Vancomycin: Drug Information

Vancomycin is a glycopeptide antibiotic that is used to treat serious infections caused by Gram-positive bacteria. It is effective against streptococci, enterococci, and staphylococci, including methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA). It functions by inhibiting bacterial cell wall synthesis, which results in the death of bacterial cells. Vancomycin is available in various forms and strengths, including capsules, oral solutions, and injections.

Dosing and Uses

The dosage and administration of vancomycin depend on several factors, including the type and severity of the infection, the patient's renal function, and the patient's age. Vancomycin can be administered intravenously or orally.

Adult Dosage

The usual adult dosage for vancomycin is 2 g per day, divided either as 500 mg every 6 hours or 1 gram every 12 hours. The initial daily dose should be no less than 15 mg/kg.

Pediatric Dosage

For pediatric patients aged 1 month and older, the usual intravenous vancomycin dosage is 10 mg/kg every 6 hours. Each dose should be administered over at least 60 minutes. Close monitoring of serum vancomycin concentrations may be warranted in these patients. For patients younger than 1 month, an initial dose of 15 mg/kg is recommended for neonates, followed by 10 mg/kg every 12 hours for pediatric patients in the first week of life and every 8 hours after that up to the age of 1 month.

Geriatric Dosage

Elderly patients are more prone to toxicity during intravenous vancomycin administration because of age-related changes in renal function, volume of distribution, and accumulation. Care should be taken in dose selection, and renal function should be monitored. Patients older than 65 years should be monitored during and following treatment to detect potential vancomycin-induced nephrotoxicity. It may take longer for older patients to respond to therapy compared to patients 65 years and younger.

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Dosage Forms and Strengths

Vancomycin is available in the following dosage forms and strengths:

Capsule (Vancocin): 125mg, 250mg
Kit, powder for oral solution (Firvanq): 3.75g, 7.5g, 10.5g, 15g
Injection, ready-to-infuse solution (Tyzavan): 500mg/100mL, 750mg/150mL, 1g/200mL, 1.25g/250mL, 1.5g/300mL, 1.75g/350mL, 2g/400mL
Injection, lyophilized powder for reconstitution (generic): 500mg, 750mg, 1g, 1.75g, 2g, 5g, 10g
Injection, single-dose flexible bag (generic): 500mg/100mL, 750mg/150mL, 1g/200mL, 1.25g/250mL, 1.5g/300mL, 1.75g/350mL, 2g/400mL

Specific Uses

Vancomycin is indicated for the treatment of various infections, including:

