What is the recommended dose of dalbavancin (dalbavancin) for an adult patient with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible Gram-positive bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA), with normal or impaired renal function?

Dalbavancin Dosing for ABSSSI

For adult patients with acute bacterial skin and skin structure infections (ABSSSI), administer dalbavancin 1000 mg intravenously on day 1, followed by 500 mg intravenously on day 8, with each infusion given over 30 minutes. 1

Standard Two-Dose Regimen

• The FDA-approved dosing is 1000 mg IV on day 1, then 500 mg IV on day 8, administered as 30-minute infusions 1
• This two-dose, once-weekly regimen demonstrated non-inferiority to vancomycin (with optional switch to oral linezolid) in two large Phase 3 trials (DISCOVER 1 and 2) involving 1,312 patients 1, 2
• Clinical success rates at 48-72 hours were 83.3% and 76.8% in the two trials, comparable to vancomycin/linezolid at 81.8% and 78.3% 1

Alternative Single-Dose Regimen

• A single 1500 mg IV infusion has been shown to be non-inferior to the two-dose regimen in a Phase 3b trial (DUR001-303) 3, 4
• This option provides maximum convenience for patients who can tolerate a single administration 4

Dose Adjustments for Renal Impairment

For patients with creatinine clearance <30 mL/min who are NOT on regular dialysis:

• Two-dose regimen: 750 mg IV on day 1, then 375 mg IV on day 8 1, 3
• Single-dose regimen: 1000 mg IV as a single dose 3

For patients on regular hemodialysis (three times weekly):

• No dose adjustment is required 1
• Dalbavancin may be administered without regard to timing of hemodialysis, as less than 6% is removed during a 3-hour dialysis session 1

For patients with mild to moderate renal impairment (CrCl 30-79 mL/min):

• No dose adjustment is necessary 1
• Mean plasma clearance is reduced by only 11-35% in this population, which is not clinically significant 1

Hepatic Impairment

• No dose adjustment is required for any degree of hepatic impairment (Child-Pugh class A, B, or C) 1

Key Pharmacokinetic Advantages

• Extremely long half-life of approximately 8.5 days (204 hours) allows for once-weekly dosing 1, 5
• Achieves therapeutic concentrations in skin blister fluid >30 mg/L for up to 7 days after a single 1000 mg dose 1
• 93% protein bound with excellent tissue penetration into skin, bone, and soft tissues 1, 5
• Linear pharmacokinetics with dose-proportional increases in AUC and Cmax 1

Safety Profile

• Dalbavancin demonstrates significantly lower nephrotoxicity compared to vancomycin (3.7% vs 9.3%, p=0.039) in pooled analysis of three clinical trials 3
• Adverse events are generally mild to moderate in severity and transient 6, 2
• No therapeutic drug monitoring is required, unlike vancomycin 2

Clinical Considerations

• Dalbavancin is active against clinically relevant Gram-positive pathogens including MRSA, making it appropriate for empiric therapy in ABSSSI 2, 4
• The pharmacodynamic target is a free AUC/MIC ratio of at least 27.1 for Staphylococcus aureus infections 1, 5
• Not a substrate, inhibitor, or inducer of CYP450 enzymes, minimizing drug-drug interaction potential 1

Common Pitfalls to Avoid

• Do not reduce the dose in patients with mild to moderate renal impairment (CrCl ≥30 mL/min)—this is unnecessary and may lead to subtherapeutic levels 1
• Do not delay hemodialysis or adjust timing around dalbavancin administration—the drug is minimally dialyzable 1
• Remember that approximately 5% of patients in clinical trials also received aztreonam for empiric Gram-negative coverage; consider this if polymicrobial infection is suspected 1