[Do we primary care doctors improve our prescription of generic medicines after the intervention of the area pharmacist?]. / Mejoramos los médicos de atención primaria la prescripción de medicamentos genéricos tras la intervención del farmacéutico del área?

OBJECTIVE: To evaluate the prescription of generic medicines by the primary care doctors in a health district after an intervention programme conducted by the area pharmacist. DESIGN: Intervention study. Two indicators were selected as indicators of pharmaceutical prescription of generics. SETTING: Primary care. District 8 of Area 3, Valencian Community, Spain. PARTICIPANTS: Eleven family doctors and 2 paediatricians. INTERVENTIONS: a) Information session in the health centre given by the area pharmacist; b) delivery of the catalogue of generic medicines; c) delivery of the control panel to every physician; and d) possibility of connection to the GAIA system. MAIN MEASUREMENTS: A before-and-after evaluation was made (at 6 months and 12 months from the intervention) of every doctor. Values were compared with the 2 indicators of pharmaceutical prescription. RESULTS: Before the intervention, no doctor was fulfilling the Indicators of pharmaceutical prescription 1 and 2. At 6 months, all the doctors had increased their prescription of generics. Seven doctors met the objective of Indicator 1; and 8, that of indicator 2. At 12 months the increase remained and even grew. CONCLUSIONS: The prescription of generics measured with indicators of pharmaceutical prescription 1 and 2 improved.

IgE antibodies to betalactams: relationship between the triggering hapten and the specificity of the immune response.

BACKGROUND: In immunoglobulin (Ig)E-mediated responses to betalactams (BL) the antibody is directed to the hapten inducing the response. For benzylpenicillin (BP) the determinant is benzylpenicilloyl (BPO) and for amoxicillin (AX), amoxicilloyl (AXO). Because of cross-reactivity, IgE from some patients reacts to both drugs whereas others have a drug-selective recognition. After an allergic episode, there is an increase in IgE that decreases over time. We analysed the response of patients allergic to BL after penicillin administration, with emphasis on IgE cross-reactivity. METHODS: Subjects who developed an IgE antibody response were studied. Sequential follow-up samples were obtained at different times during the response. Changes in IgE specificity were analysed by competition immunoassays using different penicillin monomeric conjugates. RESULTS: Two patterns of response were existed: one with IgE directed to the culprit penicillin and another with IgE mainly reactive to BPO. In both, a variable cross-reactivity with the hapten triggering the boosting response was found. This pattern was maintained with no change in specificity over time, even in subjects who experienced one boosting event. CONCLUSION: The IgE response can be specific to the drug inducing the reaction or cross-reactive to the classical BPO determinant. This pattern is maintained throughout the whole period of the response, even if re-exposure occurs. The stability of the type of response can be explained by the phenomenon of original antigenic sin: in the presence of antibodies, memory B cells are more easily triggered than naive B cells.

Delayed allergic reactions to beta-lactams. Four cases with intolerance to amoxicillin or ampicillin and good tolerance to penicillin G and V.

We present four cases of delayed allergic skin reactions to amoxicillin or ampicillin with good tolerance to benzyl penicillin and phenoxymethyl penicillin. The clinical symptoms reported by the patients, the intradermal skin tests and the controlled challenge results suggested that the mechanism was cellular mediated. In two patients these findings were supported by histopathological studies. Although delayed-type hypersensitivity reactions to beta-lactams with positive skin test seem rare, they can occur to penicillins in allergic patients. The production of these reactions by amoxicillin or ampicillin with good tolerance to benzyl penicillin and phenoxymethyl penicillin emphasizes the role of the side chain in inducing allergic reactions to beta-lactams.

Tolerance to aztreonam in patients allergic to beta-lactam antibiotics.