Staphylococcal Enterocolitis: Vancocin and Firvanq are indicated for enterocolitis caused by Staphylococcus aureus (including methicillin-resistant strains). For adults and pediatric patients <18 years, the dosage is 0.5-2 g/day PO divided every 6-8 hours for 7-10 days.
Clostridium difficile-associated Diarrhea: Vancocin and Firvanq are indicated for treatment of Clostridium difficile (C. difficile)-associated diarrhea in adults and pediatric patients <18 years. The dosage is 125 mg PO every 6 hours for 10 days.
Infective Endocarditis: Indicated for treatment of infective endocarditis due to susceptible isolates of MRSA, viridans group streptococci, Streptococcus gallolyticus, Enterococcus species, and Corynebacterium species. For enterococcal endocarditis, use in combination with an aminoglycoside. Also indicated for methicillin-susceptible staphylococci in penicillin-allergic patients or those patients who cannot receive or have failed to respond to other therapies. Indicated for treatment of early-onset prosthetic valve endocarditis caused by Staphylococcus epidermidis in combination with rifampin and an aminoglycoside. The usual dosage is 2 g divided either as 500 mg every 6 hours or 1 gram every 12 hours. The initial daily dose should be no less than 15 mg/kg.
Septicemia: Indicated for treatment of septicemia due to susceptible isolates of methicillin-resistant Staphylococcus aureus (MRSA) and coagulase negative staphylococci, methicillin-susceptible staphylococci in penicillin-allergic patients, or patients who cannot receive or who have failed to respond to other drugs, including penicillins or cephalosporins. The usual dosage is 2 g divided either as 500 mg every 6 hours or 1 gram every 12 hours. The initial daily dose should be no less than 15 mg/kg.
Skin and Skin Structure Infections: Indicated for treatment of skin and skin structure infections due to susceptible isolates of MRSA and coagulase negative staphylococci, methicillin-susceptible staphylococci in penicillin-allergic patients, or those patients who cannot receive or have failed to respond to other therapies. The usual dosage is 2 g divided either as 500 mg every 6 hours or 1 g every 12 hours. The initial daily dose should be no less than 15 mg/kg.
Bone Infections: Indicated for treatment of bone infections due to susceptible isolates of MRSA and coagulase negative staphylococci, methicillin-susceptible staphylococci in penicillin-allergic patients, or those patients who cannot receive or have failed to respond to other therapies. The usual dosage is 2 g divided either as 500 mg every 6 hours or 1 gram every 12 hours. The initial daily dose should be no less than 15 mg/kg.
Lower Respiratory Tract Infections: Indicated for treatment of lower respiratory tract infections due to susceptible isolates of MRSA and coagulase negative staphylococci, methicillin-susceptible staphylococci in penicillin-allergic patients, or those patients who cannot receive or have failed to respond to other therapies. The usual dosage is 2 g divided either as 500 mg every 6 hours or 1 gram every 12 hours. The initial daily dose should be no less than 15 mg/kg.
Preoperative Antimicrobial Prophylaxis (Off-label): For gastrointestinal (GI) and genitourinary (GU) procedures, 1 g IV is administered by slow infusion over 1 hour, beginning 1-2 hours before the procedure (with or without gentamicin 1.5 mg/kg; not to exceed 120 mg IV or IM <30 minutes before the procedure).
Surgical Prophylaxis (Off-label): For prophylaxis of infection in cardiac, thoracic, and arterial procedures; craniotomy; joint replacement; amputation, 15 mg/kg IV is administered over 1-2 hours, beginning within 2 hours before incision. The duration of prophylaxis for most procedures should be <24 hours.
Bacterial Meningitis: 15-20 mg/kg IV every 6 hours.
Other Infections: 40 mg/kg/day IV divided every 6 hours.

Dosing Modifications

Renal Impairment: For mild-to-severe renal impairment, the initial dose should be no less than 15 mg/kg. For functionally anephric patients, an initial dose of 15 mg/kg of body weight should be given to achieve prompt therapeutic serum concentration, starting at 1.9 mg/kg/24 hours after the initial dose of 15 mg/kg. Trough serum concentrations should be measured to guide therapy, especially in seriously ill patients with changing renal function.
Neonatal Dosing: After a 20 mg/kg IV loading dose, the maintenance dose should be given according to gestational age (GA) and serum creatinine (Scr).
- GA ≤28 weeks:
  - Scr <0.5: 15 mg/kg every 12 hours
  - Scr 0.5-0.7: 20 mg/kg every 24 hours
  - Scr 0.8-1: 15 mg/kg every 24 hours
  - Scr 1.1-1.4: 10 mg/kg every 24 hours
  - Scr >1.4: 15 mg/kg every 48 hours
- GA >28 weeks:
  - Scr <0.7: 15 mg/kg every 12 hours
  - Scr 0.7-0.9: 20 mg/kg every 24 hours
  - Scr 1-1.2: 15 mg/kg every 24 hours
  - Scr 1.3-1.6: 10 mg/kg every 24 hours
  - Scr >1.6: 15 mg/kg every 48 hours

Dosing Considerations

Peak values should be 18-26 mg/L; trough values should be 5-10 mg/L. However, the Infectious Diseases Society of America and other guidelines urge troughs of 15-20 mg/L. Only treat or prevent infections proven or strongly suspected to be caused by susceptible bacteria to reduce the development of drug-resistant bacteria. Oral vancomycin is not effective for other types of infections. IV vancomycin is not effective for treatment of staphylococcal enterocolitis and C. difficile-associated diarrhea.

Contraindications

Vancomycin is contraindicated in patients with a known allergy to vancomycin, corn, or corn products (for solutions containing dextrose).

