Randomized Multicenter Trial for the Validation of an Easy-to-Administer Algorithm to Define Penicillin Allergy Status in Sexually Transmitted Infection Clinic Outpatients.

BACKGROUND: Approximately 15% of patients in sexually transmitted infection (STI) clinics report penicillin allergies, complicating treatment for syphilis and gonorrhea. Nonetheless, >90% do not have a penicillin allergy when evaluated. We developed and validated an algorithm to define which patients reporting penicillin allergy can be safely treated at STI clinics with these drugs. METHODS: Randomized controlled trial to assess feasibility and safety of penicillin allergy evaluations in STI clinics. Participants with reported penicillin allergy answered an expert-developed questionnaire to stratify risk. Low-risk participants underwent penicillin skin testing (PST) followed by amoxicillin 250 mg challenge or a graded oral challenge (GOC)-amoxicillin 25 mg followed by 250 mg. Reactions were recorded, and participant/provider surveys were conducted. RESULTS: Of 284 participants, 72 (25.3%) were deemed high risk and were excluded. Of 206 low-risk participants, 102 (49.5%) underwent PST without reactions and 3 (3%) had mild reactions during the oral challenge. Of 104 (50.5%) participants in the GOC, 95 (91.3%) completed challenges without reaction, 4 (4.2%) had mild symptoms after 25 mg, and 4 (4.2%) after 250-mg doses. Overall, 195 participants (94.7%) successfully completed the study and 11 (5.3%) experienced mild symptoms. Of 14 providers, 12 (85.7%) completed surveys and 11 (93%) agreed on the safety/effectiveness of penicillin allergy assessment in STI clinics. CONCLUSIONS: An easy-to-administer risk-assessment questionnaire can safely identify patients for penicillin allergy evaluation in STI clinics by PST or GOC, with GOC showing operational feasibility. Using this approach, 67% of participants with reported penicillin allergy could safely receive first-line treatments for gonorrhea or syphilis. Clinical Trials Registration. Clinicaltrials.gov (NCT04620746).

Clinical Relevance of Specific IgE in Penicillin Allergy Investigation.

INTRODUCTION: Patients with immediate type allergic reactions to penicillins are at risk of anaphylaxis on reexposure. Diagnostic gold standard is drug provocation test (DPT) if allergy is not diagnosed by other means, such as skin testing or in vitro testing with measurement of specific IgE. Specific IgE testing carries low risk for the patient and blood sampling can be performed in primary care, but it is reported to have low sensitivity. The aim of this study was to evaluate if clinical characteristics of patients with suspected allergic reactions to penicillin and elevated specific IgE to penicillins, differed from patients without specific IgE, to identify predictors for elevated specific IgE to penicillins. METHODS: Levels of specific IgE to five penicillins (penicillin G, penicillin V, amoxicillin, ampicillin, and penicillin minor determinants) were available for 9,100 patients. Using multiple logistic regression, clinical data from 430 patients in this group who had elevated specific IgE to one or more penicillins were compared to data from 4,094 patients without specific IgE to penicillins, who had undergone DPT with a penicillin. RESULTS: In total 5.2% of patients had elevated specific IgE to one or more penicillins. Significantly more patients with elevated specific IgE had a history of immediate type reactions (<2 h) (OR = 4.34, p < 0.001); circulatory symptoms (OR = 1.63, p = 0.03) or angioedema (OR = 1.46, p = 0.005). Also, significantly more patients with elevated specific IgE had been treated with adrenaline (OR = 2.21, p = 0.005), steroids (OR = 1.76, p < 0.001), or antihistamines (OR = 1.83, p < 0.001). CONCLUSION: A history of an immediate type reaction requiring treatment, combined with elevated specific IgE to one or more penicillins is suggestive of an IgE mediated penicillin allergy and further allergy investigations may not be needed. Specific IgE to penicillins may be used early in allergy investigation of patients with severe immediate type reactions to penicillins.

Diagnosis and Clinical Management of Drug Allergies in Obstetrics and Gynecology: An Expert Review.

