Dalbavancin

Dalbavancin, a lipoglycopeptide antibiotic, is derived from teicoplanin and shares structural similarities with vancomycin. It is Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved for treating acute bacterial skin and skin structure infections (ABSSSI) triggered by susceptible Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA).

Due to its prolonged half-life, dalbavancin is administered once weekly, typically requiring only two doses for a full treatment course, making it a valuable addition to therapies targeting infections.[1,2]

Pharmacological Class: Lipoglycopeptide antibiotic

Dalbavancin is indicated for the treatment of ABSSSI triggered by susceptible Gram-positive microorganisms, including:

• Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant strains)
• Streptococcus dysgalactiae
• Streptococcus pyogenes
• Streptococcus agalactiae
• Streptococcus anginosus group (including S. intermedius, S. constellatus, S. anginosus)
• Vancomycin-susceptible Enterococcus faecalis[3]

• Dalbavancin exerts bactericidal activity primarily by inhibiting bacterial cell-wall biosynthesis.
• It binds to the terminal D-Ala-D-Ala residues of NAM/NAG peptide precursors, preventing their incorporation into the peptidoglycan matrix of Gram-positive bacterial cell walls.
• This inhibition disrupts peptidoglycan formation, a key structural component involved in bacterial cell wall integrity.
• Dalbavancin also increases bacterial cell-membrane permeability and interferes with RNA synthesis.[3]

Note: Dalbavancin is not active against gram-negative bacteria. 

• Dose depends on renal function (estimated creatinine clearance [CrCl]).
   
• In patients with estimated CrCl >30 mL/min or those on regular hemodialysis, the recommended regimen is:
  1. Single-dosage regimen: 1500 mg intravenous (IV) once
  2. Two-dosage regimen: 1000 mg IV, followed 1 week later by 500 mg
   
• In patients with estimated CrCl <30 mL/min who are not on regular hemodialysis, the recommended regimen is:
  1. Single-dosage regimen: 1125 mg IV once
  2. Two-dosage regimen: 750 mg IV, followed 1 week later by 375 mg

• All doses must be given as an intravenous infusion over 30 minutes.[4]

(a) Absorption

• Linear pharmacokinetics: In healthy people, dalbavancin shows dose-proportional increases in AUC₀–24h and Cmax after single IV doses ranging from 140 mg to 1500 mg.
• No accumulation: Repeated once-weekly IV dosing (1000 mg on day 1 followed by up to seven weekly 500 mg doses) does not lead to drug accumulation in healthy adults with normal kidney function.

(b) Distribution

• Volume of distribution: The steady-state volume of distribution is similar in healthy individuals and infected patients and approximates the extracellular fluid volume.
• Protein binding: Dalbavancin is ~93% reversibly bound to plasma proteins, mainly albumin.
• Consistency across conditions: Protein binding is not affected by drug concentration, kidney damage, or liver damage.

(c) Metabolism

• Not metabolized by CYP450: Dalbavancin is not a substrate, inducer, or inhibitor of CYP450 enzymes, indicating a low risk of metabolic drug–drug interactions.
• Minimal metabolism: Only small amounts of metabolites are detected in human plasma.
• Urinary metabolites: Hydroxy-dalbavancin and mannosyl aglycone are detected in urine, accounting for <25% of the administered dose.
• Unknown metabolic pathways: The exact pathways responsible for forming these metabolites are not fully identified.
• Lower activity: Both metabolites have lower antibacterial activity than dalb

(d) Elimination

• Route of elimination: After a single 1000 mg IV dose, about 33% of dalbavancin is excreted unchanged in urine, 12% as hydroxy-dalbavancin metabolite in urine (within 42 days), and ~20% is eliminated in feces (within 70 days).
• Half-life: The terminal half-life is approximately 346 hours, supporting infrequent dosing.
• Clearance: 0.0513 L/h.[3]

Dalbavancin is contraindicated in those with a known hypersensitivity to dalbavancin or other glycopeptide-class antibiotics.[4]

(a) Drug–Laboratory Test Interactions

Dalbavancin has not been shown to interfere with laboratory test results. At therapeutic levels, it does not elicit artificial prolongation of coagulation parameters such as prothrombin time or activated partial thromboplastin time.

