Immediate and Delayed Hypersensitivity Reactions to Antibiotics: Aminoglycosides, Clindamycin, Linezolid, and Metronidazole

Abstract

Hypersensitivity reactions including IgE-mediated and delayed cell-mediated reactions to aminoglycosides, clindamycin, linezolid, and metronidazole are rare. For aminoglycosides, allergic contact dermatitis is the most frequent reaction for which patch testing can be a useful step in evaluation. For clindamycin, delayed maculopapular exanthems are the most common reactions. There are case reports of clindamycin associated with drug rash with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), acute febrile neutrophilic dermatosis, and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). For linezolid, cases of hypersensitivity were exceedingly rare and included urticaria, angioedema, anaphylaxis, delayed rashes, and DRESS. For metronidazole, only rare cases were found across a broad spectrum of reactions including allergic contact dermatitis, fixed drug eruption, angioedema, anaphylaxis, serum sickness-like reaction, SJS/TEN, AGEP, SDRIFE, and a possible case of DRESS. IgE-mediated reactions and anaphylaxis to these types of antibiotics are uncommon, and reports of skin testing concentrations and desensitization protocols are largely limited to case reports and series. Non-irritating skin testing concentrations have been reported for gentamycin, tobramycin, and clindamycin. Published desensitization protocols for intravenous and inhaled tobramycin, oral clindamycin, intravenous linezolid, and oral and intravenous metronidazole have also been reported and are reviewed.

Fixed drug eruption due to clindamycin with tolerance to lincomycin

“…Immediate and delayed hypersensitivity reactions to clindamycin have been occasionally described, [3][4][5] but an FDE from clindamycin is considered very rare. 6 Although patch tests should be the first skin test to perform, the history in our case was not reliable enough to suspect an FDE at the initial assessment.…”

“…Given the structural similarity between clindamycin and lincomycin (the former having a chlorine atom instead of an hydroxyl group) cross‐reactivity between these drugs might be anticipated; however, we have shown that this does not necessarily occur. Although the patch test to lincomycin was negative, false‐negative patch tests readily occur, 5 and so an OCT was additionally performed, allowing us to demonstrate the effective tolerance to lincomycin. The patient has thus been recommended to avoid clindamycin, but not lincomycin.…”

Novel Strategy for Surface Modification of Titanium Implants towards the Improvement of Osseointegration Property and Antibiotic Local Delivery

“…Metronidazole is an antibacterial compound belonging to the class of imidazoles, a subgroup of nitroimidazoles, which acts against a wide variety of microorganisms [ 15 ]. It is clinically effective in the treatment of periodontitis and peri-implantitis caused by anaerobic bacteria [ 16 ].…”

“…It is clinically effective in the treatment of periodontitis and peri-implantitis caused by anaerobic bacteria [ 16 ]. It presents a good therapeutic response, but its high toxicity after continuous systemic doses can, for example, manifest gastrointestinal disorders, dizziness, and headaches, among others, often causing the patient to discontinue treatment [ 15 ]. Thus, the local delivery of metronidazole could reduce the systemic toxicity of the antibiotic and increase its efficiency even with lower doses.…”

Novel Strategy for Surface Modification of Titanium Implants towards the Improvement of Osseointegration Property and Antibiotic Local Delivery

“…It is clinically effective in the treatment of periodontitis and peri-implantitis caused by anaerobic bacteria [12]. It presents a good therapeutic response, but its high toxicity after continuous systemic doses can, for example, manifest gastrointestinal disorders, dizziness, headaches, among others, often causing the patient to discontinue treatment [13]. Thus, a local delivery of metronidazole could reduce the systemic toxicity of the antibiotic and increase its efficiency even with lower dose.…”