Drug allergies, specifically antibiotic allergies, are frequently encountered in obstetrics and gynecology as10% of the United States population reports a penicillin allergy. This poses a particular challenge to the obstetrician-gynecologist as beta-lactam antibiotics are indicated as first-line therapy for the treatment and prevention of most specialty-specific infections. Alternative antibiotic use in the setting of a reported allergy, is not benign and has been associated with increased cesarean delivery, endometritis, wound complications, and increased lengths of hospital stay in pregnant patients, increased Group B Streptococcus sepsis, neonatal length of stay and neonatal lab draws in neonates born to allergic patients and increased surgical site infections in gynecologic patients. Furthermore, alternative antibiotic use leads to increased antibiotic resistance, toxicity and healthcare cost. . Administration of antibiotics in a patient with a history of a Type I immediate hypersensitivity reaction, however, poses the risk of anaphylaxis with repeat exposure. Fortunately, over 90% of patients who report a penicillin allergy are not truly allergic and would tolerate penicillins if administered. This can be due to either mislabeling of the index reaction as an allergy (when it was due to a drug intolerance or a viral exanthem) or due to waning Immunoglobulin E-mediated immunity over time. Given this, allergy evaluation is widely recommended, even in pregnancy. Allergy evaluation involves a detailed patient history and when appropriate allergy testing with skin testing and/or oral challenge. These tools when used appropriately have been found to be safe and effective in gravid as well as non-gravid individuals and result in increased use of first line antibiotics. Furthermore, even in the setting of a true penicillin allergy, cross-reactivity with cephalosporins is extremely low and estimated at 2-3% among patients with a verified penicillin allergy and significantly lower than this among patients with an unverified penicillin allergy. Guidelines support routine use of cephalosporins without testing or additional precautions in patients with an unverified nonanaphylactic penicillin allergy as well as routine use of structurally dissimilar cephalosporins (specifically ancef) even in patients with an anaphylactic penicillin allergy. In cases where there is no appropriate alternative antibiotic than to the one which the patient is allergic such as with syphilis in a penicillin allergic pregnant patient, desensitization can be performed. This process involves temporary induction of drug tolerance through exposure of small amounts of the allergen until a therapeutic dose is achieved and has been safely performed in pregnancy. Desensitization requires expert supervision and is most often performed in the intensive care setting with a multidisciplinary team. The other two most common antibiotic allergies encountered in obstetrics and gynecology are to cephalosporins and metronidazole. Cephalosporin allergies are managed similarly to penicillin allergies with readily available skin testing and oral challenge. Skin testing for metronidazole allergy lacks sensitivity and specificity and thus oral challenge or desensitization procedure is the preferred approach for low risk and high-risk patients respectively. When it comes to drug allergies, and specifically antibiotic allergies, the role of the obstetrician-gynecologist is to identify patients with a reported allergy and to refer patients to a specialist for further evaluation as soon as possible. Allergy evaluation by means of a detailed patient history and allergy testing (skin testing and/or oral challenge) when indicated has been shown to be safe and effective and is an important part of antibiotic stewardship.

Promoting penicillin allergy de-labeling for children attending a hematology clinic.

BACKGROUND: Up to 10% of children are reported to be allergic to penicillin, but many allergy labels are unverified and may require formal testing. Inaccurate drug allergy labels are associated with a range of adverse clinical outcomes. Patients with hematological disorders may experience frequent and severe infections; those who have been incorrectly labeled penicillin allergic may benefit from allergy de-labeling (ADL) efforts to facilitate access to beta-lactam antibiotics. We developed a multidisciplinary, pharmacist-driven process that enabled non-allergist trained providers to assess and de-label penicillin allergies in a pediatric hematology center. METHODS: Volunteers, including physicians, advanced practice providers, nurses, and pharmacists, were trained in skin testing and oral challenge procedures. Patients were identified by review of electronic medical records for penicillin or penicillin-derivative allergy. Patient and family interviews were conducted in cases where a true penicillin allergy was deemed uncertain based on chart review. If allergy could not be de-labeled by chart review or interview alone, patients were offered skin and/or oral challenge testing. RESULTS: Fifty-nine patients were initially labeled as penicillin allergic. Allergy labels of 11 (19%) were removed by chart review only, and 15 (25%) after conducting interviews. A total of two (3%) patients were ineligible due to contraindications, and five (9%) declined participation. Twenty-six patients (44%) underwent allergy testing (50% skin testing, 50% oral challenge) of which 23 (88%) were negative. CONCLUSIONS: ADL was possible in most patients previously identified as penicillin allergic. Testing was well tolerated with no serious adverse effects.

A call to address penicillin allergy labels in patients with hematopoietic stem cell transplants: How to avoid rash decisions.

