Immediate allergic reactions to beta-lactams: diagnosis and therapy

Beta-lactams are the antibiotics which most frequently provoke adverse reactions mediated by specific immunological mechanisms. These reactions, classifiable as immediate or non-immediate, can be produced by the four classes of beta-lactams (penicillins, cephalosporins, carbapenems and monobactams) currently available, which share a common beta-lactam ring structure. Immediate reactions occur within the first hour after drug administration and are characterized by urticaria, angioedema, rhinitis, bronchospasm, and anaphylactic shock. Immediate reading skin tests are the quickest and most reliable method for demonstrating the presence of beta-lactam specific IgE antibodies. It is crucial to use in diagnosis the suspected beta-lactams themselves, particularly cephalosporins, in addition to penicillin determinants. Serum specific IgE assays can be used as complementary tests. Negative test results should be interpreted in light of the time elapsed from the last exposure to the responsible beta-lactam. In fact, both in vivo and in vitro test sensitivity is known to decrease over time. In some diagnostic work-ups, patients with a positive history and negative skin and in vitro tests with classic reagents undergo a controlled administration of the suspected beta-lactam. The management of immediate allergic reactions should take into consideration their severity and type. Adrenaline is the drug of choice in the treatment of anaphylactic shock. In addition to adrenaline, corticosteroids and antihistamines should be administered. Histamine H(1) receptor antagonists are the mainstay of the treatment of immediate allergic reactions such as urticaria, rhinitis and conjunctivitis.     

Delayed allergy to aminopenicillins: clinical and immunological findings

Aminopenicillins are the most used beta-lactam antibiotics. Morbilliform or maculopapular rashes are rather frequent during therapy with aminopenicillins. The pathogenesis of these reactions is often due to a cell-mediated allergy. The aim of this work is to characterize patients with cell-mediated allergy to aminopenicillins and to identify alternative beta-lactam drugs that can be safely administered to these patients. We studied 27 subjects affected by cell-mediated allergy to aminopenicillins. The diagnosis was made on the basis of positivity of patch tests with aminopenicillins. These patients then underwent an allergological evaluation (skin and patch tests, oral and/or intramuscular challenge tests) with a wide spectrum of beta-lactam antibiotics. Our work highlights the following main characteristics of cell-mediated allergy to aminopenicillins: time elapsing between drug administration and onset of symptoms of about 2 days; the maculopapular rash and delayed appearance of urticaria/angioedema were the most typical symptoms (82.8 percent of cases); a cross-reactivity with aminocephalosporins is usually absent, or it is limited to cephalexin (in our study, in fact, just 3 out of 20 patients challenged with cephalexin showed a positive oral challenge test); all the beta-lactams, other than aminopenicillins, are well tolerated. Patch tests represent a specific diagnostic tool with a good predictive value of identifying alternative drugs that can be safely administered to patients with beta-lactam allergy. Our patients could tolerate other beta-lactam drugs after a complete allergological evaluation. On the basis of our study, cell-mediated allergy to aminopenicillins should be considered a well-defined nosologic entity.     

Risk assessment of antibiotic residues of beta-lactams and macrolides in food products with regard to their immuno-allergic potential

In human medicine drug allergy is a well-established side-effect of the therapeutic use of antibiotics, especially the beta-lactams. Side-effects caused by macrolides are uncommon and only a very few of these seem to be caused by allergic mechanisms. Clinically, drug allergy is characterized by a spectrum of reactions ranging from mild skin rashes to angio-oedema or life-threatening anaphylaxis. Concern has been expressed that antibiotic residues in meat and other foods might be responsible for similar hypersensitivity reactions in a small number of individuals. This review assesses the potential risk of such reactions in general, but focuses on allergy to penicillin and macrolide residues in particular. In relation to the risk of primary sensitization, it is unlikely that residues could contribute to the overall immune response in view of the very low levels that are likely to be encountered in comparison with the high levels received during therapeutic use. No evidence has been found that any individual has become sensitized by residues of either penicillins or macrolides. Furthermore, the oral route is much less sensitizing than parenteral administration and immunochemical studies with penicillin indicate that hapten-protein complexes formed in vivo are unlikely to be immunogenic because of their low dose, low epitope density and binding to autologous carrier proteins. For performed allergens, the epitope density was also too low to be immunogenic. Because of the ubiquitous nature of penicillin-producing moulds in nature and the extensive use of beta-lactam antibiotics in human medicine, it is unlikely that epidemiological studies could be undertaken that could allow quantification of the minimal risk. The risk of allergic reactions in pre-sensitized individuals can be assessed similarly and again it is concluded that factors such as dose, oral administration and low epitope density make it unlikely that a significantly antigenic derivative could be formed. However, a review of the literature on penicillin hypersensitivity revealed a very small number of previously sensitized individuals from whom there is reasonable clinical and documentary evidence that penicillin residues in milk triggered an allergic reaction, usually a rash. Although these cases are very rare (less than 10 cases reported in the last 25 years), they illustrate the continuing need to control antibiotic residues vigilantly. Animal models have not proved useful for predicting the risk of hypersensitivity reactions to drugs, since allergy in man is determined by genetic and other factors and no validated methods exist to determine a no-effect level.(ABSTRACT TRUNCATED AT 400 WORDS)     

