Safety of Direct Drug Provocation for the Evaluation of Penicillin Allergy in Low-Risk Adults.

BACKGROUND: About 10% of patients have a penicillin allergy label, but less than 5% of them are actually allergic. Unnecessary penicillin avoidance is associated with serious medical consequences. Given the growing number of these labels, it is imperative that our diagnostic strategy for penicillin allergy be as efficient as possible. The validity of traditionally used skin tests (STs) has been questioned, whereas drug provocation testing (DPT), the criterion standard, without previous ST appears very safe in most cases. OBJECTIVE: To evaluate the safety of direct DPT without consideration for ST results and the validity of ST in the diagnosis of penicillin allergy. METHODS: In this prospective cohort study without a control group, we recruited patients consulting an allergist for penicillin allergy. Patients underwent ST followed by DPT regardless of ST results. Patients with anaphylaxis to penicillin within the past 5 years or a severe delayed reaction were excluded, as were those with significant cardiorespiratory comorbidity. RESULTS: None of the 1002 recruited patients had a serious reaction to DPT. Ten (1.0%) had a mild immediate reaction, of whom only 1 (0.1%) was considered likely IgE-mediated. The positive and negative predictive values of ST for an immediate reaction were 3.6% and 99.1%, respectively. CONCLUSIONS: In a low-risk adult population reporting penicillin allergy, ST has very poor positive predictive value. Direct DPT without ST is safe and appears to be an ideal diagnostic strategy to remove penicillin allergy labels that could be implemented in first-line practice.

Relationship between perioperative anaphylaxis and history of allergies or allergic diseases: A systematic review and meta-analysis with meta-regression.

STUDY OBJECTIVE: We conducted this meta-analysis to summarize the available evidence and evaluate the relationship between a history of allergies/allergic diseases and perioperative anaphylaxis to offer preventive decision support. DESIGN: Systematic review and meta-analysis of observational studies. SETTING: We searched the MEDLINE (OVID), EMBASE, and the Cochrane Central Register of Controlled Trials databases for observational studies. Two investigators independently performed the search, screened the articles, and collected the study details. MEASUREMENTS: Several databases were systematically searched to evaluate the relationship between a history of allergies/allergic diseases and perioperative anaphylaxis using subgroup analysis, sensitivity analysis and meta-regression. MAIN RESULTS: A total of 19 studies involving 672 anaphylaxis episodes, 5608 immune-mediated reactions, and 1126 severe episodes met the eligibility criteria and were included in this meta-analysis. Drug allergies, food allergies, a history of allergies, and atopy increased the incidence of perioperative anaphylaxis (Drug allergies, odds ratio [OR] 3.54, 95% confidence interval [CI] 1.07-11.69; Food allergies, OR 2.29, 95% CI 1.23-4.26; A history of allergies, OR 4.86, 95% CI 3.65-6.49; Atopy, OR 3.58, 95% CI 1.47-8.71), but not the presence of immune-mediated reactions and the severity of perioperative anaphylaxis. CONCLUSIONS: Patients with previous drug allergies, food allergies, a history of allergies, or atopy are more likely to develop anaphylaxis during the perioperative period. Additional studies should be carried out to determine whether a history of allergies/allergic diseases is a major factor for perioperative anaphylaxis when confounders are controlled.

DNA methylation profiling reveals potential biomarkers of ß-lactams induced fatal anaphylactic shock.

