ECC Suggested Readings
July 2025
Mark Kim BVSc MVSc DACVECC DECVECC
I studied in Sydney, Australia, and am now living in Lyon, France where I'm on the ECC team (SIAMU) at VetAgro Sup. Interesting facts about clinical practice here: we see a lot of cats, AHDS cases, are rare (!), and coming from Australia, there are surprisingly more viper envenomations (including very sick ones!) than I expected.
A paper that I recently liked…
Intravenous Ampicillin/Sulbactam in Critically Ill Dogs has Variable Pharmacokinetics
Goggs R, Robbins S, Menard J, Selman J, Beverly J, Kraus-Malett S, Papich MG
Paper Commentary
The study design
This was a prospective observational study that developed population pharmacokinetic models of IV ampicillin/sulbactam in 25 critically ill dogs (hospitalised with a life-threatening illness due to infection). Their secondary objective was to predict the probability of unbound drug maintaining a blood concentration over published MICs.
Enrolled dogs were given IV ampi/sulbactam (30 mg/kg tid) via a syringe pump over 30 min, with serial samples taken prior to drug administration, and at 6 times points between doses. Drug concentrations were measured by liquid chromatography-mass spectrometry, and nonlinear mixed-effects modeling calculated the population pharmacokinetics.
The study background
For me, this study continues the important research on antimicrobial stewardship, (still) a hot topic under the One Health umbrella and highlights our role in the fight against bacterial resistance. This large domain includes the subtopic of antimicrobial use in critically ill veterinary patients.
With increasing publications on this subtopic, it is clear that current dosing regimens we use are not adapted to our ICU dogs and cats: aggressive IV fluids, capillary leak, hypoalbuminemia, hypo/hyperdynamic CV function, and of course, multiorgan dysfunction all contribute to alterations in volume of distribution and drug clearance. Developing patient specific pharmacokinetics will hopefully improve patient management and antimicrobial stewardship.
Study considerations
The authors highlight the large PK variability in this population, underlining the problem with a standard dose across all our critically ill patients. This was not unexpected given the heterogeneous patient population (age, weight, illness, etc), however, covariate modeling did not identify a source of this large variation between individuals.
Just as interesting were the Monte Carlo simulations to calculate the probability of time above MIC of unbound ampi/sulbactam (fT > MIC), a key predictor of bacterial killing by a time-dependent antibiotic (such as ampi/sulbactam). A commonly reported dose of 30 mg/kg (20 mg/kg ampicillin) resulted in high probability (>90%) of achieving fT > MIC for at least 50% of each dosing interval, but only when targeting an MIC of 0.25 μg/mL. Whilst this sounds reasonable, several factors need to be taken into account. This MIC is considerably lower than that reported for many of the organisms in the order Enterobacterales that we encounter in a veterinary ICU, as well as the MIC reported for humans. Additionally, it is worth noting that for critically ill patients, an fT > MIC of 100% is recommended.
Samples were not taken for every dog at every time point, but as the authors report, many of the analytical tools used in population pharmacokinetic studies account for this type of limitation.
Takeaways
Advanced solutions to improve antimicrobial dosing (therapeutic drug monitoring, microdialysis catheters, AI-guided dosing) are a long way off for most veterinary ICU patients. In the meantime, studies such as this highlight for me the huge variability in PK we can encounter in these patients (resulting in ineffective dosing or increased adverse effects), and the need for more veterinary PK data in different sick animal populations. I might now be quicker to add/change antibiotic choice when Enterobacterales are suspected in our sick patients.
