Glycopeptide antibiotics

Generic and Brand Names

• Vancomycin — Vancocin, Firvanq (oral solution)

• Teicoplanin — Targocid

• Telavancin — Vibativ

• Dalbavancin — Dalvance

• Oritavancin — Orbactiv

Class

• Glycopeptides and lipoglycopeptides

• Bactericidal against Gram-positive organisms via inhibition of cell-wall synthesis

• Lipoglycopeptides (telavancin, dalbavancin, oritavancin) add membrane-targeting effects and extended half-lives

Mechanism of Action

• Vancomycin, teicoplanin: Bind D-Ala-D-Ala termini of peptidoglycan precursors → block transglycosylation and transpeptidation → impaired cell-wall synthesis

• Lipoglycopeptides: Same core mechanism plus membrane depolarization and increased permeability (due to lipophilic side chains)

• Resistance: VanA/VanB change target to D-Ala-D-Lac (↓ binding affinity); VISA/hVISA involve cell-wall thickening

Spectrum of Activity

• Strong activity vs Gram-positive cocci including MRSA, MSSA, most streptococci

• Enterococci: variable; vancomycin inactive vs VanA VRE; oritavancin retains in-vitro activity against some VanA/VanB strains; dalbavancin limited vs VanA

• No activity on Gram-negatives or atypicals

• Anaerobes: activity against many Gram-positive anaerobes; oral vancomycin active in lumen against C. difficile

Indications

• Vancomycin IV: MRSA bacteremia and endocarditis, osteomyelitis, pneumonia (HAP/VAP), serious skin and soft-tissue infections

• Vancomycin oral: Clostridioides difficile infection (not systemically absorbed)

• Teicoplanin (regions outside US): Similar to vancomycin for serious Gram-positive infections

• Telavancin: Complicated skin/skin-structure infections, hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible Gram-positive organisms

• Dalbavancin: Acute bacterial skin and skin-structure infections (ABSSSI)

• Oritavancin: ABSSSI

Dosage and Administration

• Vancomycin IV: 15–20 mg/kg (actual body weight) every 8–12 h; dose by AUC target 400–600 mg·h/L; infuse ≥60 min to limit infusion reactions

• Vancomycin oral (for C. difficile): 125 mg every 6 h (standard initial regimen)

• Teicoplanin: Loading over several doses (e.g., 6–12 mg/kg every 12 h × 3–5) then 6–12 mg/kg once daily (product/indication dependent)

• Telavancin: 10 mg/kg IV once daily; adjust for renal impairment

• Dalbavancin: Single 1500 mg IV dose, or 1000 mg IV then 500 mg IV one week later (30-min infusion)

• Oritavancin: Single 1200 mg IV dose (3-h infusion)

Monitoring

• Vancomycin: AUC-guided monitoring (or troughs where AUC not available), renal function (SCr, CrCl), signs of infusion reaction

• Teicoplanin: Levels where available (certain indications), renal function

• Telavancin: Renal function, pregnancy status, QT interval if risk, coag tests interference (see below)

• Dalbavancin, Oritavancin: Generally no routine level monitoring; renal/hepatic function as clinically indicated

Contraindications

• Known hypersensitivity to the drug or components

• Telavancin: Contraindicated in pregnancy due to fetal risk

• Oritavancin: IV unfractionated heparin contraindicated for 48 h after dosing due to false elevation of aPTT

Precautions

• Nephrotoxicity risk: Vancomycin and telavancin (avoid concomitant nephrotoxins when possible)

• Ototoxicity: Rare with vancomycin (avoid high peak exposures)

• Infusion reactions: “Red man” with vancomycin (manage with slower infusion and antihistamines)

• Coagulation test interference:

  • Telavancin and oritavancin can falsely prolong PT/INR, aPTT for up to 24–48 h (laboratory artifact; do not use these assays to monitor anticoagulation during that window)

• Long half-life agents (dalbavancin, oritavancin): Prolonged exposure; adverse effects or drug–test interferences may persist

Adverse Effects

• Vancomycin: Nephrotoxicity, infusion-related flushing/pruritus, neutropenia, rash; rare ototoxicity

• Teicoplanin: Rash, pruritus, rare nephrotoxicity; generally better tolerated on kidneys than vancomycin

• Telavancin: Nephrotoxicity, taste disturbance, foamy urine, nausea, QT prolongation, fetal risk boxed warning, coag test interference

• Dalbavancin: Nausea, headache, infusion reactions; overall favorable tolerability

• Oritavancin: Nausea, headache, infusion reactions, coag test interference

Drug Interactions

• Additive nephrotoxicity with aminoglycosides, amphotericin B, IV contrast, loop diuretics (vancomycin, telavancin)

• Oritavancin: Interferes with coagulation assays; weak CYP inducer/inhibitor potential (usually minor)

• Telavancin: Additive QT prolongation with other QT-prolonging drugs

• No significant CYP-mediated interactions for vancomycin/dalbavancin/teicoplanin

Overdose

• Supportive care

• Vancomycin: Consider hemodialysis with high-flux filters for severe toxicity

• Long half-life agents: Supportive measures; drug effect declines slowly

Patient Counselling

• Purpose is treatment of serious Gram-positive infections

• Report decreased urine output, hearing changes, severe rash, facial flushing during infusion

• Telavancin: Avoid in pregnancy; discuss contraception; possible taste changes and foamy urine are benign

• Single-dose regimens (dalbavancin, oritavancin) may allow outpatient therapy with close follow-up

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Comparison Table — Key Glycopeptides and Lipoglycopeptides

Feature	Vancomycin	Teicoplanin	Telavancin	Dalbavancin	Oritavancin
Formulation	IV, oral (for CDI only)	IV (not US-marketed)	IV	IV	IV
Dosing pattern	q8–12 h, AUC-guided	Once daily after loading	10 mg/kg q24 h	Single 1500 mg or 2-dose regimen	Single 1200 mg
Half-life	~6–12 h	~70–100 h	~8 h	~8.5 days	~10 days
Primary indications	MRSA bacteremia, endocarditis, osteomyelitis, HAP/VAP, SSTI; oral for CDI	Similar to vancomycin	cSSSI, HAP/VAP due to susceptible GP	ABSSSI	ABSSSI
MRSA activity	Yes	Yes	Yes	Yes	Yes
VRE activity	No (VanA)	Limited	No	Limited (not VanA)	In-vitro activity vs VanA/VanB (clinical use not established for bacteremia)
Pneumonia use	Yes (IV)	Yes (regional)	Yes (HAP/VAP)	No	No
Bacteremia/endocarditis	First-line standard	Yes (regional practices)	Not standard	Not indicated	Not indicated
Renal adjustment	Yes	Yes	Yes	No for mild-mod; consider severe	No
Key safety issues	Nephrotoxicity, infusion reaction, rare ototoxicity	Rash, rare nephrotoxicity	Nephrotoxicity, QT prolongation, fetal risk, coag test interference	Generally well tolerated; very long t½	Coag test interference; very long t½
Lab monitoring	AUC or trough + SCr	SCr; levels in select cases	SCr, ECG if risk, coag tests artifact	Minimal	Minimal
Practical pearls	AUC 400–600 mg·h/L target; slow infusion to avoid flushing	Convenient once-daily after load	Avoid in pregnancy; caution if QT risk	OPAT-friendly single dose	OPAT-friendly single dose; avoid UFH for 48 h due to aPTT artifact