Anaphylaxis is a serious reaction of systemic hypersensitivity with that rapid onset and sudden death. Drug hypersensitivity, particularly induced by ß-lactams, is one of the most frequent causes of anaphylaxis in adults. But identification of anaphylactic shock, in forensic sciences recently, is difficult, because it mainly depends on nonspecific characteristic morphological changes, as well as exclusion and circumstantial evidence. Here, we detected DNA methylation signatures of ß-lactams-induced fatal anaphylactic shock with the Illumina Infinium Human Methylation EPIC BeadChip, to screen potential forensic biomarkers and reveal the molecular mechanisms of drug-induced anaphylaxis with fatal shock and sudden death. Our results indicated that DNA methylation was associated with ß-lactams-induced fatal anaphylactic shock, in which the hypomethylation played a vital role. We found that 1459 differentially methylated positions (DMPs) were mainly involved in ß-lactams-induced fatal anaphylactic shock by regulating MAPK and other signaling pathways. 18 DNA methylation signatures that could separate ß-lactams-induced anaphylactic shock from healthy individuals were identified. The altered methylation of DMPs can affect the transcription of corresponding genes and promote ß-lactams-induced fatal anaphylactic shock. The results suggest that DNA methylation can detect forensic identification markers of drug-induced anaphylaxis with fatal shock and sudden death, and it is an effective method for the forensic diagnosis.

Stevens-Johnson syndrome secondary to massive inflammatory hyperplasia of bilateral lingual margins: a case report and literature review.

Stevens-Johnson syndrome (SJS), also known as the multifactorial erythematous drug eruption, is a class of adverse reactions of the skin and mucous membranes primarily caused by drug allergy often involving the oral cavity, eyes, and external genital mucosa, generally accompanied by fever, and can be life-threatening in severe cases. In February 2022, the Department of Stomatology, the First Affiliated Hospital of Zhengzhou University admitted a patient with huge inflammatory hyperplasia of bilateral lingual margins secondary to SJS. Upon admission, no other obvious symptoms were observed except for tongue hyperplasia. The patient suffered from a severe adverse drug reaction caused by acetaminophen 2 months ago and was complicated by liver dysfunction and pulmonary infection. After 1 month of treatment and rehabilitation, he developed a secondary tongue mass and was subsequently admitted to Dept. of Oral and Maxillofacial Surgery Ward 2, the First Affiliated Hospital of Zhengzhou University. After completing the examination, the tongue mass was surgically removed. After a follow-up of 11 months, the patient's condition was satisfactory and no temporary discomfort was observed. The case of tongue mass secondary to SJS is extremely rare. If a stomatologist encounters a similar case, we should carefully inquire about the drug allergy history and recent medication history, and be alert to whether or not they had adverse drug reactions recently.

Ethics of antibiotic allergy.

Antibiotic allergies are commonly reported among patients, but most do not experience reactions on rechallenge with the same agents. These reported allergies complicate management of infections in patients labelled as having penicillin allergy, including serious infections where penicillin-based antibiotics are the first-line (most effective and least toxic) treatment option. Allergy labels are rarely questioned in clinical practice, with many clinicians opting for inferior second-line antibiotics to avoid a perceived risk of allergy. Reported allergies thereby can have significant impacts on patients and public health, and present major ethical challenges. Antibiotic allergy testing has been described as a strategy to circumvent this dilemma, but it carries limitations that often make it less feasible in patients with acute infections or in community settings that lack access to allergy testing. This article provides an empirically informed ethical analysis of key considerations in this clinical dilemma, using Staphylococcus aureus bacteraemia in patients with penicillin allergies as a case study. We argue that prescribing first-line penicillin-based antibiotics to patients with reported allergies may often present a more favourable ratio of benefits to risks, and may therefore be more ethically appropriate than using second-line drugs. We recommend changes to policy-making, clinical research and medical education, in order to promote more ethically acceptable responses to antibiotic allergies than the status quo.

A Failure of Rapid Drug Desensitization.

