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Background <p>Intravenous regional limb perfusion (IVRLP) of antibiotics is a therapeutic method used to treat distal limb infections in horses. The objectives of this study were to determine the pharmacokinetic parameters and tolerance of sodium benzylpenicillin (NaBP) administered via IVRLP; to compare the feasibility, tolerance, and efficacy of performing IVRLP on a flexed limb versus a weightbearing limb; and to predict the efficacy of IVRLP using gentamicin or NaBP. A prospective crossover study was conducted with six horses, each undergoing four phases of antibiotic infusion (gentamicin at 2.2&#xa0;mg/kg vs. NaBP at 7,333 IU/kg of BP) and limb positioning (weightbearing vs. flexed). Each antibiotic administration was followed by serial synovial and blood sampling to assess antibiotic concentrations. Inflammation and sensitivity to palpation were evaluated at both the injection site and the sampled joint. A pharmacokinetic/pharmacodynamic analysis was carried out to predict the efficacy of IVRLP by estimating area under the concentration–time curve to minimum inhibitory concentration (AUC/MIC) index values for various minimum inhibitory concentrations (MICs).</p> Results <p>High synovial concentrations of NaBP and gentamicin were achieved, with notable variability between horses. NaBP IVRLP was well tolerated, although cephalic vein inflammation scores were significantly higher following NaBP infusion than gentamicin (<i>p</i> = 3.4 × 10<sup>− 11</sup>). For all horses and both antibiotics, synovial antibiotic exposures were significantly greater in weightbearing limbs than in flexed limbs (<i>p</i> = 0.04 and 0.02 for NaBP and gentamicin, respectively). Cephalic vein inflammation scores were also significantly lower in weightbearing limbs than in flexed limbs (<i>p</i> = 2.5 × 10<sup>− 5</sup>). In terms of predicted efficacy, a daily dose of 2.2&#xa0;mg/kg gentamicin should be adequate to treat synovial infections involving <i>Escherichia coli</i> or <i>Staphylococcus aureus</i>, including resistant strains. For NaBP, a daily or every-other-day dose of 7,333 IU/kg of BP should be adequate to treat infections caused by <i>Streptococcus equi</i> and sensitive <i>Staphylococcus aureus</i>.</p> Conclusions <p>These findings suggest that daily IVRLP with NaBP (7,333 IU/kg of BP) could be an effective treatment for distal limb infections caused by susceptible bacteria with a MIC of ≤ 2&#xa0;µg/mL, with only mild local inflammation at the injection site. IVRLP with 2.2&#xa0;mg/kg gentamicin appears effective for treating infections involving susceptible bacteria with an MIC of ≤ 16&#xa0;µg/mL. Performing IVRLP on a weightbearing limb resulted in higher antibiotic exposure in the metacarpophalangeal joint and better tolerance than the flexed limb method.</p>

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Pharmacokinetics, pharmacodynamics, and local tolerance at injection site of penicillin and gentamicin administered by intravenous regional limb perfusion in standing horses: comparison between weightbearing and flexed limbs

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  • 发表日期：

    2025年11月7日

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  • Marguerite Guillot,
  • Céline Mespoulhes-Rivière,
  • Alain Bousquet-Mélou,
  • Marlène Z. Lacroix,
  • Béatrice B. Roques,
  • Elodie A. Lallemand

摘要

Background

Intravenous regional limb perfusion (IVRLP) of antibiotics is a therapeutic method used to treat distal limb infections in horses. The objectives of this study were to determine the pharmacokinetic parameters and tolerance of sodium benzylpenicillin (NaBP) administered via IVRLP; to compare the feasibility, tolerance, and efficacy of performing IVRLP on a flexed limb versus a weightbearing limb; and to predict the efficacy of IVRLP using gentamicin or NaBP. A prospective crossover study was conducted with six horses, each undergoing four phases of antibiotic infusion (gentamicin at 2.2 mg/kg vs. NaBP at 7,333 IU/kg of BP) and limb positioning (weightbearing vs. flexed). Each antibiotic administration was followed by serial synovial and blood sampling to assess antibiotic concentrations. Inflammation and sensitivity to palpation were evaluated at both the injection site and the sampled joint. A pharmacokinetic/pharmacodynamic analysis was carried out to predict the efficacy of IVRLP by estimating area under the concentration–time curve to minimum inhibitory concentration (AUC/MIC) index values for various minimum inhibitory concentrations (MICs).

Results

High synovial concentrations of NaBP and gentamicin were achieved, with notable variability between horses. NaBP IVRLP was well tolerated, although cephalic vein inflammation scores were significantly higher following NaBP infusion than gentamicin (p = 3.4 × 10− 11). For all horses and both antibiotics, synovial antibiotic exposures were significantly greater in weightbearing limbs than in flexed limbs (p = 0.04 and 0.02 for NaBP and gentamicin, respectively). Cephalic vein inflammation scores were also significantly lower in weightbearing limbs than in flexed limbs (p = 2.5 × 10− 5). In terms of predicted efficacy, a daily dose of 2.2 mg/kg gentamicin should be adequate to treat synovial infections involving Escherichia coli or Staphylococcus aureus, including resistant strains. For NaBP, a daily or every-other-day dose of 7,333 IU/kg of BP should be adequate to treat infections caused by Streptococcus equi and sensitive Staphylococcus aureus.

Conclusions

These findings suggest that daily IVRLP with NaBP (7,333 IU/kg of BP) could be an effective treatment for distal limb infections caused by susceptible bacteria with a MIC of ≤ 2 µg/mL, with only mild local inflammation at the injection site. IVRLP with 2.2 mg/kg gentamicin appears effective for treating infections involving susceptible bacteria with an MIC of ≤ 16 µg/mL. Performing IVRLP on a weightbearing limb resulted in higher antibiotic exposure in the metacarpophalangeal joint and better tolerance than the flexed limb method.