Positive Penicillin Skin Test Research Articles

Relationship of Reaction History to Positive Penicillin Skin Tests

Previous data suggest that up to one-third of patients classified as allergic based on positive penicillin skin tests have a vague reaction history. Direct oral challenge (DOC) has been recommended for patients with a low-risk reaction history. A variety of published models stratify reaction risk to guide the use of DOC. To reassess the proportion of penicillin skin test-positive patients with vague or low-risk reaction histories and evaluate the relationship between the reaction risk history and the likelihood of positive skin test results. We identified patients who underwent penicillin allergy evaluation over a 5-year period. We recorded drug reaction history, demographic variables, skin testing, and challenge results. Matched controls whose skin tests were negative were identified for skin test-positive patients. Drug reaction histories were assigned a risk category based on 2 previously published risk stratification models. We used logistic regression to investigate whether reaction history risk was associated with positive skin test results. Penicillin skin testing was performed in 3382 patients; 207 (6.1%) were positive. Positive skin tests were more frequent in outpatients (P < .001), younger patients (P < .001), and female patients (P < .001). Percentages of each risk category in each model were similar in cases versus matched controls. The likelihood for positive skin tests increased with a high-risk reaction history in one stratification model. Our data confirm that a substantial proportion of patients who self-report penicillin allergy and have positive skin test results have a low-risk history and imply that penicillin skin testing is associated with a poor positive predictive value.

Single-step Direct Drug Provocation Testing is Safe for Delabelling Selected Non−low-risk Penicillin Allergy Labels

To describe the outcome of an oral amoxicillin challenge in patients labeled allergic to penicillin.One hundred forty nine patients from 1 to 98 years of age labeled allergic to penicillin were included in the study.Patients were categorized as low risk (side effects, family history of penicillin allergy, remote [>5 years] history of penicillin allergy without IgE-mediated features, or unknown reaction not requiring hospitalization, n = 64) or nonlow risk (anaphylaxis, urticaria within 2 hours of penicillin administration, or angioedema with or without urticaria, n = 85). The low risk patients underwent challenge with a single dose of oral amoxicillin (125 mg for patients 1 to 11 months of age, 250 mg for 1 to 11 years, and 500 mg for all patients more than 12 years) followed by 2 hours of observation to evaluate for Gell and Coombs type 1/IgE-mediated/immediate-type hypersensitivity reactions. The nonlow risk patients underwent penicillin skin testing and if negative, oral amoxicillin challenge. Excluded patients were those with history of: (1) Gell and Coombs type 2 reactions, for example, hemolytic anemia or thrombocytopenia; (2) type 3 reactions, for example, serum sickness or vasculitis; or (3) severe type 4 or severe cutaneous adverse reactions, for example, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis or drug reaction with eosinophilia and systemic symptoms.All (64 of 64, 100%) of the low risk patients tolerated the amoxicillin challenge without reaction during the observation period, although 3 developed a maculopapular rash subsequently. All (85 of 85, 100%) of the nonlow risk patients had negative penicillin skin testing, and 84 of 85 (99%) tolerated the amoxicillin challenge without reaction during the observation period, whereas 1 patient developed pruritus and rash that resolved with antihistamine treatment, and 2 subsequently developed a maculopapular rash.The authors conclude that a single step oral amoxicillin challenge is safe.Six percent of children are reported to be allergic to penicillin, although only about 5% of that 6% (0.3%) have positive penicillin skin tests. The remainder either never had IgE-mediated allergy or the allergy was lost over time. Being mislabeled as allergic to penicillin is not benign, but rather leads to suboptimal treatment, more side effects (eg, Clostridium difficile), higher costs, and more antibiotic resistance. Thus, there is currently a strong push to “delabel” the vast majority of children who are labeled as allergic to penicillin but are not. Children are typically referred to allergists to undergo oral amoxicillin challenges under observation with or without prior penicillin skin testing, depending on the history. However, this paper suggests that, given the safety of these challenges, consideration can be given to performing them in pediatricians’ offices. If a careful history excludes patients with histories of “nonlow risk” immediate allergic reactions and those with serious nonimmediate reactions, the remainder with low risk histories can undergo a single dose oral amoxicillin challenge, which the vast majority will tolerate and can be successfully “delabeled.”URL: www.pediatrics.org/cgi/doi/10.1542/peds.10.1016/j.anai. 2021.04.008

