Ciprofloxacin Dose Reduction Decisions Should Consider Hepatic Function, Age, and Sex

Ciprofloxacin is a useful drug when battling various types of bacterial infections; however, clinicians should be mindful of dosing when it comes to critically ill patients because pathophysiological changes can alter the pharmacokinetics of the drug, according to the investigators on a new study.

Bilirubin level, age, and sex should all be considered when assessing the need for a ciprofloxacin dose reduction, investigators in Germany reported in a new study published last week in the Journal of Antimicrobial Chemotherapy.

Specifically, the investigators recommend that it might be appropriate for minimum inhibitory concentrations (MICs) less than .25 mg/L to reduce the dose to 400 milligrams per day for elderly female subjects with high bilirubin.

“Since glomerular filtration and tubular secretion account for approximately two-thirds of ciprofloxacin clearance, a dose reduction is recommended in patients with impaired renal function,” Xia Li, MD; Michael Zoller, MD; and colleagues wrote.

“However, pharmacokinetic studies in critically ill patients have revealed that the relationship between measured creatinine clearance (calculated from serum creatinine and urine samples) and ciprofloxacin clearance might be poor,” they continued. "Therefore, non-renal elimination pathways, including hepatic metabolism, biliary excretion and transmembrane secretion across the enteric mucosa, seem to contribute substantially to the elimination of ciprofloxacin.”

For this clinical study of 15 critically ill patients in the intensive care unit (ICU) of the department of anesthesiology at the University Hospital of Munich in Munich, Germany, investigators analyzed 444 ciprofloxacin serum concentrations and explored ciprofloxacin clearance relationships to parameters involving hepatic function, creatinine clearance, Cockcroft—Gault creatinine clearance, serum creatinine, sex, weight, and age.

“Total bilirubin was identified as a potential indicator of hepatic function with a significant and consistent relationship with ciprofloxacin clearance,” Dr. Li and his colleagues wrote. “No link between creatinine clearance and ciprofloxacin clearance could be confirmed, questioning a substantial influence of kidney function on ciprofloxacin exposure in critically ill patients. Indeed, age and sex were the only components of the Cockcroft—Gault equation with a clear relationship to ciprofloxacin clearance.”

Investigators described industry concerns over recommendations to reduce ciprofloxacin doses in patients with impaired kidney function, but reported that general dose reductions are neither supported for low predicted nor creatinine clearance values in critically ill patients.

“To diminish the risk of potential overexposure, a standard dose of 800 milligrams per day seems appropriate in older female subjects with moderately elevated bilirubin while a decrease to 400 milligrams per day might be needed in females with a combination of very old age and highly elevated bilirubin,” the investigators concluded.