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Michael E Pichichero - One of the best experts on this subject based on the ideXlab platform.
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Comparison of European and U.S. results for Cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis
European Journal of Clinical Microbiology and Infectious Diseases, 2006Co-Authors: Michael E Pichichero, J. CaseyAbstract:The outcome of Cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis may differ between Europe and the USA. In the present study, Medline, Embase, reference lists, and abstract searches were used to identify randomized, controlled trials of Cephalosporin versus penicillin treatment of group A streptococcal (GAS) tonsillopharyngitis. The outcomes of interest were bacteriologic and clinical cure rates from investigations conducted in Europe versus those conducted in the USA. Forty-seven trials involving 11,426 patients were included in the meta-analyses. For the comparison of 10 days of treatment with Cephalosporins versus 10 days of treatment with penicillin, there were ten European and 25 U.S. trials, all involving pediatric subjects. The overall odds ratio (OR) favored Cephalosporins more strongly in bacteriologic cure rate in Europe (OR=4.27, p
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meta analysis of Cephalosporin versus penicillin treatment of group a streptococcal tonsillopharyngitis in children
Pediatrics, 2004Co-Authors: Janet R Casey, Michael E PichicheroAbstract:Objective. To conduct a meta-analysis of randomized, controlled trials of Cephalosporin versus penicillin treatment of group A β-hemolytic streptococcal (GABHS) tonsillopharyngitis in children. Methodology. Medline, Embase, reference lists, and abstract searches were conducted to identify randomized, controlled trials of Cephalosporin versus penicillin treatment of GABHS tonsillopharyngitis in children. Trials were included if they met the following criteria: patients Results. Thirty-five trials involving 7125 patients were included in the meta-analysis. The overall summary odds ratio (OR) for the bacteriologic cure rate significantly favored Cephalosporins compared with penicillin (OR: 3.02; 95% confidence interval [CI]: 2.49–3.67, with the individual Cephalosporins [cephalexin, cefadroxil, cefuroxime, cefpodoxime, cefprozil, cefixime, ceftibuten, and cefdinir] showing superior bacteriologic cure rates). The overall summary OR for clinical cure rate was 2.33 (95% CI: 1.84–2.97), significantly favoring the same individual Cephalosporins. There was a trend for diminishing bacterial cure with penicillin over time, comparing the trials published in the 1970s, 1980s, and 1990s. Sensitivity analyses for bacterial cure significantly favored Cephalosporin treatment over penicillin treatment when trials were grouped as double-blind (OR: 2.31; 95% CI: 1.39–3.85), high-quality (OR: 2.50; 95% CI: 1.85–3.36) trials with well-defined clinical status (OR: 2.12; 95% CI: 1.54–2.90), with detailed compliance monitoring (OR: 2.85; 95% CI: 2.33–3.47), with GABHS serotyping (OR: 3.10; 95% CI: 2.42–3.98), with carriers eliminated (OR: 2.51; 95% CI: 1.55–4.08), and with test of cure 3 to 14 days posttreatment (OR: 3.53; 95% CI: 2.75–4.54). Analysis of comparative bacteriologic cure rates for the 3 generations of Cephalosporins did not show a difference. Conclusions. This meta-analysis indicates that the likelihood of bacteriologic and clinical failure of GABHS tonsillopharyngitis is significantly less if an oral Cephalosporin is prescribed, compared with oral penicillin.
Antonino Romano - One of the best experts on this subject based on the ideXlab platform.