Minor Determinants of Penicillin and Amoxicillin Are Still Key Components of Penicillin Skin Testing

The positive rate and pattern of penicillin skin test (PST) has been reported to be decreasing and changing. Previous studies differ about which penicillin component is the dominant component in positive PST result. To characterize past and current PST patterns to determine whether different determinants in PST have changed over time. A retrospective review of electronic medical records (January 2001-December 2017) was performed for patients who underwent PST. Data were divided into 4 cohorts to see whether trends occurred over time. The cohorts were divided as follows: cohort 1 (2001-2005), cohort 2 (2006-2010), cohort 3 (2011-2015), and cohort 4 (2016-2017). A total of 30,883 patients underwent PST with the following breakdowns per cohort: cohort 1, 6,536; cohort 2, 10,372; cohort 3, 10,640; and cohort 4, 3,335. Of these, 329patients (1.0%) had a positive PST result with a wheal of 3× 3 mm or greater, with 110 in cohort 1, 130 in cohort 2, 67 in cohort 3, and 22 in cohort 4, whereas 170 patients (0.5%) had a positive PST result with a wheal of 5× 5 mm or greater, with 54 in cohort 1, 72 in cohort 2, 34 in cohort 3, and 10 in cohort 4. When the positive PST rates of cohort 2 (1.25%), cohort 3 (0.6%), and cohort 4 (0.6%) were compared with those of cohort 1 (1.7%), there was a significant decrease in positive PST rates (P= .0278; P < .0001; P < .0001, respectively). When cohort 1 positive rate to benzylpenicillin polylysine among the positive PST (wheal of 3× 3 mm or greater) was compared with those of the other cohorts (cohorts 2-4), the percent positive of benzylpenicillin polylysine in PST was 27% compared with 21% (P= .38), 34% (P= .5), and 18% (P= .6), respectively. When the positive PST result was defined as a wheal of 5× 5 mm or greater, the positive rate for benzylpenicillin polylysine in PST increased over time (cohort 2: 22%, P= .8; cohort 3: 32%, P=.3; cohort 4: 40%, P= .264) compared with cohort 1 (19%). Positive PST rate is decreasing. We demonstrate that despite benzylpenicillin polylysine solely positive rates remaining relatively stable, the minor penicillin determinants and amoxicillin play an important role in PST and their adoption into standard protocol for routine PST should be considered.

Overview and Insights into Carbapenem Allergy.

Understanding antibiotic allergies and the risk of cross-sensitivity between and within antibiotic classes can have a substantial impact on patient care. The purpose of this review article is to provide insight into carbapenem allergies, describing the overall incidence, risk factors, and in-class cross-sensitivity. A PubMed search was conducted using the following search terms: carbapenem, allergy, cross-sensitivity, incidence, imipenem/cilastatin, meropenem, ertapenem, and doripenem. Article bibliographies and relevant drug monographs were also reviewed. The overall reported incidence of carbapenem allergy is 0.3%–3.7%. Risk of cross-sensitivity between penicillins and carbapenems is less than 1% in patients with a positive penicillin skin test. Data on cross-sensitivity between cephalosporins and carbapenems are limited; however, the risk appears to also be low. No clinical studies have described cross-sensitivity between the carbapenem agents thus far. The limited data available from case reports demonstrates a lack of cross-sensitivity between the individual carbapenems, suggesting that an alternative carbapenem may cautiously be used in patients with a reported carbapenem allergy.

