Ciprofloxacin Use in Dogs

In the Literature

Papich MG. Ciprofloxacin pharmacokinetics in clinical canine patients. J Vet Intern Med. 2017;31(5):1508-1513.

The Research ...

Fluoroquinolone antibiotics are commonly used in veterinary medicine to treat susceptible bacterial infections. For large dogs, finding an antibiotic both efficacious and affordable can be challenging. Although relatively inexpensive, ciprofloxacin has variable bioavailability in healthy dogs¹; less is known in patients with active infection (which may alter drug pharmacokinetics).

Dogs (n = 34) with active infections prescribed ciprofloxacin (mean dose 23.5 mg/kg PO q24h) were prospectively evaluated in a population-based pharmacokinetic study. This population-based approach can identify covariates that can alter drug pharmacokinetics (eg, presence of azotemia, age).

The study identified body weight as the only covariate to cause variability in ciprofloxacin pharmacokinetics, where larger body weights were associated with decreased plasma drug concentrations. While using an inexpensive antibiotic such as ciprofloxacin is financially appealing, such dogs have lower plasma drug concentrations, which could lead to ineffective antimicrobial therapy.

The study also evaluated plasma drug concentrations and likelihood of killing an organism based on its minimum inhibitory concentration (MIC). Ideally, a drug dosing schedule should produce a >90% probability of clinical efficacy. The Clinical Laboratory and Standards Institute (CLSI) establishes the MIC breakpoints to define a bacterial isolate to be susceptible (S), intermediate (I), or resistant (R) to a particular antibiotic. Ciprofloxacin breakpoints are unavailable for veterinary species, so the breakpoints utilized are based on human data (< 1.0 μg/ml). This study found 25mg/kg PO q24h provides >90% probability of efficacy against isolates with a MIC of 0.06 μg/mL, but only 64% probability for those with a MIC of 0.12 μg/mL and 0% probability for isolates with a MIC of 1.0 μg/ml—a MIC that would be reported as susceptible using human breakpoints. To achieve 90% probability for a MIC of 0.12 μg/mg, a dose of 50mg/kg PO q24h is needed. A dose of 10 mg/kg PO q24h did not achieve high probability for any MIC. At MICs ≥1.0 μg/mL, even 50mg/kg of ciprofloxacin has essentially 0% probability of clinical efficacy.

The human CLSI breakpoint for bacteria susceptible to ciprofloxacin is ≤1.0 μg/mL. However, this study indicated that the human breakpoint poorly predicts likely response to treatment in dogs. Veterinarians need to be aware of the actual MIC from a culture result, not simply the interpretation of S/I/R. This study can help determine if ciprofloxacin can be effective, and what dose provides a high probability of clinical success. Because large dogs have lower blood concentrations, higher ciprofloxacin dosages may need to be considered to help increase the likelihood of bacterial eradication. At ciprofloxacin MICs ≥ 0.06 μg/mL, alternative drugs should be considered, as higher MICs have a lower probability of efficacy.

... The Takeaways

Key pearls to put into practice:

• Larger canine body weights have been shown to be associated with decreased plasma ciprofloxacin concentrations. This effect may be difficult to predict, but could lead to therapeutic drug failure. Clinicians should consider using higher dosages of ciprofloxacin or use an alternative drug in large dogs.

• Clinicians must evaluate actual MICs from culture results, not simply the interpretation of S/I/R. For ciprofloxacin, the MIC needs to be reported at low concentrations (dilutions < 1.0 μg/mL) to be clinically helpful.

• If culture and susceptibility testing indicate a MIC > 0.06 μg/mL, alternative drugs should be considered.

• Ciprofloxacin should only be an option for infections caused by pathogens with an MIC < 0.06 ug/ml, after consideration of the implications of using an off-label drug over approved veterinary fluoroquinolones.