Allergy to cloxacillin with normal tolerance to amoxicillin and cefuroxime

Introducción: La cloxacilina es un penicilina semisintética ampliamente utilizada en las infecciones por Staphylococcus aureus no resistente a meticilina. Se han descrito diferentes reacciones de hipersensibilidad a cloxacilina, aunque las IgE mediadas son raras y hay poca información sobre el control de estos pacientes en cuanto a su posible tolerancia a otras penicilinas o cefalosporinas. Presentamos dos casos con alergia a cloxacilina, con lo que se demuestra un mecanismo IgE mediado con tolerancia a amoxicilina y cefuroxima. Casos clínicos: a) mujer de 47 años que comenzó un tratamiento con cloxacilina para tratar una celulitis aguda. Tras la toma de 500 mg, presentó una erupción maculopapular y angioedema facial, y b) mujer de 55 años que, 1 h después de la toma de 500 mg de cloxacilina por un absceso cutáneo, presentó un cuadro de urticaria y angioedema labial. Las pruebas cutáneas en Prick fueron positivas a cloxacilina en la primera paciente y negativas en la segunda, aunque en ésta la prueba intradérmica fue positiva (2mg/ml). Se realizaron provocaciones orales simple-ciego con amoxicilina (1 g) y cefuroxima (500 mg), bien toleradas en ambas pacientes. Conclusiones: Presentamos los casos de dos pacientes alérgicas a cloxacilina que toleran otros antibióticos betalactámicos, lo que confirma que un mecanismo de reactividad cruzada entre ellos parece ser infrecuente. Por ello, debe plantearse siempre un estudio alergológico que incluya la provocación oral en los pacientes alérgicos a cloxacilina.

INTRODUCTION

Cloxacillin is a semisynthetic penicillinase-resistant penicillin widely used in non-methicillin resistant Staphylococcus aureus infections. Most frequent side effects of cloxacillin are gastro-intestinal manifestations like vomiting or diarrea, although there have been reported different hypersensitivity reactions ^1,2. However, IgE-mediated allergic reactions to the drug are rare and there is little previously reported information about the management of allergic patients to cloxacillin in order to demonstrate tolerance to other semi-synthetic penicillins or cephalosporins ³. We present two different patients with demonstrated IgE-mediated allergy to cloxacillin with normal tolerance to amoxicillin and cefuroxime.

CASE REPORT

Case 1. A 47-year-old woman diagnosed of chronic lymphedema after a radical mastectomy, began treatment with cloxacillin due to an acute cellulitis. Shortly after the intake of Orbenin® 500 mg (Glaxo-SmithKline-Beecham,Toledo.Spain) she experience generalized pruritic maculo-papular eruption, hives and angioedema of the face.

Case 2. A 55-year-old woman, with a personal background of smoking, who had taken cloxacillin 500 mg for an abscess involving the bulbous end of a finger. 60 minutes after the intake of the first pill, she presented an episode of acute urticaria and labial angioedema. Both patients were completely recovered after the administration of parenteral treatment (40 mg of 6-methyl-prednisolone and intravenous dyphenhydramine). They both had previously taken cloxacillin without any reaction and they had not eaten any food or had not being doing exercise in the previous 4 hours.

ALLERGIC STUDY

In the Allergy Unit at our Hospital, Skin prick tests (SPT) with benzylpenicillin (10.000 U/ml), mayor and minor determinants mixture of benzylpenicillin (BPO and MDM. Diater. Madrid. Spain), cloxacillin (20 mg/ml), amoxicillin (20 mg/ml) and cefuroxime (200 mg/ml) were performed 30 days later according to standardized procedures ⁴. If they were negative, intradermal tests were carried out. Prick test was positive only to cloxacillin in case 1 with a mean diameter of the obtained wheal of 5mm. Prick test were all negative in case 2, but the intradermal test was positive to cloxacillin (2 mg/ml) presenting a 14 mm wheal of mean diameter, double that of the histamine wheal (1 mg/ml) at the 20 min. reading. All the other tests were negative and no positive results were obtained at the 24 h reading. Simple-blind oral challenge tests with increasing doses until an accumulative dosis of amoxicillin (1 g) and cefuroxime (500mg) were performed, being well-tolerated in both patients.

DISCUSSION

Adverse reactions to betalactam antibiotics constitute a major hazard in medical practice. Although the use of cloxacillin is widely extended, data of immediate allergic reactions after using this drug are very scarce. It could be explained due to it is not frequently involved in allergic reactions ⁵ but there could exist an inssufficient communication that leads to remain cloxacillin allergic reactions to be underdiagnosed. This fact could explain the lack of reported experience in clinical management of those patients. There is a general tendency to avoid using other betalactam antibiotics due to that there are similarities in chemichal structure between them to justify a cross-reactivity mechanism between cloxacillin and amoxicillin or cephalosporins. However, if we remember that many of the allergic patients to penicillin or amoxicillin tolerate any cephalosporin, the allergologist might be asked to find out which of the other betalactam antibiotic could be used as secure alternatives in cloxacillin allergic patients. We should not forget that previous observations indicate that, in some instances, subjects allergic to cloxacillin may experience an allergic reaction after taking the drug orally but have good tolerance after being administered the same drug by parenteral route ⁶.

In conclusion, we present two different patients allergic to cloxacillin with normal tolerance to other betalactam antibiotics, confirming that cross-reactivity seems to be uncommon among those tested antibiotics. A complete allergologic study, including an oral challenge test, should be considered in these patients.

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Correspondence:
Dr. Javier Dominguez Ortega
Unit of Allergy. Hospital Universitario de Getafe
Ctra. de Toledo. Km. 12,500.
28905 Getafe. Madrid. Spain.
E-mail: [e-mail]