Evaluation and characterization of 125 patients with a history of reaction to beta-lactams

Reactions to beta-lactams are frequent and it is difficult to establish the relationship between the drug and symptoms. To describe the clinical characteristics and explore the immunological mechanisms of patients with suspected adverse reaction to beta-lactams. Retrospective study of patients with a history of beta-lactam reaction and tests for reactions to drugs. Out of 125 patients, 71 were women (56.8%); 73 had a history of immediate reaction and 52 delayed reaction; 590 allergy tests were done: specific IgE measurement, skin prick, patch, and provocation tests. The drugs most often related were amoxycillin, in 62 patients (49.6%), crystalline penicillin in 17 (13.6%), benzathine penicillin in 15 (12%), and cefalexin in 13 (10.4%). The severity of the reaction was mild in the majority (82%). 7.7% had a history of anaphylaxis and 10.8% sought care for a positive penicillin skin test, without history of reaction. Only 6.7% resulted in a positive test. More than 62% began testing two years after the reaction for which they sought care. The clinical history is insufficient to determine allergy to beta-lactams. In our sample, few patients with a history of beta-lactam reaction had evidence of immune-mediated reactions.

Increased rate of positive penicillin skin tests among patients with glioma: insights into the association between allergies and glioma risk.

Allergy and immunoglobulin E levels are inversely associated with glioma risk. Previous studies have focused on respiratory and food allergies, and little information is available regarding drug allergies. This study evaluated the rate of positive penicillin skin tests (PenSTs) and blood eosinophil counts in a large population of patients with glioma compared with nontumor controls to provide evidence for the relationship between drug allergies and glioma risk. A retrospective case-control study was conducted in patients diagnosed with glioma (n = 913) between January 2004 and June 2013. The study patients were matched with nontumor controls (n = 1091) for age, sex, and date of admission to the hospital. Preoperative results of the PenST and eosinophil counts were obtained, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using conditional logistic regression models, while a Kaplan-Meier analysis was used to assess overall survival. The percentage of positive PenSTs was higher among patients with glioma than in control subjects. The age-, sex-, and admission date-adjusted OR for positive versus negative PenSTs was 2.392 (95% CI 1.891-3.026). Eosinophil counts were also higher in glioma cases than in controls: the OR for eosinophil > 0.06 × 10(9)/L versus ≤ 0.06 × 10(9)/L was 1.923 (95% CI 1.608-2.301). There was no association between positive PenST/eosinophil counts and glioma grade or patient survival (n = 105). In contrast to previously reported relationships between allergy and glioma, in the present study a significantly higher rate of positive PenSTs and higher eosinophil counts were found in patients with glioma than in nontumor controls. These results suggest a complex relationship between allergies and glioma development.

A systematic review: can one prescribe carbapenems to patients with IgE-mediated allergy to penicillins or cephalosporins?

Cross-reactivity between penicillins or cephalosporins and carbapenems is anticipated as all have a beta lactam ring. However, the true incidence of immunoglobulin (Ig)E-mediated cross-reactivity is not known. A systematic review was conducted to collect and combine all published data on children and adults reported to have a clinical history of IgE-mediated hypersensitivity to a penicillin and/or cephalosporin who were subsequently given a carbapenem. Reactions were classified as proven, suspected, or possible IgE-mediated and non-IgE-mediated. Ten studies and 12 case reports describing 854 participants fit the study criteria. For patients with previous proven, suspected, or possible IgE-mediated penicillin reactions (N = 838), the incidence of any type of suspected hypersensitivity reaction to a carbapenem was 36/838 (4.3%; 95% confidence interval [CI], 3.1%-5.9%) and the incidence of proven (1/838), suspected (0/838), or possible (19/838) IgE-mediated reactions was 20/838 (2.4%; 95% CI, 1.6%-3.7%). Of the subset of patients with positive penicillin skin tests (n = 295), only 1 had a hypersensitivity reaction (0.3%; 95% CI, .06%-1.9%), and this was a possible IgE-mediated reaction. For patients with previous proven, suspected, or possible IgE-mediated cephalosporin reactions (N = 12), the incidence of any type of hypersensitivity reaction to a carbapenem was 3/12 (25%); this included 2 non-IgE-mediated reactions and 1 possible IgE-mediated reaction. The cross-reactivity between penicillins and carbapenems for IgE-mediated reactions is very low, but caution is still advised. Cross-reactivity rates may be higher between cephalosporins and carbapenems; however, minimal data are available.