(b) Drug–Drug Interactions

Clinical studies specifically evaluating drug–drug interactions with dalbavancin have not been carried out. However, the likelihood of interactions with medications that act as substrates, inhibitors, or inducers of the cytochrome P450 (CYP450) enzyme system is considered low.[4]

Common side effects are as follows:

• Nausea
• Vomiting
• Headache
• Diarrhea
• Rash
• Pruritus[4]

• Hypersensitivity: Severe allergic responses, including anaphylaxis, may occur. Caution is advised in those with a history of glycopeptide allergy due to potential cross-reactivity.
• Infusion Reactions: Rapid intravenous administration may trigger flushing, pruritus, rash, or back pain. Adherence to recommended infusion times reduces this risk.
• Hepatic Effects: Temporary elevations in liver enzymes (particularly alanine aminotransferase; ALT) have been witnessed. Consider monitoring hepatic function, particularly in those with underlying liver disease.
• Clostridium difficile (C. difficile)-–Associated Diarrhea: Antibiotic-associated diarrhea, including C. difficile infection, may occur during or after treatment. Evaluate promptly if diarrhea develops.
• Antimicrobial Resistance: Prescribe only for confirmed or strongly suspected bacterial infections to minimize the risk of resistant organism development.[4]

1. A pooled analysis of three phase 3 clinical trials investigated dalbavancin's efficacy and safety for ABSSSI in patients with high body mass index (BMI) and/or diabetes. Among patients treated with dalbavancin, early clinical response at 48–72 hours was 89.3% in those with normal BMI and 78.9%–87.6% in patients with elevated BMI. By the end of treatment (day 14), clinical success increased to 90.9% in patients with normal BMI and 91.0%–95.2% in those with higher BMI.

In patients with diabetes, clinical success rates were 82.4% at 48–72 hours and 90.8% at the end of treatment, compared with 86.0% and 91.6%, respectively, in patients without diabetes. Similar outcomes were noted in infections triggered by MRSA and MSSA. Overall, dalbavancin demonstrated consistent effectiveness and a comparable safety profile regardless of BMI or diabetes status.[5]

2. A systematic review of 10 clinical trials explored the effectiveness of different dalbavancin dosing regimens for treating ABSSSIs. Five studies compared single- or two-dose dalbavancin regimens with other antibiotics, including vancomycin and linezolid. Clinical outcomes were similar between dalbavancin and comparator antibiotics, with no prominent difference observed for either the two-dose regimen (odds ratio [OR] 1.13) or the single-dose regimen (OR 0.98).

Additionally, single- and two-dose dalbavancin regimens showed comparable clinical effectiveness. However, microbiological evaluation showed better outcomes with the two-dose regimen compared with the single-dose regimen (OR 2.96), particularly against both MRSA and MSSA. Overall, dalbavancin illustrated clinical efficacy comparable to standard antibiotics for ABSSSI treatment.[6]

3. In a multicentre retrospective study of patients hospitalized with ABSSSI, treatment with dalbavancin was linked with a substantially shorter hospital stay compared with standard intravenous antibiotics such as vancomycin, teicoplanin, and daptomycin. The median time to discharge after commencing therapy was 6.5 days with dalbavancin versus 11 days with standard care.

The shorter hospitalization with dalbavancin remained evident in several subgroups, including patients with MRSA infection, those receiving additional Gram-positive antibiotics, and patients with diabetes mellitus, where discharge time was reduced by about half or more.[7]

1. Smith JR, Roberts KD, Rybak MJ. Dalbavancin: A Novel Lipoglycopeptide Antibiotic with Extended Activity Against Gram-Positive Infections. Infectious Diseases and Therapy. 2015 Sep;4(3):245-58.
2. Cattaneo D, Cusato J. Proactive Therapeutic Drug Monitoring of Dalbavancin in the Long-Term Treatment of Chronic Infections: A Narrative Review. Antibiotics. 2026 Mar 1;15(3):253.
3. Dalbavancin. Drug Bank [DB06219]. Available from: https://go.drugbank.com/drugs/DB06219
4. Dalbavance. FDA Label. Available from:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021883s007lbl.pdf
5. Riccobene T, Lock J, Lyles RD, Georgiades B, Nowak M, Gonzalez PL et al. Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infection in Patients With Obesity or Diabetes: A Subgroup Analysis of Pooled Phase 3 Clinical Trials. Open Forum Infectious Diseases. 2023 May 9;10(6):ofad256.
6. Monteagudo-Martínez N, Solís-García Del Pozo J, Nava E, Ikuta I, Galindo M, Jordán J. Acute Bacterial Skin and Skin-Structure Infections, efficacy of Dalbavancin: a systematic review and meta-analysis. Expert Review of Anti-infective Therapy. 2022 Nov;20(11):1477-1489.
7. Papavramidis T, Gentile I, Cattelan AM, Magnasco L, Viale P, Francisci D et al. REDS study: Retrospective effectiveness study of dalbavancin and other standard of care of the same IV antibiotic class in patients with ABSSSI. International Journal of Antimicrobial Agents. 2023 Apr;61(4):106746.