Improved pharmacotherapy after revised dosing regimens of two slow-release formulations of benzylpenicillin in an Actinobacillus pleuropneumoniae infection model in pigs
Abstract Background Actinobacillus pleuropneumoniae (APP) is a Gram-negative bacterium that causes respiratory disease in pigs, resulting in significant economic losses and reduced animal welfare. In Sweden, the drug of choice for treatment of APP infections is benzylpenicillin. However, limited pha...
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BMC
2025-04-01
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| Series: | Acta Veterinaria Scandinavica |
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| Online Access: | https://doi.org/10.1186/s13028-025-00806-9 |
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| author | Marie Sjölund Thomas Rosendal Per Wallgren Märit Pringle Ulf Bondesson Björn Bengtsson Carl Ekstrand |
| author_facet | Marie Sjölund Thomas Rosendal Per Wallgren Märit Pringle Ulf Bondesson Björn Bengtsson Carl Ekstrand |
| author_sort | Marie Sjölund |
| collection | DOAJ |
| description | Abstract Background Actinobacillus pleuropneumoniae (APP) is a Gram-negative bacterium that causes respiratory disease in pigs, resulting in significant economic losses and reduced animal welfare. In Sweden, the drug of choice for treatment of APP infections is benzylpenicillin. However, limited pharmacokinetic and pharmacodynamic data for benzylpenicillin in pigs have led to variations in recommended dosing regimens. In this study, the impact of different dosing regimens and benzylpenicillin preparations on the progression of APP infection in pigs was investigated. Two experimental trials involving a total of 66 pigs were conducted. Pigs were intranasally inoculated with a pathogenic strain of APP serotype 2, and treatment was initiated upon the appearance of clinical signs. Two intramuscularly administered benzylpenicillin formulations, an aqueous and an oil-based suspension, were used with varying dosing regimens. The clinical outcome was assessed based on respiratory signs and rectal temperature measurements. Blood samples were collected for measuring white blood cell counts, serum antibody levels, and acute-phase protein concentrations. Necropsies were performed to evaluate lung lesions and to reisolate APP. Results The results indicated that benzylpenicillin dosing regimens of 20–30 mg/kg administered every 12 h achieved larger benzylpenicillin plasma-exposure compared to the labelled dose of 10–30 mg/kg every 24 h. The oil-based suspension demonstrated superior efficacy compared to the aqueous suspension. Dosing regimens that maintain effective plasma concentrations of benzylpenicillin were shown to have better clinical outcomes as measured by reduced lung lesions at necropsy. Increased benzylpenicillin exposure was associated with a better ranking of overall treatment response. Conclusions Several dosing regimens that increased the plasma benzylpenicillin exposure were associated with better clinical success than the labelled doses. The findings support the treatment of APP-infected pigs with optimised benzylpenicillin dosing regimens. Optimising the use of existing antibiotics is crucial given the limited development of new antimicrobial agents and the need to combat antimicrobial resistance with regards to both human and animal health. |
| format | Article |
| id | doaj-art-dda42aa2d1244e309e5df8f326c2b821 |
| institution | DOAJ |
| issn | 1751-0147 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Veterinaria Scandinavica |
| spelling | doaj-art-dda42aa2d1244e309e5df8f326c2b8212025-08-20T02:55:23ZengBMCActa Veterinaria Scandinavica1751-01472025-04-0167111710.1186/s13028-025-00806-9Improved pharmacotherapy after revised dosing regimens of two slow-release formulations of benzylpenicillin in an Actinobacillus pleuropneumoniae infection model in pigsMarie Sjölund0Thomas Rosendal1Per Wallgren2Märit Pringle3Ulf Bondesson4Björn Bengtsson5Carl Ekstrand6Department of Animal Health and Antimicrobial Strategies, Swedish Veterinary AgencyDepartment of Epidemiology, Surveillance and Risk Assessment Epidemiology, Swedish Veterinary AgencyDepartment of Animal Health and Antimicrobial Strategies, Swedish Veterinary AgencyDepartment of Animal Health and Antimicrobial Strategies, Swedish Veterinary AgencyDepartment of Medicinal Chemistry, Analytical