Hypersensitivity to non-β-lactam antibiotics

Abstract

Most allergic reactions to antibiotics are caused by β-lactam antibiotics; however non-β-lactam antibiotics are also capable of causing both immediate allergic reactions as well as late-type reactions to these drugs. This is especially true for fluoroquinolones and sulfonamides. Of these, the combination of sulfamethoxazole with trimethoprim (Cotrimoxazol, e.g., Bactrim) is most important. However, there are certain types of reactions to non-β-lactam antibiotics that are not associated with β-lactam antibiotics. These include photosensitivity to sulfonamides, tetracyclines, and fluoroquinolones as well as different patterns of drug metabolism and associations with HLA alleles that may influence their prevalence. This review is focused on recent findings regarding the pathogenesis of allergic reactions to non-β-lactam antibiotics.

Keywords: MRGPRX2; allergy; lymphocyte transformation test; non-β-Lactam-antibiotics; photosensitivity.

Figure 1. Hypothetical mechanisms of photosensitivity reactions including phototoxic and photoallergic reactions [12, 14].

Figure 2. A lymphocyte transformation test was performed on a patient who developed a spiramycin-dependent drug rash while working at a chemical plant where this drug was manufactured. Cross-reactivity was observed with azithromycin, roxithromycin, and clarithromycin. SI = stimulationindex. PHA: 8.74 (control: 8.52); TT: 3.09 (control: 25.65); concentration of antibiotics in µg/mL.

Figure 3. Example of a positive ELISpot assay with IFN-γ release after incubation with lamotrigine in a patient diagnosed with DRESS caused by lamotrigine together with clindamycin. There was no activation in the ELISpot assay to clindamycin; however, the patch test was for clindamycin as well as for lamotrigine. The patient was taking both medications when DRESS appeared.