Vancomycin - BioPharma Notes

Vancomycin is complex tricyclic glycopeptide antibiotic which was discovered in 1956 as a substitute for penicillin. It is obtained from fungus Streptomyces orientalis. It possesses bactericidal action mainly active against gram- positive bacteria.
Vancomycin is considered as ‘drug of last resort’ which is used after treatment with other antibiotics is not effective.

Antibacterial spectrum of vancomycin

It is mainly active against gram- positive bacteria. It is effective against S. aureus. S. epidermis, S. pyrogens, S. pneumonia.

Used in treatment of life-threatening Methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant Staphylococcus epidermis (MRSE).
Used in enterococcal infections.
To treat some serious infection like severe staphylococcal infection in patients allergic to both penicillin and cephalosporin.
Used in combination with aminoglycosides against S. aureus, S. bovis and S. viridans.
Preferred surgical prophylactic in MRSA prevalent areas and penicillin allergic patients. IV vancomycin is used in patients with prosthetic heart valves and in patients undergoing implantation with prosthetic devices, especially in hospitals with high rate of MRSA and MRSE.

Figure – Inhibition of bacterial cell wall synthesis by Vancomycin (source- Goodman and Gillman Manual of Pharmacology and Therapeutics)

It exerts its bactericidal effect by inhibiting cell wall synthesis. Peptidoglycan are major structural component of gram- positive bacterial cell wall. It binds to terminal dipeptide (D-ala- D-ala) sequence of peptidoglycan precursor unit i.e. NAM (N- acetyl muramic acid) and NAG (N- acetyl glucosamine). Then it prevents incorporation of NAM and NAG subunits into peptidoglycan matrix. Hence, it inhibits bacterial cell wall synthesis.
It also alters permeability of cell membrane and RNA synthesis in bacterial cell.

It is given through oral route and IV route. It is poorly absorbed after oral administration. So, oral formulation is used in limited cases like severe antibiotic associated C. difficile associated diarrhea, pseudomembranous colitis and Staphylococcal enterocolitis.
Around 30% of administered drug bind to plasma proteins. It is widely distributed in different body fluids including synovial, pericardial, ascitic and pleural fluid. It is also found in CSF when meninges are inflamed.
Its elimination half-life is around 6 hours. Around 75-80% of administered dose is eliminated via urine. Its half-life may increase in anephric patients (around 7.5 days). Dosage adjustment is required in renal patients.

There is increasing emergence of vancomycin resistant strains of bacteria. Prolonged or inappropriate treatment with vancomycin can lead to development of resistance
The resistance may be due to plasmid mediated alteration of dipeptide target site which reduces its affinity for vancomycin. The use of vancomycin should be restricted to serious infection to prevent the development of resistance.

Common hypersensitivity reactions are rashes and anaphylaxis. Vancomycin has high chances of systemic toxicity. It can cause dose dependent kidney damage and permanent nerve deafness. When administered through IV route, it can cause skin itching and decrease in BP.
Rapid IV injection can cause ‘Red man syndrome’ characterized by fever, chills, urticaria and intense flushing. The intense flushing occurs due to direct toxic action of vancomycin on mast cells to induce histamine release.
Oral vancomycin can cause GI related side effects including abdominal pain, nausea, dysgeusia or distorted sense of taste.

Contraindicated in patients with known hypersensitivity to drug or any other components.
Used with caution in renal patients.
Used with caution when co-administered with other nephrotoxic or ototoxic drugs like aminoglycosides.
When used in elderly patients, regular monitoring is required as elder patients are more prone to vancomycin toxicity due to age related changes in renal function.
Oral vancomycin is category B drug for pregnancy and IV vancomycin is category C drug. It is avoided in pregnancy unless the benefits outweigh the adverse effects.

Lippincott Illustrated Reviews Pharmacology, 6^th edition.
Pharmacology and pharmacotherapeutics. 24^th edition.
Goodman and Gillman Manual of Pharmacology and Therapeutics.
Essentials of Medical Pharmacology. 7^th edition.
Rang and Dale’s Pharmacology. 9^th edition.
https://www.ncbi.nlm.nih.gov/books/NBK459263/
https://go.drugbank.com/drugs/DB00512
Zamoner et al. Vancomycin dosing, monitoring and toxicity: Critical review of the clinical practice. Clin Exp Pharmacol Physiol. 2019; 46: 292–301.