An overview of penicillin allergies for nurses.

ABSTRACT: Antibiotics are frequently reported as allergies by patients, particularly antibiotics from the penicillin family. Most of these reported allergies are benign, and the consequences of alternative therapies can be significant. This article provides background information on penicillin allergies and serves as a guide to penicillin allergy management.Reprinted with permission from Wrynn, A.F. An overview of penicillin allergies for nurses. Nurse Pract 2022; 47(9): 30-36. Copyright Wolters Kluwer. All rights reserved.

Penicillin allergies: A guide for NPs.

ABSTRACT: Antibiotics are frequently reported as allergies by patients, particularly antibiotics from the penicillin family. Most of these reported allergies are benign, and the consequences of alternative therapies can be significant. This article will deliver background information on penicillin allergies and serve as a guide to penicillin allergy management.

Detection of Serum-Specific IgE by Fluoro-Enzyme Immunoassay for Diagnosing Type I Hypersensitivity Reactions to Penicillins.

Diagnosis of type I hypersensitivity reactions (IgE-mediated reactions) to penicillins is based on clinical history, skin tests (STs), and drug provocation tests (DPTs). Among in vitro complementary tests, the fluoro-enzyme immunoassay (FEIA) ImmunoCAP® (Thermo-Fisher, Waltham, MA, USA) is the most widely used commercial method for detecting drug-specific IgE (sIgE). In this study, we aimed to analyze the utility of ImmunoCAP® for detecting sIgE to penicillin G (PG) and amoxicillin (AX) in patients with confirmed penicillin allergy. The study includes 139 and 250 patients evaluated in Spain and Italy, respectively. All had experienced type I hypersensitivity reactions to penicillins confirmed by positive STs. Additionally, selective or cross-reactive reactions were confirmed by DPTs in a subgroup of patients for further analysis. Positive ImmunoCAP® results were 39.6% for PG and/or AX in Spanish subjects and 52.4% in Italian subjects. When only PG or AX sIgE where analyzed, the percentages were 15.1% and 30.4%, respectively, in Spanish patients; and 38.9% and 46% in Italian ones. The analysis of positive STs showed a statistically significant higher percentage of positive STs to PG determinants in Italian patients. False-positive results to PG (16%) were detected in selective AX patients with confirmed PG tolerance. Low and variable sensitivity values observed in a well-defined population with confirmed allergy diagnosis, as well as false-positive results to PG, suggest that ImmunoCAP® is a diagnostic tool with relevant limitations in the evaluation of subjects with type I hypersensitivity reactions to penicillins.

Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND & AIMS: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. METHODS: This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. RESULTS: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. CONCLUSIONS: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.

Association Between Removal of a Warning Against Cephalosporin Use in Patients With Penicillin Allergy and Antibiotic Prescribing.

