Intravenous Ampicillin/Sulbactam in Critically Ill Dogs has Variable Pharmacokinetics
Robert Goggs1,2, Sarah Robbins1, Julie Menard3
1Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Journal of Veterinary Pharmacology and Therapeutics
|June 13, 2025
Summary
Critically ill dogs receiving ampicillin/sulbactam met veterinary standards for antimicrobial drug (AMD) treatment. However, the dosage may not be sufficient to treat Enterobacterales infections due to low plasma concentrations.
Area of Science:
- Veterinary Pharmacology
- Infectious Diseases
- Critical Care Medicine
Background:
- Achieving therapeutic plasma concentrations of antimicrobial drugs (AMDs) is crucial for effective treatment, especially in critically ill patients.
- Critical illness can significantly alter drug pharmacokinetics (PK), potentially compromising AMD efficacy.
- Ampicillin/sulbactam is commonly used, but its PK and efficacy targets in critically ill dogs require evaluation.
Purpose of the Study:
- To evaluate the pharmacokinetics (PK) of intravenous (IV) ampicillin/sulbactam in critically ill dogs.
- To determine the achievement of the target efficacy of unbound plasma drug concentrations above the minimum inhibitory concentration (MIC) for ≥50% of the dosing interval.
- To assess the probability of target attainment (PTA) for various bacterial MICs using Monte Carlo simulations.
Main Methods:
- Prospective observational study involving 25 critically ill dogs receiving IV ampicillin/sulbactam (20 mg/kg ampicillin/10 mg/kg sulbactam).
- Plasma drug concentrations measured using liquid chromatography-mass spectrometry.
- PK modeling (one-compartment for ampicillin, two-compartment for sulbactam) and Monte Carlo simulations to predict PTA.
Main Results:
- Ampicillin PK was best described by a one-compartment model; sulbactam PK by a two-compartment model.
- Monte Carlo simulations showed a 90% PTA for ampicillin at the veterinary CLSI breakpoint (0.25 μg/mL) but only a 10% PTA for the human breakpoint (8 μg/mL).
- At 0.25 μg/mL, most Enterobacterales isolates are likely to be resistant.
Conclusions:
- The tested ampicillin/sulbactam dosage (20 mg/kg IV q8h) meets current veterinary CLSI standards for ampicillin.
- This dosage may be insufficient for effectively treating Enterobacterales infections in critically ill dogs due to suboptimal plasma concentrations.
- Further studies are warranted to optimize ampicillin/sulbactam dosing regimens in critically ill canine patients.
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