Drug eruption to clavulanic acid with sparing of cellulitis-affecting site

Kamiya, Eri; Kamiya, Yasunari; Niwa, Miwako; Saito, Akitoshi; Natsume, Tadashi; Niwa, Haruo; Tokura, Y.

doi:10.1016/j.alit.2014.12.007

Cited by 6 publications

(6 citation statements)

References 5 publications

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“…For instance, despite the effectiveness of amoxicillin/CA in the treatment against pathogenic bacteria with resistance to β-lactam antibiotics, it is also considered one of the most frequently associated drugs with drug injury; however, further studies are required to analyze drug integration between amoxicillin/CA and concomitant potential hepatotoxic drugs [23,24,25]. Additionally, some drug eruption to CA has been reported, e.g., a patient developed a drug eruption on the day following amoxicillin and CA administration, which was considered a delayed hypersensitivity reaction [26]. These negative effects on human health should eventually be considered for future research.…”

Section: Resultsmentioning

confidence: 99%

Bibliometric Analysis of Global Research on Clavulanic Acid

Ramírez-Malule

2018

Antibiotics

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Clavulanic acid (CA), a potent inhibitor of the β-lactam, ase enzyme, is frequently co-formulated with a broad spectrum of antibiotics to treat infections caused by β-lactamase-producing pathogens. In order to evaluate the impact and the progress of CA studies in the last four decades, a bibliometric analysis of the global scientific production of CA was carried out. A total of 39,758 records in the field of CA were indexed in the Scopus database for a 43-year period of study (1975–2017). The results indicated that CA studies have grown, showing three phases (1975–1999, 2000–2003 and 2004–2017) based on records of publications; the results showed a sigmoidal profile. Medicine was the main subject area for CA studies, whereas biochemistry, genetics and molecular biology were areas of research for CA production by Streptomyces clavuligerus (S. clavuligerus). Nevertheless, chemical engineering (as a subject area) had the highest increase in the percentage of publications related to CA production by S. clavuligerus. The United States, France, the United Kingdom, Spain and Brazil were the leading countries in the scientific production of studies on both CA and CA related to S. clavuligerus. This analysis allowed the identification of the area of knowledge with the highest impact on CA studies, the top researchers and their geographic distribution, and also helped to highlight the existence of antibiotic-resistant bacteria as an emergent area in CA research.

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Section: Resultsmentioning

confidence: 99%

Bibliometric Analysis of Global Research on Clavulanic Acid

Ramírez-Malule

2018

Antibiotics

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“…For example, addition of clavulanic acid to amoxicillin has been shown to increase the risk of drug-induced liver injury . Many hypersensitivity reactions are mediated by the amoxicillin component of the drug combination; however, we have demonstrated that certain patients develop clavulanic acid-specific reactions. − , Clavulanic acid-hypersensitive subjects tolerate other β-lactam antibiotics, including amoxicillin, presumably because of the formation of distinct antigenic determinants. Very little is known about the cellular mechanisms of β-lactamase inhibitor hypersensitivity reactions and T-cell crossreactivity between different β-lactamases inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…Clavulanic acid was initially considered as nonimmunogenic when first marketed in combination with amoxicillin . However, it has recently been reported to contribute to the hypersensitivity reactions in patients receiving amoxicillin-clavulanic acid. − Additionally, selective IgE- and T-cell-mediated reactions to clavulanic acid, with tolerance to amoxicillin, have been reported. − Piperacillin-responsive T-cells are commonly detected in piperacillin-tazobactam hypersensitive patients; however, in rare cases, tazobactam-specific peripheral blood mononuclear cell (PBMC) activation has been detected (unpublished data). Based on the structure of the β-lactamase inhibitors, it is assumed that the risk for crossreactivity to β-lactam antibiotics would be rare .…”

Section: Introductionmentioning

confidence: 99%

“… 12 − 14 Additionally, selective IgE- and T-cell-mediated reactions to clavulanic acid, with tolerance to amoxicillin, have been reported. 12 − 17 Piperacillin-responsive T-cells are commonly detected in piperacillin-tazobactam hypersensitive patients; 18 however, in rare cases, tazobactam-specific peripheral blood mononuclear cell (PBMC) activation has been detected (unpublished data). Based on the structure of the β-lactamase inhibitors, it is assumed that the risk for crossreactivity to β-lactam antibiotics would be rare.…”

Section: Introductionmentioning

confidence: 99%

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Shared Clavulanate and Tazobactam Antigenic Determinants Activate T-Cells from Hypersensitive Patients

Ariza

Jaruthamsophon

Meng

et al. 2022

Chem. Res. Toxicol.