Warnings and Precautions

Hypersensitivity: Rapid IV administration may result in flushing, pruritus, hypotension, erythema, and urticaria.
Sodium Content: Each 100 mL solution of vancomycin injection contains 354 mg of sodium, each 150 mL solution contains 531 mg of sodium, and each 200 mL solution contains 708 mg of sodium. Avoid use of vancomycin injection in patients with congestive heart failure, elderly patients, and patients requiring restricted sodium intake.
Endocarditis Prophylaxis: Use only for high-risk patients, per AHA guidelines.
Extravasation: Avoid extravasation; necrosis may occur.
Superinfection: Prolonged use may result in fungal or bacterial superinfection.
Ophthalmic Use: Hemorrhagic occlusive retinal vasculitis, including permanent loss of vision, occurred in patients receiving intracameral or intravitreal administration of vancomycin during or after cataract surgery. The safety and efficacy of vancomycin administered by intracameral or intravitreal route are not established by adequate and well-controlled trials. Vancomycin is not indicated for prophylaxis of endophthalmitis.
Oral Use Limitations: Oral vancomycin is only indicated for treatment of pseudomembranous colitis due to Clostridioides difficile (C. difficile) and enterocolitis due to S. aureus. It is not effective for systemic infections.
Systemic Absorption: Clinically significant serum concentrations have been reported in some patients who have taken multiple oral doses of vancomycin for active C. difficile-associated diarrhea.
Antibiotic Resistance: Prescribe vancomycin only for a proven or strongly suspected bacterial infection to prevent the development of drug-resistant bacteria.
Severe Dermatologic Reactions: Severe dermatologic reactions such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear lgA bullous dermatosis (LABD) have been reported in association with vancomycin. Cutaneous signs or symptoms reported include skin rashes, mucosal lesions, and blisters. Discontinue therapy at the first appearance of signs and symptoms of TEN, SJS, DRESS, AGEP, or LABD.
Nephrotoxicity: Therapy can result in acute kidney injury (AKI), including acute renal failure, mainly due to interstitial nephritis or less commonly acute tubular necrosis. AKI is manifested by increasing blood urea nitrogen (BUN) and serum creatinine (Cr). The risk of AKI increases with higher vancomycin serum levels, prolonged exposure, concomitant administration of other nephrotoxic drugs, and concomitant administration of piperacillin/tazobactam.
Hearing Loss: Hearing loss may occur while receiving this medicine. Tell your doctor if you or your child have ringing or buzzing in the ears, dizziness, feeling of fullness in the ears, or loss of balance after receiving this medicine.
Infusion Reactions: This medicine may cause infusion reactions, which can be life-threatening and require immediate medical attention. Tell your doctor right away if you or your child starts to have cough, difficulty with swallowing, dizziness, fast heartbeat, trouble with breathing, chest tightness, swelling in your face or hands, fever, chills, itching or hives, or lightheadedness or faintness while you are receiving this medicine.

Adverse Effects

Common adverse effects of intravenous vancomycin injection include nephrotoxicity, hypotension, and hypersensitivity reactions (e.g., anaphylaxis).

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Common (Oral Capsule)

Nausea (17%)
Abdominal pain (15%)
Hypokalemia (13%)
Vomiting (9%)
Diarrhea (9%)
Pyrexia (9%)
Flatulence (8%)
Urinary tract infection (8%)
Headache (7%)
Peripheral edema (6%)
Back pain (6%)
Fatigue (5%)
Nephrotoxicity (5%)

Frequency Not Defined (IV)

Immune system disorders: Hypersensitivity reactions (eg, anaphylaxis, “red man syndrome”)
Skin and subcutaneous tissue disorders: Severe dermatologic reactions such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear lgA bullous dermatosis (LABD)
Renal and urinary disorders: Acute kidney injury and interstitial nephritis
Ear and labyrinth disorders: Tinnitus, hearing loss, vertigo
Blood and lymphatic system disorders: Agranulocytosis, neutropenia, pancytopenia, leukopenia, thrombocytopenia, eosinophilia
Gastrointestinal disorders: Pseudomembranous colitis
Cardiac disorders: Cardiac arrest, chest pain
General disorders and administration site conditions: General discomfort, fever, chills, phlebitis, injection site irritation, injection site pain and necrosis following intramuscular injection, chemical peritonitis following intraperitoneal administration (Vancomycin not approved for IM and intraperitoneal administration)
Laboratory abnormalities: Elevated blood urea nitrogen, elevated serum creatinine
Musculoskeletal and connective tissue disorders: Muscle pain
Nervous system disorders: Dizziness
Respiratory, thoracic and mediastinal disorders: Wheezing, dyspnea
Vascular disorders: Hypotension, shock, vasculitis

