Vancomycin
1. Drug Name
Generic Name: Vancomycin
Brand Names: Vancocin, Firvanq, Vancoled, and others.
2. Drug Classification
Class: Antibiotic, Glycopeptide
Subclass: None (Glycopeptide class)
3. Mechanism of Action
Primary Action: Vancomycin inhibits bacterial cell wall synthesis by binding to the D-alanyl-D-alanine terminus of peptidoglycan precursors. This prevents the incorporation of these precursors into the growing peptidoglycan matrix, thereby inhibiting bacterial cell wall synthesis and leading to cell lysis.
Bactericidal Action: Vancomycin is bactericidal, meaning it kills bacteria rather than merely inhibiting their growth.
Spectrum of Activity: Vancomycin is primarily effective against gram-positive bacteria. It is particularly useful in treating infections caused by Staphylococcus aureus (including methicillin-resistant S. aureus or MRSA), Streptococcus species, and Enterococcus species.
Gram-positive organisms: Staphylococcus aureus (including MRSA), Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium.
Anaerobes: Effective against Clostridium difficile in the treatment of C. difficile-associated diarrhea (CDAD).
4. Pharmacokinetics
Absorption: Vancomycin is poorly absorbed from the gastrointestinal tract, which is why it is given intravenously for systemic infections. For localized gastrointestinal infections (such as C. difficile colitis), oral vancomycin is used, as it is not absorbed systemically.
Distribution: Vancomycin is widely distributed throughout the body, including in the lungs, bones, and heart valves. It has a volume of distribution (Vd) of about 0.4-1 L/kg. It is also able to penetrate the cerebrospinal fluid (CSF) if the meninges are inflamed.
Metabolism: Vancomycin is not significantly metabolized in the liver and is excreted unchanged in the urine. It has minimal hepatic metabolism.
Excretion: Vancomycin is primarily eliminated by the kidneys, with about 80-90% of the drug excreted unchanged in the urine. The half-life (t½) of vancomycin is about 6-8 hours in patients with normal renal function, but it can be prolonged in patients with renal impairment.
Special Considerations: In patients with renal dysfunction, vancomycin clearance is reduced, and dosage adjustments are required to avoid drug toxicity. Therapeutic drug monitoring (TDM) is recommended in these patients to ensure appropriate dosing.
5. Indications
Primary Indications:
MRSA Infections: Vancomycin is the treatment of choice for infections caused by methicillin-resistant Staphylococcus aureus (MRSA), including skin and soft tissue infections, pneumonia, and bacteremia.
Endocarditis: Particularly in patients with MRSA or other resistant gram-positive infections.
Osteomyelitis: Vancomycin is used in the treatment of bone infections caused by resistant gram-positive organisms.
C. difficile Infection: Oral vancomycin is used in the treatment of Clostridium difficile infection (C. difficile colitis) and its associated diarrhea.
Streptococcal Infections: Treatment of infections caused by Streptococcus pneumoniae and other beta-hemolytic streptococci.
Off-label Uses:
Enterococcal Infections: Vancomycin is often used in combination therapy with other antibiotics (e.g., gentamicin) for enterococcal infections, especially for Enterococcus faecium in cases of multidrug-resistant infections.
Meningitis: In combination with other antibiotics for empiric therapy of meningitis, particularly when resistant organisms are suspected.
Specific Populations: Vancomycin is commonly used in hospitalized patients, including critically ill patients, and is often used in combination with other antibiotics for polymicrobial infections.
6. Dosage and Administration
Adult Dosing:
Systemic Infections: 15-20 mg/kg IV every 8-12 hours, depending on the severity of the infection and renal function.
C. difficile Infection (oral): 125 mg orally every 6 hours for 10-14 days.
Endocarditis (IV): 15-20 mg/kg IV every 8-12 hours.
Renal Impairment Adjustments: In patients with renal dysfunction, the dose and frequency of vancomycin should be adjusted based on creatinine clearance. Dosing intervals may be extended, or dosages reduced.
Pediatric Dosing:
Pediatric infections: 10-15 mg/kg IV every 6-8 hours.
C. difficile Infection (oral): 10 mg/kg every 6 hours, adjusted to clinical response.
Renal Adjustments: Vancomycin requires dose adjustments in renal impairment. The dosing intervals should be lengthened based on the degree of renal dysfunction.
Route of Administration: Intravenous (IV) administration is the primary route for systemic infections, while oral vancomycin is used for localized infections like C. difficile.
7. Contraindications
Absolute Contraindications:
Hypersensitivity to vancomycin or any of its components.
Use in neonates for systemic infections unless clinically necessary due to the risk of nephrotoxicity.
Relative Contraindications:
Renal Dysfunction: Careful dosing adjustments are necessary in patients with impaired renal function.
Pregnancy: Vancomycin is generally considered safe for use during pregnancy (Category B), but it should only be used when the benefits outweigh the risks.
