Teicoplanin

Usage

Teicoplanin is a glycopeptide antibiotic prescribed for serious infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). It is particularly useful when other antibiotics, like flucloxacillin, are not suitable. Conditions treated include:

• Skin and soft tissue infections
• Bone and joint infections (e.g., osteomyelitis, septic arthritis)
• Pneumonia (hospital-acquired and community-acquired)
• Urinary tract infections
• Endocarditis
• Septicemia/bacteremia
• Peritonitis (especially in patients undergoing continuous ambulatory peritoneal dialysis - CAPD)
• Clostridioides difficile infections (oral administration)

Its pharmacological classification is antibiotic.

Teicoplanin’s mechanism of action involves inhibiting bacterial cell wall synthesis by binding to the D-alanyl-D-alanine terminus of peptidoglycan precursors. This prevents cross-linking of peptidoglycan chains, leading to a weakened cell wall and bacterial death.

Alternate Names

Teicoplanin is the generic name. A commonly known brand name is Targocid.

How It Works

Pharmacodynamics: Teicoplanin exerts a bactericidal effect primarily against Gram-positive bacteria. It disrupts cell wall synthesis, leading to bacterial cell death.

Pharmacokinetics:

• Absorption: Administered intravenously (IV) or intramuscularly (IM). Oral administration is used for C. difficile infections. IV administration offers rapid attainment of therapeutic levels. IM administration is also effective but may cause local reactions.
• Distribution: Distributes widely in tissues and body fluids, achieving therapeutic concentrations in bone, lung, and peritoneal fluid.
• Metabolism: Minimal metabolism occurs.
• Elimination: Primarily eliminated by renal excretion, with a long half-life (40-70 hours in adults). This allows for once-daily dosing after an initial loading dose. Dose adjustments are necessary in patients with renal impairment.

Mode of Action: Teicoplanin inhibits bacterial cell wall synthesis by binding to the D-alanyl-D-alanine terminus of peptidoglycan precursors. This action prevents the formation of peptidoglycan cross-links, leading to a weakened cell wall and bacterial lysis.

Receptor Binding/Enzyme Inhibition: Teicoplanin’s primary mechanism is not through receptor binding or enzyme inhibition but rather through direct interaction with peptidoglycan precursors.

Elimination Pathways: Primarily renal excretion.

Dosage

Standard Dosage

Adults:

• Mild to Moderate Infections: Initial loading dose of 6 mg/kg IV every 12 hours for three doses, followed by 6 mg/kg IV or IM once daily.
• Severe Infections (e.g., endocarditis, sepsis, osteomyelitis): Initial loading dose of 12 mg/kg IV every 12 hours for three doses, followed by 12 mg/kg IV or IM once daily. Higher doses (up to 12 mg/kg) might be considered for severe infections like endocarditis caused by S. aureus.
• C. difficile infections: 100-200 mg orally twice daily for 7-14 days.

Children:

• < 2 months: 16 mg/kg IV loading dose on day 1, followed by 8 mg/kg IV once daily. Administer via IV infusion over 30 minutes.
• 2 months to 12 years: 10 mg/kg IV every 12 hours for three loading doses, followed by 6-10 mg/kg IV once daily. Administer via IV injection over 3-5 minutes or IV infusion over 30 minutes.
• > 12 years: Same as adult dose.

Special Cases:

• Elderly Patients: Same as adult dose unless renal impairment is present.
• Patients with Renal Impairment: Dose adjustment is necessary based on creatinine clearance. After the initial loading dose, adjust the maintenance dose as follows:
  • CrCl > 60 mL/min: Standard dosing.
  • CrCl 30-60 mL/min: Administer half the normal dose every 24 hours or the full dose every 48 hours.
  • CrCl < 30 mL/min: Administer one-third of the maintenance dose every 24 hours or the full dose every 72 hours.
  • Dialysis patients: Administer one-third of the full dose every 24 hours or the full dose every 72 hours.
• Patients with Hepatic Dysfunction: No specific dose adjustments are usually required.
• Patients with Comorbid Conditions: Consider individual patient factors, especially for those with diabetes, cardiovascular disease, or other significant comorbidities.

Clinical Use Cases

Dosing adjustments may be needed based on clinical response, infection severity, and individual patient factors. In general, the following dosages are recommended:

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: Follow the dosing guidelines for severe infections as detailed above, adjusting as needed based on individual patient characteristics and the severity of the infection.
• Emergency Situations: Initiate treatment with a loading dose as described for severe infections and adjust subsequent dosing based on patient response and renal function.

Dosage Adjustments

Consider dose modifications for renal/hepatic impairment, other metabolic disorders, or genetic factors affecting drug metabolism. Therapeutic drug monitoring is advised for serious or deep-seated infections, prolonged treatment, and patients with intravenous drug use. Target trough levels should be maintained between 20-40 mg/L for most infections, with higher trough levels (30-40 mg/L) for endocarditis.

