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Results of Challenge Tests According to the Type of Allergic Reaction or Timing and According to Skin Test Positivity or Negativity
Source publication
Contradictory reports of the sensitivity of skin tests in quinolone allergy have been reported. Our objectives were to describe the outcome of quinolone skin and challenge tests in patients consulting because of a history of adverse reaction to quinolone and to compare the outcome of quinolone skin tests and challenge tests in the subsample of pati...
Contexts in source publication
Context 1
... trovafl oxacin in 1 (1.4%). According to adverse reaction type, the patients were classifi ed in 4 groups: 27 in group 1, 8 in group 2, 24 in group 3 and 12 in group 4 (Table 2). ...
Context 2
... skin tests were performed in all patients and in 44 patients at least one challenge test was performed. The skin and challenge test results according to reaction type are summarized in Table 2. In group 1, 62.9 % of these patients had positive skin tests and 22.2% had positive challenge tests. ...
Citations
... Of these participants, 3 had a positive prick test for ofloxacin, 1 for moxifloxacin, and 1 for pipemidic acid. 17 In our work, both the prick test with 1:10 dilution and the intradermal test with 1:100 dilution had a specificity of 93.5%, being the most recommended concentrations for skin tests to rule out hypersensitivity to quinolones. Previous use of these drugs and ADR to other medications led to higher positivity rates at a concentration of 1:100, which may suggest previous sensitization, although the difference was not statistically significant. ...
... Drug provocation tests, on the other hand, are the preferred gold standard method to confirm quinolone allergy. [5][6][7] Evidence for cross-reactivity among quinolones is limited and conflicting. There are no specific rules for predicting cross-reactivity due to quinolones, but studies and case reports have generally reported a high degree of cross-reactivity between first-generation and second-generation agents. ...
... Although the order of quinolones varies between studies, the most frequently accused quinolones in the literature are ciprofloxacin, moxifloxacin and levofloxacin, respectively, similar to our study. 5,15,17 In another study, the accused drugs were followed as moxifloxacin, ciprofloxacin and levofloxacin, respectively. 7 It is thought that the ranking in this study may be related to their higher consumption in clinical practice compared to others. ...
INTRODUCTION: There are conflicting results regarding the sensitivity of skin tests and cross-reactions between quinolones in quinolone allergy. In our study, we aimed to evaluate the results of skin tests and provocation tests performed with quinolones and to investigate the value of these tests in the diagnosis of hypersensitivity reactions due to quinolones and their usefulness in detecting possible cross-reactions between quinolones. METHODS: We analyzed the file records of the patients who applied to our clinic for the reason of antibiotic drug allergy and who underwent diagnostic or alternative in vivo diagnostic tests with quinolone group drugs between January 2006 and September 2020. We recorded and evaluated the results of these cases with demographic characteristics such as age, gender, atopy history, concomitant allergic diseases, suspected antibiotic(s), allergic reaction type and time of occurrence, skin tests for diagnosis, and drug provocation tests. RESULTS: The study included 715 patients, 73.56% of whom were women. Of the patients, 92.72% had a history of early-type drug allergic reactions. Skin tests had been applied to 219 patients. Of the 119 skin tests performed for diagnostic purposes, 48 were positive. A provocation test was performed in 31 of these patients whose skin test was found to be sensitive; 27 of them were negative. In 47 patients, 83 safe cross-over alternative drugs were obtained through provocation tests. DISCUSSION AND CONCLUSION: Provocation tests are necessary for the diagnosis of quinolone hypersensitivity reaction and in the evaluation of cross-reactivity. Before provocation tests, evaluation should be made with skin tests.
... In vitro tests such as radioimmunoassay (RIA), basophil activation test (BAT), lymphocyte transformation test (LTT) can be used for diagnostic purpose but there are contradictory results on reliability and sensitivity. Drug provocation test (DPT) is considered gold standard when all the other tests are not available and in case of delayed hypersensitivity reaction but it is time consuming and possess the risk of severe reaction depending on dose [53,54,56]. ...