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Chapter 11 – Cephalosporin Allergy
Drug Allergy Testing, 2018Co-Authors: Antonino Romano, Rocco Luigi Valluzzi, Francesco GaetaAbstract:Like penicillins, Cephalosporins may cause both IgE-mediated and T cell–mediated allergic reactions. The former usually occurs within the first hour after the last drug administration (i.e., immediate reactions) and is manifested as urticaria, angioedema, and anaphylaxis. T cell–mediated reactions occur at least 1 hour after the initial drug administration (i.e., nonimmediate reactions) and are manifested mostly as maculopapular exanthemas. Cephalosporin hypersensitivity reactions occur because of sensitization to determinants shared with penicillins or to unique Cephalosporin haptens. In particular, side-chain structures may be responsible for selective sensitization or cross-reactivity. For this reason, individual free Cephalosporins are usually employed in skin testing, in addition to the classic penicillin reagents. Cephalosporin skin tests are sensitive in diagnosing immediate reactions. Nonimmediate reactions can be evaluated by both patch tests and delayed-reading skin tests. In the case of severe reactions, patch tests should be used as the first line of investigation. In vitro tests can be used as complementary tests. In selected cases displaying negative results in allergy tests, graded challenges with the implicated Cephalosporins can be carried out. Performing allergy tests with Cephalosporins other than the culprit, as well as with penicillin reagents, allows the identification of cross-reactivity with penicillins, selective responses, or cross-reactivity among Cephalosporins. In the latter group, cross-reactivity is more frequently related to R1 than R2 side-chain recognition. Cephalosporin hypersensitivity does not seem to be a class hypersensitivity. In assessing Cephalosporin-allergic subjects, negative results in skin testing with Cephalosporins other than the responsible one appear to be a reliable indicator of tolerability.
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IgE-mediated hypersensitivity to Cephalosporins: Cross-reactivity and tolerability of alternative Cephalosporins
The Journal of allergy and clinical immunology, 2015Co-Authors: Antonino Romano, Rocco Luigi Valluzzi, Francesco Gaeta, Cristiano Caruso, Michela Maggioletti, Alessandra Zaffiro, Donato QuaratinoAbstract:Background Studies regarding the cross-reactivity and tolerability of alternative Cephalosporins in large samples of subjects with an IgE-mediated hypersensitivity to Cephalosporins are lacking. Objective We sought to evaluate the possibility of using alternative Cephalosporins in subjects with Cephalosporin allergy who especially require them. Methods One hundred two subjects with immediate reactions to Cephalosporins and positive skin test results to the responsible drugs underwent serum specific IgE assays with cefaclor and skin tests with different Cephalosporins. Subjects were classified in 4 groups: group A, positive responses to 1 or more of ceftriaxone, cefuroxime, cefotaxime, cefepime, cefodizime, and ceftazidime; group B, positive responses to aminoCephalosporins; group C, positive responses to Cephalosporins other than those belonging to the aforementioned groups; and group D, positive responses to Cephalosporins belonging to 2 different groups. Group A subjects underwent challenges with cefaclor, cefazolin, and ceftibuten; group B participants underwent challenges with cefuroxime axetil, ceftriaxone, cefazolin, and ceftibuten; and group C and D subjects underwent challenges with some of the aforementioned Cephalosporins selected on the basis of their patterns of positivity. Results There were 73 subjects in group A, 13 in group B, 7 in group C, and 9 in group D. Challenges with alternative Cephalosporins (ceftibuten in 101, cefazolin in 96, cefaclor in 82, and cefuroxime axetil and ceftriaxone in 22 subjects) were well tolerated. Conclusions Cephalosporin hypersensitivity does not seem to be a class hypersensitivity. Subjects with Cephalosporin allergy who especially require alternative Cephalosporins might be treated with compounds that have side-chain determinants different from those of the responsible Cephalosporins and have negative pretreatment skin test responses.
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Diagnosing nonimmediate reactions to Cephalosporins.
