Diagnostic workup including CD203c‐based basophil activation test in immediate hypersensitivity due to metronidazole and ornidazole and evaluation of cross‐reactivity in between

Abstract

Background Little is known about the diagnostic approaches for immediate hypersensitivity reactions (IHRs) due to 5‐nitroimidazole antibiotics. The aim was to evaluate the usefulness of in vivo tests and basophil activation test (BAT) for the diagnosis of IHRs due to metronidazole and ornidazole and to determine possible cross‐reactivity in between. Methods Forty‐nine patients with a clear history of IHRs due to these drugs and 20 healthy subjects who were known to tolerate these drugs were included. Skin tests (STs) and single‐blind placebo‐controlled drug provocation tests (SBPCDPTs) were performed with both drugs whereas BAT was applied only with the culprit drug. Results The most and least common reaction types were urticaria/angioedema (34.7%) and anaphylaxis (14.3%), respectively. SBPCDPTs were positive in 15 out of 47 patients, and only 7 had positive STs. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of STs for metronidazole/ornidazole were 33.3%/16.6%, 94.2%/97.3%, 60%/50%, and 84.6%/88.1%, respectively. BAT was positive in 12 out of 15 patients and negative in 10 control subjects, giving a sensitivity rate of 71.4% (CI, 29.0%‐96.3%) for metronidazole and 83.3% (CI, 35.8%‐99.5%) for ornidazole. The optimal concentration of both drugs for BAT was determined as 5 mg/mL. No cross‐reactivity among two drugs was observed according to in vivo tests. Conclusions Our study showed that SBPCDPT and BAT are both useful diagnostic tools for IHRs due to 5‐nitroimidazole antibiotics and can be used as supplementary to each other. No cross‐reactivity between metronidazole and ornidazole in IHRs exists.

Antibiotic Allergy De-Labeling: A Pathway against Antibiotic Resistance

“…Sensitivity for penicillins ranges from 22% to 55% and for clavulanic acid up to 52.7%, both of them with a good specificity (79–96%) [ 28 , 68 , 69 , 70 , 71 ]. Moreover, recent studies have demonstrated that the basophil activation test is a promising technique, complementary to skin tests, for diagnosing allergy to amoxicillin–clavulanic acid [ 72 , 73 ], cefazolin (sensitivity rate up to 66.7%) [ 74 ] and 5-nitroimidazole (sensitivity rate up to 83.3%) [ 75 ].…”

Drug hypersensitivity, in vitro tools, biomarkers, and burden with COVID‐19 vaccines

“…Moreover, two studies have demonstrated that BAT can be used as diagnostic tool for IHSRs to different groups of antibiotics, 5‐nitroimidazole and cefazolin, showing sensitivity rate up to 83.3% 3 and 66.7%, respectively 19 . In addition, BAT was able to diagnose patients allergic to quinolones, with a higher sensitivity than skin prick test (SPT) 20 .…”

“…In addition, prior known cellular tests for IHSR and NIHSR, such as basophil activation test (BAT), lymphocyte transformation test (LTT), enzyme‐linked ImmunoSpot (EliSpot), and T‐cells clonality have been deeply analysed and tuned up their techniques. 2 , 3 , 4 , 5 , 6 …”

“…In addition, prior known cellular tests for IHSR and NIHSR, such as basophil activation test (BAT), lymphocyte transformation test (LTT), enzyme-linked ImmunoSpot (EliSpot), and T-cells clonality have been deeply analysed and tuned up their techniques. [2][3][4][5][6] Moreover, biomarkers are valuable parameters for precision medicine that provide information on the endotypes, diagnosis, prognosis, and prediction of HSR development, as well on the identification of therapeutic targets and treatment efficacy monitoring. 7 Apart from the in vitro tests mentioned before that help in the determination of previously identified biomarkers, new and promising molecules and mediators have been identified as the biomarkers for specific indications.…”

Basophil and mast cell activation tests by flow cytometry in immediate drug hypersensitivity: Diagnosis and beyond

“…Another advantage of the BAT lies in its capacity to simultaneously and safely test different compounds, including products that are not intended for human use. This asset is particularly useful when exploring the absence or presence of cross-reactivity [60][61][62][63][64] , incrimination of (hidden) excipients [65][66][67][68] , identification of specific antigenic determinants or changes thereof 69,70 . For example, we used the BAT to demonstrate that the sugammadex-rocuronium inclusion complex (S-R-Cx) can be allergenic and is capable of triggering sIgE/FcεRI-dependent anaphylaxis due to a shape alteration involving the thio(carboxyethyl)sodium side chains attached at the primary rim of the host sugammadex molecule.…”