Allergic reactions to beta-lactams

Allergy to beta-lactam antibiotics is the most frequent cause of drug-induced immunological reactions, although the prevalence is not exactly known. IgE- and T-cell-dependent responses are the main mechanisms involved, although other immunological mechanisms can also participate, especially in haematological abnormalities, such as immune haemolytic anaemia or thrombocytopoenia. Aside from their frequency, the clinical entities reported nowadays have changed little since penicillin was first used. The variation in beta-lactams consumption through the year has modified the pattern and specificities of allergic reactions for IgE and T cell responses. Benzylpenicillin is no longer the beta-lactams most frequently prescribed and other chemical structures, with new or modified haptens, have progressively replaced it. This is relevant for the diagnostic evaluation and management of beta-lactam hypersensitivity.     

Allergy to antibacterials: the problem with beta-lactams and sulfonamides

This paper reviews the incidence, clinical manifestations, differential diagnosis, risk factors and pathogenesis of allergic reactions of two important classes of antimicrobials: beta-lactams and sulfonamides. The diagnostic work-up of a patient with a history of an allergic reaction will be discussed as well as the possibility of safe administration of the drug in the face of an allergy using desensitization. Emerging concepts of beta-lactam side-chain allergy, the role of cellular immune mechanisms and the clinical importance of cross-reactivity of allergic reactions to different classes of beta-lactams will be emphasized.     

The prevalence of suspected and challenge-verified penicillin allergy in a university hospital population

Suspected penicillin allergy is common among hospitalised patients, but the quality of the information given by the patient is often doubtful. Alleged penicillin allergic are likely to be treated with more toxic, broad-spectrum, and more expensive antibiotics, with effects on microbial resistance patterns and public economy as a consequence. We performed a cross-sectional case-control study with two visits to all clinical departments of a large university hospital in order to find in-patients with medical files labelled "penicillin allergy" or who reported penicillin allergy upon admission. Patient histories were obtained via a questionnaire, and they were offered investigation for penicillin allergy with specific IgE, basophil histamine release, skin prick tests, intradermal tests and drug challenge tests. Finally, the pharmaco-economical consequences of the penicillin allergy were estimated. In a cohort of 3642 patients, 96 fulfilled the inclusion criteria giving a point-prevalence of alleged penicillin allergy of 5% in a hospital in-patient population. Mean time elapsed since the alleged first reaction to penicillin was 20 years. The skin was the most frequently affected organ (82.2%), maculo-papular exanthema (35.4%) and urticaria (10.4%) being the most frequently reported reactions. 25% did not recall the time of their reaction. 82.2% did not remember the name of the penicillin they reacted to. 34.8% had been treated with penicillins after suspicion of penicillin allergy had been raised. None of these reacted to penicillins. 33.3% of the patients receiving antibiotics during their current hospitalisation were prescribed penicillins. 2% developed non-severe exanthema. The average acquisition costs for antibiotics to penicillin allergic patients were euro 278, compared to euro 119 had they been non-allergic. The prevalence of suspected penicillin allergy was lower than reported elsewhere. A substantial number of patients failed to recall basic information about their alleged allergy. Patients reporting penicillin allergy upon admission and labels stating penicillin allergy on medical files are ignored in almost a third of patients receiving antibiotics. The acquisition costs for antibiotics to penicillin allergic patients were higher, compared to the cost had the patients been non-allergic.     

