title: High-dose ciprofloxacin for serious gram-negative infection in an obese, critically ill patient receiving continuous venovenous hemodiafiltration.
abstract: 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.
  
  
  METHODS
  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 (C(max)) and calculated minimum (C(min)) 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 AUC(0-24)/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.
  
  
  CONCLUSIONS
  Pharmacodynamic outcome studies suggest that AUC(0-24)/MIC ratios >125 and plasma C(max)/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.
authors.affiliation: Department of Pharmacy, Beth Israel Deaconess Medical Center, Boston, MA, USA. tutrup@bidmc.harvard.edu
authors.forename: Theresa R
authors.initials: TR
authors.lastname: Utrup
authors.forename: Eric W
authors.initials: EW
authors.lastname: Mueller
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Healy
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Callcut
authors.forename: John D
authors.initials: JD
authors.lastname: Peterson
authors.forename: William E
authors.initials: WE
authors.lastname: Hurford
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016638:Critical Illness; D021902:Enterobacter aerogenes; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000209:etiology; D017809:Fatal Outcome; D017583:Hemodiafiltration; D006801:Humans; D007262:Infusions, Intravenous; D008159:Lumbar Vertebrae / Q000293:injuries; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology*; D009765:Obesity / Q000150:complications*; D010019:Osteomyelitis / Q000188:drug therapy / Q000209:etiology; D016103:Spinal Fractures / Q000150:complications
chemical_list: D000890:Anti-Infective Agents; D002939:Ciprofloxacin