Among patients with hematopoietic stem cell transplants, infections, particularly multidrug-resistant infections, pose a grave threat. In this setting, penicillin allergy labels are both common and harmful. Though the majority of patients who report penicillin allergy can actually tolerate penicillin, penicillin allergy labels are associated with use of alternative antibiotics, which are often more broad spectrum, less effective, and more toxic. In turn, they are associated with more severe infections, multidrug-resistant infections, Clostridium difficile, and increased mortality. Evaluating penicillin allergy labels can immediately expand access to preferred therapeutic options, which are critical to care in patients with recent hematopoietic stem cell transplants. Point-of-care assessment and clinical decision tools now exist to aid the nonallergist in assessment of penicillin allergy. This can aid in expanding use of other beta-lactam antibiotics and assist in risk-stratifying patients to determine a testing strategy. In patients with low-risk reaction histories, direct oral challenges can be employed to efficiently delabel patients across clinical care settings. We advocate for multidisciplinary efforts to evaluate patients with penicillin allergy labels prior to transplantation.

Antepartum vs postpartum amoxicillin oral challenge in pregnant patients with a reported penicillin allergy: A two-center prospective cohort study.

INTRODUCTION: While 10% of pregnant individuals report a penicillin allergy, there is no established best practice for penicillin allergy delabeling in pregnancy. To better understand options for penicillin delabeling, we aimed to evaluate two penicillin allergy delabeling protocols in pregnancy regarding efficacy, adverse events, and patient satisfaction. MATERIAL AND METHODS: From July 2019 to December 2022, we completed a two-center prospective cohort study, where each site recruited pregnant patients over 24 weeks gestational age with a reported penicillin allergy. One center offered antepartum amoxicillin oral challenges, either directly or after negative skin testing (i.e., antepartum oral challenge site). Our other centers completed a two-step approach with antepartum penicillin skin testing only and deferred oral challenges to the postpartum period (i.e., postpartum oral challenge site). Our primary outcome was the rate of penicillin allergy delabeling, defined as tolerating an antibiotic challenge with penicillin or amoxicillin. Univariate analyses were completed using chi-squared, Fisher's exact, and Wilcoxon rank tests. RESULTS: During the study period, 276 pregnant patients were assessed, with 207 in the antepartum oral challenge site and 69 in the postpartum oral challenge site. Among the 204 patients who completed antepartum oral challenges, 201 (98%) passed without reactions. Deferring oral challenges to the postpartum period led to a loss of follow-up for 37/53 (70%) of eligible individuals. Overall, 97% (201/207) of patients at the antepartum oral challenge site were delabeled from their penicillin allergy-compared to 38% (26/69) of patients referred to the postpartum oral challenge site (p < 0.0001). Three antepartum oral challenge reactions were noted, including two mild cutaneous reactions and a case of transient abdominal discomfort. CONCLUSIONS: Antepartum amoxicillin oral challenge is a more effective method to delabel pregnant patients from their penicillin allergy. Deferral of oral challenges to the postpartum period introduces a significant barrier for penicillin allergy delabeling.

Polymorphisms of HLA genes and hypersensitivity to penicillin among patients in a Taiwanese population.

Penicillin allergy is a potentially life-threatening condition that is common among patients. However, the genetic associations with penicillin allergy are not yet recognized for prevention or diagnosis, particularly in East Asian populations. We conducted a retrospective case-control study using data from the Taiwan Precision Medicine Initiative and analysing DNA samples to identify eight major MHC Class I and Class II loci. We employed imputation methods for accurate HLA typing and enrolled 17,827 individuals who received penicillin. Logistic regression analyses were utilized to explore associations between HLA genotypes, comorbidities and allergy risk, while simultaneously conducting a subgroup analysis to explore the association between HLA genotypes, comorbidities and the severity of allergic reactions. Our study assigned 496 cases to the penicillin allergy group and 4960 controls to a matched group. The risk of penicillin allergy was significantly higher with HLA-DPB1*05:01 (OR = 1.36, p = .004) and HLA-DQB1*05:01 (OR = 1.54, p = .03), with adjusted p-values of .032 and .24, respectively. Urticaria was identified as a separate risk factor (OR = 1.73, p < .001). However, neither the HLA alleles nor the comorbidities had a significant relationship with the risk of severe penicillin-induced allergy. HLA-DPB1*05:01 was found to be significantly associated with penicillin allergy reactions among the Taiwanese population.

