Pharmacokinetic and Pharmacodynamic Interactions with Levofloxacin in Renal Transplant Patients with Suspected Pneumonia

ABSTRACT

Ciprofloxacin, a fluoroquinolone antibiotic, has been linked to an increased risk of acute cellular rejection and drug interactions with the calcineurin inhibitors in renal transplant recipients. Little is known about the effects of levofloxacin. We report our evaluation for pharmacokinetic and pharmacodynamic interaction between levofloxacin and the calcineurin inhibitors. A retrospective review was conducted of renal transplant recipients with known or suspected community acquired pneumonia who received levofloxacin. Patients were assessed for rejection at 90-day follow-up, and compared to a historical ciprofloxacin cohort. Assessment of the drug-drug interaction between levofloxacin and the calcineurin inhibitors required stable dose of the immunosuppressants, a baseline trough level, and follow-up levels. Rejection occurred in 1 of the 26 included patients (3.8%), less than the rate in the historical ciprofloxacin group at 4 weeks (28.6%; p=0.012) and 12 weeks (45.2%; p<0.001). There was no significant drug-drug interaction between levofloxacin and cyclosporine (n=8) or tacrolimus (n=6) when trough levels were evaluated. In summary, renal transplant patients receiving levofloxacin for pneumonia did not appear to have a temporally-related elevated risk of ACR or a pharmacokinetic drug-drug interaction with the calcineurin inhibitors.