Penicillin Skin Testing Is a Safe and Effective Tool for Evaluating Penicillin Allergy in the Pediatric Population

Penicillin skin testing has been validated in the evaluation of adult patients with penicillin allergy. However, the commercially available benzylpenicilloyl polylysine (Pre-Pen) is not indicated in the pediatric population. Moreover, the safety and validity of penicillin skin testing in the pediatric population has not been well studied. We describe the safety and validity of penicillin skin testing in the evaluation of children with a history of penicillin allergy. Children (<18 years) with a history of penicillin allergy were evaluated with penicillin skin tests and were reviewed for basic demographics, penicillin skin test results, adverse drug reaction to penicillin after penicillin skin test, and adverse reaction to penicillin skin test. By using the χ(2) test, we compared the differences in the proportion of children and adults with a positive penicillin skin test. P value (<.05) was considered statistically significant. The institutional review board approved the study, and all the subjects signed written informed consents. A total of 778 children underwent penicillin skin testing; 703 of 778 patients had a negative penicillin skin test (90.4%), 66 had a positive test (8.5%), and 9 had an equivocal test (1.1%). Children were more likely to have a positive penicillin skin test (P < .0001) compared with adults (64 of 1759 [3.6%]); 369 of 703 patients with negative penicillin skin test (52%) were challenged with penicillin, and 14 of 369 patients (3.8%) had an adverse drug reaction. No adverse reactions to penicillin skin testing were observed. Penicillin skin testing was safe and effective in the evaluation of children with a history of penicillin allergy.

Desensitization in patients with beta-lactam drug allergy

BackgroundPatients with a history of beta-lactam antibiotic allergy are often admitted to the hospital with severe or life-threatening infections requiring beta-lactam antibiotics. Strict avoidance of beta lactams to such patients may prevent them from getting adequate coverage and can lead to an increase in the use of alternative antibiotics, which can predispose to antibiotic resistance. Past studies revealed a lower incidence of pen allergy then patients’ histories suggest. Fortunately today, there are three options for patients presenting with a history of beta-lactam allergy. Penicillin skin testing, beta-lactam challenge or beta-lactam desensitization.Recently Pre Pen has been FDA re-approved and when combined with Pen G is a valid way to determine if patients are able to tolerate beta-lactam antibiotic. When these agents are not available one must decide about desensitization or challenge. When a patient has a positive penicillin skin test, desensitization or beta-lactam avoidance are the only options.This paper reviews the safety of beta-lactam desensitization. ObjectiveTo perform a chart review on patients desensitised with beta lactam to determine if desensitizations can be performed safely without minimal complications. MethodsA retrospective chart review was performed on allergy and immunology inpatient consultations for beta-lactam desensitization between September 2003 and August 2006 at the Cedars-Sinai Medical Centre in Los Angeles. Patient data and outcomes of desensitization were analysed. ResultsA total of 13 intravenous desensitizations were performed on 12 patients. The patients consisted of eight females and four males with an average age of 65 years. Age range was 36–92 years old. All 13 intravenous desensitizations were completed without complications. No patient required a slower rate of desensitization or discontinuance of the desensitization. Patients were able to tolerate the initial therapeutic dose of their beta-lactam antibiotic and were then able to complete full therapeutic courses of their antibiotic. ConclusionBeta-lactam antibiotic sensitivity continues to present a challenging problem for physicians. Patients with drug resistant infections who are unable to obtain skin testing or who test positive to skin tests may need either a challenge or desensitization. Desensitization, saved for those with a convincing beta-lactam hypersensitivity history is often the choice of last resort given the associated cost and risk of anaphylaxis. However, once desensitization is complete, patients are usually able to tolerate full doses of antibiotics for full treatment length with minimal side effects.

