OBJECTIVE: To describe the pharmacokinetic profile and clinical outcome associated with high-dose ciprofloxacin therapy in a patient with the triad of extreme obesity, multiple organ failure, and deep-seated infection. CASE SUMMARY: A 45-year-old, class 3 obese (185 kg; body mass index 53.7), critically ill trauma patient receiving continuous venovenous hemodiafiltration (CVVHDF) was treated with ciprofloxacin 800 mg intravenously every 12 hours for presumed Enterobacter aerogenes(ciprofloxacin minimum inhibitory concentration [MIC] ≤1 μg/mL) lumbar spine osteomyelitis. Four sequential plasma ciprofloxacin samples were obtained and analyzed to determine the steady-state pharmacokinetic profile. The observed steady-state maximum (Cmax) and calculated minimum (Cmin) ciprofloxacin plasma concentrations measured on treatment day 8 were 13 μg/mL and 4.8 μg/mL, respectively, corresponding to an estimated half-life, area under the curve (AUC 0-24), total systemic clearance, and clearance by CVVHDF of 7.6 hours, 192 μg·h/mL, 139 mL/min, and 26 mL/min, respectively. These concentrations produced AUC0-24/MIC ratios >125 and plasma C max/MIC ratios >10 for MICs ≤1 μg/mL. Intravenous colistin and polymyxin B lumbar wound irrigation were initiated on ciprofloxacin days 12 and 15, respectively, for concomitant multidrug-resistant Acinetobacter baumannii infection. Lumbar tissue cultures on day 24 of ciprofloxacin therapy demonstrated no growth, coinciding with overall improvement of the invasive wound. A week later, the patient developed worsening septic shock and died secondary to an occult subdiaphragmatic abscess. DISCUSSION: Pharmacodynamic outcome studies suggest that AUC0-24/MIC ratios >125 and plasma Cmax/MIC ratios >10 are good predictors of clinical and microbiologic success of ciprofloxacin against gram-negative pathogens. These pharmacodynamic goals were achieved in the plasma with high-dose ciprofloxacin for MICs ≤1 μg/mL. CONCLUSIONS: Critically ill obese patients with deep-seated infection involving organisms with MICs >0.5 μg/mL likely require ciprofloxacin dosages greater than traditional daily doses of 400-800 mg during CVVHDF to achieve optimal pharmacodynamic targets.
- Continuous venovenous hemodiafiltration
- Critically ill
ASJC Scopus subject areas
- Pharmacology (medical)