Importance: Electronic health records (EHRs) often include default alerts that can influence physician selection of antibiotics, which in turn may be associated with a suboptimal choice of agents and increased antibiotic resistance. Objective: To examine whether removal of a default alert in the EHR to avoid cephalosporin use in patients with penicillin allergies is associated with changes in cephalosporin dispensing or administration in these patients. Design, Setting, and Participants: This retrospective cohort study of a natural experiment included data on patients who had received antibiotic treatment in the hospital or outpatient setting in 2 regions of a large, integrated health system in California from January 1, 2017, to December 31, 2018. Of 4 398 792 patients, 4 206 480 met the eligibility criteria: enrollment in the health system during antibiotic use, availability of complete demographic data, and use of antibiotics outside of the washout period. Interventions or Exposures: Oral or parenteral antibiotics dispensed or administered after removal of an EHR alert to avoid cephalosporin use in patients with a recorded penicillin allergy. Main Outcomes and Measures: Probability that an antibiotic course was a cephalosporin. A multinomial logistic regression model was used to examine the change in rates of cephalosporin use before and after an EHR penicillin allergy alert was removed in 1 of the study regions. Temporal changes in use rates were controlled for by comparing changes in cephalosporin use among patients with or without a penicillin allergy at the site that removed the warning and among patients at a comparison site that retained the warning. Regression models were used to examine adverse events. Results: Of the 4 206 480 patients who met all inclusion criteria, 2 465 849 (58.6%) were women; the mean (SD) age was 40.5 (23.2) years. A total of 10 652 014 antibiotic courses were administered or dispensed, divided approximately evenly between the period before and after removal of the warning. Before removal of an alert in the electronic health record system to avoid prescribing of cephalosporins to patients with a penicillin allergy at 1 of the 2 sites, 58 228 courses of cephalosporins (accounting for 17.9% of all antibiotic use at the site) were used among patients with a penicillin allergy; after removal of the alert, administration or dispensing of cephalosporins increased by 47% compared with cephalosporin administration or dispensing among patients without a penicillin allergy at the same site and patients at the comparison site that retained the warning (ratio of ratios of odds ratios [RROR], 1.47; 95% CI, 1.38-1.56) . No significant differences in anaphylaxis (9 total cases), new allergies (RROR, 1.02; 95% CI, 0.93-1.12), or treatment failures (RROR, 1.02; 95% CI, 0.99-1.05) were found at the course level. No significant differences were found in all-cause mortality (ratio of ratios of rate ratios [RRRR], 1.03; 95% CI, 0.94-1.13), hospital days (RRRR, 1.04; 95% CI, 0.99-1.10), and new infections (Clostridioides difficile: RRRR, 1.02; 95% CI, 0.84-1.22; methicillin-resistant Staphylococcus aureus: RRRR, 0.87; 95% CI, 0.75-1.00; and vancomycin-resistant Enterococcus: RRRR, 0.82; 95% CI, 0.55-1.22) at the patient level. Conclusions and Relevance: In this cohort study, removal of a warning in the electronic health record to avoid cephalosporin use in patients with penicillin allergies was associated with increased administration and dispensing of cephalosporin. This simple and rapidly implementable system-level intervention may be useful for improvement in antibiotic stewardship.

Susceptibility-guided therapy for Helicobacter pylori-infected penicillin-allergic patients: A prospective clinical trial of first-line and rescue therapies.

BACKGROUND: Helicobacter pylori (H pylori) treatment remains a challenge for penicillin-allergic patients. AIM: To evaluate the efficacy and tolerability of susceptibility-guided first-line and rescue treatment in H pylori-infected penicillin-allergic patients. METHODS: Consecutive H pylori-infected patients with penicillin allergy received a 14-day triple or quadruple therapy based on susceptibility to clarithromycin, levofloxacin, and metronidazole. All received esomeprazole 20 mg twice a day. Metronidazole-susceptible infections received metronidazole plus clarithromycin or levofloxacin triple therapy if susceptible. Clarithromycin- and levofloxacin-resistant infections received metronidazole plus tetracycline triple therapy. Metronidazole-resistant infections received a bismuth-high-dose metronidazole plus clarithromycin or levofloxacin quadruple therapy. Triple-resistant infections received classical bismuth quadruple therapy with high-dose metronidazole. Antimicrobial susceptibility was assessed using the E test method. RESULTS: 112 patients were entered (34.8% men, average 47.1 years). Infections in 83.8% (31/37) of treatment-naive subjects and 12.0% (9/75) (P < .001) receiving rescue treatment were susceptible to at least one of the three tested antibiotics. Overall, susceptibility-guided therapy achieved eradication rates of 92.9% (104/112, 95% CI 88.1%-97.7%) by intent-to-treat analysis and 99% (100/101, 95% CI 97.1%-100%) by per-protocol analysis. All regimens achieved eradication rates greater than 90% (P = .327) in the PP populations. Adverse events were relatively frequent; however, compliance remained high. CONCLUSION: Susceptibility-guided therapy proved highly effective for penicillin-allergic patients. When available and proven locally effective, the alternative was empiric classical bismuth quadruple therapy. This trial is registered with ClinicalTrials.gov as NCT03708848.

Penicillin skin testing in methicillin-sensitive staphylococcus aureus bacteremia: A cost-effectiveness analysis.