The Journal of allergy and clinical immunology, 2012Co-Authors: Antonino Romano, Rocco Luigi Valluzzi, Francesco Gaeta, Marinella Viola, Cristiano Caruso, C. Alonzi, Philippe BousquetAbstract:Summary Background After penicillins, Cephalosporins are the betalactams that most often induce IgE-mediated reactions. The development of diagnostic tests has been delayed, however, because the Cephalosporin allergenic determinants have not been properly identified. Objective To evaluate the usefulness of skin tests, serum specific IgE assays, and challenges in diagnosing immediate reactions to Cephalosporins and to clarify the pathogenic mechanism of such reactions. Methods We studied 76 adults with immediate reactions to Cephalosporins, mainly ceftriaxone, cefotaxime, and ceftazidime. Skin tests and serum specific IgE assays were performed for culprit Cephalosporins and cefaclor, as well as for penicillin, amoxicillin, and ampicillin. Some subjects with negative results underwent challenges and re-evaluations. Responses to Cephalosporins other than the culprit ones were also studied. Results In the first allergologic work-up, an IgE-mediated hypersensitivity to penicillins and/or Cephalosporins was diagnosed in 63 (82.9%) of the 76 patients on the basis of skin-test and/or specific IgE assay positivity. Of the 13 negative patients, eight accepted challenges and underwent re-evaluations. Considering both first- and second-evaluation results, the skin-test-positivity rate increased from 76.3% to 85.5% and that of sepharose-radioimmunoassay positivity from 67.1% to 74.3%. Overall, an IgE-mediated hypersensitivity was diagnosed in 70 patients (in seven after retesting). On the basis of skin-test and CAP-FEIA results, we classified our 76 patients into five groups: group A (three patients), positive only to penicillin reagents; B (17), positive to both Cephalosporin and penicillin reagents; C (24), positive to more than one Cephalosporin; D (21), positive only to the responsible Cephalosporin; E (11) negative to skin tests and CAP-FEIA, including five sepharose-radioimmunoassay positive. Conclusions Most immediate reactions to Cephalosporins appear to be IgE-mediated. Cephalosporin skin testing and sepharose-radioimmunoassay are useful tools for evaluating these reactions. Cephalosporin IgE-mediated hypersensitivity may be a transient condition; therefore, allergologic exams should be repeated in patients with negative initial allergologic work-ups, including challenges.
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IgE-Mediated Hypersensitivity to Cephalosporins
Current pharmaceutical design, 2006Co-Authors: Jean-louis Guéant, Rocco Luigi Valluzzi, Rosa-maria Guéant-rodriguez, Marinella Viola, Antonino RomanoAbstract:Like penicillins, Cephalosporins may cause IgE-mediated reactions such as urticaria, angioedema, and anaphylactic shock, which occur because of sensitization to determinants shared with penicillins or to unique Cephalosporin haptens. In particular, side-chain structures may be responsible for selective sensitization or cross-reactivity. For this reason, individual free Cephalosporins are usually employed in skin testing, in addition to the classic penicillin reagents. Cephalosporin skin tests are sensitive in diagnosing immediate hypersensitivity to these betalactams. As far as in vitro tests are concerned, IgE assays for Cephalosporins, specifically sepharose-radioimmunoassays, are a potentially useful tool in evaluating immediate reactions and could be used as complementary tests. In selected cases displaying negative results in both skin tests and IgE assays, a graded challenge with the implicated Cephalosporin can be performed. Cephalosporin IgE-mediated hypersensitivity may be a transient condition; therefore, allergologic exams should be repeated in patients with negative initial allergologic work-ups, including challenges. Performing allergologic tests with Cephalosporins other than the culprit, as well as with penicillin reagents, allows the identification of cross-reactivity with penicillins, selective responses, or cross-reactivity among Cephalosporins. In the latter group, cross-reactivity is more frequently related to R1 than to R2 side-chain recognition. In assessing the selectivity of the response, negative results in skin testing with Cephalosporins other than the responsible one appear to be a reliable indicator of tolerability.
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Immediate hypersensitivity to Cephalosporins.
Allergy, 2002Co-Authors: Antonino Romano, Cristobalina Mayorga, Jean-louis Guéant, M.j. Torres, Farès Namour, Maria Cristina Artesani, A. Venuti, M. BlancaAbstract:Like penicillins, Cephalosporins may provoke allergic reactions, especially IgE-mediated ones, such as urticaria and anaphylactic shock. They may occur because of sensitization to determinants shared with penicillins or to unique Cephalosporin haptens. Skin tests are sensitive in diagnosing immediate hypersensitivity to Cephalosporins, but their sensitivity appears to decrease with time. For evaluating immediate reactions to Cephalosporins, it is crucial to test the suspect drug in addition to penicillin determinants. In fact, allergic reactions to Cephalosporins, especially second- and third-generation ones, may not be detected by tests performed only with penicillin determinants, particularly in cases where side chains are important in sensitization. As far as in vitro tests are concerned, IgE assays for Cephalosporins are a potentially useful tool in evaluating immediate reactions. Even though they appear to be less sensitive than skin tests, IgE assays could be used as complementary tests, as has been observed in penicillin-allergic subjects. In assessing the selectivity of the response, negative results in skin testing with Cephalosporins other than the culprit one appear to be a reliable indicator of tolerability.