Clinical Outcome in the Use of Cephalosporins in Pediatric Patients with a History of Penicillin Allergy

Background: The risk of cephalosporin administration in patients with a history of penicillin allergy is unclear. Few studies have looked at the risk of cephalosporin administration in children following penicillin skin testing for suspected penicillin allergy. The goal of this study was to determine whether children with penicillin allergy were at increased risk for adverse drug reactions when administered a cephalosporin. Methods: A retrospective chart review was conducted in pediatric patients (≤18 years) with a history of penicillin allergy and a positive or negative penicillin skin test who were administered a cephalosporin after testing. Charts were reviewed for adverse drug reactions to the cephalosporin. Results: A total of 173 patients (91 males) were included in this study. The mean age of the patients was 4.1 ± 3.1 years. Twenty-one patients (12%) tested positive in a penicillin skin test and 152 patients (88%) tested negative. One patient with a negative penicillin skin test (0.7%) had an adverse drug reaction (eye swelling) to cephalexin. None of the patients with a positive penicillin skin test who received a course of cephalosporin had an adverse drug reaction. Conclusion: Among all patients with a history of penicillin allergy (penicillin skin test positive and negative), only 1 person had an adverse drug reaction. Further large prospective studies examining the safety of administering cephalosporins in pediatric patients with confirmed penicillin allergy are needed.

Alkali-treated penicillin G solution is a better option than penicillin G as an alternative source of minor determinants for penicillin skin test

Both benzylpenicilloyl-polylysine (PPL) and minor determinant mixture (MDM) are the recommended standard reagents for penicillin skin testing. However, penicillin G is commonly suggested as an alternative source of minor determinants. This study evaluated the accuracy of penicillin G and alkali-treated penicillin G compared with the standardized MDM for skin testing. Sixty-eight patients with histories of allergies to penicillin or semisynthetic penicillins were skin tested with commercial Kit penicillin allergenic determinants (DAP) (PPL and DAP-MDM; Diater Laboratorios, Madrid, Spain). The in-house MDM (IH-MDM), prepared by alkali-treated aged penicillin, and fresh penicillin G sodium (PGs) were tested alongside DAP-MDM. Positive penicillin skin test results were identified in 22 patients (32.4%) using commercial reagents (PPL+ DAP-MDM) and 19 of them reacted to DAP-MDM alone or together with PPL. The accuracy of IH-MDM and PGs compared with DAP-MDM was 89.7 and 76.5%, respectively. Our study shows that alkali-treated penicillin G is a better option than penicillin G as an alternative source of MDM for skin testing in case the commercialized MDM is not available. Minor determinants play a significant role for penicillin allergy in Thailand and should be included in the penicillin skin test panel to verify suspected cases of penicillin allergy. (ClinicalTrials.gov number: NCT00789217).

Pediatric Patients with a History of Penicillin Allergy and a Positive Penicillin Skin Test May Not Be at an Increased Risk for Multiple Drug Allergies

Pediatric Patients with a History of Penicillin Allergy and a Positive Penicillin Skin Test May Not Be at an Increased Risk for Multiple Drug Allergies

Use of commercial anti–penicillin IgE fluorometric enzyme immunoassays to diagnose penicillin allergy