Hypersensitivity reactions to drugs: evaluation and management

Most hypersensitivity reactions to drugs occur within several weeks of administration; signs and symptoms are often consistent with known immune-mediated reactions, including anaphylaxis, rashes, fever, cytopenias and vasculitis. The culprit immune mechanisms range from immunoglobulin E antibody to T cells inducing apoptosis of keratinocytes, in the case of bullous exfoliative rashes. Many drugs induce reactions via altered hepatic metabolism, with production of reactive intermediates which induce a common syndrome of rash and fever plus variable types of other signs. Examples of this reactive metabolite syndrome include the rash and fever in HIV-positive patients given sulfamethoxazole and reactions to the aromatic anticonvulsants. With the notable exception of anaphylaxis and severe bullous exfoliative rashes, most immune reactions to drugs are not life-threatening and generally resolve once the drug is discontinued. The key is prevention. Specific immune testing is standardized only for penicillin. If test results are negative, however, the patient can tolerate all beta-lactam antibiotics. Of those patients with a positive penicillin skin test, only 2% develop reactions when given cephalosporins. Sulfa and quinolone antibiotics, and muscle relaxants, also frequently induce reactions. If there is a history of bullous rash, the patient should never again receive sulfa or quinolone, or related drugs. In other cases, a cautious graded challenge or desensitization can be done. Vancomycin, protamine, and radiocontrast media induce non-immune reactions secondary to their irritant effects on vascular endothelium. Narcotic pain medications cause histamine release by binding to a specific receptor on mast cells in sensitive patients. In contrast to true immune reactions, most patients can receive these medications again, if they are pretreated and the drugs are given slowly. Angiotensin-converting enzymes, aspirin, and non-steroidal anti-inflammatory drugs induce adverse reactions by their effect on enzymes. Readministration usually results in repeat symptoms. It is possible to desensitize patients to aspirin. Some patients appear to develop similar adverse symptoms with multiple unrelated drugs. Although these cases present management problems, most patients can complete a therapeutic course of a vital drug, after careful review of the history, immune testing when possible, and graded challenge or desensitization.     

Th(1)/Th(2) responses to drugs

T lymphocytes can be characterized by their pattern of cytokine secretion and be divided into type I (Th(l)/Tc(l)) and type 2 (Th(2)/Tc(2)) subsets. The involvement of type-1 or type 2-like responses in sensitization has been studied in the mouse, with reference contact and respiratory contact sensitizers. One interesting feature with certain drugs, such as beta-lactam antibiotics, is the diversity of clinical manifestations associated with immune-mediated hypersensitivity reactions in humans: immediate reactions such as urticaria, Quincke oedema and anaphylactic shock, and delayed hypersensitivity reactions, such as maculopapular rashes, allergic contact dermatitis and skin reactions of other types. In the mouse, Th(1) and Th(2) cytokines have been shown to regulate primary and secondary benzylpenicilloyl- (BPO-) specific antibody responses. Peripheral blood lymphocytes isolated from patients with a clear history of beta-lactam allergy were assessed for type-1 and type-2 phenotypes. Immediate reactions involved mixed Th(1), Tc(1), and Tc(2) responses, whereas allergic contact dermatitis involved Tc(1) and Th(1) cells. Other delayed hypersensitivity reactions to beta-lactams were restricted to Th(1) responses. It has been demonstrated that both CD4(+) and CD8(+)-lidocaine-specific T cell clones isolated from patients with allergic contact dermatitis produced IFN-gamma, even though CD8(+) clones only produce IFN-gamma, while IFN-gamma producing CD4(+) cells concomitantly produced IL-5 and IL-4. Together these data illustrate the heterogeneity of drug-specific T-cell responses.     

