Can fluoroquinolones be safely used in patients with immediate hypersensitivity reaction to penicillin?

Main Article Content

Elif Açar https://orcid.org/0000-0002-4669-5034
Murat Türk
Serpil Köylüce
Hatice Eylül Bozkurt Yılmaz
Serhat Şeker
Elif Aktaş Yapıcı
İnsu Yılmaz

Keywords

cross-reactivity, drug hypersensitivity, fluoroquinolone hypersensitivity, oral provocation testing, penicillin allergy

Abstract

Objective: The aim of this study was to evaluate whether fluoroquinolone antibiotics, which are structurally distinct from penicillins, can be safely prescribed as alternatives for patients with a history of immediate-type hypersensitivity reactions (HSRs) to penicillin in the absence of multidrug allergy and without the need for provocation testing.


Methods: We conducted a retrospective analysis of the medical records of patients who presented to the Erciyes University Adult Immunology and Allergy Outpatient Clinic with a documented history of penicillin allergy between 2015 and 2024. Inclusion criteria for immediate hypersensitivity to penicillin included at least one of the following: (1) a history of at least two separate immediate HSRs to the same penicillin; or (2) positive results from penicillin G/V (Penicillin G and Penicillin V) serum-specific immunoglobulin E (SsIgE) and/or skin prick testing. Patients who met these criteria and subsequently underwent oral provocation testing with fluoroquinolone antibiotics were included in the study.


Results: This study included 76 patients (72% female, mean age: 45.63 ± 11.76 years), 47.4% of whom had comorbid allergic diseases. The diagnosis was primarily based on clinical history (80%), while the remainder were confirmed by SsIgE testing, skin tests, or drug provocation. A history of urticaria-angioedema was reported in 59.2% of the patients, while 40.8% had a history of anaphylaxis. Following oral provocation testing with fluoroquinolones, only two patients (2.6%) developed mild, self-limited urticaria or angioedema, without systemic involvement.


Conclusions: Our study demonstrates a low positive rate (2.6%) for fluoroquinolone oral provocation testing among patients with penicillin allergy. These findings suggest that fluoroquinolones may be a viable and safe alternative in patients with a confirmed penicillin hypersensitivity and no history of multidrug allergy, and may be considered without prior provocation testing in selected cases.

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References

1 Romano A, Atanaskovic-Markovic M, Barbaud A, Bircher AJ, Brockow K, Caubet JC, et al. Towards a more precise diagnosis of hypersensitivity to beta-lactams—An EAACI position paper. Allergy. 2020;75(6):1300–15. 10.1111/all.14122

2 Çelik G, Karakaya G, Öztürk A, Gelincik A, Abadoğlu Ö, Sin A, et al. Drug allergy in tertiary care in Turkey: Results of a national survey. The ADAPT study: Adult drug allergy perception in Turkey. Allergol Immunopathol. 2014;42(6):573–9. 10.1016/j.aller.2013.07.007

3 Broyles AD, Banerji A, Barmettler S, Biggs CM, Blumenthal K, Brennan PJ, et al. Practical guidance for the evaluation and management of drug hypersensitivity: Specific drugs. J Allergy Clin Immunol Pract. 2020;8(9):S16–116. 10.1016/j.jaip.2020.08.002

4 Andriole VT. The future of the quinolones. Drugs. 1999;58(2): 1–5. 10.2165/00003495-199958002-00001

5 Doña I, Blanca-Lopez N, Torres M, García-Campos J, García-Núñez I, Gómez F, et al. 7 drug hypersensitivity reactions: response patterns, drug involved, and temporal variations in a large series of patients. J Investig Allergol Clin Immunol. 2012;22(5):363.

6 Wall GC, Taylor MJ, Smith HL. Prevalence and characteristics of hospital inpatients with reported fluoroquinolone allergy. Int J Clin Pharm. 2018;40:890–4. 10.1007/s11096-018-0613-0

7 Doña I, Romano A, Torres MJ. Algorithm for betalactam allergy diagnosis. Allergy. 2019;74(9). 10.1111/all.13844

8 Wijnakker R, van Maaren MS, Bode LG, Bulatovic M, Hendriks BJ, Loogman MC, et al. The Dutch working party on antibiotic policy (SWAB) guideline for the approach to suspected antibiotic allergy. Clin Microbiol Infect. 2023;29(7):863–75. 10.1016/j.cmi.2023.04.008

9 Blumenthal KG, Kuper K, Schulz LT, Bhowmick T, Postelnick M, Lee F, et al. Association between penicillin allergy documentation and antibiotic use. JAMA Intern Med. 2020;180(8):1120–2. 10.1001/jamainternmed.2020.2227

10 Bertram CM, Postelnick M, Mancini CM, Fu X, Zhang Y, Schulz LT, et al. Association of β-lactam allergy documentation and prophylactic antibiotic use in surgery: A national cross-sectional study of hospitalized patients. Clin Infect Dis. 2021;72(11):e872–5. 10.1093/cid/ciaa1762

11 Portilho NC, Aun MV, Kalil J, Giavina-Bianchi P. Quinolone-induced anaphylaxis. Curr Treat Options Allergy. 2020;7:370–80. 10.1007/s40521-020-00260-0

12 Blanca-López N, Ariza A, Doña I, Mayorga C, Montañez M, Garcia-Campos J, et al. Hypersensitivity reactions to fluoroquinolones: Analysis of the factors involved. Clin Exp Allergy. 2013;43(5):560–7. 10.1111/cea.12099

13 Lobera T, Audícana M, Alarcón E, Longo N, Navarro B, Muñoz D. Allergy to quinolones: Low cross-reactivity to levofloxacin. J Investig Allergol Clin Immunol. 2010;20(7):607–11.