The intermittent unavailability of penicilloyl-polylysine since September 2000 has focused interest on commercial anti-penicillin IgE fluorometric enzyme immunoassay (FEIA) tests to evaluate penicillin allergy. There has been no published comparison of commercial anti-penicillin IgE FEIAs and penicillin skin testing performed in the United States. To determine whether the current commercial anti-penicillin IgE FEIAs can replace or augment penicillin skin testing and oral challenges when evaluating individuals with a history of penicillin allergy for future therapeutic penicillin tolerance. A prospective convenience sample of 150 individuals with a history of penicillin allergy were evaluated between January 23, 2007, and August 4, 2009, with both penicillin skin tests and commercial anti-penicillin IgE FEIAs to penicillin G, penicillin V, and amoxicillin. All individuals with a negative penicillin skin test result underwent oral penicillin class antibiotic challenges. All individuals with a positive anti-penicillin IgE FEIA result also underwent oral penicillin class antibiotic challenges. Six individuals (4.0%; 95% confidence interval [CI], 0.9% to 7.1%) had positive penicillin skin test results, and none had positive FEIA results. Four individuals (2.7%; 95% CI, 0.1% to 5.3%) had positive FEIA results, and none had positive penicillin skin test results. Three individuals (2.0%; 95% CI, -0.2% to 4.2%) had positive oral challenge results, 1 with hives at 6 hours after challenge and 2 with delayed-onset (at >24 hours) nonurticarial rashes, and none had positive FEIA results. The current commercial anti-penicillin IgE FEIAs are not useful in diagnosing penicillin allergy in patients with remote histories of penicillin allergy. Penicillin skin testing and, if the results are negative, an oral challenge remain the criterion standard tests to determine therapeutic penicillin tolerance.

Increased Adverse Drug Reactions to Cephalosporins in Penicillin Allergy Patients with Positive Penicillin Skin Test

Background: Cephalosporin administration in patients with a history of penicillin allergy is controversial. Studies looking at the safety of cephalosporin in patients with a history of penicillin allergy lacked a control group, had a small number of patients, and/or lacked confirmation of penicillin allergy by penicillin skin testing. The purpose of this study was to determine whether patients with penicillin allergy were at increased risk of adverse drug reactions when administered cephalosporin. Methods: A cohort study of patients with a history of penicillin allergy and a positive or negative penicillin skin test when administered cephalosporin was conducted. Charts were reviewed for adverse drug reactions to cephalosporin after penicillin skin testing. Results: Eighty-five patients with a history of penicillin allergy and positive penicillin skin test and 726 patients with a history of penicillin allergy and negative penicillin skin test were administered cephalosporin. Five (6%) of 85 cases had an adverse drug reaction to cephalosporin as compared to 5 (0.7%) of 726 of the referent population (p = 0.0019). The rate of presumed IgE-mediated adverse drug reactions to the cephalosporins amongst the cases was 2 (2%) of 85 compared to 1 (0.1%) of 726 amongst the referent population (p = 0.0304). Conclusion: A greater risk of an adverse drug reaction to cephalosporin exists in patients with penicillin allergy. We recommend penicillin skin testing if cephalosporin, especially a first-generation cephalosporin, is to be administered to patients with a history of penicillin allergy.

The Falling Rate of Positive Penicillin Skin Tests from 1995 to 2007

Data on the rate of positive penicillin skin test (PenST) results over time in large populations are rare. The factors that influence positive PenST results are incompletely understood. We sought to correlate demographic variables to the rate of positive PenST results over time in a large group of patients with a history of penicillin allergy. RESULTS from the first test for all patients tested for penicillin allergy in the Kaiser Permanente Health Care Program in San Diego County, CA, between 1995 and 2007 are reported. All patients were tested with penicillin, penicilloyl-poly-lysine, penilloate, penicilloate, and amoxicillin. There were 255 positive PenST results in 3469 individuals. The rate of positive PenST results declined from >10% to <5% during the 13 years studied. The positive PenST result rate could be accounted for by the year of testing (R(2) = 0.56; p = 0.003) without any significant contribution from the patient's age or the time since reaction (TSR). If the TSR was ≤13 years, the relative risk of a positive PenST result was 2.1 (95% confidence interval = 1.6-2.8). If the study subject's age was ≤38 years, the relative risk of a positive PenST result was 2.1 (95% confidence interval = 1.6-2.7). Females reported higher rates of penicillin allergy history than males did (11% compared with 6.6%; p < 0.0001), but there were no significant sex differences in the rate of positive PenST results. There has been a steady decline in the proportion of positive PenST results between 1995 and 2007, independent of study subject age and TSR. Increasing age and increasing TSR were associated with a lower rate of positive PenST results.