依据目前β-内酰胺类抗菌药物交叉过敏反应研究探索相关规范化管理流程

目的：了解国内外关于β-内酰胺类抗菌药物过敏相关的临床研究及处理流程，探索我国对于这一问题的规范化管理流程。方法：对近年来国内外β-内酰胺类抗菌药物过敏相关的作用机制、流行病学数据及处理流程进行汇总分析。结果：β-内酰胺类抗菌药物交叉过敏反应发生率低，经临床相关的过敏风险评估后大部分患者可安全使用侧链结构不同的β-内酰胺类抗菌药物；结合国外相关处理流程建立了对于β-内酰胺类抗菌药物过敏患者可能的规范化管理流程。结论：对某种β-内酰胺类抗菌药物过敏的患者不应该完全排除使用该类抗菌药物的可能性；可通过制定相关管理流程，加强对β-内酰胺类抗菌药物过敏患者的抗菌药物使用管理。     

Recognising antibacterial hypersensitivity in children

Adverse reactions to antibacterial agents are not uncommon in children. They are classified as 'immediate' or 'nonimmediate' according to the time interval between drug administration and onset. Immediate reactions occur within 1 hour and are manifested by urticaria and/or angioedema, bronchospasm and anaphylactic shock; immunological reactions are mediated by IgE antibodies. The main nonimmediate reactions (occuring after more than 1 hour) are maculopapular rash, urticaria and serum sickness; T lymphocytes may participate in maculopapular rash. Clinical assessment of such reactions is complex. The patient's history is fundamental; the allergological examination includes in vivo and in vitro tests selected on the basis of the clinical features and the phase of reaction. In the late phase, prick and intradermal tests are sensitive in evaluating beta-lactam allergy. Together with delayed-reading intradermal testing, patch testing seems to be useful in diagnosing maculopapular reactions to systemically administered aminopenicillins. Determination of specific IgE levels is the most common in vitro method for diagnosing immediate reactions. In the acute phase, serum tryptase and urinary N-methylhistamine assays are reliable in diagnosing type I pathogenic mechanisms in immediate reactions. Unfortunately, there are few in vitro tests for evaluating other reactions, and most are not fully validated. In selected cases, provocation tests should be performed.     

Penicillin Allergy Skin Testing: What Do We Do Now?

Drug-induced anaphylaxis remains a relatively infrequent event. However, penicillin and associated beta-lactam antibiotics remain a primary cause of anaphylaxis. Penicillin allergies are undoubtedly overreported, and patients with suspected penicillin allergy can be treated with antibiotic alternatives. Penicillin allergy skin testing is a simple and effective way to identify true penicillin allergy. Skin testing involves testing for both major and minor determinants and should be conducted in a facility with available life-support equipment. The commercial major determinant product, benzylpenicilloyl-polylysine, was removed from the market in 2004; this action compromised the ability of clinicians to evaluate a patient's likely response to penicillin therapy. Alternatives to skin testing include laboratory synthesis of major determinants, use of the radioallergosorbent test (RAST), or a combination of RAST and minor determinant skin testing. Patients with suspected penicillin allergy can undergo desensitization if they require penicillin therapy. The planned return of a commercial major determinant will hopefully resolve this issue.     

缩宫素致过敏反应文献报道分析

目的：了解缩宫素过敏反应发生情况。方法：对1994-2009年中国期刊全文数据库和中文科技期刊全文数据库报道的缩宫素所致过敏反应病例进行统计、分析。结果：以一般过敏反应最常见,其次是过敏性休克与药物热。临床症状表现多样,易误诊为羊水栓塞。大剂量快速给药可能是引起反应的一个原因。结论：临床医务工作者必须重视缩宫素的过敏反应,在加强患者过敏史询问的同时合理、安全用药。     

Beta-lactams as versatile synthetic intermediates for the preparation of heterocycles of biological interest