Postmarketing Reports (All Formulations)

Ototoxicity: Hearing loss associated IV administration (most cases had coexisting renal impairment or pre-existing hearing loss, or were coadministered an ototoxic drug), vertigo, dizziness, and tinnitus
Hematopoietic: Reversible neutropenia, thrombocytopenia
Miscellaneous: Anaphylaxis, drug fever, chills, nausea, eosinophilia, rashes, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, pruritus, flushing of the upper body (“vancomycin infusion reaction”), and vasculitis

Single-dose flexible bags only

Skin and subcutaneous tissue disorders: Drug rash with eosinophilia and systemic symptoms (DRESS)

Interactions

The coadministration of other medications, along with vancomycin, may increase the risk of adverse effects and toxicity. Therefore, dosing adjustments, additional monitoring, and consideration of alternative treatment should merit attention when combining vancomycin with certain medications.

Mechanism of Action

Vancomycin is a glycopeptide antibiotic that exerts its bactericidal effect by inhibiting the polymerization of peptidoglycans in the bacterial cell wall. The bacterial cell wall contains a rigid peptidoglycan layer with a highly cross-linked structure composed of long polymers of N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG). Vancomycin binds to D-alanyl D-alanine, which inhibits glucosyltransferase (peptidoglycan synthase) and the P-phospholipid carrier, thereby preventing the synthesis and polymerization of NAM and NAG within the peptidoglycan layer.

Pharmacokinetics

Absorption: Oral vancomycin has a bioavailability of less than 10%. Vancomycin has a rapid onset of action with a serum peak concentration immediately following the completion of the intravenous infusion.
Distribution: Vancomycin is distributed widely (0.4 to 1.0 L/kg) in body tissues and fluids, excluding cerebrospinal fluid with non-inflamed meninges.
Metabolism: Vancomycin does not undergo any significant metabolism and is primarily excreted unchanged.
Elimination: Intravenous vancomycin injection is primarily eliminated by glomerular filtration in the kidney (75% via urine). Vancomycin exhibits a biphasic elimination half-life, with a relatively quick initial phase and a terminal half-life of 4 to 6 hours in healthy adults with normal renal function.

Storage

Store vancomycin hydrochloride capsules between 68°F and 77°F (20°C and 25°C).
Store reconstituted (mixed) oral solutions of vancomycin hydrochloride in a refrigerator between 36°F and 46°F (2°C and 8°C). Discard the oral solution after 14 days or if the solution looks hazy or contains any visible particles.
Store vancomycin hydrochloride injection at or below -4°F (-20°C). See the vancomycin hydrochloride injection label for instructions on how to thaw the containers before use.
Keep vancomycin hydrochloride in the container that it came in and keep the container tightly closed.
Do not use vancomycin hydrochloride if the original seal over the container opening is broken or missing.

Vancomycin Resistance

The increasing emergence of vancomycin-resistant enterococci (VRE) has resulted in the development of guidelines for use by the Centers for Disease Control Hospital Infection Control Practices Advisory Committee. Vancomycin resistance evolved in more common pathogenic organisms during the 1990s and 2000s, including vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA). One mechanism of resistance to vancomycin involves the alteration to the terminal amino acid residues of the NAM/NAG-peptide subunits, under normal conditions, D-alanyl-D-alanine, to which vancomycin binds.

History

Vancomycin was first isolated in 1953 by Edmund Kornfeld (working at Eli Lilly) from a bacteria in a soil sample collected from the interior jungles of Borneo by a missionary, William M. The compound was initially called compound 05865 but was later given the generic name vancomycin, derived from the term "vanquish."

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