We present the case of a patient who was unable to tolerate rapid drug desensitization protocol to receive a continuous penicillin (PCN) G infusion for the treatment of neurosyphilis. A 38-year-old male with past medical history for human immunodeficiency virus, migraines, PCN allergy, doxycycline allergy, shellfish allergy, and untreated latent syphilis presented to the emergency room for a posterior migraine with associated nausea, vomiting, photophobia, right-sided paresthesias, and "shaky" vision. He was diagnosed with neurosyphilis and underwent rapid drug desensitization with the goal to receive a continuous infusion of PCN G. The patient's hospital course was complicated by intermittent drug reactions consisting of tachycardia, rash, and dyspnea, followed by periods of being able to tolerate the infusion. After being able to tolerate the recommended dose of PCN infusion, the patient was discharged home to complete the course. However, he returned almost immediately after a recurrence of symptoms at home requiring the use of intramuscular epinephrine. Ultimately, the patient was transitioned to ceftriaxone and completed the infusion course as an inpatient because of continued intermittent recurrence of drug reaction symptoms.

Allergic contact dermatitis to topical medicaments: Revisited.

BACKGROUND: Allergic reaction to topical drugs varies depending on use and availability of topical drugs and self-medication. OBJECTIVE: We aimed to determine the incidence of contact dermatitis to topical medicaments among patients referred for patch testing. METHODS: All patients with suspected allergic contact dermatitis were patch tested with standard and medicament series. The characterization was performed according to the MOAHLFA index. RESULTS: 59/215 (27.4%) patients had positive reactions to at least 1 medicament but only 13/59 (22.0%) had a relevant history. The 3 most common positive medicaments were framycetin 23/215 (10.7%), miconazole 22/215 (10.2%), and econazole 17/215 (7.9%). Among those positive to medicament, face was the most common location 22/59 (37.3%). 39/215 (18.1%) had more than 2 co-positive standard allergens and showed significant higher rate of topical medicament sensitization. The contributing factors of medicament allergy were the history of suspected allergens in personal care products (OR = 2.09, P = 0.038), topical drugs (OR = 2.93, P = 0.002), topical treatment (OR = 2.47, P = 0.011), and history of drug allergy (OR = 1.78, P = 0.023). CONCLUSIONS: The study showed a high rate of medicament sensitization especially antibiotic and antifungal drugs. The incidence of positive medicament patch test result was associated with facial dermatitis. Polysensitization and history of previous exposure, either as treatment or overusing of drugs, significantly associated with medicament positive patients. This study supports the inclusion of medicaments within the standard series of patch test.

Risk factors of anaphylaxis in Korea: Identifying drug-induced anaphylaxis culprits using big data.

Drug-induced anaphylaxis is a fatal medical condition whose incidence has been increasing continuously. Due to differences between genetic backgrounds and health care systems, different populations may be prone to various causative drugs. Using the Health Insurance Service and Assessment Service database, we investigated culprit drugs for drug-induced anaphylaxis and common medication risk factors in the Korean general population. We collected medical prescription histories within 3 days prior to anaphylaxis between January 2011 and December 2019 from the HIRA database. Designed as a case-crossover study, the attributable visits (case visits) were matched to medical visits (control visits) with the drug sets for each visit. We collected a list of medication risk factors for anaphylaxis and calculated the risk ratio of each agent using the chi-square test and conditional logistic regression analysis. A total of 159,473 individuals were listed in the database with a diagnosis of anaphylaxis in the HIRA from 2011 to 2019. After evaluating the suitability of control visits for matching with a case visit, 8168 subjects and 767 drugs were analyzed. The chi-square analysis identified 31 drugs as potential risk factors for drug-induced anaphylaxis in Korea. After applying a conditional logistic regression analysis for each agent, 5 drugs were found to be the common medication risk factors for drug-induced anaphylaxis: cefaclor, iopromide, iohexol, iomeprol, and tolperisone. We found 5 medication risk factors that showed the highest risk of drug-induced anaphylaxis and their degree of risk using an objective methodology in the Korean general population.

Advances in immunoglobulin E mediated antibiotic allergy.

