# Improved pharmacotherapy after revised dosing regimens of two slow-release formulations of benzylpenicillin in an Actinobacillus pleuropneumoniae infection model in pigs

## TL;DR

This study finds that adjusting the dosage and formulation of benzylpenicillin improves treatment outcomes in pigs infected with Actinobacillus pleuropneumoniae.

## Contribution

The study introduces optimized dosing regimens and formulations of benzylpenicillin for treating APP infections in pigs.

## Key findings

- Benzylpenicillin dosing regimens of 20–30 mg/kg every 12 hours provided greater plasma exposure than the labeled dose.
- The oil-based suspension of benzylpenicillin was more effective than the aqueous suspension in treating APP infections.
- Higher plasma concentrations of benzylpenicillin correlated with reduced lung lesions and better clinical outcomes in pigs.

## Abstract

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.

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.

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.