Female sex as a risk factor for penicillin allergy

Identification of risk factors is an integral part of a physician's evaluation of a patient. To determine whether female sex is an independent risk factor for penicillin allergy. Rates of positive penicillin skin test (PST) results, according to sex, were determined in patients with a history of penicillin allergy undergoing penicillin allergy evaluation with major and minor determinants of penicillin between June 1, 2002, and June 30, 2004. Univariate and multivariate logistic regression analyses were used to calculate unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for sex differences in the rates of positive PST results. Of the 1,921 patients, 1,759 underwent PST and 157 did not; 5 medical records were not available for review. The mean patient age was 60 years. Sixty-four patients (4%) had a positive PST reaction; of these, 53 (83%) were females and 11 (17%) were males (OR, 3.6; 95% CI, 1.9-7.2; P < .001). In a multivariate logistic regression analysis adjusted for age, history of multiple drug allergies, and elapsed time from the initial penicillin adverse drug reaction to PST, female sex again had a significant risk of a positive PST reaction (OR, 3.2; 95% CI, 1.6-6.7; P = .001). A greater risk of penicillin allergy exists in association with female sex in patients with a history of penicillin allergy.

Clinical Importance of Carbapenem Hypersensitivity in Patients with Self‐Reported and Documented Penicillin Allergy

The risk of carbapenem hypersensitivity in patients with self-reported or documented penicillin allergy needs to be determined so that practitioners can make better-informed decisions regarding antibiotic therapy for this patient population. The risk of cross-reactivity between penicillin and carbapenem antibiotics initially was reported to approach 50%. Recent retrospective studies have suggested that the clinical risk of cross-hypersensitivity between these two drug classes is 9.2-11%, which is significantly lower than initially reported. Patients whose history of penicillin allergy is self-reported and is not type 1 may be at moderate risk for hypersensitivity when treated with a carbapenem antibiotic. The risk of hypersensitivity appears to be higher in patients whose penicillin allergy was documented by a health care provider, those with several antibiotic allergies, and those with a positive penicillin skin test result or a history of type 1 penicillin hypersensitivity.

Clinical history as a predictor of penicillin skin test outcome

Up to 10% of the population reports an "allergy" to penicillin, whereas approximately 1.1% has positive penicillin skin test results. Where penicillin skin tests are unavailable, some have advocated using history to decide whether to use a penicillin-related antibiotic. To determine if clinical history predicts penicillin skin test results. Retrospective medical record review of 94 consecutive patients who had previously taken penicillin referred for penicillin allergy. Case histories were taken, penicillin skin tests performed, and an oral challenge recommended if skin test results were negative. Of 91 cases studied, the average patient age was 27 years (range, 6 months to 82 years; 36% female). Fifty-two (57%) experienced hives as their main adverse reaction. Sixteen (18%) had at least 1 positive test result. Of this group, 9 had hives as their main symptom, whereas 1 had respiratory problems and 1 had angioedema. Most patients with positive skin test results had experienced their reaction at least 3 years ago. Regression analysis showed that age, sex, and clinical history, including type of reaction, time of reaction after penicillin ingestion, or time since the last reaction, were not associated with skin test positivity. Seventy-two (96%) of the 75 patients who had negative skin test results underwent oral challenge. Seventy had negative challenge results. The negative predictive value of a negative penicillin skin test result was 97%. Clinical history was not predictive of subsequent penicillin skin test results.