14 Jones SC, Budnitz DS, Sorbello A, Mehta H. US-based emergency department visits for fluoroquinolone-associated hypersensitivity reactions. Pharmacoepidemiol Drug Saf. 2013;22(10):1099–106. 10.1002/pds.3499

15 Blanca-López N, Andreu I, Jaén MJT. Hypersensitivity reactions to quinolones. Curr Opin Allergy Clin Immunol. 2011;11(4):285–91. 10.1097/ACI.0b013e3283489bc3

16 Renaudin JM, Beaudouin E, Ponvert C, Demoly P, Moneret-Vautrin DA. Severe drug-induced anaphylaxis: analysis of 333 cases recorded by the Allergy Vigilance Network from 2002 to 2010. Allergy. 2013;68(7):929–37. 10.1111/all.12168

17 Doña I, Pérez-Sánchez N, Salas M, Barrionuevo E, Ruiz-San Francisco A, de Rojas DHF, et al. Clinical characterization and diagnostic approaches for patients reporting hypersensitivity reactions to quinolones. J Allergy Clin Immunol Pract. 2020;8(8):2707–14. e2. 10.1016/j.jaip.2020.04.051

18 Salvo F, Polimeni G, Cutroneo PM, Leone R, Confortic A, Moretti U, et al. Allergic reactions to oral drugs: A case/non-case study from an Italian spontaneous reporting database (GIF). Pharmacol Res. 2008;58(3–4):202–7. 10.1016/j.phrs.2008.07.003

19 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;29:1087–100. 10.2165/00002018-200629110-00008

20 Lapi F, Tuccori M, Motola D, Pugi A, Vietri M, Montanaro N, et al. Safety profile of the fluoroquinolones: Analysis of adverse drug reactions in relation to prescription data using four regional pharmacovigilance databases in Italy. Drug Saf. 2010;33:789–99. 10.2165/11536810-000000000-00000

21 Kowalski ML, Agache I, Bavbek S, Bakirtas A, Blanca M, Bochenek G, et al. Diagnosis and management of NSAID-exacerbated respiratory disease (N-ERD)—A EAACI position paper. Allergy. 2019;74(1):28–39. 10.1111/all.13599

22 Mayorga C, Ebo DG, Lang DM, Pichler WJ, Sabato V, Park MA, et al. Controversies in drug allergy: In vitro testing. J Allergy Clin Immunol. 2019;143(1):56–65. 10.1016/j.jaci.2018.09.022

23 Dhopeshwarkar N, Sheikh A, Doan R, Topaz M, Bates DW, Blumenthal KG, et al. Drug-induced anaphylaxis documented in electronic health records. J Allergy Clin Immunol Pract. 2019;7(1):103–11. 10.1016/j.jaip.2018.06.010

24 Tai Y-H, Tai Y-J, Hsu H-C, Lee S-P, Chen Y-Y, Chiang Y-C, et al. Risk factors of hypersensitivity to carboplatin in patients with gynecologic malignancies. Front Pharmacol. 2017;8:800. 10.3389/fphar.2017.00800

25 Sohn K-H, Kang D-Y, Kim J-Y, Lee S-Y, Lee K-H, Han S-W, et al. Incidence and risk of oxaliplatin-induced hypersensitivity in patients with asymptomatic prior exposure: A prospective observational study. J Allergy Clin Immunol Pract. 2018;6(5):1642–8.e2. 10.1016/j.jaip.2017.12.026

26 Van Boeckel TP, Gandra S, Ashok A, Caudron Q, Grenfell BT, Levin SA, et al. Global antibiotic consumption 2000 to 2010: An analysis of national pharmaceutical sales data. Lancet Infect Dis. 2014;14(8):742–50. 10.1016/S1473-3099(14)70780-7

27 Solensky R, Earl HS, Gruchalla RS. Clinical approach to penicillin-allergic patients: A survey. Ann Allergy Asthma Immunol. 2000;84(3):329–33. 10.1016/S1081-1206(10)62782-2

28 Díaz ID. Clinical practice guidelines for diagnosis and management of hypersensitivity reactions to quinolones. J Investig Allergol Clin Immunol. 2021;31. 10.18176/jiaci.0669

29 Demir S, Gelincik A, Akdeniz N, Aktas-Cetin E, Olgac M, Unal D, et al. 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. Allergy Asthma Immunol Res. 2017;9(4):347. 10.4168/aair.2017.9.4.347

30 Landry Q, Zhang S, Ferrando L, Bourrain JL, Demoly P, Chiriac A-M. Multiple drug hypersensitivity syndrome in a large database. J Allergy Clin Immunol Pract. 2020;8(1):258–66.e1. 10.1016/j.jaip.2019.06.009

31 Khoury L, Warrington R. The multiple drug allergy syndrome: A matched-control retrospective study in patients allergic to penicillin. J Allergy Clin Immunol. 1996;98(2):462–4. 10.1016/S0091-6749(96)70172-0

32 Broyles AD, Banerji A, Castells M. Practical guidance for the evaluation and management of drug hypersensitivity: General concepts. J Allergy Clin Immunol Pract. 2020;8(9):S3–15. 10.1016/j.jaip.2020.08.002