RESUMO
Background: ß-Lactams are the most widely used antibiotic family in the world. Nevertheless, they also stand out as the primary culprits for inducing drug hypersensitivity reactions (HSR). Methods: Between May 2018 and March 2023, patients with suspected HSRs to ß-lactams, who underwent skin tests (ST), were retrospectively screened. The determinants of allergenic penicillin (DAP) tests, which include penicillin minor and major determinants, clavulanic acid, and amoxicillin, along with ampicillin, sulbactam, the identified culprit drugs, and alternative cephalosporins, which include cefuroxime, ceftriaxone prick and/or intradermal tests, were administered. The analysis focused on identifying positive ST results and determining the true HSRs rates in this patient cohort. Results: Of the 147 patients, 78.9% (n = 116) were women and the median (minimum-maximum) age was 41 years (18-71 years). Mild HSRs (grades 1-2) were observed in 72.78% (n = 107), whereas 24.4% (n = 36) had severe reactions (grades 3-4) and 2.7% (n = 4) had an unknown grade. Of the patients, 64% (n = 94) experienced HSRs within the first hour after the last dose of the identified culprit drug. The overall positivity rate for all STs was 26.5% (n = 39). ST positivity rates were notably higher in individuals who had experienced HSRs within the past 6 months (p = 0.02) and those with severe anaphylaxis (p < 0.001). Conclusion: ß-Lactam ST positivity is higher, especially in those with grades 3-4 reactions and consulted a physician within the first 6 months after their HSRs.
Assuntos
Antibacterianos , Hipersensibilidade a Drogas , Testes Cutâneos , beta-Lactamas , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Hipersensibilidade a Drogas/diagnóstico , beta-Lactamas/efeitos adversos , beta-Lactamas/imunologia , Adolescente , Idoso , Adulto Jovem , Estudos Retrospectivos , Antibacterianos/efeitos adversos , Índice de Gravidade de Doença , Alérgenos/imunologiaAssuntos
Antibacterianos , Hipersensibilidade a Drogas , Combinação Piperacilina e Tazobactam , beta-Lactamas , Humanos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/imunologia , Hipersensibilidade a Drogas/etiologia , Combinação Piperacilina e Tazobactam/efeitos adversos , beta-Lactamas/efeitos adversos , beta-Lactamas/imunologia , Masculino , Feminino , Antibacterianos/efeitos adversos , Antibacterianos/imunologia , Pessoa de Meia-Idade , Idoso , Rotulagem de Medicamentos , Adulto , Piperacilina/efeitos adversos , Piperacilina/imunologiaAssuntos
Antibacterianos/uso terapêutico , Neutropenia Febril/tratamento farmacológico , beta-Lactamas/imunologia , beta-Lactamas/uso terapêutico , Antibacterianos/imunologia , Cefalosporinas/efeitos adversos , Cefalosporinas/imunologia , Cefalosporinas/uso terapêutico , Estudos Transversais , Hipersensibilidade a Drogas/imunologia , Humanos , Meropeném/efeitos adversos , Meropeném/imunologia , Meropeném/uso terapêutico , Penicilinas/efeitos adversos , Penicilinas/imunologia , Penicilinas/uso terapêuticoRESUMO
Background: As desensitization protocols become more readily available and published, more institutions are implementing them and searching for ways to streamline the process. There have been no published studies to date on the effect that electronic medical record systems (EMR) have on the safety and efficiency of ß-lactam antibiotic desensitization. Objective: The purpose of this study was to evaluate the changes in workflow, efficiency, and medical errors after implementation of ß-lactam antibiotic desensitization. Methods: A collaborative effort between the Allergy/Immunology Division and the Pharmacy Department led to the creation and implementation of antibiotic desensitization order sets. Pre- and postimplementation of ß-lactam antibiotic surveys were sent to pharmacists and allergy/immunology fellows and attendings at a single-center tertiary care center. Results: There were only 26 valid respondents (12.3%) to both the pre- and postimplementation surveys. The percentage of respondents who thought that the time needed to prepare desensitization materials was < 4 hours increased from 23% to 77% (p < 0.001). The percentage of respondents who thought that the time needed to input electronic desensitization orders was < 1 hour increased from 19% to 54% (p = 0.002). The percentage of respondents who identified zero errors increased from 42% to 92% (p = 0.001). The perception of the overall desensitization process efficiency significantly increased (p < 0.001). Conclusion: Creation of standardized electronic ß-lactam antibiotic desensitization order sets significantly decreased the time taken to order and prepare materials and increased overall efficiency.