PURPOSE OF REVIEW: The purpose of this review is to identify recent advances in our understanding and management of immunoglobulin E (IgE)-mediated antibiotic allergy. RECENT FINDINGS: Antibiotics remain a leading cause of fatal anaphylaxis reported to the FDA. However, recent advances have defined the features of adult and pediatric patients without true IgE-mediated allergy or any mechanism of anaphylaxis when tested. This has created opportunities to use direct challenges to disprove these allergies at the point-of-care and improves antibiotic stewardship. Additional advances have highlighted cross-reactive structural considerations within classes of drugs, in particular the R1 side-chain of cephalosporins, that appear to drive true immune-mediated cross-reactivity. Further advances in risk-based approaches to skin testing, phenotyping, and re-exposure challenges are needed to standardize antibiotic allergy evaluation. SUMMARY: Recent advances in defining true IgE-mediated drug allergy have helped to identify patients unlikely to be skin-test positive. In turn, this has identified patients who can skip skin testing and proceed to direct ingestion challenge using history risk-based approaches. The ability to identify the small number of patients with true IgE-mediated allergy and study their natural history over time, as well as the vast majority without true allergy will facilitate important and novel mechanistic discoveries.

Incidence of immediate allergic reactions to mRNA COVID-19 vaccines in adults with drug allergies and other allergic disorders.

Concerns have been raised about allergic reactions to messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccines. A history of allergic reactions, including anaphylaxis to drugs, has been frequently reported in individuals with anaphylaxis to mRNA vaccines. To estimate the rate of immediate allergic reactions in patients with a history of drug allergy or other allergic disorders. We included adult patients who had received at least 1 dose of an mRNA COVID-19 vaccine at the Special Hospital for Pulmonary Diseases between March 1, 2021, and October 1, 2021, and who reported a history of drug allergy or other allergic diseases (asthma, allergic rhinitis, atopic dermatitis, food or insect venom allergy, mastocytosis, idiopathic anaphylaxis, acute or chronic urticaria, and/or angioedema). Immediate allergic reactions, including anaphylaxis, occurring within 4 hours of vaccination were recorded. Six immediate allergic reactions were noted in the cohort of 1679 patients (0.36%). One patient experienced anaphylaxis (0.06%), which resolved after epinephrine administration, and the other reactions were mild and easily treatable. Most patients with a history of allergies can safely receive an mRNA COVID-19 vaccine, providing adequate observation periods and preparedness to recognize and treat anaphylaxis.

The Conundrum of Lung Disease and Drug Hypersensitivity-like Reactions in Systemic Juvenile Idiopathic Arthritis.

An unusual form of lung disease has begun to affect some children with systemic juvenile idiopathic arthritis (JIA), coincident with increasing utilization of interleukin-1 (IL-1) and IL-6 antagonists. Many children with systemic JIA-associated lung disease (SJIA-LD) have a history of clinical and laboratory features resembling drug reaction with eosinophilia and systemic symptoms (DRESS), a presentation now convincingly associated with HLA-DRB1*15. Treatment of DRESS typically requires drug discontinuation, a daunting prospect for clinicians and families who rely upon these agents. Here we review SJIA-LD and its associated DRESS-like phenotype. We suggest an alternative explanation, the cytokine plasticity hypothesis, proposing that IL-1 and IL-6 blockers modulate the milieu in which T cells develop, leading to a pathologic immune response triggered through exposure to common microbes, or to other exogenous or endogenous antigens, rather than to the drugs themselves. This hypothesis differs from DRESS in mechanism but also in clinical implications, predicting that control of pathogenic T cells could permit continued use of IL-1 and IL-6 antagonists in some individuals. The spectrum posed by these two hypotheses provides a conceptual framework that will guide investigation into the pathogenesis of SJIA-LD and may open up new therapeutic avenues for patients with systemic JIA.

Documented ß-Lactam Allergy and Risk for Cesarean Surgical Site Infection.