Robert E Reisman - One of the best experts on this subject based on the ideXlab platform.
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risk of administering Cephalosporin antibiotics to patients with histories of penicillin allergy
Annals of Allergy Asthma & Immunology, 1995Co-Authors: Suresh Anne, Robert E ReismanAbstract:OBJECTIVES: The purpose of this review was to analyze available relevant data regarding the safety of administering Cephalosporins to penicillin-allergic patients, including the significance of penicillin skin test reactions and any difference related to first, second, or third generation Cephalosporins. BACKGROUND: Penicillin and Cephalosporins both contain a beta-lactam ring. This structural similarity has led to considerable confusion about the cross-allergenicity of these drugs and the risks of allergic reactions from Cephalosporins in penicillin-allergic patients. METHODS: Published reports and post-marketing data from pharmaceutical corporations provided the basis for this analysis. RESULTS: The overall incidence of adverse reactions from Cephalosporins ranges from 1% to 10%, with rare anaphylaxis (< 0.02%). In patients with histories of penicillin allergy the incidence of Cephalosporin reactions is minimally, if at all increased. Post-marketing studies of second and third generation Cephalosporins showed no increase in allergic reactions in patients with penicillin allergy histories. Penicillin skin tests do not predict the likelihood of allergic reactions to Cephalosporins in patients with histories of penicillin allergy. One reaction occurred in 98 patients (1%) with positive penicillin skin tests and six reactions occurred in 310 patients (2%) with negative tests. CONCLUSIONS: These data indicate that it is safe to administer Cephalosporin antibiotics to penicillin-allergic patients and penicillin skin tests do not identify potential reactors.
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risk of administering Cephalosporin antibiotics to patients with histories of penicillin allergy
Annals of Allergy Asthma & Immunology, 1995Co-Authors: Suresh Anne, Robert E ReismanAbstract:Objectives: The purpose of tits review was to analyze available relevant data regarding the safety of administering Cephalosporins to penicillin-allergic patients, including the significance of penicillin skin test reactions and any difference related to first, second, or third generation Cephalosporins. Background: Penicillin and Cephalosporins both contain a beta-lactam ring. This structural similarity has led to considerable confusion about the cross-allergenicity of these drugs and the risk of allergic reactions from Cephalosporins in penicillin-allergic patients. Methods: Published reports and post-marketing data from pharmaceutical corporations provided the basis for this analysis. Results: The overall incidence of adverse reactions from Cephalosporins ranges from 1% to 10%, with rare anaphylaxis (<0.02%). In patients with histories of penicillin allergy the incidence of Cephalosporin reactions is minimally, if at all increased. Post-marketing studies of second and third generation Cephalosporins showed no increase in allergic reactions in patients with penicillin allergy histories. Penicillin skin tests do not predict the likelihood of allergic reactions to Cephalosporins in patients with histories of perucillin allergy. One reaction occurred in 98 patients (1%) with positive penicillin skin tests and six reactions occurred in 310 patients (2%) with negative tests. Conclusions: These data indicate that it is safe to administer Cephalosporin antibiotics to penicillin-allergic patients and penicillin skin tests do not identify potential reactors
J. Casey - One of the best experts on this subject based on the ideXlab platform.
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Comparison of European and U.S. results for Cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis
European Journal of Clinical Microbiology and Infectious Diseases, 2006Co-Authors: Michael E Pichichero, J. CaseyAbstract:The outcome of Cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis may differ between Europe and the USA. In the present study, Medline, Embase, reference lists, and abstract searches were used to identify randomized, controlled trials of Cephalosporin versus penicillin treatment of group A streptococcal (GAS) tonsillopharyngitis. The outcomes of interest were bacteriologic and clinical cure rates from investigations conducted in Europe versus those conducted in the USA. Forty-seven trials involving 11,426 patients were included in the meta-analyses. For the comparison of 10 days of treatment with Cephalosporins versus 10 days of treatment with penicillin, there were ten European and 25 U.S. trials, all involving pediatric subjects. The overall odds ratio (OR) favored Cephalosporins more strongly in bacteriologic cure rate in Europe (OR=4.27, p
Keith P Klugman - One of the best experts on this subject based on the ideXlab platform.