Assuntos
Antibacterianos/administração & dosagem , Dessensibilização Imunológica , Hipersensibilidade a Drogas/terapia , Registros Eletrônicos de Saúde , beta-Lactamas/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/imunologia , Dessensibilização Imunológica/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/imunologia , Eficiência , Humanos , Tolerância Imunológica , Erros Médicos/prevenção & controle , Avaliação de Programas e Projetos de Saúde , Fatores de Tempo , Resultado do Tratamento , Fluxo de Trabalho , beta-Lactamas/efeitos adversos , beta-Lactamas/imunologiaRESUMO
BACKGROUND: Beta-lactam antibiotics are a relatively common cause of immune thrombocytopenia. Because the many beta-lactam drugs now in clinical use have structural similarities, when a patient experiences this complication the question of whether an alternative member of this drug family can safely be used often arises but there are little data available to guide this decision. STUDY DESIGN AND METHODS: Drug-dependent, platelet-reactive antibodies from 32 patients who experienced thrombocytopenia while being treated with a beta-lactam drug of the penam (piperacillin, etc.) or cephem (ceftriaxone etc.) groups were studied for serologic cross-reactivity with other drugs from these families using flow cytometry. Cross-reactions observed were analyzed for correlations with structural features of the drugs tested. RESULTS: Among 14 antibodies specific for penam drugs, five "strong" cross-reactions with other penam drugs were found. Among 18 antibodies specific for cephem drugs, 8 "strong cross-reactions were identified. Antibodies induced by penam drugs did not cross-react strongly with cephem drugs and vice versa. A strong correlation between cross-reactions and similar or identical R1 side groups of the beta-lactams studied was observed. DISCUSSION: The findings suggest that patients who experience immune thrombocytopenia while being treated with a beta-lactam of the penam group can safely be treated with a cephem drug and vice versa. If a patient is to be switched to another beta lactam within the same group, the likelihood of serologic cross-reactivity can be minimized by choosing an agent with a distinctly different R1 side group.
Assuntos
Antibacterianos/efeitos adversos , Púrpura Trombocitopênica Idiopática/induzido quimicamente , beta-Lactamas/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/imunologia , Anticorpos/sangue , Anticorpos/imunologia , Reações Cruzadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/imunologia , Adulto Jovem , beta-Lactamas/imunologiaRESUMO
BACKGROUND AND OBJECTIVE: Being labeled as allergic to penicillin (unverified ß-lactam allergy) can result in patients receiving broader-spectrum antibiotics than necessary that may be more toxic, less effective, and/or more expensive than alternative options. Objective: We aimed to evaluate the real costs of evaluating ß-lactam allergy. METHODS: We performed a prospective real-life observational study designed to evaluate all adult patients who consulted for suspected ß-lactam allergy over a 1-year period. Direct and indirect costs were systematically recorded. Direct health costs were calculated based on the number of visits and all additional and diagnostic tests performed, direct nonhealth costs based on the number of visits and the distance from their homes to the Allergy Department, and indirect costs based on absenteeism. RESULTS: A total of 296 patients with suspected allergy to ß-lactams were evaluated in our outpatient clinic from June 1, 2017 to May 31, 2018. Total direct health care costs were 28 176.70, with a mean (SD) cost of 95.19 (37.20). Direct nonhealth costs reached 6551.73, that is, 22.13 (40.44) per patient. Indirect health costs reached 20 769.20, with a mean of 70.17 (127.40). In summary, the total cost was 55 497.63, that is, a cost per patient of 187.49 (148.14). CONCLUSIONS: When all possible costs are taken into account, the evaluation of ß-lactam allergy is not expensive and can reduce future expense arising from unnecessary use of more expensive and less effective antibiotics.
