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Background:
"Ampicillin rash," a phenomenon unique to patients with Epstein-Barr virus acute infectious mononucleosis (AIM) treated with ampicillin, was first reported in the 1960s. The incidence was estimated as being between 80% and 100%, and the figures have not been reviewed since those first accounts. We sought to establish the current incide...
Context in source publication
Context 1
... highest incidence of an antibiotic- induced rash was associated with amoxicillin (29.5%, 95% confidence in- terval: 18.52-42.57). All other anti- biotics were associated with a lower rash incidence (Table 1). Comparison of amoxicillin with other included antibiotics revealed that the inci- dence of a rash after treatment with ARTICLE amoxicillin was significantly higher than after treatment with penicillin (8%), with amoxicillin and clavulanate (15%), with cephalosporins (15%), or with macrolides (9%) (P , .001). ...
Citations
... 33 The initial incidence of combined EBV and aminopenicillins induced exanthemas was higher compared to the percentages more recently reported (80% vs 10-30%). [34][35][36] Up to now, a rash occurring during an EBV infection and antibiotic treatment was considered a transient loss of tolerance due to a virusmediated immune alteration (mainly p-i mechanism) and many patients tolerate aminopenicillins upon later re-exposure showing negative skin tests results. 37 Conversely recent studies demonstrated that a true long-lasting antibiotic hypersensitivity (mainly hapten/pro-hapten mechanism) might be a lot more prevalent than previously thought during EBV infection and concomitant amoxicillin therapy. ...
The majority of viral rashes occurring during an antibiotic therapy are considered as a drug hypersensitivity reaction (DHR). Differentiating a viral rash versus a DHR is difficult or even impossible. In delayed DHRs the interplay between viruses and drugs is summarized according to the recent literature. The question is if the same reaction will again occur in case of drug re-exposure in absence of the concomitant viral infection because of persistent immune reactivity. Epstein Barr Virus (EBV) and Human Herpes virus 6 (HHV-6) models are analyzed in case of maculopapular exanthemas (MPEs) and drug reaction with eosinophilia and systemic symptoms (DRESS) over a course of drug therapy. MPEs are the most common skin manifestation during a viral infection and a concomitant drug therapy. In type IVb reactions to drugs a hapten/pro-hapten mechanism and a pharmacological interaction (p-i mechanism) are described as the 2 major ways to make T cells response functional. Rarely the altered repertoire model is involved. The Human Leukocyte Antigen (HLA) predisposition is an additional essential factor that can facilitate DHR. In MPEs rarely a DHR is confirmed by allergy testing. Severity and duration of MPEs, the presence of eosinophilia and systemic symptoms make more reliable the persistent nature of the reaction. Research on this topic is needed in order to provide the clinicians with instruments to decide when to suspect future reactions upon drug re-exposure even in the absence of a viral infection, because those patients should be investigated by a complete drug allergy work up.
... Although IM has some distinctive symptoms (such as exudative pharyngitis, hepatosplenomegaly, and lymphadenopathy), other pathogens, including bacterial infections, are difficult to distinguish from IM. In practice, 53.10-72.69% of patients with IM receive antibiotics for a diagnosed bacterial infection [4,5]. ...
Background:
The incidence of tonsillopharyngitis is especially prevalent in children. Despite the fact that viruses cause the majority of infections, antibiotics are frequently used as a treatment, contrary to international guidelines. This is not only an inappropriate method of treatment for viral infections, but it also significantly contributes to the emergence of antibiotic-resistant strains. In this study, EBV and CMV-related tonsillopharyngitis were distinguished from other pathogens by using machine learning techniques to construct a classification tree based on clinical characteristics.
Materials and methods:
In 2016 and 2017, we assessed information regarding 242 children with tonsillopharyngitis. Patients were categorized according to whether acute cytomegalovirus or Epstein-Barr virus infections were confirmed (n = 91) or not (n = 151). Based on symptoms and blood test parameters, we constructed decision trees to discriminate the two groups. The classification efficiency of the model was characterized by its sensitivity, specificity, positive predictive value, and negative predictive value. Fisher's exact and Welch's tests were used to perform univariable statistical analyses.
