Vancomycin

Generic name: Vancomycin 

Brand names:  Firvanq , Vancocin, Vinjec

Drug class: Glycopeptide antibiotics

What is Vancomycin?

Vancomycin is a potent antibiotic primarily used to treat bacterial infections caused by gram-positive bacteria. It belongs to the glycopeptide class of antibiotics and works by inhibiting the synthesis of the bacterial cell wall, ultimately leading to the death of the bacteria.

Vancomycin is often reserved for treating infections caused by bacteria that are resistant to other antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus species. These bacteria are notorious for their resistance to multiple antibiotics, making vancomycin a critical treatment option in such cases.

How does vancomycin produce its action?

Mechanism of action:

1. Inhibition of Cell Wall Synthesis: Vancomycin binds to the D-alanyl-D-alanine terminus of the growing peptidoglycan chain, thereby preventing the cross-linking of peptidoglycan strands essential for the formation of the bacterial cell wall.
2. Blocking Transpeptidation: By inhibiting transpeptidation, vancomycin effectively prevents the final stage of bacterial cell wall synthesis, leading to the weakening and eventual lysis of the bacterial cell.
3. Bactericidal Activity: Vancomycin’s disruption of cell wall synthesis results in bacterial cell death, making it a bactericidal antibiotic.

Pharmacokinetics of vancomycin

1. Absorption: Vancomycin is poorly absorbed when administered orally, so it is typically administered intravenously for systemic infections. However, oral vancomycin can be used for certain gastrointestinal infections, like Clostridium difficile-associated diarrhea.
2. Distribution: Vancomycin has a large volume of distribution, leading to good penetration into various tissues and body fluids, including bone, pleural fluid, and cerebrospinal fluid (CSF). However, its ability to cross the blood-brain barrier is limited unless the meninges are inflamed.
3. Metabolism: Vancomycin is not significantly metabolized in the body.
4. Elimination: Vancomycin is primarily eliminated unchanged by the kidneys through glomerular filtration. The elimination half-life can vary widely depending on kidney function and patient characteristics. In individuals with normal renal function, the half-life is around 6 to 12 hours, but it can be significantly prolonged in patients with impaired renal function.

Therapeutic uses

1. Serious Gram-Positive Infections: Vancomycin is primarily used to treat infections caused by Gram-positive bacteria, particularly those that are resistant to other antibiotics. These include infections caused by:
   • Methicillin-resistant Staphylococcus aureus (MRSA): Vancomycin is often the first-line treatment for MRSA infections, including skin and soft tissue infections, pneumonia, and bloodstream infections.
   • Methicillin-resistant coagulase-negative staphylococci (MRCoNS): Vancomycin may also be used to treat infections caused by other coagulase-negative staphylococci resistant to methicillin.
   • Vancomycin-resistant Enterococci (VRE): Despite its name, vancomycin can still be effective against some strains of VRE, especially when other treatment options are limited.
2. Endocarditis: Vancomycin is commonly used in the treatment of infective endocarditis caused by Gram-positive bacteria, including MRSA and penicillin-resistant strains of Streptococcus viridans.
3. Surgical Prophylaxis: In certain surgical procedures where there is a high risk of MRSA infection, such as cardiac surgery or orthopedic procedures, vancomycin may be used as prophylaxis to prevent surgical site infections.
4. Bone and Joint Infections: Vancomycin is effective in treating osteomyelitis and septic arthritis caused by MRSA or other resistant Gram-positive bacteria.
5. Meningitis: While vancomycin does not penetrate the blood-brain barrier well in the absence of inflammation, it may be used in combination with other antibiotics to treat bacterial meningitis caused by susceptible organisms.
6. Clostridium difficile infection (CDI): Vancomycin is one of the antibiotics of choice for treating severe cases of Clostridium difficile-associated diarrhea (CDAD) when metronidazole is ineffective or contraindicated.
7. Empirical Therapy: In settings where the causative organism of an infection is unknown or where there is a high likelihood of antibiotic-resistant bacteria, vancomycin may be used empirically until culture and sensitivity results are available.

Routes of administration

1. Intravenous (IV) Route: This is the most common route of administration for systemic infections. Vancomycin is typically infused slowly over a period of time to minimize the risk of adverse reactions, such as Red Man Syndrome. Intravenous administration allows for rapid delivery of the medication into the bloodstream.

2. Oral Route: While less common than intravenous administration, vancomycin can also be given orally for certain gastrointestinal infections, such as Clostridium difficile-associated diarrhea (CDAD). Oral vancomycin is not absorbed systemically and works locally in the gastrointestinal tract to treat the infection.

3. Topical Route: Vancomycin is sometimes formulated into topical preparations, such as creams or ointments, for the treatment of localized skin and soft tissue infections caused by susceptible bacteria. Topical application allows for direct delivery of the medication to the site of infection.

Dosing of vancomycin 

The dosing of vancomycin can vary depending on the dosage form (intravenous, oral, or topical) and the age of the patient. 