Objectives
Ciprofloxacin (CIPRO) is a fluroquinolone class antibiotic used commonly for the treatment of various acute and chronic bacterial infections. However, recently there is increase in the case reports of CIPRO-induced Cutaneous Adverse Drug Reactions (CADRs). We aim to systematically review all the descriptive studies of CIPRO induced CADRs.
Methods
Medline (via PubMed) was searched without any language or date restriction from inception to March 2019 using search terms of “Ciprofloxacin” and “Cutaneous reactions.” We included only the descriptive studies, which elucidate the CADRs experienced by the patients following the administration of CIPRO. Two reviewers involved in study selection, data extraction and quality assessment of the included studies. Discrepancies were resolved by consensus between the reviewers.
Results
Thirty-nine studies (out of 446) were found to be eligible for the final inclusion. The dose of CIPRO among the included studies was ranging from 500 to 1,000 mg/day and duration of treatment was between 7 and 10 days. The most common CADRs observed were toxic epidermal necrolysis, Stevens–Johnson syndrome, fixed drug eruptions, bullous fixed drug reaction, acute generalized pustulosis, erythema multiforme, drug rash with eosinophilia and systemic symptoms and erythema nodosum.
Conclusions
Management of the CIPRO-induced CADRs is recommended with the complete cessation of the CIPRO, followed by supportive management with oral or topical glucocorticoids, emollients, and topical moisturizers. CIPRO is likely to cause CADRs, physicians should be vigilant while prescribing it to the patients.
... 109,110,112,114 Table XII summarizes quinolone concentrations most frequently recommended in the current literature. 112,114,115 Therefore, drug challenge is the most useful diagnostic assay, and procedure-related anaphylaxis is rare in properly selected patients. Table XIII presents the recommended procedures for drug challenge tests. ...
... Recommended concentrations of quinolones for skin testing*80,112,115 ...
... The value of skin tests (STs) is uncertain, and they have shown false-positive results when quinolones are tested at high concentration. [22][23][24][25] The presence of specific IgE to quinolones has been reported using the sepharose radioimmunoassay, with a sensitivity of 54.5%. 26 The basophil activation test (BAT) has shown promising results for the diagnosis of patients with IRs to quinolones. ...
... In our study, more than 50% of patients reported anaphylaxis, most of whom suffered from IRs, in agreement with previously published short series. 24,26,27,30,34 Moreover, data suggest that the risk of an HSR is different depending on the quinolone. Analyses of spontaneous reports implicate that moxifloxacin triggers anaphylaxis in a higher proportion of cases than levofloxacin or ciprofloxacin, 8,9,37 which is in line with our results. ...
... Some authors consider they are useful, with a sensitivity of 71%, specificity of 86%, and positive and negative predictive values of 50% and 94%, respectively, having been reported previously. 24 However, other studies suggest that STs are not valid because they can produce false-negatives, 34,35 potentially missing important reactions and putting patients at risk; moreover, they can produce a large number of false-positive results when tested at high concentrations, which is attributed to nonspecific histamine release by quinolones due to mast cell activation. 35,[43][44][45][46][47][48] We decided not to perform intradermal tests in our patients on the basis of this consideration. ...
Background
Quinolones are the second most frequent cause of hypersensitivity reactions (HSRs) to antibiotics. A marked increase in the number of patients with HSRs to quinolones has been detected.
Objective
To describe the clinical characteristics of patients with HSRs to quinolones and present methods for their diagnosis.
Methods
Patients attending the allergy unit due to reactions suggestive of HSRs to quinolones were prospectively evaluated between 2005-2018. Diagnosis was achieved using clinical history, skin tests (STs), basophil activation tests (BATs), and drug provocation tests (DPTs) if ST and BAT were negative.