Results:
The best decision tree distinguished EBV/CMV infection from non-EBV/CMV group with 83.33% positive predictive value, 88.90% sensitivity and 90.30% specificity. GPT (U/l) was found to be the most discriminatory variable (p < 0.0001). Using the model, unnecessary antibiotic treatment could be reduced by 66.66% (p = 0.0002).
Discussion:
Our classification model can be used as a diagnostic decision support tool to distinguish EBC/CMV infection from non EBV/CMV tonsillopharyngitis, thereby significantly reducing the overuse of antibiotics. It is hoped that the model may become a tool worth considering in routine clinical practice and may be developed to differentiate between viral and bacterial infections.
... Since fever, pharyngitis, fatigue, and lymphadenopathy are common presenting symptoms in the outpatient setting, IM is often mistaken for other entities, such as acute bacterial tonsillitis (3). However, despite the fact that IM is a benign self-limiting disease that does not require antimicrobial therapy, previous studies have demonstrated that 54.30% to 84.00% of IM patients continue taking antibiotics empirically throughout the course of their disease (4)(5)(6)(7)(8)(9)(10)(11)(12). ...
... Both the Nelson Textbook of Pediatrics (14) and Principles and Practice of Infectious Disease (15) stated that the incidence of rash caused by ampicillin or amoxicillin in IM was up to 80%. However, later studies from 2013 to 2018 (9)(10)(11) reported the prevalence of rash in IM patients receiving amoxicillin as only ;12.50% to 29.51%, suggesting that its true incidence may be much lower than that for ampicillin. Moreover, in addition to aminopenicillins, a similar rash was observed in IM patients treated with other antibiotics, including other penicillins (6)(7)(8)16), tetracyclines (4)(5)(6), sulfonamides (8), cephalosporins (11), clindamycin (11), cephalexin (17), macrolides (18), levofloxacin (19), and piperacillin-tazobactam (20). ...
... A review (24) of 17 case reports suggested the necessity of reassessing the longheld belief that antibiotic-induced skin rash occurs with high incidence in IM patients. Recently, three cohort studies (9)(10)(11) demonstrated that no significant difference in the incidence of antibiotic-related rash was found between antibiotic-treated and -untreated IM patients, which calls into question the higher rate of rash in IM patients receiving antibiotics. Moreover, a systematic review (25) including 10 cohort studies and 1,325 IM patients also concluded that the administration of amoxicillin in IM patients might not increase the risk of rash (risk ratio [RR], 0.85; 95% confidence interval [CI], ;0.53 to 1.33; P = 0.45) and the incidence of rash in IM patients with aminopenicillin treatment might not be higher than that with other antibiotic treatments. ...
Present evidence suggests that the administration of antibiotics, particularly aminopenicillins, may increase the risk of rash in children with infectious mononucleosis (IM). This retrospective, multicenter cohort study of children with IM was conducted to explore the association between antibiotic exposure in IM children and the risk of rash. A robust error generalized linear regression was performed to address the potential cluster effect, as well as confounding factors such as age and sex. A total of 767 children (aged from 0 to 18 years) with IM from 14 hospitals in Guizhou Province were included in the final analysis. The regression analysis implied that exposure to antibiotics was associated with a significantly increased incidence of overall rash in IM children (adjusted odds ratio [AOR], 1.47; 95% confidence interval [CI], ~1.04 to 2.08; P = 0.029). Of 92 overall rash cases, 43 were probably related to antibiotic exposure: two cases (4.08%) in the amoxicillin-treated group and 41 (8.15%) in the group treated with other antibiotics. Regression analysis indicated that the risk of rash induced by amoxicillin in IM children was similar to that induced by other penicillins (AOR, 1.12; 95% CI, ~0.13 to 9.67), cephalosporins (AOR, 2.45; 95% CI, ~0.43 to 14.02), or macrolides (AOR, 0.91; 95% CI, ~0.15 to 5.43). Antibiotic exposure may be associated with an increased risk of overall rash in IM children, but amoxicillin was not found to be associated with any increased risk of rash during IM compared to other antibiotics. We suggest that clinicians be vigilant against the occurrence of rash in IM children receiving antibiotic therapy, rather than indiscriminately avoiding prescribing amoxicillin.
... This rash has been mostly reported after the use of penicillin class drugs, but has also been described with tetracyclines, cephalosporins, and macrolides. [31][32][33] Abdominal Findings ...