Assuntos
Alérgenos/imunologia , Hipersensibilidade a Drogas/economia , beta-Lactamas/imunologia , Adulto , Idoso , Custos e Análise de Custo , Farmacoeconomia , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Many patients report questionable drug hypersensitivity reactions (DHR) to betalactam antibiotics. A workup is required for objectivation. Direct drug provocation tests (DPTs) omitting a prior allergy workup are increasingly recommended as the primary diagnostic approach. However, apart from the risk of severe side effects, DPTs often are a scarce resource in overloaded healthcare-systems. We investigated how many cases can be solved by drug-specific history, drug-specific IgE, and skin tests obviating the need for DPT. METHODS: We conducted a chart review in a retrospective cohort of 932 patients in an allergy outpatient centre from 2016 to 2017. Patients had been submitted to drug-specific history and specific IgE-, skin prick-, intradermal- and patch-tests with early and late readings with a series of penicillins and cephalosporins but DPTs were no option. RESULTS: Overall, positive in vitro and/or skin tests were found in 96/932 (10.3%) patients. Drug-specific IgE was detected in 40/932 (4.3%) patients, 61/787 (7.8%) patients had positive skin tests. In vitro tests to Pencillin V showed the highest rate of positivity 24/479 (5.0%) and early readings of ampicillin the highest amongst the skin tests (3/49, 6.1%). Immediate skin tests were more often positive than delayed ones (75:45). The combination of all parameters including drug-specific history solved 346/932 (37.1%) cases while 586/932 (62.9%) remained unresolved. Self-reported DHR could be less often confirmed in females and young children (p < 0.05). CONCLUSIONS: Testing with betalactams applying simple, cheap, and safe skin and blood tests can solve a third of DHR-cases on a high throughput scale.
Assuntos
Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , beta-Lactamas/efeitos adversos , Adolescente , Adulto , Antibacterianos/imunologia , Criança , Pré-Escolar , Reações Cruzadas , Hipersensibilidade a Drogas/sangue , Hipersensibilidade a Drogas/imunologia , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Testes Cutâneos , Triptases/sangue , Adulto Jovem , beta-Lactamas/imunologiaRESUMO
ß-lactams (BLCs) are the most widely used antibiotics and consequently the most common cause of drug allergy in the world. The diagnosis of drug allergy is complex and represents a serious challenge that includes a wide variety of methods. In vitro tests are based on the immunological determination of allergen-specific IgE, but the tests in the market lack the required sensitivity and specificity. In addition, the large sample volume, long incubation times, and single-plex configuration have brought their use into question to complement the clinical information. Here, we report a chemiluminescence immunoassay (CLIA) for multiparametric quantification of specific IgE to penicillin G, penicillin V, amoxicillin, and piperacillin, using histone H1 as a carrier. The developed CLIA allowed the determination of BLC-specific IgE below 0.1 IU/mL, thus allowing identification of allergic patients with better sensitivity, using only 25 µL of a sample (serum). The immunoassay was successfully applied in a cohort of 140 human serum samples, showing good sensitivity (64.6%) as well as specificity (100%), which significantly improve the predictive character of existing BLC-allergy in vitro tests.
