Pharmacokinetics and penetration of ciprofloxacin into bronchial secretions of critically ill patients with chronic obstructive pulmonary disease
Abstract number: O520
Kontou P., Chatzika K., Pitsiou G., Boutou A., Argyropoulou P., Kioumis I.
Objective: Ciprofloxacin (CIP) is one of the antibiotics of choice for the treatment of severe exacerbations of Chronic Obstructive Pulmonary Disease (COPD). Antibiotic penetration into the site of infection is critical for obtaining an optimal clinical outcome. Since in COPD patients the infection develops within the airway lumen, it is important to know the drug concentrations that are achieved in bronchial secretions (BS). The purpose of this study was to evaluate CIP's pharmacokinetic (PK) profile in plasma and penetration into BS of mechanically ventilated COPD patients, when administered at the currently recommended dose of 1200 mg per day.
Methods: Ninenteen critically ill COPD patients received a 1-hour infusion of 400 mg CIP q8 h. They all had a respiratory infection as well as risk factors for Ps. aeruginosa and they were intubated. Serial blood and BS samples were obtained at steady state. Concentrations were determined by a validated HPLC assay. Penetration ratio was calculated by dividing the 24 h area under the curve (AUC024) of BS by the AUC024 of plasma. The pharmacodynamic (PD) parameters for CIP were also calculated.
Results: Mean±SD values for volume of distribution, clearance, half-life and AUC0®24 were 174.31±85.42 L, 27.32±9.53 L/h, 5.5±2.34 h and 47.58±18.07, respectively. The mean peak (Cmax) and trough levels in plasma were 5.32±1.76 and 1.05±0.59 mg/L respectively. In BS, a mean Cmax of 3.11±1.27 mg/L was achieved in 3±1.03 hours and the penetration ratio was 1.17±0.61. Thirteen patients demonstrated penetration equal to or even more than 100%. The PD target of AUC0®24/MIC 125 in plasma, that has been shown to be predictive of efficacy for Gram-negative infections, was attained in all patients and in the majority of them (74%) at MICs of 0.125 and 0.25 mg/ml respectively but in only 3 patients and in none at higher MICs (0.5 and 1 mg/ml). Slightly better results were obtained for the PD threshold of Cmax/MIC 10.
Conclusions: CIP exhibits excellent penetration into BS. There is wide interindividual variability in its PK parameters in critically ill COPD patients and inadequate PD exposure against bacteria with MICs 0.5 mg/ml. Our data confirm the need for combination therapy against pathogens with high MICs such as Ps. aeruginosa, as well as the institution of therapeutic drug monitoring for individualizing antimicrobial dosing in order to optimize the efficacy of antibiotic therapy in the ICU.
|Session name:||Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Vienna, Austria, 10 - 13 April 2010|
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