Intravenous and Intraperitoneal Pharmacokinetics of Dalbavancin in Peritoneal Dialysis Patients

Abstract

Dalbavancin offers a possible treatment option for infectious peritonitis associated with peritoneal dialysis (PD) due to its coverage of Gram-positive bacteria and pharmacokinetic properties. We aimed to evaluate the clinical pharmacokinetics (PK) and pharmacodynamics of dalbavancin in a prospective, randomized, open-label, crossover PK study of adult patients with end-stage renal disease ESRD who were receiving PD. Sampling occurred prior to a single 30-min infusion of dalbavancin at 1,500 mg and at 1, 2, 3, 4, and 6 h and 7 and 14 days postadministration. Concentration-time data were analyzed via noncompartmental analysis. Pharmacodynamic parameters against common infectious peritonitis-causing pathogens were evaluated. Ten patients were enrolled. Patients were a median of 55 years old and had a median weight of 78.2 kg, 50% were female, and 70% were Caucasian. The terminal plasma half-life of dalbavancin was 181.4 ± 35.5 h. The day 0 to day 14 dalbavancin mean area under the curve (AUC) was 40,573.2 ± 9,800.3 mg·h/liter. The terminal-phase half-life of dalbavancin within the peritoneal fluid was 4.309 × 108 ± 1.140 × 109 h. The day 0 to day 14 dalbavancin mean peritoneal fluid AUC was 2,125.0 ± 1,794.3 mg·h/liter. The target plasma AUC/MIC was attained with the intravenous dose in all 10 patients for all Staphylococcus and Streptococcus species at the recommended MIC breakpoints. The intraperitoneal arm of the study was stopped early, because the first 3 patients experienced moderate to severe pain and bloating within 1 h following the administration of dalbavancin. Dalbavancin at 1,500 mg administered intravenously can be utilized without dose adjustment in peritoneal dialysis patients and will likely achieve the necessary peritoneal fluid concentrations to treat peritonitis caused by typical Gram-positive pathogens.

ISPD peritonitis guideline recommendations: 2022 update on prevention and treatment

“…218 IP use of dalbavancin is also not recommended because of the concern about chemical peritonitis. 227…”

“…With the emergence of VRE isolates showing resistance to currently available drugs, newer agents, including dalbavancin 227 and combination treatment strategies (including tigecycline, fosfomycin), are potential options.…”

“…Daptomycin, on the other hand, has established stability in PD solutions (including dextrose, amino acid-based fluids and icodextrin) 218 and effective peritoneal concentrations have been achieved by IP administration. 196 With the emergence of VRE isolates showing resistance to currently available drugs, newer agents, including dalbavancin 227 and combination treatment strategies (including tigecycline, fosfomycin), are potential options.…”

Real-World Use of Dalbavancin in the Era of Empowerment of Outpatient Antimicrobial Treatment: A Careful Appraisal Beyond Approved Indications Focusing on Unmet Clinical Needs

“…18 No dalbavancin dose adjustment is required in mild-moderate renal impairment, any degree of hepatic impairment, and different modalities of renal replacement therapy (i.e., intermittent haemodialysis, peritoneal dialysis, or continuous renal replacement therapy). [19][20][21] Dose reduction should be implemented only in patients affected by severe renal impairment. 19 Dalbavancin exhibits in vitro a potent activity against established biofilms due to Staphylococcus aureus, Staphylococcus epidermidis, and vancomycin-susceptible Enterococci, [22][23][24] thus possibly playing a crucial role in the management of relevant infections characterized by bacterial biofilm production (e.g., endocarditis, osteomyelitis, device-related infections).…”

Rapid and Effective Treatment of Peritonitis in Peritoneal Dialysis Patients with Intravenous Dalbavancin

“…Dalbavancin, a synthetic lipoglycopeptide, has a similar mechanism of action to vancomycin, yet has shown improved potency against gram-positive organisms and longer half-life (approximately 1 week) when compared to older glycopeptide antibiotics [ 7 ]. One pharmaco-kinetic study demonstrated that throughout a 14-day period, a single 1500-mg IV dose of dalbavancin achieved sufficient plasma and peritoneal fluid concentrations necessary to treat peritonitis caused by gram-positive pathogens [ 8 ]. Dalbavancin offers a convenient and effective option for PD patients as a one-time dose without the need for routine plasma concentration monitoring.…”