Assuntos
Especificidade de Anticorpos , Imunoensaio/métodos , Imunoglobulina E/análise , Limite de Detecção , Luminescência , beta-Lactamas/imunologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologiaRESUMO
New antigens deriving from -lloyl and -llanyl, major and minor determinants, respectively, were produced for ß-lactam antibiotics cefuroxime, cefotaxime, ceftriaxone, meropenem and aztreonam. Twenty ß-lactam antigens were produced using human serum albumin and histone H1 as carrier proteins. Antigens were tested by multiplex in vitro immunoassays and evaluated based on the detection of specific IgG and IgE in the serum samples. Both major and minor determinants were appropriate antigens for detecting specific anti-ß-lactam IgG in immunised rabbit sera. In a cohort of 37 allergic patients, we observed that only the minor determinants (-llanyl antigens) were suitable for determining specific anti-ß-lactam IgE antibodies with high sensitivity (< 0.01 IU/mL; 24 ng/L) and specificity (100%). These findings reveal that not only the haptenisation of ß-lactam antibiotics renders improved molecular recognition events when the 4-member ß-lactam ring remains unmodified, but also may contribute to develop promising minor antigens suitable for detecting specific IgE-mediated allergic reactions. This will facilitate the development of sensitive and selective multiplexed in vitro tests for drug-allergy diagnoses to antibiotics cephalosporin, carbapenem and monobactam.
Assuntos
Hipersensibilidade a Drogas/imunologia , beta-Lactamas/imunologia , Antibacterianos/imunologia , Aztreonam/química , Aztreonam/imunologia , Carbapenêmicos/imunologia , Carbapenêmicos/farmacologia , Cefotaxima/química , Cefotaxima/imunologia , Ceftriaxona/química , Ceftriaxona/imunologia , Cefuroxima/química , Cefuroxima/imunologia , Cefalosporinas/imunologia , Cefalosporinas/farmacologia , Reações Cruzadas , Humanos , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Meropeném/química , Meropeném/imunologia , Monobactamas/imunologia , Monobactamas/farmacologia , Penicilinas/imunologia , Testes CutâneosRESUMO
BACKGROUND: Drug allergies are reactions within the context of drug hypersensitivity reactions, which are caused by immunological mechanisms due to a previously sensitising drug. Beta-lactam antibiotics (BLA) are the leading agents causing drug hypersensitivity reactions in children. The aim of this study is to evaluate the diagnostic importance of in vivo and in vitro diagnostic tests in children with suspected immediate-type BLA hypersensitivity and to investigate the frequency of their use for the final diagnosis. METHODS: Patients admitted to the Outpatient Clinic of Division of Paediatric Allergy and Immunology with suspicion of immediate-type BLA hypersensitivity between December 2014 and December 2018 were investigated. Patients with a history of immediate reactions to BLA were examined by performing drug specific IgE, skin prick tests, intradermal tests and drug provocation tests (DPT). RESULTS: During the study period, 148 patients were admitted to our clinic with suspected immediate-type BLA hypersensitivity. Forty-eight patients completed all assessment steps and were enrolled in the study. It has been shown that 27 patients did not have drug allergy. BLA hypersensitivity was proven in 21 patients by using in vivo test algorithm. More than half of the patients were diagnosed via skin tests with culprit drug. CONCLUSION: Allergy work-up should be performed in patients with immediate reactions to BLA. A skin test can demonstrate BLA hypersensitivity in most patients. Thus, skin tests should be performed prior to the drug provocation test.
