The pharmacokinetics of intravenous ciprofloxacin 400 mg 12 hourly in patients with severe sepsis: the effect of renal function and intra- abdominal disease

Abstract

Serum concentrations of ciprofloxacin were reviewed in 22 patients given ciprofloxacin 400 mg intravenously 12 hourly for severe infection. No dosage modifications were made in patients with renal impairment. Patients who had either bowel or liver pathology in addition to renal failure had significantly higher serum concentrations than all other patients. Dosage reduction of ciprofloxacin in patients with severe sepsis and impaired renal function is not required unless they have co-existent intra-abdominal disease.

Pharmacokinetics of Levofloxacin and Ciprofloxacin during Continuous Renal Replacement Therapy in Critically Ill Patients

“…Normally, 30 to 50% of ciprofloxacin is eliminated through hepatic metabolism and biliary excretion. It has been demonstrated that ciprofloxacin CL S does not always correlate well with creatinine clearance (1,6,11,23,26), and it has been suggested that increases in biliary clearance may effectively compensate for a reduction in renal clearance in patients with renal impairment (12,13,14). In the present study, 5 of the 10 patients receiving ciprofloxacin also had severe hepatic impairment.…”

Pharmacokinetics and Pharmacodynamics of Imipenem during Continuous Renal Replacement Therapy in Critically Ill Patients

“…Nonrenal mechanisms of drug elimination thus accounted for 70 to 75% of CL S compared to only 25 to 45% of CL S in healthy normal volunteers (5,28). Increased proportions of imipenem clearance due to nonrenal mechanisms have been previously reported in anuric patients and patients receiving CRRT (25,38,43), as well as for other antimicrobials in patients with severe renal insufficiency (16,23). Although critically ill patients with severe acute renal failure are typically fluid overloaded, no apparent increase in the V of imipenem was noted in this study compared to that previously described in healthy volunteers and patients with renal insufficiency (14,15,22,43).…”

How severe is antibiotic pharmacokinetic variability in critically ill patients and what can be done about it?

“…Renal replacement therapy is an effective Cl mechanism for antimicrobial agents but marked variability in performance of Cl by renal replacement therapy has been described (Tegeder et al 1999;Krueger et al 2003;Lipman et al 2003;Arzuaga et al 2005;Dagenais and Keller 2009;Bilgrami et al 2010). Hepatic dysfunction in critically ill patients also affects elimination of drugs, such as ciprofloxacin, moxifloxacin and ceftriaxone, which are metabolised by the liver or undergo transintestinal Cl (Heinemeyer et al 1990;Jones et al 1997;Stass et al 2002).…”