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β-Lactamase inhibitors such as clavulanic acid and tazobactam were developed to overcome β-lactam antibiotic resistance. Hypersensitivity reactions to these drugs have not been studied in detail, and the antigenic determinants that activate T-cells have not been defined. The objectives of this study were to (i) characterize clavulanate-and tazobactam-responsive Tcells from hypersensitive patients, (ii) explore clavulanate and tazobactam Tcell crossreactivity, and (iii) define the antigenic determinants that contribute to T-cell reactivity. Antigen specificity, pathways of T-cell activation, and crossreactivity with clavulanate-and tazobactam-specific T-cell clones were assessed by proliferation and cytokine release assays. Antigenic determinants were analyzed by mass spectrometry-based proteomics methods. Clavulanateand tazobactam-responsive CD4 + T-cell clones were stimulated to proliferate and secrete IFN-γ in an MHC class II-restricted and dose-dependent manner. T-cell activation with clavulanate-and tazobactam was dependent on antigen presenting cells because their fixation prevented the T-cell response. Strong crossreactivity was observed between clavulanate-and tazobactam-T-cells; however, neither drug activated β-lactam antibiotic-responsive T-cells. Mass spectrometric analysis revealed that both compounds form multiple antigenic determinants with lysine residues on proteins, including an overlapping aldehyde and hydrated aldehyde adduct with mass additions of 70 and 88 Da, respectively. Collectively, these data show that although clavulanate and tazobactam are structurally distinct, the antigenic determinants formed by both drugs overlap, which explains the observed Tcell cross-reactivity.

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“…Amoxicillin yielded negative results; however, after a cumulative dose of 16 mg of amoxicillin–clavulanate, she developed urticaria, conjunctivitis, throat swelling, and hypotension. A 46-year-old woman developed erythematous macules and papules over her abdomen within 24 h of receiving amoxicillin–clavulanate [27]. Upon allergy testing, she had a positive skin-prick test to amoxicillin–clavulanate but not amoxicillin alone.…”

Section: Beta-lactamase Inhibitor Allergic Reactionsmentioning

confidence: 99%

Allergic Reactions and Cross-Reactivity Potential with Beta-Lactamase Inhibitors

Stover¹,

Barber²,

Wagner³

2019

Pharmacy

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Although beta-lactam allergies are an emerging focus of stewardship programs and interventions, less is publicly released regarding allergies to beta-lactamase inhibitors. This review presents and evaluates the data regarding allergic reactions with beta-lactamase inhibitors. Clavulanate, sulbactam, and tazobactam are beta-lactam-based beta-lactamase inhibitors that are combined with several penicillins or cephalosporins in order to preserve antimicrobial activity in the presence of beta-lactamases. Avibactam, relebactam, and vaborbactam are non-beta-lactam beta-lactamase inhibitors that are combined with cephalosporins or carbapenems in order to expand the antimicrobial activity against broader-spectrum beta-lactamases. Case reports document hypersensitivity reactions to clavulanate, sulbactam, and tazobactam, but not to avibactam, relebactam, or vaborbactam. Based on these reports and considering the chemical structures, cross-allergenicity with beta-lactams is likely with sulbactam and tazobactam. Considering the slightly altered beta-lactam structure, cross-allergenicity is less likely with clavulanate, but still possible. It appears that cross-allergenicity between beta-lactam antimicrobials and the newer, non-beta-lactam beta-lactamase inhibitors is unlikely. It is important for clinicians to perform allergy testing to both the beta-lactam and the beta-lactamase inhibitor in order to confirm the specific allergy and reaction type.

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Drug eruption to clavulanic acid with sparing of cellulitis-affecting site

Cited by 6 publications

References 5 publications

Bibliometric Analysis of Global Research on Clavulanic Acid

Bibliometric Analysis of Global Research on Clavulanic Acid

Shared Clavulanate and Tazobactam Antigenic Determinants Activate T-Cells from Hypersensitive Patients

Allergic Reactions and Cross-Reactivity Potential with Beta-Lactamase Inhibitors

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