BACKGROUND: Beta-lactams are the mainstay for treating methicillin-susceptible Staphylococcus aureus (MSSA) infections complicated by bacteremia due to superior outcomes compared with vancomycin. With approximately 11% of inpatients reporting a penicillin (PCN) allergy, many patients receive suboptimal treatment for MSSA bacteremia. OBJECTIVE: Evaluate the cost-effectiveness of penicillin skin testing (PST) in adult patients with self-reported PCN allergy in an inpatient setting undergoing treatment for MSSA bacteremia. METHODS: A decision analytic model was developed comparing an acute care PST intervention to a scenario with no confirmatory allergy testing. The primary outcome was the incremental cost-effectiveness ratio (ICER) from the health-sector perspective over a 1-year time horizon using quality-adjusted life years (QALYs) as the measure for effectiveness. One-way and probabilistic sensitivity analyses were conducted to assess the uncertainty of the ICER estimation. RESULTS: Over a 1-year time horizon, PST services applied to all MSSA bacteremia patients reporting a PCN-allergy would result in a cost per patient of $12,559 and 0.73 QALYs while no PST services would have a higher cost per patient of $13,219 and 0.66 QALYs per patient. This resulted in a cost-effectiveness estimate of -$9,429 per QALY gained. Varying the cost of implementing PST services determined a break-even point of $959.98 where any PST cost less than this amount would actually be cost saving. CONCLUSIONS: Patients reporting a PCN allergy on admission may receive sub-optimal alternative therapies to beta-lactams, such as vancomycin, for MSSA bacteremia. This economic analysis demonstrates that inpatient PST services confirming PCN allergy are cost-effective for patients with MSSA bacteremia.

Trends in culprit drugs and clinical entities in cutaneous adverse drug reactions: a retrospective study.

PURPOSE: Morbidity due to cutaneous adverse drug reactions (CADRs) is quite common. The specific culprit drugs change over time and clinicians must be kept informed with updated knowledge, thus preventing potential CADRs. This retrospective study is a survey of CADRs encountered in a hospital-based population in Southern China during three time intervals, from 1984 to 2015. MATERIALS AND METHODS: The clinical records were review of 306 patients with CADRs who were admitted to our hospital from 2011 to 2015. These data were compared with patients visiting our hospital during 1984-1994 and 2003-2010. RESULTS: From 2011 to 2015, the most common CADRs were exanthematous reactions (40.8%) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN; 17.0%). There were eight cases (2.6%) of CADRs related to targeted therapy in oncology. In the 205 CADR cases that were due to single medications, the most common offending drugs were allopurinol (21.5%), cephalosporins (10.7%) and carbamazepine (10.2%). The percentages of CADR cases due to allopurinol, carbamazepine, or epidermal growth factor receptor inhibitors were significantly higher from 2011 to 2015 compared with 1984-1994 or 2003-2010. The rate of SJS/TEN occurrence was significantly higher in the two recent periods compared with 1984-1994. CONCLUSIONS: Changes in drug prescriptions are a major factor that affects the CADRs seen in clinical records. Newer drugs can be culpable for CADRs, and more CADRs are now documented with increased severity at clinical presentation. Reliable screening tests for specific drugs are urgently required to eliminate possible fatalities.

The Impact of Reporting a Prior Penicillin Allergy on the Treatment of Methicillin-Sensitive Staphylococcus aureus Bacteremia.

BACKGROUND: Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a morbid infection with mortality benefit from receipt of parenteral ß-lactam therapy. A substantial portion of MSSA bacteremia patients report penicillin allergy, but infrequently have true allergy. OBJECTIVE: To determine the frequency and predictors of optimal and adequate therapy in patients with MSSA bacteremia. DESIGN: Retrospective cohort. PARTICIPANTS: Adult inpatients with MSSA bacteremia, January 2009 through October 2013. MAIN MEASURES: The primary measure was a trial of optimal therapy (OT), defined as ≥3 inpatient days or discharge on any first-line agents (nafcillin, oxacillin, cefazolin, or penicillin G, if susceptible). The secondary measure was completion of adequate therapy (AT), defined as ≥10 inpatient days or discharge on an agent appropriate for MSSA bacteremia. Data were electronically gathered with key variables manually validated through chart review. Log-binomial regression models were used to determine the frequency and predictors of outcomes. KEY RESULTS: Of 456 patients, 346 (76%) received a trial of OT. Patients reporting penicillin allergy (13%) were less likely to receive OT trial than those without penicillin allergy (47% vs. 80%, p <0.001). Adjusting for other factors, penicillin allergy was the largest negative predictor of OT trial (RR 0.64 [0.49, 0.83]). Infectious Disease (ID) consultation was the largest positive predictor of OT trial across all patients (RR 1.34 [1.14, 1.57]). Allergy/Immunology consultation was the single most important predictor of OT trial among patients reporting penicillin allergy (RR 2.33 [1.44, 3.77]). Of 440 patients, 391 (89%) completed AT, with ID consultation the largest positive predictor of the outcome (RR 1.28 [1.15, 1.43]). CONCLUSIONS: Nearly 25% of patients with MSSA bacteremia did not receive OT trial and about 10% did not receive AT completion. Reported penicillin allergy reduced, and ID consult increased, the likelihood of OT. Allergy evaluation, coupled with ID consultation, may improve outcomes in MSSA bacteremic patients.