Assuntos
Alérgenos/administração & dosagem , Antibacterianos/administração & dosagem , Hipersensibilidade a Drogas/diagnóstico , Imunoglobulina E/imunologia , beta-Lactamas/administração & dosagem , Administração Oral , Alérgenos/efeitos adversos , Alérgenos/imunologia , Antibacterianos/efeitos adversos , Antibacterianos/imunologia , Criança , Pré-Escolar , Estudos Transversais , Hipersensibilidade a Drogas/sangue , Hipersensibilidade a Drogas/imunologia , Estudos de Viabilidade , Feminino , Humanos , Imunoglobulina E/sangue , Técnicas In Vitro/normas , Técnicas In Vitro/estatística & dados numéricos , Injeções Intradérmicas , Masculino , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Testes Cutâneos/métodos , Testes Cutâneos/normas , Testes Cutâneos/estatística & dados numéricos , beta-Lactamas/efeitos adversos , beta-Lactamas/imunologiaRESUMO
BACKGROUND: Beta-lactam (BL)-antibiotics are the most frequent reason for drug-induced hypersensitivity reactions. Because they are more efficient, less toxic, and less costly than other antibiotics, confirmation or exclusion of BL allergy is worthwhile. However, allergy tests for drug allergies are often false-negative. OBJECTIVES: To evaluate the components of a stepwise diagnostic algorithm for immediate BL hypersensitivity with regard to sensitivity (SENS). METHODS: Consecutive patients with suspected allergy to BL antibiotics were retrospectively analyzed with regard to increasing sensitivity (plausible history of immediate BL hypersensitivity serving as external criterion) of (i) skin prick test (SPT) by adding a second reading (n = 746), (ii) BL-specific IgE-determination in vitro at two cut-offs (n = 539), and (iii) adding in vivo testing of minor and major BL determinants (n = 288). RESULTS: In the history-based population indicative of immediate BL hypersensitivity (n = 457), SPT with a sole 20-minute reading identified 99 (SENS: 0.21) and SPT with 20- and 40-minute-reading identified 133 cases (SENS: 0.29). in vitro specific IgE-examination identified 31 positives at a cut-off ≥0.35 kUA/L (5.8% of tested) and 99 at cut-off ≥0.11 kUA/L (18.4% of tested). In 203 SPT-negative individuals, immediate BL hypersensitivity was identified by additional tests: in 79 by specific IgE (cut-off ≥0.11 kUA/L) (thereof 53 identified solely by this test) and in 150 by in vivo testing of BL determinants in combination with Penicillin and Ampicillin intradermally (thereof 124 solely by this test); in 26 individuals both additional tests were positive. The combination of the three outpatient-based test modalities-(i) optimized SPT, (ii) specific IgE at optimized cut-off, and (iii) in vivo testing of BL determinants/Penicillin/Ampicillin-identified altogether 336/457 individuals with immediate BL-hypersensitivity (SENS: 0.73), whereas the combination of the two (i) + (ii) identified 212/457 (SENS: 0.46); (i) + (iii) 283/457 (SENS: 0.61). CONCLUSIONS: To overcome the low sensitivity of allergological tests, optimized reading times of the SPT of BL, a lower cut-off for in vitro detection of BL-specific IgE, and intradermal testing of Penicillin, Ampicillin, and BL-determinants contribute to overall sensitivity under real life conditions to diagnose immediate BL-hypersensitivity.
Assuntos
Antibacterianos/imunologia , Dermatite Alérgica de Contato/diagnóstico , Hipersensibilidade a Drogas/diagnóstico , Imunoglobulina E/sangue , beta-Lactamas/imunologia , Adulto , Alérgenos/imunologia , Dermatite Alérgica de Contato/imunologia , Hipersensibilidade a Drogas/imunologia , Feminino , Humanos , Testes Intradérmicos/métodos , Masculino , Pessoa de Meia-Idade , Testes CutâneosRESUMO
Patients identified as allergic to ß-lactams are frequently exposed to treatment with broad-spectrum antibiotics. However, the risk of carriage of extended-spectrum ß-lactamase (ESBL)-producing isolates in this population has been poorly investigated. The aim of this study was to evaluate the characteristics and clinical outcomes of patients admitted to the intensive care unit (ICU) with and without declared ß-lactam allergy at admission. A retrospective monocentric study was performed including adult patients admitted to the ICU between 2007 and 2012. The presence of multidrug-resistant bacteria was documented in rectal and nasal swabs at admission and discharge. Patients labelled allergic to ß-lactams and unlabelled patients were compared. Patients labelled allergic had significantly higher rates of ESBL at admission (13.3% vs. 4.3%; P = 0.0220) and discharge (20.0% vs. 9.0%; P = 0.0460) compared with unlabelled patients, but no significant difference in rates of ESBL acquisition in the ICU was detected. No differences in mortality, duration of hospitalisation or typical risk factors for ESBL acquisition (intubation, central venous catheter and duration of hospitalisation) were reported. No differences in carriage of methicillin-resistant Staphylococcus aureus were detected. This study showed that patients with declared ß-lactam allergy had a higher risk of ESBL carriage at ICU admission and discharge.
