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High-Dose Ciprofloxacin for Serious Gram-Negative Infection in an Obese, Critically III Patient Receiving Continuous Venovenous Hemodiafiltration

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 (CVVHOF) 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 (AUC0-24), total systemic clearance, and clearance by CVVHDF of 7.6 hours, 132 μg·h/mL, 139 mL/min, and 26 mL/min, respectively. These concentrations produced AUC0-24/MIC ratios >125 and plasma Cmax/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.