Adult penicillin allergy programmes in Australian hospitals: a practical guide from the National Antibiotic Allergy Network.

Penicillin allergy is a significant burden on patient, prescribing and hospital outcomes. There has been increasing interest in the incorporation of penicillin allergy testing (i.e. delabelling) into antimicrobial stewardship (AMS) programmes to reduce the burden of penicillin allergy labels and improve prescribing. In particular, there has been a focus on point-of-care penicillin allergy assessment and direct oral challenge for low-risk phenotypes. The National Antibiotic Allergy Network has provided a guide to assist AMS clinicians with the incorporation of penicillin allergy programmes, in particular direct oral challenge, into Australian hospitals.

After primary shoulder arthroplasty appropriate vancomycin antibiotic prophylaxis does not lead to increased infectious complications when compared to cefazolin.

BACKGROUND: In primary shoulder arthroplasty (SA), intravenous (IV) cefazolin has demonstrated lower rates of infectious complications when compared to IV vancomycin. However, previous analyses included SA cohorts with both complete and incomplete vancomycin administration. Therefore, it is currently unclear whether cefazolin still maintains a prophylactic advantage to vancomycin when it is appropriately indicated and sufficiently administered at the time of surgical incision. This study evaluated the comparative efficacy of cefazolin and complete vancomycin administration for surgical prophylaxis in primary shoulder arthroplasty with respect to infectious complications. METHODS: A retrospective cohort study was conducted utilizing a single institution total joint registry database, where all primary SA types (hemiarthroplasty, anatomic total shoulder arthroplasty, and reverse shoulder arthroplasty) performed between 2000 to 2019 for elective and trauma indications using IV cefazolin or complete vancomycin administration as the primary antibiotic prophylaxis were identified. Vancomycin was primarily indicated for patients with a severe self-reported penicillin or cephalosporin allergy and/or MRSA colonization. Complete administration was defined as at least 30 minutes of antibiotic infusion prior to incision. All included SA had at least 2 years of clinical follow-up. Multivariable Cox proportional hazard regression was used to evaluate all-cause infectious complications including survival free of prosthetic joint infection (PJI). RESULTS: The final cohort included 7177 primary SA, 6879 (95.8%) received IV cefazolin and 298 (4.2%) received complete vancomycin administration. Infectious complications occurred in 120 (1.7%) SA leading to 81 (1.1%) infectious reoperations. Of the infectious complications, 41 (0.6%) were superficial infections and 79 were (1.1%) PJIs. When categorized by administered antibiotics, there were no differences in rates of all infectious complications (1.6% vs. 2.3%; P = .352), superficial complications (0.5% vs. 1.3%; P = .071), PJI (1.1% vs. 1.0%; P = .874), or infectious reoperations (1.1% vs. 1.0%; P = .839). On multivariable analyses, complete vancomycin infusion demonstrated no difference in rates of infectious complications compared to cefazolin administration (hazard ratio [HR], 1.50 [95% confidence interval (CI), 0.70 to 3.25]; P = .297), even when other independent predictors of PJI (male sex, prior surgery, and Methicillin-resistant Staphylococcus aureus colonization) were considered. CONCLUSIONS: In comparison to cefazolin, complete administration of vancomycin (infusion to incision time greater than 30 minutes) as the primary prophylactic agent does not adversely increase the rates of infectious complications and PJI. Prophylaxis protocols should promote appropriate indications for the use of cefazolin or vancomycin, and when necessary, ensure complete administration of vancomycin to mitigate additional infectious risks after primary SA.

Perioperative Cefazolin for Total Joint Arthroplasty Patients Who Have a Penicillin Allergy: Is It Safe?