Pharmaceutical Chemistry, Faculty of Pharmacy, Uppsala UniversityDepartment of Animal Health and Antimicrobial Strategies, Swedish Veterinary AgencyDepartment of Animal Biosciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural SciencesAbstract Background Actinobacillus pleuropneumoniae (APP) is a Gram-negative bacterium that causes respiratory disease in pigs, resulting in significant economic losses and reduced animal welfare. In Sweden, the drug of choice for treatment of APP infections is benzylpenicillin. However, limited pharmacokinetic and pharmacodynamic data for benzylpenicillin in pigs have led to variations in recommended dosing regimens. In this study, the impact of different dosing regimens and benzylpenicillin preparations on the progression of APP infection in pigs was investigated. Two experimental trials involving a total of 66 pigs were conducted. Pigs were intranasally inoculated with a pathogenic strain of APP serotype 2, and treatment was initiated upon the appearance of clinical signs. Two intramuscularly administered benzylpenicillin formulations, an aqueous and an oil-based suspension, were used with varying dosing regimens. The clinical outcome was assessed based on respiratory signs and rectal temperature measurements. Blood samples were collected for measuring white blood cell counts, serum antibody levels, and acute-phase protein concentrations. Necropsies were performed to evaluate lung lesions and to reisolate APP. Results The results indicated that benzylpenicillin dosing regimens of 20–30 mg/kg administered every 12 h achieved larger benzylpenicillin plasma-exposure compared to the labelled dose of 10–30 mg/kg every 24 h. The oil-based suspension demonstrated superior efficacy compared to the aqueous suspension. Dosing regimens that maintain effective plasma concentrations of benzylpenicillin were shown to have better clinical outcomes as measured by reduced lung lesions at necropsy. Increased benzylpenicillin exposure was associated with a better ranking of overall treatment response. Conclusions Several dosing regimens that increased the plasma benzylpenicillin exposure were associated with better clinical success than the labelled doses. The findings support the treatment of APP-infected pigs with optimised benzylpenicillin dosing regimens. Optimising the use of existing antibiotics is crucial given the limited development of new antimicrobial agents and the need to combat antimicrobial resistance with regards to both human and animal health.https://doi.org/10.1186/s13028-025-00806-9AntibioticAntimicrobial treatmentPharmacokineticsPleuropneumoniaPorcineRespiratory disease |
| spellingShingle | Marie Sjölund Thomas Rosendal Per Wallgren Märit Pringle Ulf Bondesson Björn Bengtsson Carl Ekstrand Improved pharmacotherapy after revised dosing regimens of two slow-release formulations of benzylpenicillin in an Actinobacillus pleuropneumoniae infection model in pigs Acta Veterinaria Scandinavica Antibiotic Antimicrobial treatment Pharmacokinetics Pleuropneumonia Porcine Respiratory disease |
| title | Improved pharmacotherapy after revised dosing regimens of two slow-release formulations of benzylpenicillin in an Actinobacillus pleuropneumoniae infection model in pigs |
| title_full | Improved pharmacotherapy after revised dosing regimens of two slow-release formulations of benzylpenicillin in an Actinobacillus pleuropneumoniae infection model in pigs |
| title_fullStr | Improved pharmacotherapy after revised dosing regimens of two slow-release formulations of benzylpenicillin in an Actinobacillus pleuropneumoniae infection model in pigs |
| title_full_unstemmed | Improved pharmacotherapy after revised dosing regimens of two slow-release formulations of benzylpenicillin in an Actinobacillus pleuropneumoniae infection model in pigs |
| title_short | Improved pharmacotherapy after revised dosing regimens of two slow-release formulations of benzylpenicillin in an Actinobacillus pleuropneumoniae infection model in pigs |
| title_sort | improved pharmacotherapy after revised dosing regimens of two slow release formulations of benzylpenicillin in an actinobacillus pleuropneumoniae infection model in pigs |
| topic | Antibiotic Antimicrobial treatment Pharmacokinetics Pleuropneumonia Porcine Respiratory disease |
| url | https://doi.org/10.1186/s13028-025-00806-9 |
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