To evaluate the safe use of aztreonam (AZT) in patients allergic to penicillins and other beta-lactam antibiotics we studied 29 patients from a group of subjects allergic to beta-lactams, diagnosed by presenting systemic reactions after skin tests or challenge tests. Skin tests with benzylpenicilloyl (BPO), benzylpenicilloate, benzylpenicillin, ampicillin, amoxicillin, cephamandole and AZT, radioallergosorbent test (RAST) to BPO and AZT, RAST inhibition and challenge tests were performed. One patient was skin test-positive to AZT, another patient was RAST AZT-positive. IgE antibodies were specific to AZT as demonstrated by RAST inhibition studies with AZT coupled to epsilon-amino caproic acid. Nevertheless, AZT was unable to inhibit either a pool of sera or individual sera positive to BPO. Although all our 29 patients tolerated the administration of AZT (including those with skin test or RAST positive) and AZT appears to be safe in these subjects, this does not indicate that all beta-lactam-allergic patients tolerate AZT administration.

Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing.

BACKGROUND: Penicillin is no longer the most commonly prescribed beta-lactam, and the pattern of reactions has changed. We studied the diagnostic value of skin testing in penicillin-allergic subjects from a population where benzylpenicillin is not now the most frequently used beta-lactam. METHODS: Patients with a history of immediate allergic reactions to penicillins were studied with: skin tests with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin, and ampicillin; in vitro determination of specific IgE; and controlled administration for those with a positive history but negative skin and in vitro tests. A reaction was considered immediate when symptoms appeared within a maximum of 1 h after drug intake. RESULTS: After testing, 290 patients (71% having anaphylaxis and 29% having urticaria) proved to be allergic. Amoxicillin was involved in 64.8% and benzylpenicillin in 2.8% of the patients. Skin test positivity to at least one determinant appeared in 70% of cases, amoxicillin being the most frequent. The overall sensitivity decreased markedly when only BPO and MDM were considered. In 13.1% of patients, the diagnosis was established by in vitro test and in 16.9% by controlled administration. Of the 290 patients, 42.1% were positive to determinants generated from benzylpenicillin and 57.9% were selective responders. CONCLUSIONS: Sensitivity of skin tests to BPO was lower than reported, being partly replaced by minor determinants, mostly amoxicillin. The incorporation of additional reagents and the development of new tests are required, and these will probably change as the patterns of consumption vary.

Clinical evaluation of Pharmacia CAP System RAST FEIA amoxicilloyl and benzylpenicilloyl in patients with penicillin allergy.

BACKGROUND: The diagnosis of IgE-mediated immediate reactions to penicillins can be supported by in vivo or in vitro tests using classical benzylpenicillin determinants. The wide variety of beta-lactams and the description of new specificities requires a re-evaluation of the different tests available. The objective was to evaluate the diagnostic capacity of Pharmacia CAP System RAST FEIA amoxicilloyl c6 (AXO) and benzylpenicilloyl c1 (BPO) in patients with a documented IgE-mediated penicillin allergy. METHODS: We studied 129 patients in five groups. Groups 1, 2, and 3 had developed an immediate reaction after penicillin treatment. Group 1 (n=19) were skin test positive to amoxicillin (AX) and/or BPO and/or minor determinant mixture (MDM); group 2 (n=29) were skin test positive to AX but negative to BPO and MDM; and group 3 (n=26) were skin test negative to all determinants, the diagnosis being confirmed by a previous repetitive history or controlled administration. Two control groups, one with nonimmediate reactions -- group 4 (n=25) -- and one with good tolerance to penicillin -- group 5 (n=30) -- were included. All samples were analyzed in vitro for AXO and BPO, and the results compared to the in vivo diagnosis. RESULTS: AX was the drug most often involved. In group 1, 53% were in vitro positive for AXO and 68% for BPO, but 74% had at least one positive test result. In group 2, only 10% had a positive in vitro test to BPO compared to 41% to AXO. In group 3, 42% had positive BPO and/or AXO in vitro tests. In the control groups 4 and 5, the negative in vitro results for AXO were 96% and 100%, and for BPO 100% and 97%, respectively. A positive correlation between specific IgE levels and the time interval from the reaction to the evaluation was found only for group 3. CONCLUSIONS: This in vitro assay is beneficial for evaluating subjects allergic to beta-lactams. It is necessary to test for specific IgE to AXO in addition to BPO in patients with immediate allergic reactions after AX. The combination of in vivo and in vitro tests for estimating IgE antibodies to penicillins is important because of the existence of patients with a positive history but negative skin test.