BACKGROUND: Cefazolin is the standard of care for perioperative antibiotic prophylaxis in total joint arthroplasty (TJA) in the United States. The potential allergic cross-reactivity between cefazolin and penicillin causes uncertainty regarding optimal antibiotic choice in patients who have a reported penicillin allergy (rPCNA). The purpose of this study was to determine the safety of perioperative cefazolin in PCNA patients undergoing primary TJA. METHODS: We identified all patients (n = 49,842) undergoing primary total hip arthroplasty (n = 25,659) or total knee arthroplasty (n = 24,183) from 2016 to 2022 who received perioperative intravenous antibiotic prophylaxis. Patients who had an rPCNA (n = 5,508) who received cefazolin (n = 4,938, 89.7%) were compared to rPCNA patients who did not (n = 570, 10.3%), and to patients who did not have an rPCNA (n = 43,359). The primary outcome was the rate of allergic reactions within 72 hours postoperatively. Secondary outcomes included the rates of superficial infections, deep infections, and Clostridioides difficile infections within 90 days. RESULTS: The rate of allergic reactions was 0.1% (n = 5) in rPCNA patients who received cefazolin, compared to 0.2% (n = 1) in rPCNA patients who did not (P = .48) and 0.02% (n = 11) in patients who have no rPCNA (P = .02). Allergic reactions were mild in all 5 rPCNA patients who received cefazolin and were characterized by cutaneous symptoms (n = 4) or dyspnea in the absence of respiratory distress (n = 1) that resolved promptly with antibiotic discontinuation and administration of antihistamines and/or corticosteroids. We observed no differences in the rates of superficial infections (0.1 versus 0.2%, P = .58), deep infections (0.3 versus 0.4%, P = .68), or C difficile infections (0.04% versus 0%, P = .99) within 90 days in rPCNA patients who received cefazolin versus alternative perioperative antibiotics. CONCLUSIONS: In this series of more than 5,500 patients who had an rPCNA undergoing primary TJA, perioperative prophylaxis with cefazolin resulted in a 0.1% incidence of allergic reactions that were clinically indolent. Cefazolin can be safely administered to most patients, independent of rPCNA severity. LEVEL OF EVIDENCE: III.

Second-Line Antibiotic Agents in Patient-Reported Penicillin or Cephalosporin Allergy Have No Negative Impact on Antibiotic Resistance After Hip and Knee Arthroplasty.

BACKGROUND: The aim of the present study was to compare causative bacteria and their antibiotic resistance profiles in patients developing a periprosthetic joint infection (PJI) based on preoperative prophylactic antibiotic regimens in primary total hip (THA) and primary total and unicompartmental knee arthroplasty (TKA/UKA). METHODS: We reviewed all cases of PJI occurring after primary THA and primary TKA/UKA, between 2011 and 2020 in a tertiary referral hospital. The standard preoperative prophylactic antibiotic for primary joint arthroplasty was cefuroxime and recommended second-line agent was clindamycin. Patients were divided by the replaced joint and analyzed independently. RESULTS: In the THA group, culture-positive PJI was detected in 61 of 3,123 (2.0%) cefuroxime-administered cases and 6 of 206 (2.9%) noncefuroxime-administered cases. In the TKA/UKA group, culture positive PJI was identified in 21 of 2,455 (0.9%) cefuroxime-administered cases and in 3 of 211 (1.4%) noncefuroxime administered cases. The most commonly isolated bacteria in both groups were coagulase negative staphylococci (CNS). There were no statistically significant differences of pathogen spectrum depending on the preoperative antibiotic regimen detected. Antibiotic resistance of isolated bacteria was significantly different in 4 of 27 (14.8%) analyzed antibiotics in THA and in 3 of 22 (13.6%) analyzed antibiotics in TKA/UKA. In all cohorts, a high occurrence of oxacillin-resistant CNS (50.0 to 100.0%) and clindamycin-resistant CNS (56.3 to 100.0%) has been observed. CONCLUSION: The use of the second-line antibiotic did not influence the pathogen spectrum or antibiotic resistance. However, an alarmingly high proportion of CNS strains was resistant to clindamycin.

ß-Lactam allergy delabeling is safe and saves costs in Primary Care.