• Intravenous (IV) Vancomycin:
  • For adult patients (age 12 and older), the typical dosage for most infections is 15-20 mg/kg of body weight, given every 8–12 hours. The dosage may be adjusted based on factors such as renal function and the severity of the infection. 
  • For pediatric patients under 12 years old, dosing is usually based on age, weight, and clinical condition. 
• Oral Vancomycin:
  • For adults with Clostridium difficile-associated diarrhea (CDAD), the typical dosage is 125–500 mg orally four times daily for 7–10 days. The exact dosage and duration may vary depending on the severity of the infection.
  • Pediatric dosing for oral vancomycin in the treatment of CDAD is based on age, weight, and clinical condition and is determined by the healthcare provider.
• Topical Vancomycin:
  • The dosing of topical vancomycin for skin and soft tissue infections varies depending on the formulation and the severity of the infection. Typically, a thin layer of the topical preparation is applied to the affected area several times daily, as directed by the healthcare provider.

Side effects of vancomycin

• Nephrotoxicity: Vancomycin can cause damage to the kidneys, particularly when administered at high doses or to individuals with pre-existing kidney problems. Symptoms may include decreased urine output, elevated serum creatinine levels, and acute kidney injury.
• Ototoxicity: Vancomycin can lead to damage to the inner ear, resulting in hearing loss, ringing in the ears (tinnitus), and balance disturbances. Ototoxicity is more common with high doses, prolonged therapy, or in patients with pre-existing hearing impairment.
• Red Man Syndrome: A rapid infusion of vancomycin can cause a histamine-mediated reaction known as Red Man Syndrome. Symptoms include flushing of the skin, rash, itching, and sometimes hypotension. Slowing the rate of infusion can help prevent this reaction.
• Thrombophlebitis: Vancomycin administered intravenously can irritate the veins, leading to inflammation and the formation of blood clots (thrombophlebitis) at the injection site.
• Allergic Reactions: While rare, some individuals may experience allergic reactions to vancomycin, ranging from mild skin rashes to severe anaphylaxis.
• Neutropenia: Vancomycin has been associated with a decrease in white blood cell counts, particularly neutrophils, which can increase the risk of infections.
• Superinfections: Prolonged or repeated use of vancomycin can disrupt the balance of normal bacterial flora in the body, leading to the overgrowth of opportunistic pathogens such as Clostridium difficile, resulting in Clostridium difficile-associated diarrhea (CDAD).
• Thrombocytopenia: In some cases, vancomycin use has been associated with a decrease in platelet counts, leading to an increased risk of bleeding.
• Liver Toxicity: Vancomycin has rarely been associated with liver damage, including elevated liver enzymes and hepatitis.
• Fever and chills: Some patients may experience fever and chills as a reaction to a vancomycin infusion.

Interactions of vancomycin with other drug

Nephrotoxic Drugs: Concurrent use of nephrotoxic drugs, such as gentamicin, amphotericin B, cyclosporine, and non-steroidal anti-inflammatory drugs (NSAIDs), may increase the risk of kidney damage when used with vancomycin.

Ototoxic Drugs: Drugs with potential ototoxic effects, such as gentamicin and loop diuretics (e.g., furosemide), may increase the risk of hearing loss when used concurrently with vancomycin.

Other Antibiotics: Concurrent use of other antibiotics, particularly those with similar mechanisms of action, may increase the risk of toxicity or promote the development of antibiotic resistance.

Drugs Affecting Kidney Function: Drugs that affect kidney function, such as diuretics, should be used cautiously with vancomycin, as they may alter vancomycin levels in the blood and increase the risk of nephrotoxicity.

Warfarin: Vancomycin may potentiate the effects of warfarin, leading to an increased risk of bleeding.

Contraindication of vancomycin

Hypersensitivity: Patients with a known hypersensitivity or allergy to vancomycin should not receive the medication.

Previous History of Ototoxicity or Nephrotoxicity: Individuals who have experienced severe ototoxicity or nephrotoxicity with previous vancomycin therapy should avoid further use of the medication unless the benefits clearly outweigh the risks.

Concomitant Use with Nephrotoxic or Ototoxic Drugs: Vancomycin should be used with caution or avoided when administered concurrently with other nephrotoxic or ototoxic medications, such as aminoglycosides or loop diuretics, as this can increase the risk of adverse effects on the kidneys and ears.

Pregnancy and Lactation

While vancomycin is generally considered safe for use during pregnancy and breastfeeding, caution is advised, and the potential risks and benefits should be carefully weighed before administration.

Precaution and Warning

Due to the potential for nephrotoxicity and ototoxicity, as well as the variability in vancomycin’s pharmacokinetics, therapeutic drug monitoring is often employed. This involves measuring vancomycin levels in the blood to ensure they remain within the therapeutic range while minimizing the risk of toxicity.

Irrational use of vancomycin and its outcome

The irrational use of vancomycin includes inappropriate prescribing for infections where it is not indicated, such as viral or mild bacterial infections. Overuse or misuse, including prolonged or unnecessary courses of therapy, can lead to the development of antibiotic resistance, an increased risk of adverse effects such as nephrotoxicity and CDAD, and unnecessary healthcare costs. Adherence to evidence-based guidelines and antimicrobial stewardship programs is essential to prevent the irrational use of vancomycin and preserve its efficacy for serious Gram-positive infections.

CONCLUSION

Overall, vancomycin remains an essential antibiotic in the treatment of serious gram-positive bacterial infections, particularly those resistant to other antibiotics, but its use should be carefully managed to minimize the risk of adverse effects and the development of antibiotic resistance.