Results
We included 128 subjects confirmed as having HSRs to quinolones and 42 found to be tolerant. Anaphylaxis was the most frequent entity in immediate HSRs and was most commonly induced by moxifloxacin. Patients were evaluated a median of 150 days (interquartile range: 60-365) after the reaction. Of patients who underwent ST and BAT, 40.7% and 70% respectively were positive. DPT with a quinolone was performed in 48 cases, giving results depending on the culprit drug: when moxifloxacin was involved, 62.5% of patients gave a positive DPT to ciprofloxacin, whilst none reacted to levofloxacin. The risk of HSR was 96 times higher in subjects who reported moxifloxacin-induced anaphylaxis and 18 times higher in those reporting immediate reactions compared to clinical entities induced by quinolones other than moxifloxacin and non-immediate reactions.
Conclusions
The diagnosis of HSR to quinolones is complex. The use of clinical history is essential as a first step. BAT shows higher sensitivity than STs. DPTs can be useful for finding safe alternative quinolones.
... Delayed urticaria and maculopapular exanthemas (MPE) are the most common NIRs, being usually not severe [12,15,37,68,69] ( Table 1) (level of evidence 2+). Ciprofloxacin has been reported as the main responsible [12], although other quinolones can be involved [12,15,[68][69][70] (level of evidence 2+). Another common type of NIR is fixed drug eruption (FDE) [12,68], which has been reported with ciprofloxacin [12,71], norfloxacin [12,72], levofloxacin [73], moxifloxacin [12], and gemifloxacin [37], with the possibility of cross-reactivity among them described [71][72][73][74] In addition, less frequent entities such as SJS and TEN have been reported [76], being quinolones described as a causative agent in 8.48% of this type of reactions [76] (level of evidence 3). ...
... The sensitivity of STs is estimated to range from 41% to 80%, with specificity ranging from 46.5% for all STs to 29% for IDTs [12,37,70,122,123] (level of evidence 2-). The positive predictive value has been reported to range from 14.8% for all STs to 12% for IDTs [45,123,125] and the negative predictive value of 94-95.2% for all STs and 90% ...
... for IDTs [45,123], similarly to other publications [37,70,122,123] (level of evidence 2-). Due to the facts that most of studies include a low number of patients, that quinolones produce a large number of false-positive results attributed to non-specific histamine release, mainly by IDTs [38,40], and that the negative value of STs is For NIRs, the evaluation includes delayed-reading IDTs and patch tests (PTs) [100]. ...
Over recent years, the consumption of quinolones as first-line treatment has increased, leading to a growth in incidence of hypersensitivity reactions (HSRs) to this group of antibiotics. Both diagnosis and management of HSRs to quinolones are complex and controversial. These practical guidelines aim to provide recommendations for an effective clinical practice. With this purpose, an expert panel reviewed the literature regarding HSRs to quinolones and analyzed controversies in this area. Most HSRs to these drugs are immediate and severe, being the risk for HSR higher in subjects who reported allergy to betalactams, moxifloxacin-induced anaphylaxis and immediate reactions (IRs) compared with patients who reported reactions to quinolones inducing other symptoms. Regarding diagnosis of HSRs to quinolones, the usefulness of skin tests is controversial, with sensitivity and specificity varying among studies. Most in vitro tests are produced in-house, with no validated commercial ones and basophil activation test being useful for diagnosing IRs although with diverse results regarding sensitivity. Drug provocation test is nowadays the gold standard for confirming or excluding the diagnosis as well as to find safe alternatives, although contraindicated for severe reactions. Cross-reactivity among quinolones is controversial among different studies, with the lowest cross-reactivity for levofloxacin. Desensitization may be considered in allergy to quinolones when no other alternative exist.
... In cases where patient history is not reliable, other diagnostic tests may be necessary to assess quinolone allergy. In recent years, multiple studies have been conducted to evaluate various diagnostic tests including skin tests, drug provocation tests (DPT), and in-vitro laboratory tests [24,[27][28][29][30][31][32][33][34][35][36][37][38]. However, skin tests and in vitro tests have displayed low sensitivity and specificity, limiting their diagnostic utility [24,30,32,33,35,36,38]. ...