Lactation: Vancomycin is excreted into breast milk in small amounts. It is generally considered safe during lactation, but caution is advised in newborns.
8. Warnings and Precautions
Nephrotoxicity: Vancomycin can cause renal toxicity, especially at high doses or with prolonged use. Renal function should be monitored, particularly in patients with pre-existing kidney disease or when used in combination with other nephrotoxic drugs.
Ototoxicity: Vancomycin has the potential to cause ototoxicity, especially in high serum concentrations. Audiometric testing should be performed if the patient develops symptoms of hearing loss or tinnitus.
Red Man Syndrome: This is a histamine-mediated reaction that can occur if vancomycin is infused too rapidly, leading to symptoms such as flushing, rash, hypotension, and tachycardia. This can be prevented by infusing vancomycin slowly (over at least 60 minutes).
Extravasation: Vancomycin can cause severe tissue damage if it leaks into the surrounding tissue during intravenous infusion.
Superinfection: Prolonged use can lead to secondary infections such as candidiasis or C. difficile infection.
9. Adverse Effects
Common Adverse Effects (≥10%):
Phlebitis or pain at the injection site.
Nausea and vomiting.
Less Common but Clinically Significant:
Nephrotoxicity: Elevated creatinine levels, renal failure, especially in patients with pre-existing kidney disease or those on other nephrotoxic drugs.
Ototoxicity: Tinnitus, hearing loss (typically reversible upon discontinuation).
Rash and allergic reactions: Including drug fever, and rarely, anaphylaxis.
Serious Adverse Reactions:
Red Man Syndrome: Flushing, pruritus, hypotension.
Severe Renal Injury: Acute kidney injury (AKI) can occur, particularly in patients with pre-existing renal dysfunction.
Anaphylaxis: Rare but can occur.
10. Drug Interactions
Major Drug Interactions:
Nephrotoxic Drugs: The risk of nephrotoxicity is increased when vancomycin is used in combination with other nephrotoxic drugs (e.g., aminoglycosides, NSAIDs, or diuretics).
Ototoxic Drugs: Combining vancomycin with other ototoxic drugs (e.g., aminoglycosides) may increase the risk of hearing loss.
Muscle Relaxants: The concomitant use of vancomycin with muscle relaxants like atracurium may increase the neuromuscular blocking effect.
Food-Drug Interactions: There are no significant food-drug interactions associated with vancomycin.
11. Clinical Pharmacology
Pharmacodynamics: Vancomycin exhibits time-dependent bactericidal activity. Its clinical efficacy is related to the time that plasma concentrations remain above the minimum inhibitory concentration (MIC) for the target pathogen.
Pharmacokinetics: Due to its poor gastrointestinal absorption, vancomycin is administered parenterally for systemic infections. Therapeutic drug monitoring (TDM) is often employed to adjust the dose to achieve an optimal drug concentration, particularly in severe infections or in patients with renal impairment.
12. Special Populations
Pregnancy: Category B. Vancomycin should be used during pregnancy only if the benefits outweigh the risks.
Lactation: Excreted into breast milk in low amounts. It is considered safe for breastfeeding mothers.
Pediatrics: In children, vancomycin is commonly used for serious infections, and dosing adjustments should be made based on age, weight, and renal function.
Geriatrics: Elderly patients may be more prone to nephrotoxicity. Renal function should be closely monitored in this population.
13. Therapeutic Uses
First-Line Therapy:
MRSA infections (including bacteremia, endocarditis, osteomyelitis).
C. difficile infection (oral vancomycin).
Combination Therapy: Used in combination with other antibiotics for polymicrobial infections or in cases of enterococcal infections resistant to other agents.
14. Monitoring and Follow-Up
Lab Tests: Renal function (serum creatinine, BUN), liver enzymes, audiometric tests (in cases of prolonged therapy), and vancomycin serum levels.
Patient Follow-up: Regular follow-up to monitor for signs of toxicity, especially in patients with impaired renal function or receiving high doses.
15. Overdose Management
Symptoms of Overdose: Renal toxicity, ototoxicity, and hypotension.
Treatment Protocols: There is no specific antidote for vancomycin overdose. Supportive care is the mainstay of treatment, and dose adjustments based on renal function are crucial.
Supportive Measures: Hydration and monitoring renal function are important in the management of overdose.
16. Patient Counseling Information
Key Points to Discuss with Patients:
Advise patients on the importance of completing the full course of therapy, even if they start feeling better.
Inform patients that if they are receiving intravenous vancomycin, it should be infused slowly to avoid the risk of Red Man Syndrome.
Advise patients to report any symptoms of hearing loss, ringing in the ears, or any skin reactions.
Signs/Symptoms to Watch For:
Signs of an allergic reaction (e.g., rash, swelling, difficulty breathing).
Symptoms of kidney problems (e.g., decreased urine output, swelling).
Ringing in the ears, dizziness, or hearing loss (potential ototoxicity).