Since the advent of penicillin, the beta-lactam antibiotics have been the subject of much discussion and investigation, within both the scientific and public sectors. The primary biological targets of the beta-lactam antibacterial drugs are the penicillin binding proteins, a group of transpeptidases anchored within the bacterial cellular membrane, which mediate the final step of cell wall biosynthesis. The extensive use of common beta-lactam antibiotics such as penicillins and cephalosporins in medicine has resulted in an increasing number of resistant strains of bacteria through mutation and beta-lactamase gene transfer. Thus, a handful of nonconventional fused polycyclic beta-lactams have been described in the literature in order to overcome the defence mechanisms of the bacteria. In fact, tricyclic beta-lactam antibiotics, generally referred to as trinems, are a new class of synthetic antibacterial agents featuring good resistance to beta-lactamases and dehydropeptidases. In addition, recent discoveries have shown other biological properties of these compounds apart from their antibacterial action. In this sense, beta-lactams can serve as inhibitors of serine proteases, such as human leukocyte elastase (HLE) or thrombin, acyl-CoA cholesterol acyltransferase inhibitors and inhibitors of human cytomegalovirus. Additional impetus for research efforts on beta-lactam chemistry has been provided by the introduction of the beta-lactam synthon method, a term coined by Ojima 20 years ago, according to which 2-azetidinones can be employed as useful intermediates in organic synthesis. The usefulness of beta-lactams in the stereocontrolled synthesis of heterocycles of biological significance is based on the impressive variety of transformations, which can be derived from this system, due inter alia to a high chirality content that can be transferred into a variety of products. The cyclic 2-azetidinone skeleton has been extensively used as a template on which to build the heterocyclic structure fused to the four-membered ring, using the chirality and functionalisation of the beta-lactam nucleus as a stereocontrolling element. Alternatively, the direct one-pot generation of fused nitrogen heterocyclic systems from the nitrogen framework of 2-azetidinone derivatives has been achieved by selective bond breakage and rearrangement. It is our aim in this Review to highlight the state of the art in this endeavour, consisting either of the stereocontrolled synthesis of fused polycyclic beta-lactams of antibacterial interest, or stereoselective synthesis of different sized heterocycles of biological significance. Representative examples of the latter include indolizidines, pyrrolizidines, pirrolidines, pyrroles, taxoids and macrolide natural products.     

34例克林霉素注射剂致不良反应的分析及合理应用

目的：研究克林霉素注射剂所致不良反应发生的类型与特点。方法：结合Excel电子表格和手工筛选,建立不良反应报表数据库,对2007年11月12日—2010年2月21日我院上报北京市药品不良反应监测中心的34例克林霉素注射剂不良反应报表进行统计分析,统计内容包括患者的一般情况、不良反应的表现及导致的系统和（或）器官损害、不良反应死亡病例等。结果：我院克林霉素注射剂主要用于18岁以上成人抗感染治疗,不良反应发生多为皮肤及其附件损害,其构成比为79.41%。尚无严重的导致死亡的不良反应发生。但有抗菌药物联合应用发生不良反应的病例,构成比为29.41%。结论：应重视克林霉素导致的不良反应,对于有药物过敏史或过敏体质的患者应严密观察用药过程中的反应,及早发现过敏性休克的发生,并及时采取抢救措施,以防范过敏性休克导致死亡的严重不良反应的发生。合理应用抗菌药物,避免不必要的联合应用。     

β-内酰胺类抗菌药物皮肤过敏试验探讨

目的:为β-内酰胺类抗菌药物使用前是否需作皮肤过敏试验(下简称皮试)提供参考。方法:根据近年国内有关文献报道、药学资料记载及多年的用药经验,从过敏反应发生机制方面对β-内酰胺类抗菌药物是否需作皮试进行分析讨论。结果与结论:β-内酰胺类抗菌药物中的头孢菌素类(下简称头孢类)的β-内酰胺环较青霉素类稳定,所以头孢类过敏反应发生率较低;头孢类各药物间缺乏共同的抗原决定簇,所以头孢类极少发生交叉过敏反应。此外相对于青霉素类,头孢类的皮试符合率太低,因此β-内酰胺类抗菌药物使用前是否作皮试应严格按照规范药品说明书要求执行,青霉素类抗菌药物只需作青霉素皮试,不应盲目扩大β-内酰胺类抗菌药物皮试的品种范围,造成患者不必要的负担。     

Tolerability of aztreonam in patients with IgE-mediated hypersensitivity to beta-lactams