Ceftriaxone Potentiates Warfarin Activity Greater Than Other Antibiotics in the Treatment of Urinary Tract Infections.

BACKGROUND: The cephalosporin class has been associated with an increased risk of bleeding among elderly patients receiving warfarin. Urinary tract infections (UTI) are the most prevalent infection in elderly patients. OBJECTIVE: To determine the extent of interaction between antibiotics used in the treatment of UTI, particularly specific cephalosporins and warfarin. METHODS: A retrospective chart review was conducted on chronic warfarin patients with a diagnosis of UTI treated with ceftriaxone, a first-generation cephalosporin, penicillin, or ciprofloxacin. The primary outcome was the comparison of the extent of international normalized ratio (INR) change from baseline between each antibiotic group. RESULTS: The ceftriaxone group was found to have a statistically significant higher peak INR value compared to all other studied antibiotics (ceftriaxone: 3.56, first-generation cephalosporins: 2.66, penicillins: 2.98, ciprofloxacin: 2.3; P = .004), a statistically significant greater extent of change in INR value (+1.19, +0.66, +0.8, +0.275; P = .006), and a statistically significant greater percentage change in INR value when compared to ciprofloxacin (54.4% vs 12.7%; P = .037). CONCLUSION: Ceftriaxone interacts with warfarin to increase a patient's INR value more than other commonly administered antibiotics for UTI treatment. Other antibiotics should be preferred for UTI treatment in patients on warfarin.

Risk factors for resistance in urinary tract infections in women in general practice: A cross-sectional survey.

OBJECTIVES: In 2012 and 2013, a cross-sectional survey was conducted in women visiting a general practitioner for a urinary tract infection (UTI) to i) describe the patterns of antibiotic resistance of Enterobacteriaceae involved in community-acquired UTIs and ii) identify the factors associated with UTIs due to a multi-drug-resistant Enterobacteriaceae (MDREB). METHODS: Urine analyses were performed systematically for all adult women presenting with signs of UTI. Characteristics of women with UTI due to MDREB were compared to those with UTI due to non-MDREB. Weighted logistic regressions were performed to adjust for the sampling design of the survey. RESULTS: Significant factors associated with MDREB included the use of penicillin by the patient in the last three months (OR = 3.1; [1.2-8.0]); having provided accommodation in the previous 12 months to a resident from a country at high risk for drug resistance (OR = 4.0; [1.2-15.1]); and the consumption of raw meat within the previous three months (OR = 0.3; [0.1-0.9]). CONCLUSIONS: In the community, antibiotic use and exposure to a person returning from an area with a high risk of drug resistance are associated with UTIs due to MDREB. The potentially protective role of raw meat consumption warrants further study.

Amoxicillin plus temocillin as an alternative empiric therapy for the treatment of severe hospital-acquired pneumonia: results from a retrospective audit.

