Ampicillin/Sulbactam in Critically Ill Dogs

In the Literature

Goggs R, Robbins S, Menard J, et al. Intravenous ampicillin/sulbactam in critically ill dogs has variable pharmacokinetics. J Vet Pharmacol Ther. 2025;48(6):445-456. doi:10.1111/jvp.70004

The Research …

IV ampicillin/sulbactam is commonly used in critically ill dogs due to its safety and availability.¹ Ampicillin, an aminopenicillin beta-lactam antibiotic, is considered broad spectrum; however, its activity against gram-negative bacterial infections at sites other than the lower urinary tract is debated.²

This study determined the pharmacokinetics of ampicillin/sulbactam administered to dogs admitted to the intensive care unit for treatment of critical illness. Efficacy of ampicillin was evaluated based on its ability to reach a pharmacokinetic/pharmacodynamic target of free drug concentrations above the minimum inhibitory concentration for at least 50% of the administration interval when given every 8 hours.

Client-owned dogs (n = 25) were administered IV ampicillin/sulbactam at 30 mg/kg (ampicillin, 20 mg/kg; sulbactam, 10 mg/kg). Blood samples were drawn before administration and at set intervals up to 8 hours after administration. Plasma concentrations were determined and analyzed.

A high degree of variability in plasma concentrations of ampicillin was noted, but no specific patient characteristics demonstrated associations with variability. Prolonged clearance has been reported in dogs with azotemia (median creatinine, 5.6-7.2 mg/dL),^3,4 but overall clearance in the present study was not prolonged. Azotemia (ie, creatinine >1.4 mg/dL) was only present in 6 dogs.

Results demonstrated that a probability of ≥90% of sick dogs treated with ampicillin at the study dose (20 mg/kg) would achieve the Clinical and Laboratory Standards Institute breakpoint for skin and soft tissue infections in dogs of 0.25 micrograms/mL.⁵ The probability that sick dogs treated with the study dose of ampicillin would achieve the human breakpoint of ≤8 micrograms/mL was only 10%. At 0.25 micrograms/mL, most gram-negative Enterobacterales (eg, Escherichia coli, Klebsiella pneumoniae) would be resistant.

… The Takeaways

Key pearls to put into practice:

• Ampicillin/sulbactam administered at 30 mg/kg IV every 8 hours likely will not treat most E coli or K pneumoniae infections at sites other than the lower urinary tract and should not be used alone for treatment of critical illness caused by gram-negative bacteria.

• If broad-spectrum injectable coverage is needed, ampicillin/sulbactam should be combined with antibiotics that have a better gram-negative aerobic spectrum (eg, fluoroquinolones, aminoglycosides).

• Ampicillin, with or without sulbactam, can be used for surgical antimicrobial prophylaxis against GI contamination with E coli only when administered 80 minutes prior to the incision and with readministration every 90 minutes during surgery.⁶

• The laboratory used for culture and susceptibility testing should use canine specific breakpoints whenever available.