Assuntos
Hipersensibilidade a Drogas/imunologia , Farmacorresistência Bacteriana Múltipla/genética , Unidades de Terapia Intensiva/estatística & dados numéricos , beta-Lactamases/genética , beta-Lactamas/imunologia , Idoso , Hipersensibilidade a Drogas/patologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Feminino , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Estudos Retrospectivos , beta-Lactamas/uso terapêuticoRESUMO
BACKGROUND: Extending the drug provocation test (DPT) period is recommended for patients with suspected nonimmediate beta-lactam antibiotic (BLA) allergy and negative DPT. No consensus has been reached regarding the duration of prolonged provocation. OBJECTIVE: We aimed to determine the negative predictive value (NPV) of the 5-day extended DPT. METHODS: Parents of patients with suspected nonimmediate mild cutaneous reactions with BLAs who had been subjected to 5-day DPT with culprit drugs were questioned by telephone interview about reexposure to the tested drug. Patients with reported reaction during reexposure were reevaluated. Skin tests and serum-specific immunoglobulin E (IgE) analysis were not performed before first DPT. RESULTS: A total of 355 patients had negative results in 5-day DPT. The median age at DPT was 4.2 years, and 52.9% were male. The families of 255 patients (72%) could be contacted. Of these 255 patients, 179 (70%) had used the same drug, and reactions were reported for 6 (3.4%) of those patients, who were subsequently reevaluated. Five of the 6 patients had DPT with amoxicillin-clavulanate and 1 with cefixime. When detailed history was taken, 2 of the 5 patients with amoxicillin-clavulanate reaction were found to have used the drug unintentionally after their reaction to reexposure and did not have any symptoms. One of the patients underwent allergy workup and tested negative, and the other 2 refused the test. The patient with reported cefixime reaction underwent repeated allergy workup and tested negative. Therefore, the NPV of 5-day prolonged DPT was 98.9%. CONCLUSION: The 5-day prolonged DPT has high NPV and seems appropriate in duration for children with suspected nonimmediate-BLA allergy.
Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/uso terapêutico , Cefixima/uso terapêutico , Hipersensibilidade a Drogas/diagnóstico , Imunização/métodos , Fatores de Tempo , beta-Lactamas/uso terapêutico , Administração Oral , Alérgenos/imunologia , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Combinação Amoxicilina e Clavulanato de Potássio/imunologia , Antibacterianos/efeitos adversos , Antibacterianos/imunologia , Cefixima/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Hipersensibilidade Tardia , Imunoglobulina E/metabolismo , Lactente , Masculino , Valor Preditivo dos Testes , beta-Lactamas/efeitos adversos , beta-Lactamas/imunologiaAssuntos
Hipersensibilidade a Drogas/genética , Genótipo , Hipersensibilidade Imediata/genética , Fator de Crescimento Transformador beta1/genética , Alérgenos/imunologia , Antibacterianos/imunologia , Interação Gene-Ambiente , Estudos de Associação Genética , Humanos , Interferon gama/genética , Interleucina-4/genética , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-1/genética , beta-Lactamas/imunologiaRESUMO
The Allergic Reactions to Betalactam Antibiotics are adverse events that cannot be explained by their pharmacological action, but mediated by an immunological mechanism. They are the most frequent cause of drug allergy in the world. Betalactam antibiotics include penicillins, cephalosporins, carbapenems, monobactams, cefems (moxalactam, cefoxitin), and clavulanic acid. They can produce immediate, accelerated or delayed allergic reactions. Its diagnostic methodology is complex and it is carried out by well-defined stages. Its timely diagnosis is very important due to the risk involved and the associated costs that demand the alternative use of other antibiotics that supplant them.