A formulary decision was made at a large provider of acute hospital services in Surrey to replace piperacillin/tazobactam with amoxicillin+temocillin for the empiric treatment of severe hospital-acquired pneumonia. This decision was made because the use of broad-spectrum-ß-lactam antibiotics is a known risk factor for Clostridium difficile infection (CDI) and for the selection of resistance. After the antibiotic formulary was changed, a retrospective audit was conducted to assess the effect of this change. Data from patients hospitalised between January 2011 and July 2012 for severe hospital-acquired pneumonia and treated empirically with piperacillin/tazobactam or amoxicillin+temocillin were reviewed retrospectively. Clinical characteristics of patients, data related to the episode of pneumonia, clinical success and incidence of significant diarrhoea and CDI were analysed. One hundred ninety-two episodes of severe hospital-acquired pneumonia in 188 patients were identified from hospital records. Ninety-eight patients received piperacillin/tazobactam and 94 amoxicillin+temocillin. At baseline, the two treatment groups were comparable, except that more patients with renal insufficiency were treated with piperacillin/tazobactam. Clinical success was comparable (80 versus 82 %; P = 0.86), but differences were observed between piperacillin/tazobactam and amoxicillin+temocillin for the rates of significant diarrhoea (34 versus 4 %, respectively; P < 0.0001) and for CDI (7 versus 0 %, respectively; P < 0.0028). This preliminary study suggests that the combination amoxicillin+temocillin is a viable alternative to piperacillin/tazobactam for the treatment of severe hospital-acquired pneumonia. This combination appears to be associated with fewer gastrointestinal adverse events. Further studies are needed to evaluate the place of amoxicillin+temocillin as empiric treatment of severe hospital-acquired pneumonia.

Optogenetic control of thalamus as a tool for interrupting penicillin induced seizures.

Penicillin epilepsy model, whose discharge resembles that of human absence epilepsy, is one of the most useful acute experimental epilepsy models. Though closed-loop optogenetic strategy of interrupting seizures was proved sufficient to switch off epilepsy by controlling thalamus in the post-lesion partial chronic epilepsy model, doubts still exist in absence epilepsy attenuation through silencing thalamus. Here we directly arrested the thalamus to modulate penicillin-induced absence seizures through pseudorandom responsive stimulation on eNpHR-transfected rats. Our data suggested that the duration of epileptiform bursts under light conditions, compared with no light conditions, did not increase or decrease when modulated specific eNpHR-expressing neurons in thalamus.

Simplified antibiotic regimens for the management of clinically diagnosed severe infections in newborns and young infants in first-level facilities in Karachi, Pakistan: study design for an outpatient randomized controlled equivalence trial.

BACKGROUND: Infection in young infants is a major cause of morbidity and mortality in low-middle income countries, with high neonatal mortality rates. Timely case management is lifesaving, but the current standard of hospitalization for parenteral antibiotic therapy is not always feasible. Alternative, simpler antibiotic regimens that could be used in outpatient settings have the potential to save thousands of lives. METHODS: This trial aims to determine whether 2 simplified antibiotic regimens are equivalent to the reference therapy with 7 days of once-daily (OD) intramuscular (IM) procaine penicillin and gentamicin for outpatient management of young infants with clinically presumed systemic bacterial infection treated in primary health-care clinics in 5 communities in Karachi, Pakistan. The reference regimen is close to the current recommendation of the hospital-based intravenous ampicillin and gentamicin therapy for neonatal sepsis. The 2 comparison arms are (1) IM gentamicin OD and oral amoxicillin twice daily for 7 days; and (2) IM penicillin and gentamicin OD for 2 days, followed by oral amoxicillin twice daily for 5 days; 2250 "evaluable" infants will be enrolled. The primary outcome of this trial is treatment failure (death, deterioration or lack of improvement) within 7 days of enrollment. Results are expected by early 2014. DISCUSSION: This trial will determine whether simplified antibiotic regimens with fewer injections in combination with high-dose amoxicillin are equivalent to 7 days of IM procaine penicillin and gentamicin in young infants with clinical severe infection. Results will have program and policy implications in countries with limited access to hospital care and high burden of neonatal deaths.

Responsive electrical stimulation suppresses epileptic seizures in rats.

BACKGROUND: A responsive electrical stimulation pattern based on our recently developed novel seizure prediction method was designed to suppress the penicillin-induced epileptic seizures. METHODOLOGY: Seizures were induced by Penicillin injection at rat cortex. A responsive electrical stimulation system was triggered prior to seizures predicted with phase synchronisation. Rats with induced seizures were stimulated by the electrical pulses at a responsive or 1 Hz periodic pattern of an open system. The effectiveness of stimulation on seizures suppression was assessed by measuring the average number and duration of seizures per hour. RESULTS: The prediction algorithm reliably identified seizures in real time and triggered the responsive stimulation. This type of electrical stimulation dramatically suppressed seizure activity and the performance was better than the open stimulation system with fewer and shorter seizures. CONCLUSIONS: A responsive electrical stimulation system triggered by the phase synchronisation prediction is able to significantly suppress seizures. SIGNIFICANCE: Responsive electrical stimulation could achieve superior treatment performance and reduce power consumption and side effects.