Objective: To examine the relationship between documented ß-lactam allergy and cesarean delivery (CD) surgical site infection (SSI). Study Design. We conducted a retrospective cohort analysis of women who underwent CD at Ben Taub Hospital and Texas Children's Pavilion for Women (Houston, TX) from August 1, 2011, to December 31, 2019. The primary exposure was a documented ß-lactam allergy, and the second exposure of interest was the type of perioperative antibiotic received. The primary outcome was the prevalence of SSI. Maternal characteristics were stratified by the presence or absence of a documented ß-lactam allergy, and significance was evaluated using Pearson's chi-squared test for categorical variables and t-test for continuous variables. A logistic regression model estimated odds of SSI after adjusting for possible confounders. Results: Of the 12,954 women included, 929 (7.2%) had a documented ß-lactam allergy while 12,025 (92.8%) did not. Among the 929 women with a ß-lactam allergy, 495 (53.3%) received non-ß-lactam perioperative prophylaxis. SSI occurred in 38 (4.1%) of women who had a ß-lactam allergy versus 238 (2.0%) who did not (p ≤ 0.001). ß-Lactam allergy was associated with higher odds of SSI compared to no allergy (adjusted odds ratio (aOR) = 1.97; 95%confidence interval (CI) = 1.24-3.14; p = 0.004) after controlling for age, race, ethnicity, insurance status, delivery body mass index (BMI), tobacco use, intra-amniotic infection in labor, duration of membrane rupture, preterm delivery, delivery indication, diabetes, hypertension, group B Streptococcus colonization, and type of perioperative antibiotic received. Conclusion: The presence of a ß-lactam allergy is associated with increased odds of developing a CD SSI after controlling for possible confounders, including the type of perioperative antibiotic received.

Atypical, Levetiracetam-induced Hypersensitivity Syndrome Complicated by Fulminant Liver Failure in a Patient Undergoing Hemodialysis.

A 59-year-old man undergoing hemodialysis was administered levetiracetam, after which he developed a systemic rash, high fever, severe liver dysfunction, and leukocytopenia with reactivation of human herpes virus 6. Atypical drug-induced hypersensitivity (DIHS) was diagnosed, and prednisolone was administered at 60 mg/day. However, liver failure rapidly progressed, and the patient died 12 days following treatment. Despite the rarity of DIHS with concomitant fulminant liver failure from levetiracetam and sufficient clearance thereof by hemodialysis, our case suggests that this syndrome may still ensue, resulting in mortality, even in hemodialysis patients. Although no treatment has yet been established, strict monitoring and aggressive treatment may be required.

The Role of Na+/K+-ATPase in the Development of Hyponatrenemia under Conditions of Hypoxic Stress in Patients with SARS-CoV-2 Infection.

We studied laboratory parameters of patients with COVID-19 against the background of chronic pathologies (cardiovascular pathologies, obesity, type 2 diabetes melitus, and cardiovascular pathologies with allergy to statins). A decrease in pH and a shift in the electrolyte balance of blood plasma were revealed in all studied groups and were most pronounced in patients with cardiovascular pathologies with allergy to statin. It was found that low pH promotes destruction of lipid components of the erythrocyte membranes in patients with chronic pathologies, which was seen from a decrease in Na+/K+-ATPase activity and significant hyponatrenemia. In patients with cardiovascular pathologies and allergy to statins, erythrocyte membranes were most sensitive to a decrease in pH, while erythrocyte membranes of obese patients showed the greatest resistance to low pH and oxidative stress.

The Etiology, Clinical Features, and Severity of Anaphylaxis in Childhood by Age Groups.