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in vitro evaluation of the antimicrobial activity of ceftaroline against Cephalosporin resistant isolates of streptococcus pneumoniae
Antimicrobial Agents and Chemotherapy, 2009Co-Authors: Donald Biek, Yigong Ge, Magderie Klugman, Mignon Du Plessis, Anthony M Smith, Cynthia G Whitney, Bernard Beall, Lesley Mcgee, Keith P KlugmanAbstract:Increasing pneumococcal resistance to extended-spectrum Cephalosporins warrants the search for novel agents with activity against such resistant strains. Ceftaroline, a parenteral Cephalosporin currently in phase 3 clinical development, has demonstrated potent in vitro activity against resistant gram-positive organisms, including penicillin-resistant Streptococcus pneumoniae. In this study, the activity of ceftaroline was evaluated against highly cefotaxime-resistant isolates of pneumococci from the Active Bacterial Core surveillance program of the Centers for Disease Control and Prevention and against laboratory-derived Cephalosporin-resistant mutants of S. pneumoniae . The MICs of ceftaroline and comparators were determined by broth microdilution. In total, 120 U.S. isolates of cefotaxime-resistant (MIC ≥ 4 μg/ml) S. pneumoniae were tested along with 18 laboratory-derived R6 strains with known penicillin-binding protein (PBP) mutations. Clinical isolates were characterized by multilocus sequence typing, and the DNAs of selected isolates were sequenced to identify mutations affecting pbp genes. Ceftaroline (MIC 90 = 0.5 μg/ml) had greater in vitro activity than penicillin, cefotaxime, or ceftriaxone (MIC 90 = 8 μg/ml for all comparators) against the set of highly Cephalosporin-resistant clinical isolates of S. pneumoniae . Ceftaroline was also more active against the defined R6 PBP mutant strains, which suggests that ceftaroline can overcome common mechanisms of PBP-mediated Cephalosporin resistance. These data indicate that ceftaroline has significant potency against S. pneumoniae strains resistant to existing parenteral Cephalosporins and support its continued development for the treatment of infections caused by resistant S. pneumoniae strains.
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outcome of Cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended spectrum β lactamases implications for the clinical microbiology laboratory
Journal of Clinical Microbiology, 2001Co-Authors: Keith P Klugman, David L Paterson, Anne Von Gottberg, Jose Maria Casellas, Lutfiye Mulazimoglu, Robert A Bonomo, Louis B Rice, J G MccormackAbstract:Although extended-spectrum beta-lactamases (ESBLs) hydrolyze Cephalosporin antibiotics, some ESBL-producing organisms are not resistant to all Cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia coli for ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology laboratories did not make efforts to detect ESBLs. We performed a prospective, multinational study of Klebsiella pneumoniae bacteremia and identified 10 patients who were treated for ESBL-producing K. pneumoniae bacteremia with Cephalosporins and whose infecting organisms were not resistant in vitro to the utilized Cephalosporin. In addition, we reviewed 26 similar cases of severe infections which had previously been reported. Of these 36 patients, 4 had to be excluded from analysis. Of the remaining 32 patients, 100% (4 of 4) patients experienced clinical failure when MICs of the Cephalosporin used for treatment were in the intermediate range and 54% (15 of 28) experienced failure when MICs of the Cephalosporin used for treatment were in the susceptible range. Thus, it is clinically important to detect ESBL production by klebsiellae or E. coli even when Cephalosporin MICs are in the susceptible range (≤ 8 μg/ml) and to report ESBL-producing organisms as resistant to aztreonam and all Cephalosporins (with the exception of cephamycins).