Successful desensitization to cloxacillin in a patient with sepsis, with infective endocarditis and clinical suspicion of hypersensitivity to penicillins, a case report.

WHAT IS KNOWN AND OBJECTIVE: Beta-lactam antibiotic (BLA) therapy is frequently needed to treat infective endocarditis (IE). Hypersensitive reactions to BLA restrict BLA therapy in allergic patients. In the current case, we aim to describe the utility of desensitization (DS) in this context. Although the evidence is limited, DS is recommended. CASE DESCRIPTION: This case report deals with a 79-year-old woman with a clinical suspicion of allergy to BLA and a methicillin-sensitive Staphylococcus aureus (MSSA) IE. A cloxacillin DS protocol was developed to enable treatment with cloxacillin. WHAT IS NEW AND CONCLUSION: Alternative antibiotic treatments may be less effective or not available in MSSA IE. In this case report, DS allowed optimal cloxacillin treatment.

Selective allergic reaction to oral cloxacillin.

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.

Enzyme immunoassay for the detection of isoxazolyl penicillin antibiotics in milk.

Polyclonal antibodies were raised against isoxazolyl penicillins in rabbits after immunization with a cloxacillin-human serum albumin conjugate. The antisera were tested in direct and indirect competitive enzyme immunoassays (EIAs), using glucose oxidase or horseradish peroxidase conjugates of oxacillin, cloxacillin, or dicloxacillin, respectively, as the labelled antigen. The relative cross-reactivities of each test system with oxacillin, cloxacillin, and dicloxacillin, determined from the amount of antibiotic required for 50% inhibition of labelled antigen binding, were dependent on the antibiotic used as the labelled antigen. Other beta-lactam antibiotics did not cross-react in these test systems. In a direct EIA using a cloxacillin-horseradish peroxidase conjugate, cloxacillin and dicloxacillin in milk were detected at levels of 10 and 30 ng ml-1; the average recoveries at these levels were 102 and 84%, respectively.

Cross-antigenicity between penams and cephems by intradermal skin test and leucocyte migration test in guinea pigs.

The delayed-type hypersensitivity (DTH) reactions for penams or cephems of beta-lactam antibiotics were investigated by intradermal skin test and leucocyte migration test (LMT) in guinea pigs. The animals were immunized with ampicillin (ABPC) or cephalexin (CEX) using Freund's complete adjuvant. The cross-reactivities among ABPC, penicillin G (PCG) and cloxacillin as penam and CEX, cephalothin (CET) and cephalosporin C (CEPC) as cephem and phenylglycine (PhGly), which is the amino acyl side chain of ABPC and CEX, were examined. By intradermal reaction, ABPC-sensitized animals showed a cross-reaction with CEX, PCG and CET, but CEX-sensitized animals did not cause cross-reaction with ABPC. The CEX-sensitized group exhibited slight cross-reactions to CET and PhGly. PhGly exhibited low immunogenicity only in maximization test of guinea pig. The above results indicate that there is the difference in cross-reactivity between penams and cephems in skin test. In LMT, all the ABPC-sensitized animals reacted with ABPC and showed cross-reactions with all drugs tested. The CEX-sensitized group reacted with 4 out of 7 animals with CEX and exhibited cross-reactivities to ABPC, PCG, CET, CEPC and PhGly. The cross-reactivity between intradermal skin reaction and LMT elicited some different results.

Contact sensitivity in guinea pigs to different penicillins.

The ability of penicillins of varying lipophilicity to induce and elicit cellular allergic responses were analysed in guinea pigs. Epicutaneous application of the penicillins benzylpenicillin (Bp), cloxacillin (Clox) and Bacampicillin (Bamp) did not cause any unspecific skin irritation. Intracutaneously injected, however, Bamp, Clox and to a lesser extent Bp caused irritation at concentrations of 1.25%. Solutions of 0.12% of penicillins were inactive in this respect. Cellular allergic responses were induced with Bp, Bamp and Clox after repeated epicutaneous application. The magnitude of responses was related to the lipophilic properties of the penicillins, Bamp being superior. In the guinea pig maximization (GPM) test of Magnusson and Kligman employing intradermal injections of the penicillins with Freund's complete adjuvant, similar sensitizing abilities of the three penicillins were observed. The cellular allergic responses were elicited with Bp, Bamp, Clox and in addition ampicillin and the 1'-ethoxycarbonyloxyethyl ester of Bp. An extensive cross-reactivity between the penicillins was seen in Bp- and Bamp-sensitized animals, whereas the Clox-sensitized animals showed a specificity limited to Clox. Bamp was shown to possess a superior activity to elicit reactions, possibly due to its lipophilic properties together with an irritating effect exerted by the NH2 group.

Transient monoclonal proteins in drug hypersensitivity reactions.

Two patients were studied in whom monoclonal (M) immunoglobulin G (IgG) proteins developed during the course of a serum sickness-like drug hypersensitivity reaction to cloxacillin (Orbenin) and sodium cephalothin (Keflin), respectively. The clinical evidence and time sequence of events support this association. In both patients there was evidence of an active antibody response to the given antibiotic and to the benzylpenicilloyl group as well. However, protein fractions obtained by agar gel preparative electrophoresis failed to show a higher antibody concentration where the M peak was located, and absorption experiments performed with penicillin G-, cloxacillin- and cephalothin-coated red cells failed to absorb these M proteins. These transient paraproteins can be seen in association with antibiotic(s) administration in the context of a hypersensitivity reaction and do not apparently represent a specific immune response.