... 34 The reliability of physical examination in detecting splenomegaly has demonstrated wide variability. 31 An early study evaluated the clinical utility of physical examination and found that if palpation and percussion tests were positive, the sensitivity was 46%, although the specificity was 97%. 35 The ability to teach clinical techniques to examine the spleen has not been assessed, and the reliability in patients with well-developed abdominal musculature or who have a large body size is inconsistent. ...
Infectious mononucleosis (IM) is a common illness in children and young adults caused primarily by the Epstein-Barr Virus (EBV). Transmission occurs primarily through sharing oral secretions, thus IM is known as the "kissing disease." Common clinical manifestations include fever, pharyngitis, posterior cervical lymphadenopathy, and splenomegaly. Atypical lymphocytosis and transaminase elevations are common, and the diagnosis of IM is confirmed with laboratory findings of a positive heterophile antibody ("Monospot"), polymerase chain reaction, or antibodies specific to EBV. Individuals with acute IM may be quite symptomatic and not feel well enough to participate in sports. Splenic enlargement is common, with rupture a relatively rare occurrence, typically occurring within a month of symptom onset, but this risk complicates sports participation, and is often the reason for restricting activity. The management of IM is primarily supportive, with no role for antivirals or corticosteroids. The variability of clinical presentation and the risk of splenic rupture in patients with IM present clinicians with challenging return to play/return to sport (RTS) decisions. This position statement updates the Evidence-Based Subject Review on Mononucleosis by the American Medical Society for Sports Medicine published in 2008 and reviews the epidemiology, clinical manifestations, laboratory assessment, and management including RTS for the athlete with IM. This statement also addresses complications, imaging, special considerations, diversity and equity considerations, and areas for future clinical research. Understanding the evidence regarding IM and sport is essential when communicating with athletes and their families and incorporating shared decision-making in the RTS decision.
... A legoptimálisabb a tesztelés a tünetek regressziója után 4 hét-6 hónap múlva; az évekkel korábbi hiperszen-pustulosus tünet, melyeket a maculopapulosus exanthema (MPE), az akut generalizált exantematosus pustulosis (AGEP), a Stevens-Johnson szindróma (SJS) és a toxikus epidermális nekrolízis (TEN) során látunk (2,3). A korai reakciók hátterében a valódi allergiás, IgE mediálta reakciók mellett direkt basofil/mastocita aktivációt okozó egyéb mechanizmusok állhatnak. ...
... SJS, TEN esetében 4-28 napos gyógyszerszedés után várhatóak a bőr-és nyálkahártya tünetek. DRESS-szindróma (gyógyszer reakció eosinofíliával és szisztémás szimptómákkal) elhúzódóbb, 2-8 hetes gyógyszerszedés esetén alakulhat ki (2,3). ...
The authors present protocols of the options, available panels in drug allergy testing applied at the Department of Dermatology and Allergy, University of Szeged. In suspicion of drug induced hypersensitivity reaction we recommend performing lymphocyte transformation test (LTT), prick testing, intradermal testing and patch testing according to the assumed immune -mechanism. If these examinations are negative, the next step is the drug provocation test, which is the gold standard in the diagnosis of drug allergy. We summarize methods, indications, and the evaluation of each tests. There are increasing patients presenting hypersensitivity reactions who require proper identification of the culprit drug.
... 13 Por ejemplo, el exantema maculopapular suele asociarse con infección viral subyacente por virus de Epstein Barr, sobre todo en niños, y se diagnostica erróneamente como alergia a la penicilina. 14 ...
Background:
Any substance used as a treatment for any disease can produce harmful or unpleasant events called adverse drug reactions (ADRs). They are due to inherent biological effects of the drug and are caused by immunological and non-immunological mechanisms.
Objectives:
To describe the immunological mechanisms of hypersensitivity reactions (HSR) to drugs, their epidemiology, risk factors, classification, clinical manifestations, diagnosis, treatment, and prognosis.
Methods:
A review of the most current literature in English and Spanish was carried out, in the main databases, related to the HSR of various drug groups.
Results:
This study describes the terms used to define ADRs and HSRs, their classification and clinical manifestations, current diagnostic tools, treatment algorithms and prognosis of the most frequently used medications and with the highest prevalence of reported adverse events.