OBJECTIVE: To determine whether the ß-lactam allergy delabeling was safe and cost-saving in Primary Care (PC) patients. DESIGN: We have conducted a retrospective chart review of PC patients with ß-lactam allergy label evaluated in our Allergy Unit between 2017 and 2022. SITE: Allergy Department. Hospital Virgen del Rocio (Sevilla). PARTICIPANTS: A total of 391 patients labeled for ß-lactam allergy in PC were studied. MAIN MEASUREMENTS: (a) Outcome evaluation of a ß-lactam allergy delabeling procedure. (b) A ratio between the total e-prescribed antibiotic cost and the number of treatment days (the experimental daily antibiotic cost or EDAC) before and after delabeling was analyzed in delabeled and truly allergic patients. RESULTS: The results of skin testing were positive in 9.2% of the reported cases (36 of 391 patients). The reactions to oral provocation challenge (OPC) occurred in 2.14% of the patients who underwent negative skin testing to offending ß-lactam (in 15 of 699 OPC). A total of 307 patients (78.5%) were delabeled; 70 (17.9%) had a ß-lactam selective response and 14 (3.59%) reacted to both penicillin and cephalosporin. The EDAC before and after the procedure in delabeled patients was significantly lower (0.88 € vs 0.62 €, p<10-3), than that observed in truly allergic group (0.87 € vs. 0.76 €, p=not significant). CONCLUSION: To delabel ß-lactam allergy in Primary Care patients is safe in most patients, cost-saving in antibioticotherapy, and allows identify the main clinical ß-lactam allergy phenotypes that benefit from this procedure.

Genome-wide Study Identifies Association between HLA-B∗55:01 and Self-Reported Penicillin Allergy.

Hypersensitivity reactions to drugs are often unpredictable and can be life threatening, underscoring a need for understanding their underlying mechanisms and risk factors. The extent to which germline genetic variation influences the risk of commonly reported drug allergies such as penicillin allergy remains largely unknown. We extracted data from the electronic health records of more than 600,000 participants from the UK, Estonian, and Vanderbilt University Medical Center's BioVU biobanks to study the role of genetic variation in the occurrence of self-reported penicillin hypersensitivity reactions. We used imputed SNP to HLA typing data from these cohorts to further fine map the human leukocyte antigen (HLA) association and replicated our results in 23andMe's research cohort involving a total of 1.12 million individuals. Genome-wide meta-analysis of penicillin allergy revealed two loci, including one located in the HLA region on chromosome 6. This signal was further fine-mapped to the HLA-B∗55:01 allele (OR 1.41 95% CI 1.33-1.49, p value 2.04 × 10-31) and confirmed by independent replication in 23andMe's research cohort (OR 1.30 95% CI 1.25-1.34, p value 1.00 × 10-47). The lead SNP was also associated with lower lymphocyte counts and in silico follow-up suggests a potential effect on T-lymphocytes at HLA-B∗55:01. We also observed a significant hit in PTPN22 and the GWAS results correlated with the genetics of rheumatoid arthritis and psoriasis. We present robust evidence for the role of an allele of the major histocompatibility complex (MHC) I gene HLA-B in the occurrence of penicillin allergy.

Delabeling of Penicillin Allergy: Room for Improvement.

BACKGROUND: Penicillin allergy labels have been shown to be associated with suboptimal treatment, negative health outcomes, and increased antibiotic resistance. Many inpatients claim to have penicillin allergy, but studies show that allergy can be disproved and the label removed in up to 90% of cases. OBJECTIVES: The purpose of the study was to investigate the proportion of patients with a penicillin allergy label in a Danish hospital and to classify patients according to the risk of having penicillin allergy in "no risk," low, and high risk. METHODS: For 22 days, inpatients with penicillin allergy labels were interviewed, had their dispensed penicillin prescriptions examined, and were subsequently categorized into risk groups based on the risk evaluation criteria in national guidelines. RESULTS: In total, 260 patients had a penicillin allergy label (10% of the inpatients). Out of 151 included patients, 25 were "no risk" patients (17%), who could potentially have their penicillin allergy label removed without testing. 42 were low-risk patients (28%). 10 "no risk" patients and 20 low-risk patients had been prescribed and dispensed one or more penicillins despite an allergy label. CONCLUSION: Ten percent of inpatients have a penicillin allergy label in a Danish hospital. 17% of these could potentially have their penicillin allergy label removed without allergy testing.

New regimens as first-line eradication therapy for Helicobacter pylori infection in patients allergic to penicillin: A randomized controlled trial.