Las reacciones alérgicas a antibióticos betalactámicos son eventos adversos no explicables por su acción farmacológica, sino mediados por un mecanismo inmunológico. Son la causa más frecuente de alergia a los fármacos en el mundo. Incluyen penicilinas, cefalosporinas, carbapenems, monobactámicos, cefems (moxalactam, cefoxitina) y ácido clavulánico. Pueden producir reacciones alérgicas inmediatas, aceleradas o tardías. Su metodología diagnóstica es compleja y se realiza por etapas bien definidas. Es muy importante su diagnóstico oportuno, debido al riesgo que implican y a los costos asociados, que demandan el uso alternativo de otros antibióticos que los reemplacen.
Assuntos
Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , beta-Lactamas/efeitos adversos , Antibacterianos/imunologia , Hipersensibilidade a Drogas/imunologia , Hipersensibilidade a Drogas/terapia , Humanos , beta-Lactamas/imunologiaRESUMO
Cephalosporins are commonly used antibiotics both in hospitalized patients and in outpatients. Hypersensitivity reactions to cephalosporins are becoming increasingly common with a wide range of immunopathologic mechanisms. Cephalosporins are one of the leading causes for perioperative anaphylaxis and severe cutaneous adverse reactions. Patients allergic to cephalosporins tend to tolerate cephalosporins with disparate R1 side chains but may react to other beta-lactams with common R1 side chains. Skin testing for cephalosporins has not been well validated but appears to have a good negative predictive value for cephalosporins with disparate R1 side chains. In vitro tests including basophil activation tests have lower sensitivity when compared with skin testing. Rapid drug desensitization procedures are safe and effective and have been used successfully for immediate and some nonimmediate cephalosporin reactions. Many gaps in knowledge still exist regarding cephalosporin hypersensitivity.
Assuntos
Anafilaxia/imunologia , Cefalosporinas/efeitos adversos , Reações Cruzadas/imunologia , Toxidermias/imunologia , Hipersensibilidade a Drogas/imunologia , Anafilaxia/induzido quimicamente , Anafilaxia/epidemiologia , Teste de Degranulação de Basófilos , Cefalosporinas/química , Cefalosporinas/imunologia , Dessensibilização Imunológica , Toxidermias/epidemiologia , Toxidermias/etiologia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/terapia , Humanos , Período Perioperatório , Variantes Farmacogenômicos , Doença do Soro , Testes Cutâneos , beta-Lactamas/efeitos adversos , beta-Lactamas/imunologiaRESUMO
Within the broad category of adverse drug reactions in children, there has been a recent focus specifically on the evaluation of children with antibiotic allergy, in particular, beta-lactam allergy. The potential consequences of being labeled beta-lactam allergy are increasingly recognized. Appropriate evaluation of children with suspected reactions to antibiotics is essential as it is increasingly being recognized that the label of "penicillin allergy" is associated with adverse health and economic outcomes. This review will focus on the 3 main classes of antibiotics reported to cause allergic reactions in children: beta lactams (penicillin derivatives and cephalosporins), macrolides, and sulfonamides. This article is a narrative review of the prevalence, diagnosis, and management of different types of antibiotic allergies in children. Our review reveals that antibiotic allergy is often overreported and not appropriately diagnosed in the pediatric age groups. There is a recent shift in the diagnostic paradigm from the use of skin tests and if negative challenges to the use of challenge only in the pediatric age group. Larger studies to establish the usefulness and safety of this new approach as well as updated guidelines are needed.
