit (increase in frequency of infectious complications, which results in mortality increase).…”

“…Thus, it is advisable to prescribe systemic glucocorticoids in the dosage of 1-2 mg/kg per day within the first 72 hours of Stevens-Johnson syndrome as soon as possible, whereas prescription of systemic glucocorticoids at Lyell's syndrome is not advisable: there has been a sufficient number of cases where risk exceeded benefit (increase in frequency of infectious complications, which results in mortality increase). There is information that it is reasonable to prescribe intravenous immunoglobulin in high dosage (0.8-3 g/day) at toxic epidermal necrolysis, as it reduces general mortality down to 20% [58]. The "Drug allergy: an updated practice parameter" (USA, 2010) states that reasonability of prescribing glucocorticoids at multiform exudative erythema and Stevens-Johnson syndrome and of intravenous immunoglobulin at toxic epidermal necrolysis is disputable, although not repudiated [30].…”