... In recent years, multiple studies have been conducted to evaluate various diagnostic tests including skin tests, drug provocation tests (DPT), and in-vitro laboratory tests [24,[27][28][29][30][31][32][33][34][35][36][37][38]. However, skin tests and in vitro tests have displayed low sensitivity and specificity, limiting their diagnostic utility [24,30,32,33,35,36,38]. ...
... Therefore, it is recommended that the procedure be performed after weighing the risks vs. the benefits and by trained personnel in a clinical setting where treatment for possible severe reactions is readily available [6,36]. Different doses and numbers of test doses have been utilized for a DPT, as depicted in Table 1 [5,6,8,15,25,[32][33][34]36]. The initial dose is typically 1/100th of the usual full dose and is progressively increased to reach a therapeutic dose. ...
Quinolones are the second most common antibiotic class associated with drug-induced allergic reactions, but data on quinolone allergy are scarce. This review article discusses the available evidence on quinolone allergy, including prevalence, risk factors, diagnosis, clinical manifestations, cross-reactivity, and management of allergic reactions. Although the incidence of quinolone allergy is still lower than beta-lactams, it has been increasingly reported in recent decades, most likely from its expanded use and the introduction of moxifloxacin. Thorough patient history remains essential in the evaluation of quinolone allergy. Many diagnostic tools have been investigated, but skin tests can yield false-positive results and in vitro tests have not been validated. The drug provocation test is considered the test of choice to confirm a quinolone allergy but is not without risk. Evidence regarding cross-reactivity among the quinolones is limited and conflicting. Quinolone allergy can be manifested either as an immediate or delayed reaction, but is not uniform across the class, with moxifloxacin posing the highest risk of anaphylaxis. Quinolone should be discontinued when an allergic reaction occurs and avoided in future scenarios, but desensitization may be warranted if no alternatives are available.
... If the results were negative, intradermal tests were performed with the culprit drugs in 3 incremental dilutions (1: 1,000, 1: 100, and 1: 10) if they had a parenteral form. The intradermal tests were interpreted 20 min after the injection, and wheals > 5 mm were considered positive [35,36]. SPTs and intradermal testing with drugs were performed with the commercial forms of the drugs as described in the literature [31,37]. ...
Aim: To investigate the potential risk factors in patients who have experienced anaphylaxis from drugs. Method: The study included 281 adult patients (median age 40 years; 76.5% female) who experienced immediate types of hypersensitivity reaction to a drug. The patients were divided into an anaphylaxis group and a nonanaphylaxis group. The anaphylaxis group was diagnosed according to the criteria of the World Allergy Organization. Skin testing with culprit drugs was performed. In the nonanaphylaxis group, drug provocation tests were performed with culprit drugs, including aspirin or diclofenac, to determine nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Atopy was determined by skin prick tests with the common inhalant allergens. Patients' demographics, clinical features, and baseline tryptase and total IgE levels were compared between the 2 groups. Results: The median interval between the last reaction in the patient's history and the study evaluation was 7 months (range 1-120 months). In 52.3% of the patients, reactions were defined as anaphylaxis. The most common culprit drugs were NSAIDs (56.9%) and β-lactams (34.7%). The culprit drugs were used parenterally in 13.2% of the patients. 34.9% of the patients had comorbid diseases and 24.6% used additional drugs, the most common being antihypertensives (10%). Atopy was determined in 28.8% and 28.1% of the patients were smokers. The median serum level of baseline tryptase and total IgE was 3.5 μg/L and 77 kU/L, respectively. In 46.3% of the patients, skin tests with culprit drugs were positive and the positivity ratio was higher in the anaphylaxis group (p = 0.002). Anapyhlaxis was more common in patients who were: hypertensive, atopic, using angio-tensin-converting enzyme inhibitors/angiotensin receptor blockers, and received the culprit drug parenterally (p = 0.034, p = 0.04, p = 0.03, p = 0.035, p = 0.013, and p < 0.001). In the multivariate analysis, it was observed that the parenteral usage of the drug and the presence of atopy were significantly higher in the anaphylaxis group (p < 0.001, odds ratio [OR] = 20.05, confidence interval [CI] 4.75-88.64; p = 0.012, OR = 2.1, CI 1.17-3.74). Age, smoking, family history, and serum levels of baseline tryptase and total IgE did not differ between groups. Conclusion: The parenteral route and atopy increase the risk of drug-induced anaphylaxis. IgE-mediated sensitivity to the culprit drug seems to facilitate anaphylaxis.