Assuntos
Hipersensibilidade a Drogas/imunologia , Macrolídeos/imunologia , Testes Cutâneos/métodos , Sulfonamidas/imunologia , beta-Lactamas/imunologia , Anafilaxia/imunologia , Criança , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Humanos , LactenteRESUMO
Site-specific antibody-drug conjugate (ADC) technologies are highly desirable for the production of therapeutics with well-defined biochemical and pharmacological characteristics. We have developed a strategy to produce site-specific ADCs using a highly reactive lysine residue embedded in a dual-variable-domain (DVD) format. Here we provide protocols for the engineering, expression, and purification of the DVDs used for this strategy. We also provide a protocol for DVD-drug conjugation and describe methods for their biochemical characterization, including a catalytic assay to monitor conjugation efficiency.
Assuntos
Imunoconjugados/genética , Imunoglobulinas/genética , Engenharia de Proteínas/métodos , Trastuzumab/genética , Humanos , Imunoconjugados/imunologia , Imunoglobulinas/imunologia , Lisina/genética , Lisina/imunologia , Domínios Proteicos/imunologia , Trastuzumab/química , beta-Lactamas/química , beta-Lactamas/imunologiaRESUMO
Hypersensitivity reactions to betalactam antibiotics are the most commonly mentioned drug allergies. Up to 10 percent of patients report to suffer from a penicillin allergy. However, classical side effects of antibiotics are often misdiagnosed as an allergy. Many of these patients with suspected betalactam allergy tolerate betalactam antibiotics well. Therefore, a thorough allergy workup is essential to confirm a suspected allergy or to enable again a treatment with betalactam antibiotics. Most important is a good documentation as skin- and in-vitro tests have a reduced sensitivity. Gold standard is the provocation test to help exclude a supposed allergy or to test alternative, potential cross reactive betalactam antibiotics. Cross-reactions between penicillins and cephalosporins, especially cephalosporins of the third and fourth generation are unusual. Cross reactions to carbapenem antibiotics are rare.
Assuntos
Hipersensibilidade a Drogas , Penicilinas/imunologia , beta-Lactamas/efeitos adversos , beta-Lactamas/imunologia , Antibacterianos , Reações Cruzadas , Humanos , Penicilinas/efeitos adversosRESUMO
PURPOSE OF REVIEW: Cutaneous drug hypersensitivity reactions (CDHRs) are a complicated area with multiple clinical manifestations and differential diagnoses, requiring differentiated diagnostic measurements and optimized therapeutic management. RECENT FINDINGS: Disseminated CDHRs to classical drugs can be classified by a simple algorithm, whereas chemotherapeuticals or biopharmaceuticals may show drug-specific and atypical clinical presentations. Controversies in drug hypersensitivity diagnosis exist about the benefit and accuracy of in-vitro tests. Although skin tests are the best means of detecting sensitization to drugs, methods have not been sufficiently standardized. The necessity for skin tests before performing drug provocation test (DPT) and of prolonged DPTs is discussed in selected patients. If a suspicion has been documented, ß-lactam allergy should be excluded. The standard allergy diagnosis is done by an allergist. In case of urgent need because of an infection and low risk according to history, faster delabeling pathways have been developed. There is weak evidence that patients with mastocytosis may have a slightly increased risk of developing immediate-type drug hypersensitivity; however, if considerations are taken, drugs do not have to be withheld for this patient group. There is particular need for improved diagnostic measurements in patients with drug-induced severe cutaneous adverse reactions (SCARs), both identifying the offending drug and detecting individuals at risk. Further challenges encompass appropriate treatments during the acute as well as chronic phase of SCARs. SUMMARY: Recent literature has contributed to our understanding of clinical manifestations and existing controversies and future needs in this area.