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. 2017 Jul;9(4):347-359.
doi: 10.4168/aair.2017.9.4.347.

Usefulness of In Vivo and In Vitro Diagnostic Tests in the Diagnosis of Hypersensitivity Reactions to Quinolones and in the Evaluation of Cross-Reactivity: A Comprehensive Study Including the Latest Quinolone Gemifloxacin

Affiliations

Usefulness of In Vivo and In Vitro Diagnostic Tests in the Diagnosis of Hypersensitivity Reactions to Quinolones and in the Evaluation of Cross-Reactivity: A Comprehensive Study Including the Latest Quinolone Gemifloxacin

Semra Demir et al. Allergy Asthma Immunol Res. 2017 Jul.

Abstract

Purpose: Reports evaluating diagnosis and cross reactivity of quinolone hypersensitivity have revealed contradictory results. Furthermore, there are no reports investigating the cross-reactivity between gemifloxacin (GFX) and the others. We aimed to detect the usefulness of diagnostic tests of hypersensitivity reactions to quinolones and to evaluate the cross reactivity between different quinolones including the latest quinolone GFX.

Methods: We studied 54 patients (mean age 42.31±10.39 years; 47 female) with 57 hypersensitivity reactions due to different quinolones and 10 nonatopic quinolone tolerable control subjects. A detailed clinical history, skin test (ST), and single-blind placebo-controlled drug provocation test (SBPCDPT), as well as basophil activation test (BAT) and lymphocyte transformation test (LTT) were performed with the culprit and alternative quinolones including ciprofloxacin (CFX), moxifloxacin (MFX), levofloxacin (LFX), ofloxacin (OFX), and GFX.

Results: The majority (75.9%) of the patients reported immediate type reactions to various quinolones. The most common culprit drug was CFX (52.6%) and the most common reaction type was urticaria (26.3%). A quarter of the patients (24.1%) reacted to SBPCDPTs, although their STs were negative; while false ST positivity was 3.5% and ST/SBPCDPTs concordance was only 1.8%. Both BAT and LTT were not found useful in quinolone hypersensitivity. Cross-reactivity was primarily observed between LFX and OFX (50.0%), whereas it was the least between MFX and the others, and in GFX hypersensitive patients the degree of cross-reactivity to the other quinolones was 16.7%.

Conclusions: These results suggest that STs, BAT, and LTT are not supportive in the diagnosis of a hypersensitivity reaction to quinolone as well as in the prediction of cross-reactivity. Drug provocation tests (DPTs) are necessary to identify both culprit and alternative quinolones.

Keywords: Quinolone hypersensitivity; basophil activation test; lymphocyte transformation test.

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Conflict of interest statement

There are no financial or other issues that might lead to conflict of interest.

Figures

Fig. 1
Fig. 1. LTT results of quinolone specific CD4+ T cells. Graphic represents the comparison of the mean stimulation index in healthy controls and the patients. Although SI values of LTT performed with LFX, MFX, and CFX were less than 2, these were significantly higher in patients than in healthy controls (Mann-Whitney U test was used to determine significance between groups. P<0.05 was accepted as statistical significance level) (A). FlowJo program imagesare representative dot plots of patient number 11. The expansion of CD4+ T cells during culture with MFX and CFX was shown and SI values were also indicated (B). LTT, lymphocyte transformation test; SI, International System of Units; LFX, levofloxacin; MFX, moxifloxacin; CFX, ciprofloxacin.
Fig. 2
Fig. 2. Results of the in vivo and in vitro test with the culprit drugs. CFX, ciprofloxacin; MFX, moxifloxacin; LFX, levofloxacin; OFX, ofloxacin; GFX, gemifloxacin; DPT, drug provocation test; BAT, basophil activation test; LTT, lymphocyte transformation test; Ptn, patient; NP, not performed.
Fig. 3
Fig. 3. Evaluation of cross-reactivity between quinolones. Each box represents the quinolone responsible for the reaction in the history and the colorful bars in the graphs stand for positive DPT results with alternative quinolones indicating the cross-reactivity. For example; The orange box at the top of the first column shows the patients with CFX hypersensitivity. The blue bar in this graph shows the number of positive results in DPT performed with MFX. In CFX hypersensitive patients, cross-reactivity with MFX is 30% (9/30). CFX, ciprofloxacin; MFX, moxifloxacin; LFX, levofloxacin; OFX, ofloxacin; GFX, gemifloxacin; DPT, drug provocation test.
Fig. 4
Fig. 4. Suggestions which were extrapolated from the study for choosing alternative quinolone in a quinolone hypersensitive patient. CFX, ciprofloxacin; MFX, moxifloxacin; LFX, levofloxacin; OFX, ofloxacin; GFX, gemifloxacin; BAT, basophil activation test; SBPCDPT, single blind placebo controlled drug provocation test.

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References

    1. Van Bambeke F, Michot JM, Van Eldere J, Tulkens PM. Quinolones in 2005: an update. Clin Microbiol Infect. 2005;11:256–280. - PubMed
    1. Ball P. Quinolone generations: natural history or natural selection? J Antimicrob Chemother. 2000;46:17–24. - PubMed
    1. Bertino J, Jr, Fish D. The safety profile of the fluoroquinolones. Clin Ther. 2000;22:798–817. - PubMed
    1. Doña I, Blanca-López N, Torres MJ, García-Campos J, García-Núñez I, Gómez F, et al. Drug hypersensitivity reactions: response patterns, drug involved, and temporal variations in a large series of patients. J Investig Allergol Clin Immunol. 2012;22:363–371. - PubMed
    1. Sachs B, Riegel S, Seebeck J, Beier R, Schichler D, Barger A, et al. Fluoroquinolone-associated anaphylaxis in spontaneous adverse drug reaction reports in Germany: differences in reporting rates between individual fluoroquinolones and occurrence after first-ever use. Drug Saf. 2006;29:1087–1100. - PubMed