... Quinolones have been increasingly used in children and adults, particularly in those with CF, and immediate and nonimmediate allergic reactions have become more commonly reported [64,144,145]. Skin testing and in vitro tests are not considered a completely reliable tool for diagnosing HSR to quinolones, mainly because it can induce both false-positive and false-negative results [87,97,98,101,102,104,146]. Therefore, DPT is considered the gold standard in the diagnosis of nonsevere HSR to quinolones [146][147][148]. ...
... Skin testing and in vitro tests are not considered a completely reliable tool for diagnosing HSR to quinolones, mainly because it can induce both false-positive and false-negative results [87,97,98,101,102,104,146]. Therefore, DPT is considered the gold standard in the diagnosis of nonsevere HSR to quinolones [146][147][148]. A broad pattern of crossreactivity among quinolones was demonstrated in patients with IgE-mediated and non-IgE-mediated DHR [144,147,148]. ...
... The best approach is to avoid all quinolones in cases with suspected quinolone allergy. Alternatively, if a quinolone is required, it is prudent to perform skin tests and especially DPT thereafter with the other quinolones, in order to find a safe one [146][147][148]. ...
Purpose of studyCystic fibrosis (CF) is a complex genetic disease with high mortality, of which 85% is a result of lung disease characterized by serious endobronchial infections. Recent findingsAntibiotic therapy is one of the main treatments of CF, both during acute exacerbations and as chronic maintenance medications, contributing to a prolonged survival. Since neonatal CF screening programs have been implemented universally and the longevity of patients with CF steadily increases, antibiotic hypersensitivity reactions (HSRs) are becoming more important. HSR to antibiotics in CF has been reported since the 1980s and was estimated to occur up to three times more frequently in these patients, probably owing to high rates of antibiotic exposure and boosting stimuli such as infections and inflammation. However, recent studies including large groups of CF patients with a suspicion of antibiotic allergy have used diagnostic algorithms including skin tests and drug provocation tests and showed that true incidence was much lower. The mechanism of the reactions and the clinical presentations are not different in CF than in the general population. Both the immediate and nonimmediate type HSRs are seen, and among the latter, drug fever and drug-induced hemolytic anemia are distinctive presentations. Beta-lactam (BL) agents are the most common cause, with higher rates for ureidopenicillins (piperacillin, mezlocillin, and piperacillin/tazobactam) and cephalosporins (especially ceftazidime), intermediate rates for carbapenems, and lowest rates for aztreonam, and also HSRs to aminoglycosides, macrolides, and quinolones are encountered. Since the available choices for antibiotic therapy are limited due to relevant organisms, management becomes a challenge. It is essential to evaluate the patients according to the mechanism of the HSR and determine the risk of repeat administration of the culprit drug and also safety of alternative drugs with prior skin and provocation tests. The chemical structure and side chains must be taken into account when selecting a safe alternative drug. SummaryContrary to what was previously thought, recent data on cross-reactions between BL antibiotics showed that some BLs can be an option of treatment for patients allergic to other BLs. Desensitization is a useful procedure in immediate and some delayed reactions, if a suitable alternative antibiotic is not available.
... However, skin tests have been shown to give a sensitivity of up to 71% and a specificity of up to 86%, with positive and negative predictive values of up to 50 and 94%, respectively [11], suggesting that a specific IgE mechanism might explain a high proportion of cases of immediate hypersensitivity to quinolones. Moreover, quinolone-specific serum IgE has been detected using radioimmunoassay in up to 55% of patients experiencing immediate hypersensitivity reactions to quinolones [8,12]. ...
