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Assistant Maladies Respiratoires, Inserm U454 Hôpital Arnaud de Villeneuve University Hospital of Montpellier Montpellier, France
Consultant Maladies Respiratoires, Inserm U454 Hôpital Arnaud de Villeneuve
Professor Maladies Respiratoires, Inserm U454 Hôpital Arnaud de Villeneuve
Professor, Head of the Allergy Department Maladies Respiratoires Inserm U454 Hôpital Arnaud de Villeneuve University Hospital of Montpellier 34 295 Montpellier Cedex France FAX (33) 4 67 04 27 08 E-mail demoly{at}montp.inserm.fr
Published Online, June 10, 2003. www.theannals.com, DOI 10.1345/aph.1C285
Case Report. A 28-year-old white woman, admitted for elective abortion, received mifepristone, nalbuphine, propofol, misoprostol, and amoxicillin as prophylaxis. The day after, because of fever, she received intravenous amoxicillin/clavulanate 1 g twice daily and experienced generalized urticaria, facial angioedema, malaise, and dyspnea within 15 minutes after the fourth injection. Blood pressure remained normal. The antibiotic was discontinued, and she was treated with intravenous methylprednisolone and dexchlorpheniramine. The reaction subsided within 24 hours. The woman had a history of exercise-induced asthma and maculopapular eruptions following dihydroergotamine and spiramycin.
Use of the Naranjo probability scale indicated a probable relationship between the anaphylaxis and amoxicillin/clavulanate therapy.2 However, a firm diagnosis was lacking. One year later, the woman was referred for allergologic workup. Prick and intradermal tests with penicilloylpolylysine 35 µg/mL; minor determinant mixture 1.1 mg/mL; benzylpenicillin 250, 2500, and 25 000 IU/mL; amoxicillin 0.25, 2.5, and 25 mg/mL; and amoxicillin/clavulanic acid at the same concentrations (all diluted in NaCl 0.9%) were all negative after 20 minutes, 24 hours, and 48 hours. One week later, an oral single-blind drug provocation test with amoxicillin/clavulanic acid was performed, with 1 mg, then 5 and 10 mg. The dosage was intended to be increased up to 1 g at 30-minute intervals. At a cumulative dose of 16 mg, she developed generalized urticaria, conjunctivitis, throat swelling, and hypotension. She was treated with intramuscular epinephrine, intravenous methylprednisolone, and dexchlorpheniramine, and was hospitalized for 24 hours; there was no recurrence of allergic reactions. Four weeks later, an oral provocation test with amoxicillin (0.01 mg increased to the therapeutic dose of 500 mg) was negative. We concluded that our patient was allergic to clavulanate alone, advised her to avoid antibiotics containing clavulanate, and gave her an allergy card. Skin tests repeated 8 months later remained negative.
Discussion. Clavulanate, a ß-lactamase inhibitor, has no intrinsic antibacterial activity, but combining it with another ß-lactam confers greater stability toward ß-lactamases and a broader spectrum of activity. Combined with amoxicillin, it is one of the most frequently prescribed antibiotics worldwide. To our knowledge, only 3 cases of allergy to clavulanate have been reported. In the first article, 2 cases were described,3 skin tests were positive with clavulanate alone in both patients, and drug provocation test with clavulanate was positive in 1 patient. In the second article, only skin testing was performed.4 The scratch test with amoxicillin/clavulanate and the prick test with clavulanate alone were both positive. Our case is the fourth case of selective immediate reaction to clavulanate. Unlike the previous cases, skin testing was negative with amoxicillin/clavulanate and the allergic reaction was only proven by oral provocation tests. The reaction is probably immunoglobulin E dependent, as suggested in the literature. We failed to demonstrate this because skin testing was negative, although we did not test clavulanate alone.
References
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