Glycopeptides and Lipoglycopeptides

Mechanism

💊 Generic and Commercial Names

Glycopeptides: vancomycin (Vancocin), teicoplanin (Targocid). Lipoglycopeptides: dalbavancin (Xydalba).

🔬 Pharmacological Group

Glycopeptides and lipoglycopeptides. Inhibitors of bacterial cell wall synthesis.

Mechanism of Action

Its target is the terminal peptide substrate, not the bacterial enzyme:

• Strict Binding to the D-Ala-D-Ala Terminus: Glycopeptides are electrostatically linked by hydrogen bonds to the terminal dipeptide. D-alanyl-D-alanine of cell wall precursors in the extracellular space. This union forms a voluminous steric cap that absolutely prevents the access of transpeptidases (PBPs) and transglycosylases, interrupting both linear polymerization and cross-linking of peptidoglycan.
• Membrane Anchoring of Lipoglycopeptides (Dalbavancin): They incorporate a lipid side chain (hydrophobic) that allows them to anchor directly to the bacterial cell membrane, drastically increasing their binding affinity and bactericidal potency, in addition to prolonging their plasma half-life to more than 300 hours.

Pharmacokinetics

Key Pharmacokinetics

Antimicrobial Spectrum

• Exclusive Gram-Positives: Excellent against methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, multidrug-resistant Streptococcus pneumoniae, Enterococcus faecalis (sensitive to glycopeptides) and Clostridioides difficile (oral). They lack activity against Gram-negative bacteria due to their large molecular weight that prevents passage through endothelial porins of the external wall.

Indicators and dose

Dosage and Adjustment

• Vancomycin (IV): 15 to 20 mg/kg every 8 to 12 hours in adults with normal renal function. The use of an initial loading dose of 25 to 30 mg/kg is preferred in critically ill patients with sepsis or septic shock to achieve rapid target concentrations.
• Vancomycin (Oral): 125 mg every 6 hours orally (single dose for the management of C. difficile colitis, does not require systemic absorption).
• Dalbavancin: 1500 mg as a single dose IV once, or divided regimen of 1000 mg on day 1 followed by 500 mg on day 8.
• Adjustment of Vancomycin in Renal Failure:
  • Requires estimation of creatinine clearance to prolong the dosing interval (e.g., every 24, 48, or 72 hours) and guide treatment based on weekly analytical trough levels.

Security

Contraindications and ADRs

• Contraindications: Proven severe allergy to glycopeptides.
• Adverse Effects (ADR):
  • Vancomycin Infusion Reaction ("Red Man Syndrome"): Non-immunological anaphylactoid reaction due to direct degranulation and systemic release of histamine by mast cells, induced after excessively rapid intravenous infusions. It is manifested by intense pruritus, maculopapular erythema and flushing of the face, neck, chest and upper extremities, sometimes accompanied by hypotension and dyspnea. It is prevented by reducing the infusion rate to a minimum of 1 hour for each gram of vancomycin.
  • Nephrotoxicity (Dose-dependent): Acute renal tubular necrosis associated with cellular oxidative stress. The risk increases synergistically with the coadministration of aminoglycosides or loop diuretics.
  • Ototoxicity: Dural vestibular and cochlear damage of a generally irreversible course, associated with persistently elevated serum levels.

Strategy for Monitoring Serum Vancomycin Levels

Due to its narrow therapeutic window and exposure-dependent kinetics (fAUC₂₄/MIC ≥ 400), vancomycin dosing requires routine monitoring of its serum plasma levels. The classic clinical objective is to measure trough serum levels (minimum concentration immediately before the next dose at steady state), which should be between 15 and 20 mcg/mL for serious deep infections (bacteremia, endocarditis, osteomyelitis or pneumococcal pneumonia). Currently, international guidelines suggest direct estimation of the 24-hour AUC using Bayesian models for greater safety.