Increased Adverse Drug Reactions to Cephalosporins in Patients with a Positive Penicillin Skin Test

RATIONALE: The American Academy of Pediatrics has endorsed the use of cephalosporins for patients with reported allergies to penicillin (PCN). However, a study of fatal anaphylaxis in England from 1992 to 1997 revealed that 3 of the 6 fatalities were due to cephalosporins in patients known to be allergic to amoxicillin and one to PCN. Hence, caution is still advised if a cephalosporin is to be given in patients with a history of PCN allergy. We conducted a retrospective cohort study comparing the rates of adverse drug reactions (ADR) to cephalosporins in patients with a positive PCN skin test compared to a negative PCN skin test.METHODS: Patients with a history of PCN allergy who underwent PCN skin testing had medical records reviewed for antibiotic administration outcomes. Using the χ2 test, we compared the differences in the proportion of ADR among study patients and historical controls (negative penicillin skin test challenged with a cephalosporin). P value ≤ 0.05 was considered statistically significant.RESULTS: 37 of 125 (30%) patients with a positive PCN skin test received a cephalosporin. 2 of 37 (5%) developed an ADR (rashes) compared to 5 of 675 (0.7%) with a negative PCN skin test (p < 0.01).CONCLUSIONS: Patients with reported PCN allergy and a positive PCN skin test are at a higher risk of an ADR to cephalosporins. PCN skin testing in patients with a reported PCN allergy may be a safe and effective method in stratifying the risk of an ADR before the administration of a cephalosporin. RATIONALE: The American Academy of Pediatrics has endorsed the use of cephalosporins for patients with reported allergies to penicillin (PCN). However, a study of fatal anaphylaxis in England from 1992 to 1997 revealed that 3 of the 6 fatalities were due to cephalosporins in patients known to be allergic to amoxicillin and one to PCN. Hence, caution is still advised if a cephalosporin is to be given in patients with a history of PCN allergy. We conducted a retrospective cohort study comparing the rates of adverse drug reactions (ADR) to cephalosporins in patients with a positive PCN skin test compared to a negative PCN skin test. METHODS: Patients with a history of PCN allergy who underwent PCN skin testing had medical records reviewed for antibiotic administration outcomes. Using the χ2 test, we compared the differences in the proportion of ADR among study patients and historical controls (negative penicillin skin test challenged with a cephalosporin). P value ≤ 0.05 was considered statistically significant. RESULTS: 37 of 125 (30%) patients with a positive PCN skin test received a cephalosporin. 2 of 37 (5%) developed an ADR (rashes) compared to 5 of 675 (0.7%) with a negative PCN skin test (p < 0.01). CONCLUSIONS: Patients with reported PCN allergy and a positive PCN skin test are at a higher risk of an ADR to cephalosporins. PCN skin testing in patients with a reported PCN allergy may be a safe and effective method in stratifying the risk of an ADR before the administration of a cephalosporin.

Penicillin sensitivity among children without a positive history for penicillin allergy.

To establish the prevalence of positive penicillin skin tests among outpatients without any drug reaction history. Skin testing was performed in 147 children (aged 6-13 years) who had had received a penicillin preparation at least three times in the last 12 months without any allergic reaction. Before testing, detailed pediatric and allergy history were learned and then all children were tested with benzyl penicilloyl polylysin (PPL) and mixture of minor antigenic determinants. The test procedures were made epidermally and intradermally subsequently in every subject. The overall frequency of positive skin reactions to penicillin antigens was 10.2%. A mild systemic reaction was observed in one of the children during testing with PPL. We concluded that frequent use of penicillin and other beta-lactam antibiotics leads to sensitization of children in our study population despite these children seem to be asymptomatic during testing time.