Conclusion:
ADRs are a challenging entity, with a complex pathophysiology that has not been fully understood. Its approach requires a careful consideration since not all drugs have validated tests for their diagnosis nor a specific treatment. When indicating the use of any drug, the severity of the disease, the availability of other treatments and the potential risks of developing future adverse events should always be taken into consideration.
... However, retrospectively, it has been pointed out that insufficient methodology and sample size limitations may have hampered data reliability [1]. More recent studies have stated that the incidence may be much lower than previously reported [3][4][5]. ...
A link between amoxicillin-induced rash in infectious mononucleosis and allergy has been previously reported. However, the pathophysiological cause and aspects are unclear. Additionally, the complex immunological interaction between the host and Epstein-Barr virus needs to be studied.
This article reports a case of amoxicillin-induced rash in infectious mononucleosis resulting in an exuberant rash, facial edema, and marked eosinophilia, which prompted additional workup. Both the eosinophilia and the rash brought to light a possible association with a persistent delayed-type hypersensitivity. Further scientific discussion and investigation can identify predictive indicators that can portend clinical outcome.
... Such connections between viral infections and drug hypersensitivity (DH) were particularly apparent in young children experiencing their first encounter with various respiratory viruses and in adult patients with Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) infections. [1][2][3][4][5] While the clinical manifestation of the interplay between viral infections and DH has been widely acknowledged for many years, an explanation for this increased incidence is missing. Indeed, the topic is complex due to virus diversity, the number of causative drugs, and the varied clinical manifestations involved. ...
... 37 However, current data report a much lower incidence of aminopenicillin-induced exanthema (10-30%). 3,13 Moreover, many patients tolerate aminopenicillins upon later re-exposure, and skin tests show negative results. ...
... , GranzymeB, perforin, granulysin, others), in severe cases cytokine storm3 Enhanced expression of HLA and/or adhesion molecules on tissue cells like keratinocytes etc.; higher number of TCR/cell during virus activation 4 DHR appear as a result of a. hapten (e.g., β-lactams) binding and presentation by already activated APC, thus providing 1st and 2nd signal for drug specific T-cell activation; or b.enhanced p-i binding (TCR-drug-HLA), which per se can be sufficient for T-cell stimulation/cytotoxicity: The activated T cells secrete cytokines like IL-5 and kill tissue cells, leading to variable clinical pictures. Clinical examples of viral infection preceding DHR 1 Acute primary viral infections in childhood with mostly mild and transient exanthema 2 Herpes virus (mostly EBV) infection and high incidence of exanthemas during aminopenicillin others 42,43 and ourselves, most of these DHRs were observed during the first wave of infections in 2020 and mostly in patients with a severe disease course. ...
Virus infections and T‐cell‐mediated drug hypersensitivity reactions (DHR) can influence each other. In most instances, systemic virus infections appear first. They may prime the reactivity to drugs in two ways: First, by virus‐induced second signals: certain drugs like β‐lactam antibiotics are haptens and covalently bind to various soluble and tissue proteins, thereby forming novel antigens. Under homeostatic conditions, these neo‐antigens do not induce an immune reaction, probably because co‐stimulation is missing. During a virus infection, the hapten‐modified peptides are presented in an immune‐stimulatory environment with co‐stimulation. A drug‐specific immune reaction may develop and manifest as exanthema. Second, by increased pharmacological interactions with immune receptors (p‐i): drugs tend to bind to proteins and may even bind to immune receptors. Without viral infections, this low affine binding may be insufficient to elicit T‐cell activation. During a viral infection, immune receptors are more abundantly expressed and allow more interactions to occur. This increases the overall avidity of p‐i reactions and may even be sufficient for T‐cell activation and symptoms. There is a situation where the virus‐DHR sequence of events is inversed: in drug reaction with eosinophilia and systemic symptoms (DRESS), a severe DHR can precede reactivation and viremia of various herpes viruses. One could explain this phenomenon by the massive p‐i mediated immune stimulation during acute DRESS, which coincidentally activates many herpes virus‐specific T cells. Through p‐i stimulation, they develop a cytotoxic activity by killing herpes peptide‐expressing cells and releasing herpes viruses. These concepts could explain the often transient nature of DHR occurring during viral infections and the often asymptomatic herpes‐virus viraemia after DRESS.