INTRODUCTION: Anaphylaxis is a severe, potentially fatal systemic hypersensitivity reaction with an acute onset. Etiology, clinical presentation, risk factors, comorbidities of pediatric anaphylaxis may vary depending on the age of the child. OBJECTIVE: The aim of this study was to investigate the etiology, clinical features, management of anaphylaxis in infants, preschoolers, school-age children, and adolescents. METHODS: The patients presenting with anaphylaxis between January 2015 and December 2018 in a single pediatric tertiary hospital were evaluated retrospectively. Demographic data, the triggers, sign-symptoms, severity, and the management of anaphylaxis were recorded. RESULTS: 239 patients were included in the study, 62.3% of whom were boys. The median age was 6.7 (IQR 2.33-12.83) years. 23.8% of the patients were infants, 15.5% were preschoolers, 33.5% were school-age children, and 27.2% were adolescents. Anaphylaxis mostly occurred at home. The most common causative agents were foods (39.3%), drugs (30.1%), and venoms (15.9%) of all cases. Main food allergens were cow's milk and hen's eggs in infants, cow's milk and tree nuts in preschoolers, and tree nuts and legumes in school-age children. Cases of drug-induced anaphylaxis (DIA) were recorded mostly with antibiotics (40.3%), followed by NSAIDs (23.6%). The primary trigger of anaphylaxis was foods in infants and preschoolers and drugs in school-age children and adolescents. There was no difference between age groups in terms of the system involved and severity. Severe anaphylaxis was more common with DIA. Adrenaline was used in 69.8% of all cases with no significant difference between age groups. CONCLUSION: Etiology and symptoms of anaphylaxis may differ between age groups. Raising awareness, educating patients and their parents on anaphylaxis and its management is essential.

Clinical Characteristics of Atopic Dermatitis in Korean School-Aged Children and Adolescents According to Onset Age and Severity.

BACKGROUND: Atopic dermatitis (AD) is a heterogeneous disease with different age of onset, disease course, clinical symptoms, severity, and risk of comorbidity. The characteristics of children with AD also vary by age or country. However, little is known about the clinical characteristics of AD in Korean school-aged children and adolescents. Furthermore, there are few studies on phenotypic differences according to onset age. This study aimed to explore the clinical characteristics and phenotypes according to onset age and severity of AD in children and adolescents in Korea. METHODS: AD patients aged 6-18 years who presented to 18 hospitals nationwide were surveyed. The patients were examined for disease severity by pediatric allergy specialists, and data on history of other allergic diseases, familial allergy history, onset age, trigger factors, lesion sites, treatment history and quality of life were collected. The results of the patient's allergy test were also analyzed. The patients were classified into infancy-onset (< 2 years of age), preschool-onset (2-5 years of age), and childhood-onset (≥ 6 years of age) groups. Study population was analyzed for clinical features according to onset-age groups and severity groups. RESULTS: A total of 258 patients with a mean age of 10.62 ± 3.18 years were included in the study. Infancy-onset group accounted for about 60% of all patients and presented significantly more other allergic diseases, such as allergic rhinitis and asthma (P = 0.002 and P = 0.001, respectively). Food allergy symptoms and diagnoses were highly relevant to both earlier onset and more severe group. Inhalant allergen sensitization was significantly associated with both infancy-onset group and severe group (P = 0.012 and P = 0.024, respectively). A family history of food allergies was significantly associated with infancy-onset group (P = 0.036). Severe group was significantly associated with a family history of AD, especially a paternal history of AD (P = 0.048 and P = 0.004, respectively). Facial (periorbital, ear, and cheek) lesions, periauricular fissures, hand/foot eczema, and xerosis were associated with infancy-onset group. The earlier the onset of AD, the poorer the quality of life (P = 0.038). Systemic immunosuppressants were used in only 9.6% of the patients in the severe group. CONCLUSION: This study analyzed the clinical features of AD in Korean children and adolescents through a multicenter nationwide study and demonstrated the phenotypic differences according to onset age and severity. Considering the findings that the early-onset group is more severe and accompanied by more systemic allergic diseases, early management should be emphasized in young children and infants.

Risk factors for and prognosis of carboplatin-related hypersensitivity in patients with epithelial ovarian cancer.

