Optimization of Dalbavancin in Patients with Hepatic or Renal Impairment

Abstract

Dalbavancin is a novel semi-synthetic glycopeptide antibiotic. In this study, we aimed to optimize the dosage regimen of dalbavancin in patients with hepatic or renal impairment by Mote Carlo simulation. Pharmacokinetic parameters and microbiological data were collected about dalbavancin. 10,000 patients with renal or hepatic impairment analyzed by Crystal Ball to calculate probability of target attainment (PTA) and cumulative fraction of response (CFR). We found that all bacterial PTA and CFR were more than 90% for dalbavancin in patients with hepatic or renal impairment, except for Enterococcus faecium. There is no need to adjust the dosage regimen of dalbavancin in patients with hepatic or renal impairment.

Long-Acting Lipoglycopeptide Antibiotics (Dalbavancin and Oritavancin) for the Treatment of Endotipsitis in a Patient With Cirrhosis

“…In their study, 10,000 patients with renal or hepatic dysfunction were evaluated, and it was found that no dose adjustments were necessary for this population of patients. 2 Similarly, Rubino and colleagues 11 conducted a population pharmacokinetic analysis on Oritavancin published in 2015 and concluded that no dose adjustments are necessary for patients with mild to moderate hepatic dysfunction.…”

“…The extended half-lives of dalbavancin (346 hours) and oritavancin (245 hours) offer significant benefits for patients. 2,3 Before the approval of LaLGPs, patients requiring long-term antimicrobial therapy were treated with costly and prolonged hospitalizations, placed in subacute nursing facilities, or prescribed outpatient parenteral intravenous antibiotic therapy (OPAT). 4 Outpatient parenteral antibiotic therapy has limitations, including medication noncompliance, costs, line-associated deep vein thromboses of the upper extremities, and blood-stream infections.…”

“…1 The United States Food and Drug Administration approved dalbavancin and oritavancin in 2014 for the treatment of acute bacterial skin and skin structure infections and recommended a dosing regimen of 1000 mg on day 1 followed by 500 mg on day 8 for dalbavancin, and a single dose of 1200 mg for oritavancin. 2,3 Dalbavancin and oritavancin have been used off-label for the treatment of bone and joint infections, prosthetic joint infections, catheter-related blood-stream infections 4 and endocarditis. 5 In a 2018 publication, Rappo et al 6 demonstrated efficacy of a 2-dose regimen of dalbavancin (1500 mg per dose) for the treatment of osteomyelitis to provide 6 weeks of antibiotic coverage.…”

“…Although pharmacokinetic studies have reported that dose alterations of dalbavancin and oritavancin are not required for patients with cirrhosis, there is a lack of reporting on clinical use of these drugs in this patient population. 2,3 Moreover, to our knowledge, there have been no reports on the use of LaLGPs in the treatment of endotipsitis, an infection of the transjugular intrahepatic portosystemic shunt (TIPS) system. Here, we describe the treatment of endotipsitis with LaLGPs in a patient with cirrhosis.…”