Plasma Concentrations of Benzylpenicillin and Cloxacillin in Infective Endocarditis—With Special Reference to Delayed Hypersensitivity Reactions
Background: Current antibiotic regimens for infective endocarditis (IE) are effective but pose a high risk of delayed hypersensitivity reactions (DHR). Dose adjustments guided by therapeutic drug monitoring (TDM) could mitigate these risks while maintaining treatment efficacy. This study aimed to in...
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2025-01-01
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| author | Malin Hägglund Ulrika Snygg-Martin Lars Olaison Michael Stofkoper Bert Ove Larsson Magnus Brink |
| author_facet | Malin Hägglund Ulrika Snygg-Martin Lars Olaison Michael Stofkoper Bert Ove Larsson Magnus Brink |
| author_sort | Malin Hägglund |
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| description | Background: Current antibiotic regimens for infective endocarditis (IE) are effective but pose a high risk of delayed hypersensitivity reactions (DHR). Dose adjustments guided by therapeutic drug monitoring (TDM) could mitigate these risks while maintaining treatment efficacy. This study aimed to investigate the plasma concentration of benzylpenicillin and cloxacillin in patients with IE and explore associations between antibiotic concentrations and DHR. Methods: Plasma concentrations of benzylpenicillin and cloxacillin were measured as centre (midpoint concentrations between consecutive doses) and trough values during the first and third weeks of treatment in patients with IE. Patient characteristics and outcomes, including DHR, were documented. Results: A total of 55 patients were included, with 37 patients (67%) receiving benzylpenicillin and 18 (33%) receiving cloxacillin. The 90-day mortality rate was 3%. Both centre and trough concentration exhibited substantial interpatient variation for the two antibiotics, while intra-patient variability between weeks 1 and 3 remained low for most patients. Kidney function could explain, at best, 54% of the variation, and a multiple regression model including kidney function, body mass index, age, and albumin explained up to 68% of the variation for benzylpenicillin. There was no relation between high plasma concentration and the prevalence of DHR; conversely, we observed a tendency of low plasma concentrations in these patients. Conclusions: This study revealed significant interindividual variation in plasma concentrations for both studied penicillins. TDM might be useful in situations where concentrations are hard to predict, such as severe obesity or kidney failure. Additionally, we found no indication that high plasma concentrations are related to the prevalence of DHR. |
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| institution | Kabale University |
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| series | Antibiotics |
| spelling | doaj-art-462e3581b9d44dc68da9824a685f81122025-01-24T13:18:46ZengMDPI AGAntibiotics2079-63822025-01-011415610.3390/antibiotics14010056Plasma Concentrations of Benzylpenicillin and Cloxacillin in Infective Endocarditis—With Special Reference to Delayed Hypersensitivity ReactionsMalin Hägglund0Ulrika Snygg-Martin1Lars Olaison2Michael Stofkoper3Bert Ove Larsson4Magnus Brink5Department of Infectious Diseases, Sahlgrenska University Hospital, Region Västra Götaland, Diagnosvägen 21, SE-41650 Gothenburg, SwedenDepartment of Infectious Diseases, Sahlgrenska University Hospital, Region Västra Götaland, Diagnosvägen 21, SE-41650 Gothenburg, SwedenDepartment of Infectious Diseases, Sahlgrenska University Hospital, Region Västra Götaland, Diagnosvägen 21, SE-41650 Gothenburg, SwedenDepartment of Infectious Diseases, Södra Älvsborgs Sjukhus, Region Västra Götaland, Samaritvägen 1, SE-50740 Borås, SwedenDepartment of Infectious Diseases, Norra Älvsborgs Länssjukhus, Regions Västra Götaland, Lärketorpsvägen 20, SE-46173 Trollhättan, SwedenDepartment of Infectious Diseases, Sahlgrenska University Hospital, Region Västra Götaland, Diagnosvägen 21, SE-41650 Gothenburg, SwedenBackground: Current antibiotic regimens for infective endocarditis (IE) are effective but pose a high risk of delayed hypersensitivity reactions (DHR). Dose adjustments guided by therapeutic drug monitoring (TDM) could mitigate these risks while maintaining treatment efficacy. This study aimed to investigate the plasma concentration of benzylpenicillin and cloxacillin in patients with IE and explore associations between antibiotic concentrations and DHR. Methods: Plasma concentrations of benzylpenicillin and cloxacillin were measured as centre (midpoint concentrations between consecutive doses) and trough values during the first and third weeks of treatment in patients with IE. Patient characteristics and outcomes, including DHR, were documented. Results: A total of 55 patients were included, with 37 patients (67%) receiving benzylpenicillin and 18 (33%) receiving cloxacillin. The 90-day mortality rate was 3%. Both centre and trough concentration exhibited substantial interpatient variation for the two antibiotics, while intra-patient variability between weeks 1 and 3 remained low for most patients. Kidney function could explain, at best, 54% of the variation, and a multiple regression model including kidney function, body mass index, age, and albumin explained up to 68% of the variation for benzylpenicillin. There was no relation between high plasma concentration and the prevalence of DHR; conversely, we observed a tendency of low plasma concentrations in these patients. Conclusions: This study revealed significant interindividual variation in plasma concentrations for both studied penicillins. TDM might be useful in situations where concentrations are hard to predict, such as severe obesity or kidney failure. Additionally, we found no indication that high plasma concentrations are related to the prevalence of DHR.https://www.mdpi.com/2079-6382/14/1/56therapeutic drugmonitoringinfective endocarditisbeta-lactamsdelayed hypersensitivity reactionbeta-lactam fever |
| spellingShingle | Malin Hägglund Ulrika Snygg-Martin Lars Olaison Michael Stofkoper Bert Ove Larsson Magnus Brink Plasma Concentrations of Benzylpenicillin and Cloxacillin in Infective Endocarditis—With Special Reference to Delayed Hypersensitivity Reactions Antibiotics therapeutic drug monitoring infective endocarditis beta-lactams delayed hypersensitivity reaction beta-lactam fever |
| title | Plasma Concentrations of Benzylpenicillin and Cloxacillin in Infective Endocarditis—With Special Reference to Delayed Hypersensitivity Reactions |
| title_full | Plasma Concentrations of Benzylpenicillin and Cloxacillin in Infective Endocarditis—With Special Reference to Delayed Hypersensitivity Reactions |
| title_fullStr | Plasma Concentrations of Benzylpenicillin and Cloxacillin in Infective Endocarditis—With Special Reference to Delayed Hypersensitivity Reactions |
| title_full_unstemmed | Plasma Concentrations of Benzylpenicillin and Cloxacillin in Infective Endocarditis—With Special Reference to Delayed Hypersensitivity Reactions |
| title_short | Plasma Concentrations of Benzylpenicillin and Cloxacillin in Infective Endocarditis—With Special Reference to Delayed Hypersensitivity Reactions |
| title_sort | plasma concentrations of benzylpenicillin and cloxacillin in infective endocarditis with special reference to delayed hypersensitivity reactions |
| topic | therapeutic drug monitoring infective endocarditis beta-lactams delayed hypersensitivity reaction beta-lactam fever |
| url | https://www.mdpi.com/2079-6382/14/1/56 |
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