PURPOSE: We aimed to identify the predictive risk factors for carboplatin-related hypersensitive reactions (HRs) and investigate their impact on survival outcomes in patients with epithelial ovarian cancer (EOC). METHODS: This retrospective study included 222 patients with EOC who received carboplatin infusion between July 2016 and November 2019. We compared the clinicopathologic characteristics and survival outcomes between carboplatin-related hypersensitivity and non-hypersensitivity groups. Hypersensitivity data were classified using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, categorizing grades from 1 to 5 as mild/moderate/severe/life-threatening/death. Multiple logistic regression analysis was used to analyze risk factors of HRs. The Cox proportional hazard regression model was used to determine the factors of being significantly associated with overall survival. RESULTS: Of the 222 patients, eight exhibited HRs (incidence rate, 3.6%). All HRs were of grade 3 or 4 (life-threatening). In all cases, a desensitization protocol was followed. Advanced stage (III or IV) (P = 0.022), previous history of carboplatin use (P < 0.001), and recurrent ovarian cancer (P = 0.001) were significantly associated with HR to carboplatin. Multivariate logistic analysis showed that a previous history of carboplatin was the only independent risk factor for carboplatin-related hypersensitivity (OR, 20.19; 95% CI 1.22 - 3034.10; P = 0.034). However, HR to carboplatin did not influence the overall survival (P = 0.526). CONCLUSION: In EOC patients, prior use of carboplatin was an independent risk factor for carboplatin-related HRs; HRs to carboplatin did not influence the overall survival. Clinicians should not underestimate the possibility risk of carboplatin HSRs when re-administrating carboplatin in EOC patients.

Impact of Beta-Lactam Allergies on Selection of Antimicrobials in an Inpatient Setting Among Veteran Population.

PURPOSE: Beta-lactam antibiotics are among the most common and widely used antibiotics. However, reported allergy to this class of antibiotics is also common, leading to the use of alternative broad-spectrum antibiotics by healthcare providers. This has led to the emergence of various negative health outcomes. The purpose of the study is to investigate the impact of using alternative antibiotics secondary to a beta-lactam allergy among U.S. veterans who have otherwise multiple comorbidities. METHODS: This retrospective observational analysis was conducted over a 5-year period (January 1, 2011 to December 31, 2016) at the Memphis Veterans Affairs Medical Center (VAMC). Admitted patients with a documented beta-lactam allergy were categorized to preferred or non-preferred status based on initial antibiotic therapy antibiotic, allergy history, published guidelines, and local antibiogram. Preferred therapy was defined as the optimal antibiotic treatment for a given indication based on patient allergy history, published Infectious Disease Society of America guidelines, and local antibiogram of Memphis VAMC. The therapy was classified as "non-preferred" if it did not satisfy the preferred therapy criteria. Non-preferred treatments were further assessed for appropriateness based on indication and patient-specific factors. Chi-square and Fisher's exact tests were conducted to find a difference in rates of negative sequelae among patients receiving preferred vs. non-preferred treatments and appropriate vs. inappropriate treatments. FINDINGS: Of the 1806 admissions identified, data were collected on 95 unique patients with 147 different antibiotic regimens. There were 68 (52%) preferred treatment regimens and 64 (48%) non-preferred treatment regimens. Of the 64 non-preferred treatments, 43 (67%) were inappropriate. There was a statistically significant decrease in the number of adverse drug events and in the combined negative sequelae outcome among patients receiving preferred therapy vs. non-preferred therapy (2 vs. 12; P < .01 and 11 vs. 23; P < .01, respectively). IMPLICATIONS: The receipt of non-preferred antibiotic therapy among veterans with a recorded beta-lactam allergy may be associated with an increased risk of developing negative outcomes. Among military personnel, removing unnecessary beta-lactam allergies would improve readiness with optimal antibiotic choices and avoidance of unnecessary risks, expediting return to full duty.