Side Effects

Common Side Effects:

• Pain, swelling, or redness at the injection site
• Fever
• Itching
• Skin rash
• Nausea
• Vomiting
• Diarrhea
• Headache
• Dizziness

Rare but Serious Side Effects:

• Severe allergic reactions (anaphylaxis)
• Toxic epidermal necrolysis (TEN)
• Stevens-Johnson syndrome (SJS)
• Thrombocytopenia
• Neutropenia
• Ototoxicity (tinnitus, hearing loss)
• Nephrotoxicity (renal impairment)
• Clostridioides difficile-associated diarrhea and pseudomembranous colitis

Long-Term Effects: With prolonged use, monitor for ototoxicity, nephrotoxicity, and the development of resistant organisms.

Adverse Drug Reactions (ADR): Anaphylaxis, SJS/TEN, and severe thrombocytopenia/neutropenia require immediate medical attention.

Contraindications

• Hypersensitivity to teicoplanin
• Known history of anaphylactic reactions to glycopeptide antibiotics (e.g., vancomycin)

Drug Interactions

• Aminoglycosides: Increased risk of nephrotoxicity and ototoxicity.
• Amphotericin B: Increased risk of nephrotoxicity.
• Ciclosporin: Increased risk of nephrotoxicity.
• Furosemide: Increased risk of nephrotoxicity and ototoxicity.
• Neuromuscular blocking agents (e.g., cisatracurium): Enhanced neuromuscular blockade.
• Anticoagulants (e.g., warfarin): Monitor for altered anticoagulant effects.

Pregnancy and Breastfeeding

• Pregnancy: Limited data available. Animal studies show potential for fetal harm at high doses. Use only if clearly necessary and potential benefit outweighs risk.
• Breastfeeding: Excretion in breast milk unknown. Weigh the benefits of breastfeeding against potential risk to the infant. Consider discontinuing breastfeeding or teicoplanin.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial cell wall synthesis.
• Side Effects: Injection site reactions, rash, fever, nausea, vomiting, diarrhea, rare cases of severe allergic reactions, thrombocytopenia, ototoxicity, and nephrotoxicity.
• Contraindications: Hypersensitivity to teicoplanin.
• Drug Interactions: Aminoglycosides, amphotericin B, ciclosporin, furosemide, neuromuscular blockers.
• Pregnancy & Breastfeeding: Use with caution in pregnancy; unknown safety during breastfeeding.
• Dosage: Varies based on infection and patient factors. See detailed dosage section.
• Monitoring Parameters: Renal function, complete blood count, teicoplanin trough levels (for serious infections or prolonged treatment), hearing (for long-term use).

Popular Combinations

Teicoplanin can be combined with other antibiotics, such as gentamicin, for synergistic effects in treating certain infections, particularly endocarditis caused by S. aureus.

Precautions

• General Precautions: Assess for allergies, renal function, and hepatic function before initiating therapy. Monitor for adverse effects.
• Specific Populations:
  • Pregnant Women: Use with caution, considering potential fetal risks.
  • Breastfeeding Mothers: Weigh risks and benefits. Consider discontinuing breastfeeding or teicoplanin.
  • Children & Elderly: Adjust dosage as needed based on age and renal function.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Teicoplanin?

A: The dosage varies depending on the infection, patient age, and renal function. See the detailed dosage section above.

Q2: How is Teicoplanin administered?

A: Intravenously (IV) or intramuscularly (IM). Orally for C. difficile infections.

Q3: What are the common side effects of Teicoplanin?

A: Pain/swelling at the injection site, fever, itching, rash, nausea, vomiting, diarrhea.

Q4: What are the serious side effects of Teicoplanin?

A: Allergic reactions (including anaphylaxis), thrombocytopenia, ototoxicity, nephrotoxicity.

Q5: What are the contraindications to using Teicoplanin?

A: Hypersensitivity to teicoplanin or history of anaphylactic reactions to glycopeptides.

Q6: Does Teicoplanin interact with other medications?

A: Yes, it can interact with aminoglycosides, amphotericin B, ciclosporin, furosemide, and neuromuscular blockers.

Q7: Can Teicoplanin be used during pregnancy and breastfeeding?

A: Use with caution during pregnancy only if clearly needed. Its safety during breastfeeding is unknown.

Q8: How should I monitor patients receiving Teicoplanin?

A: Monitor renal function, complete blood count, teicoplanin trough levels (in certain cases), and hearing (with prolonged use).

Q9: When should I consider therapeutic drug monitoring (TDM) for Teicoplanin?

A: TDM is recommended for patients with serious infections, those receiving prolonged treatment, and intravenous drug users.

Q10: What is the maximum recommended duration of treatment with Teicoplanin?

A: Treatment should generally not exceed 4 months.