... It is not well explained yet, whether a true allergic drug reaction or virus-dependent rash. The rash may be due to the viral infection itself, the incidence of skin eruption development in acute IM is 4.2-13% without drug intake, but often these patients are put on antibiotics, frequently amoxicillin, and the rash appears a few days after the initiation of the antibiotic therapy [59,60]. Following amoxicillin intake within acute IM the incidence of skin reactions ranges between 27.8% and 69% in adults while in children, morbilliform skin eruptions nearly always develop following amoxicillin intake within acute IM [60,61]. ...
Background :
Antimicrobial resistance (AMR) is currently one of the global public health threats. Increased antibiotic consumption in humans, animals, and agriculture has contributed directly to the spread of AMR.Upperrespiratory tract infections (URIs) are one of the most common conditions treated by antibiotics, even if unnecessary as in cases of viral infections and self-limited conditions which represent the most cases of URIs. Investigating physicians’ knowledge, attitudes, and practice regarding antibiotic prescriptions in children with acute URIs mayreflect the problem of antibiotic over prescription. This study aims to assess the problem in our community and provide information for further planning of appropriate interventions to optimize antibiotic prescriptions.
Methods:
This is a cross-sectional study for all non-specialized physicians dealing with acute upper respiratory tract infections (URIs) in pediatrics sittings in Assiut district, Egypt. We used a self-administered questionnaire to assess physicians’ knowledge, attitudes, and practice. In addition, four clinical vignettes addressing different URI scenarios were included in the questionnaire to assess the patterns of antibiotic prescriptions in common cases.
Results:
Ourstudy included 153 physicians whose mean agewas 32.2 ±8.7,most ofwhom were pediatric residents in different health institutes in Assiut district. They had good knowledge as out of the 17knowledge questions,the mean number of correct answers was 12.4 ± 2.9. Regarding their attitudes, mean attitude scores for inappropriate antibiotic prescribing were low. However, of those scores, the responsibility of others had the highest score (3.8 ± 0.61). Prescribing practice in special conditions of URIs showed that 80% of participants prescribed antibiotics if fever continued for more than five days and 61.4% if the child had a yellowish or greenish nasal discharge. Among 612 clinical vignettes, 326 contained antibiotic prescriptions (53.3%), and appropriate antibiotic prescriptions represented only 8.3% overall.
Conclusions:
Physicians dealing with acute URIs in outpatients’ clinics in the Assiut district have good knowledge about antibiotic use and resistance and demonstrate a good attitude toward appropriate antibiotic use. Although the percentage of inappropriate prescriptions in clinical vignettes in high, more research is required to investigate the factors of antibiotic inappropriate prescribing practice and non-adherence to guidelines. Also, it is essential to set up a national antibiotic stewardship program to improve antibiotic prescribing and contain antimicrobial resistance problems.
... Náuseas, vómitos y anorexia son también frecuentes, probablemente en relación con una hepatitis leve que se produce en el 90% de los pacientes. Ocasionalmente los pacientes presentan un rash cutáneo asociado al uso de betalactámicos (principalmente amoxicilina y ampicilina), cuando se describió se pensaba que ocurría entre un 70% y un 90% de los pacientes tratados con esta medicación, estudios recientes confirman que esta frecuencia es bastante menor, y que se produce tanto asociado al tratamiento con amoxicilina (32,9%) como en pacientes en los que no se ha usado ningún tipo de antibiótico (23,1%) 6 . ...
Infectious mononucleosis (MI) is a generally benign and self-limited condition in childhood and adolescence due to the primary EBV infection characterized by the triad of pharyngitis, fever, and lymphadenopathies. The risk of complications increases with age and immunosuppression. The most frequent fatal complications are those associated with splenic rupture, neurological alterations, and airway obstruction due to increased tonsillar size. Cervical abscesses associated with MI are rare, being mostly peritonsillar and intra-tonsil. We present two surgical cases of big deep cervical abscesses with retropharyngeal and parapharyngeal involvement in healthy very young adolescents (14 and 15 years old), without any type of immunosuppression or risk factors, one of them associated with a clinically relevant spontaneous tonsillar bleeding, which had not been described in the literature associated with MI in such young patient.