BACKGROUND: Helicobacter pylori eradication in penicillin-allergic patients is challenging. The effective regimen is lacking in areas with high antibiotic resistance and tetracycline unavailable. Minocycline, cefuroxime, and full-dose metronidazole are promising drugs. AIMS: To compare the eradication rate, safety, and compliance among three new bismuth quadruple therapies for first-line H. pylori eradication in penicillin-allergic patients. METHODS: This randomized trial was conducted on 450 naive patients with H. pylori infection and penicillin allergy. The 14-day minocycline-metronidazole-containing (minocycline 100 mg twice daily and metronidazole 400 mg four times/day), minocycline-cefuroxime-containing (minocycline 100 mg twice daily and cefuroxime 500 mg twice daily), and cefuroxime-metronidazole-containing (cefuroxime 500 mg twice daily and metronidazole 400 mg four times/day) bismuth quadruple therapies were randomly assigned to the participants. Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed 4-8 weeks after eradication to evaluate outcome. RESULTS: The differences of eradication rates in either intention-to-treat (84.0%, 82.7%, and 23 82.0%, p = .896) or per-protocol (91.7%, 90.9%, and 88.2%, p = .599) analysis among minocycline-metronidazole, minocycline-cefuroxime, and cefuroxime-metronidazole-containing bismuth quadruple therapies were statistically insignificant. The incidence of adverse events (35.1%, 22.6%, and 28.9%) and compliance (90.5%, 91.8%, and 91.9%) were similar. Taste distortion, nausea, and anorexia were more common in metronidazole-containing regimens, and dizziness was more common in minocycline-containing regimens. The allergy was rare (~3%). CONCLUSIONS: The efficacies of three bismuth quadruple therapies containing minocycline, cefuroxime, and full-dose metronidazole (pairwise) for first-line H. pylori eradication in penicillin-allergic patients were similarly satisfactory with relatively good safety and compliance. The study was registered in the Chinese Clinical Trials Registration (ChiCTR1900023702).

Management of the Pregnant Patient with Beta-Lactam Allergy.

PURPOSE OF REVIEW: We review the literature and discuss the logistics of testing pregnant patients for penicillin allergy. RECENT FINDINGS: As in the general population, pregnant patients commonly report a penicillin allergy, but most patients are able to tolerate penicillin. Avoidance of beta-lactams in pregnancy is associated with increased morbidity: longer hospitalizations, more frequent infections, and more complications. Penicillin allergy testing is safe in pregnant patients, and obstetricians are eager for allergists to offer this procedure to their patients. As allergists, we can improve our patients' health outcomes by offering penicillin allergy testing in our practices. The protocols for testing both with and without skin testing in pregnant patients have been studied, and future studies will continue to clarify the safety and efficacy of penicillin allergy delabeling in pregnant patients.

Antibiotic choice for Group B Streptococcus prophylaxis in mothers with reported penicillin allergy and associated newborn outcomes.

OBJECTIVE: To evaluate the choice of antibiotic used for intrapartum Group B Streptococcus (GBS) prophylaxis in pregnant individuals with reported penicillin allergies compared to those without reported penicillin allergies and investigate whether there are associated differences in neonatal outcomes. STUDY DESIGN: This retrospective cohort study included mother-infant dyads of GBS positive pregnant individuals who labored and delivered newborns ≥ 35 weeks of gestation at a high-volume urban hospital (2005-2018). The type of antibiotic administered to the mothers for GBS prophylaxis (beta-lactam prophylaxis defined as penicillin-class drug or cefazolin; alternative prophylaxis defined as vancomycin or clindamycin) was compared between those with a penicillin allergy documented in their medical record versus those who did not. Neonatal outcomes included number of postnatal blood draws, antibiotic administration, neonatal intensive care unit (NICU) admission, bacteremia, and hospital length of stay and were compared between groups. Bivariable and multivariable analyses were performed. RESULTS: Of 11,334 mother-infant pairs, 1170 (10.3%) mothers had a penicillin allergy documented in their medical record. Of them, 49 (4.2%) received a penicillin, 259 (22.1%) received cefazolin, 449 (38.4%) received clindamycin, and 413 (35.3%) received vancomycin. Patients with a reported penicillin allergy were significantly more likely to receive alternative GBS prophylaxis compared to those without penicillin allergy (73.7% vs. 0.2%, p < 0.01). Neonates of patients who received alternative GBS prophylaxis were significantly more likely to undergo a postnatal lab draw compared to neonates of patients who received beta-lactam antibiotics (20.8% vs. 17.3%, OR 1.25 (95% CI 1.08-1.46)). This significant association persisted after adjusting for potential confounders (aOR 1.23, 95% CI 1.06-1.43). There were no other significant differences seen in other newborn outcomes. CONCLUSION: Pregnant individuals who report a penicillin allergy were more likely to receive alternative antibiotics for GBS prophylaxis compared to those without a penicillin allergy. This was associated with an increased frequency of postnatal blood draws among neonates of mothers with a reported penicillin allergy. Administration of alternative intrapartum antibiotic prophylaxis with vancomycin or clindamycin is common in individuals with self-reported penicillin allergy, and maternal alternative antibiotic administration may impact neonatal care, particularly via increased lab draws.