Cross-reactivity between aztreonam and penicillins is poor, but clinical tolerance of aztreonam has been assessed, by means of tolerance challenge tests, only in a few groups of penicillin-allergic patients. The aim of this study is to evaluate the tolerability of aztreonam in a large group of beta-lactam-allergic patients. We studied all patients (greater than 14 years of age), with a clinical history of immediate reactions to any beta-lactam and with positive immediate-type skin tests and/or positive specific IgE to any of the studied beta-lactam; they were studied by means of: skin prick and intradermal tests with penicilloyl polylysine, minor determinant mixture, semisynthetic penicillins, cephalosporins, aztreonam and imipenem; detection of specific IgE to penicillin G, penicillin V, ampicillin, amoxicillin, cefaclor and ceftriaxone. Patients with negative immediate-type skin tests with aztreonam then underwent a graded intramuscular challenge. Forty-five patients (mean age 46.1 +/- 15.2 years), 27 females and 18 males, had positive skin tests and/or specific IgE to at least one of the studied beta-lactams. The most involved drugs were amoxicillin (23 cases), ampicillin (9 cases), penicillin G (8 cases) and other beta-lactams in the remaining cases. The most frequent reactions were anaphylaxis (27 cases) and urticaria (15 cases). All patients had negative intradermal tests with aztreonam and all patients tolerated the intramuscular graded challenge. Our data confirm the lack of cross-reactivity between beta-lactams and aztreonam. Immediate-type skin tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in beta-lactam-allergic patients who urgently need this drug.     

Cutaneous allergic drug reactions: update on pathophysiology,diagnostic procedures and differential diagnosic

Important changes in the understanding and management of drug hypersensitivity reactions during the last years result from the increasing importance of biologics in medical practice, which differ in their spectrum of adverse drug reactions (ADRs) from the classical covalent drugs. With regard to covalent drugs, ampicillin and amoxicillin as well as clavulanic acid play an increasing role among ADRs to betalactam antibiotics. Fluoroquinolones are mainly the cause of anaphylactic and photosensitivity reactions. Especially in allergic reactions to NSAIDs, pseudoallergic reactions should be considered in the differential diagnosis. In opposite to the main cutaneous allergic drug reactions such as urticaria or maculopapular skin rash, in which antibiotics are the main culprits, in severe drug allergic reactions such as SJS (Stevens-Johnson Syndrome), TEN (Toxic Epidermal Necrolysis), or DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) Syndrome, compounds like allopurinol and anticonvulsants are the main causes. Similar mutations in the IL36R gene, which were found in both patients with an AGEP (Acute Generalized Exanthematous Pustulosis) and pustular psoriasis, make the differential diagnosis more difficult and raise the question whether there is a difference between these diseases or whether AGEP is not just a drug induced pustular psoriasis. Finally, some special aspects of side effects of biologics and targeted therapies respectively are discussed.     

平阳霉素治疗血管瘤与脉管畸形临床观察

目的 总结平阳霉素治疗血管瘤及脉管畸形所致不良反应及并发症,探讨其发生的原因及防治措施.方法 用平阳霉素或平阳霉素联合其他药物瘤内注射治疗血管瘤及脉管畸形234例,治疗期间观察并防治不良反应及并发症.结果 234例患者中28例出现不良反应,不良反应率为12.0%,主要为发热、食欲不振、皮疹、局部溃疡、过敏性休克.结论 注射平阳霉素前肌内注射地塞米松或平阳霉素混合地塞米松注射,可预防或减少平阳霉素发热反应,注射前平阳霉素皮肤试验可预防过敏反应发生.

Abstract：

Objective To evaluate the treatment of vascular tumors and vascular malformations with Pingyangmycin, including adverse reactions and complications. Methods Totally 234 cases of vascular tumors and vascular malformations were treated by Pingyangmycin or intratumoral injection in combination with other drugs. Adverse reactions and complications during treatment were observed. Results Two hundred thirty-four patients had adverse reactions( 12.0% ) which included fever, loss of appetite, rash, local ulceration and anaphylactic shock.Conclusion The intramuscular injection of dexamethasone or Pingyangmycin before mixing dexamethasone injection can prevent or reduce fever bleomycin. Meanwhile bleomycin skin test prior to injection can prevent allergic reactions.     

Hypersensitivity reactions to cephalosporins

At present, cephalosporins represent one of the most prescribed classes of antibiotics. Although allergic reactions have been estimated to be infrequent, the number of reactions to cephalosporins is increasing due to their wide use. Cross-reactivity with penicillins has mainly been evaluated in patients with penicillin allergy. It is higher between first- and second-generation cephalosporins with the same or similar side chain than between cephalosporins with different side chains. Unlike penicillins, cephalosporin haptens or determinants have not been defined, and therefore the diagnosis is complicated. Nevertheless, skin tests with cephalosporins are useful in the evaluation of several allergic reactions. Although more studies are necessary, a negative result in skin testing to penicillin and cephalosporins with different side chains seems to be a good predictor of tolerance, and could be used in select cases.