Background: Previous observations indicate that in some instances subjects allergic to penicillins may experience an allergic reaction after taking the drug by one route but have good tolerance after being administered the same drug by a different route.
Objective: The purpose was to establish if cloxacillin (CLX) induced a selective response only after oral route administration in a suspected case and to study if there were differences between the oral and parenteral formulations.
Methods: Skin tests were carried out using benzylpenicillin (BP) conjugated to poly-L-lysine (BPO-PLL), minor determinant mixture of benzylpenicillin (MDM), ampicillin (AMP), amoxicillin (AX) and cloxacillin (CLX). Radioallergosorbent assay (RAST) was carried out using BPO-PLL, AX-PLL and CLX-PLL sensitized discs. In the case the skin tests and RAST were negative, a controlled challenge administering the drug by both oral and parenteral route was made. Urine samples were taken at prechallenge (basal levels) and at three periods after challenge (1-3, 3-6 and 6-9 h). Analysis of oral and parenteral formulations was made by HPLC chromatography.
Results: All skin tests and RASTs were negative. With the challenge tests the patient tolerated parenteral BP and oral phenoxymethyl penicillin (PV) and oral and parenteral AMP up to therapeutic concentrations. Parenteral CLX (500 mg) was also tolerated but 30 min after administering 50 mg by the oral route progressive generalized erythema with pruritus, facial angioedema and tachycardia developed. Urine samples taken during the challenge tests showed an increased excretion of N-methyl histamine (N-MH) 3 h after challenge with oral CLX but no change in N-MH levels after challenge with parenteral CLX or the other penicillins, indicating that histamine was released during the allergic episode with oral CLX. HPLC analysis of the oral and parenteral CLX formulations indicated that there were no differences and that neither polymers no other contaminant materials were present.
Conclusion: Although the nature of the allergenic determinant involved in the induction of the reaction is not yet known, the oral route may have favoured the production of a metabolite not generated by the parenteral route.