Life-years gained with meropenem over ciprofloxacin in penicillin-allergic patients with gram-negative bacilli sepsis: results of a probabilistic model.

STUDY OBJECTIVE: To compare meropenem with ciprofloxacin for treatment of gram-negative bacilli sepsis in penicillin-allergic patients in the intensive care unit (ICU) to determine if increased anaphylaxis risk with meropenem precluded its use when weighed against risks of inactive therapy with ciprofloxacin. DESIGN: A decision model constructed from probability distributions from the literature and data from a local ICU antibiogram. A probabilistic sensitivity analysis was performed to evaluate uncertainty in variable estimates by using one-way analyses, two-way analyses, and Monte Carlo simulation. MEASUREMENTS AND MAIN RESULTS: Microbiologic activity of treatment, anaphylaxis according to treatment regimen, curability of infection according to patient morbidity status, risk of superinfection, and recovery from gram-negative bacilli sepsis were the variables modeled. Effectiveness was defined by long-term survival and was modeled as life-years (LYs) and quality-adjusted life-years (QALYs) gained according to treatment group. Base case results were the incremental differences between the average effectiveness of each strategy calculated from the Monte Carlo simulation. Mean LYs and QALYs gained with meropenem were 9.9 (95% confidence interval [CI] 8.9-10.8) and 5.9 (95% CI 4.8-6.7), respectively. Mean LYs and QALYs gained with ciprofloxacin were 8.9 (95% CI 8.1-9.6) and 5.3 (95% CI 4.4-6.3), respectively. The incremental difference in effectiveness-or average benefit expected by selecting meropenem over ciprofloxacin-was 1.0 LY (95% CI 0.3-1.7 LYs) and 0.6 QALY (95% CI 0.2-1.1 QALYs) favoring meropenem. CONCLUSION: Use of empiric meropenem over ciprofloxacin may be justified in patients in the ICU who are allergic to penicillin.

Drug provocation tests in children: Indications and interpretation

Drug provocation tests in children are always a problematic task. In the present article the most important aspects of this technique are reviewed, including the differences between children and adults; the main mechanisms involved in drug reaction; how to perform the different tests; and when they are indicated(AU)

Hypersensitivity reactions to penicillins: studies in a group of patients with negative benzylpenicillin G skin test.

BACKGROUND: Although skin tests are usually employed to evaluate current penicillin allergy status, a negative result does not exclude hypersensitivity. There is a need for accurate in vitro tests to exclude hypersensitivity. A radioallergosorbent test (RAST) is a potentially good supplementary approach, but there is little information on the suitability of this method to diagnose penicillin hypersensitivity in subjects with a negative skin test to benzylpenicillin. METHODS: A total of 133 patients with a negative skin test to benzylpenicillin G (PG) and all of whom developed allergic reactions to PG were studied. RAST was used to detect eight kinds of specific IgE antibodies to penicillins in serum, which included four kinds of major and minor antigenic determinants to four penicillin drugs. The combination sites for the specific IgE antibodies were studied by RAST inhibition test. RESULTS: The rate of positive reactions for the specific IgE antibodies was 59.40% (79/133). Of the eight kinds of antigenic determinants, the positive rates for specific IgE against the major and minor determinants were 39.10% (52) and 42.86% (57) respectively. Of the four drugs, positive cases only to PG were 10 (7.5%), were significantly fewer than the cross-reacting positive cases (36) to PG (P < 0.01). In the RAST inhibition studies all drugs exhibited good inhibitory potencies, and in some instances the side-chain of the penicillins could induce specific responses with a variable degree of cross-reactivity among the different penicillins. CONCLUSION: Radioallergosorbent test is a good complementary test in persons who are skin-test negative with PG, and the sensitivity of RAST increases with increasing specificity of IgE antibodies to be detected. 6-APA and the groups, making part of the different side-chains on penicillins, all contributed to the cross-reactivity.