Proton pump inhibitors and the risk of acquiring a penicillin allergy label.

The negative consequences of having a penicillin allergy label are well established. Penicillin allergy de-labelling improves healthcare outcomes; however, less attention is paid to modifying risk factors leading to penicillin allergy development. In this propensity score-matched retrospective cohort study, we used a de-identified population-based database (TriNetX Research Network) and examined the 30-day risk of acquiring a penicillin allergy label in patients using proton pump inhibitors (PPIs). We demonstrated a higher risk of acquiring a penicillin allergy label among PPI users compared to controls.

Outcome of preoperative cefazolin use for infection prophylaxis in patients with self-reported penicillin allergy.

BACKGROUND: Cephalosporins are the preferred antibiotics for prophylaxis against surgical site infections. Most studies give a rate of combined IgE and non-IgE penicillin allergy yet it is recommended that cephalosporins be avoided in patients having the former but can be used in those with the latter. Some studies use penicillin allergy while others penicillin family allergy rates. The primary goal of this study was to determine the rates of IgE and non-IgE allergy as well as cross reactions to both penicillin and the penicillin family. Secondary goals were to determine the surgical services giving preoperative cefazolin and the types of self reported reactions that patients' had to penicillin prompting their allergy status. METHODS: All patients undergoing elective and emergency surgery at a University Health Sciences Centre were retrospectively studied. The hospital electronic medical record was used for data collection. RESULTS: 8.9% of our patients reported non-IgE reactions to penicillin with a cross reactivity rate of 0.9% with cefazolin. 4.0% of our patients reported IgE reactions to penicillin with a cross reactivity rate of 4.0% with cefazolin. 10.5% of our patients reported non-IgE reactions to the penicillin family with a cross reactivity rate of 0.8% with cefazolin. 4.3% of our patients reported IgE reactions to the penicillin family with a cross reactivity rate of 4.0% with cefazolin. CONCLUSIONS: Our rate of combined IgE and non-IgE reactions for both penicillin and penicillin family allergy was within the range reported in the literature. Our rate of cross reactivity between cefazolin and combined IgE and non-IgE allergy both to penicillin and the penicillin family were lower than reported in the old literature but within the range of the newer literature. We found a lower rate of allergic reaction to a cephalosporin than reported in the literature. We documented a wide range of IgE and non-IgE reactions. We also demonstrated that cefazolin is frequently the preferred antibiotics for prophylaxis against surgical site infections by many surgical services and that de-labelling patients with penicillin allergy is unnecessary.

Preoperative allergy testing for patients reporting penicillin and cephalosporin allergies is economically justified in preventing infection after total shoulder arthroplasty.

BACKGROUND: The use of alternative antibiotics to cefazolin has been associated with increased risk of infection after shoulder arthroplasty. Routine preoperative allergy testing in patients reporting penicillin and cephalosporin allergies increases the number able to receive cefazolin and may reduce the occurrence of infection after shoulder arthroplasty, but the financial viability of this practice is unclear. We used break-even modeling to determine the economic viability of routine preoperative allergy testing for infection prevention in total shoulder arthroplasty patients reporting penicillin and cephalosporin allergies. METHODS: Allergy testing cost ($248.24), infection rates after shoulder arthroplasty following use of noncefazolin antibiotics (3.09%), and infection-related care costs ($55,243) were derived from the literature. A break-even equation using these variables was developed to determine the absolute risk reduction (ARR) in the infection rate that would economically justify the routine implementation of preoperative allergy testing. The number needed to treat was calculated from the ARR. RESULTS: Preoperative allergy testing is considered economically justified if it prevents at least 1 infection out of 223 shoulder arthroplasties (ARR = 0.45%). These protocols remained economically viable at varying allergy testing costs, initial infection rates, and infection-related care costs. CONCLUSIONS: Routine preoperative penicillin allergy testing is an economically justified infection prevention strategy among patients reporting penicillin and cephalosporin allergies in the setting of elective shoulder arthroplasty. Widespread implementation of this practice may considerably reduce the economic and societal burden associated with prosthetic infections.