Teicoplanin Pharmacology Overview
Mechanism of Action and Spectrum
Teicoplanin is a glycopeptide antibiotic that inhibits bacterial cell wall synthesis and demonstrates potent bactericidal activity exclusively against Gram-positive organisms, including methicillin-resistant staphylococci, enterococci, and anaerobes. 1, 2
- The drug's mechanism targets cell wall synthesis similarly to vancomycin but with distinct pharmacokinetic advantages 3
- Active against Staphylococcus aureus (including MRSA), coagulase-negative staphylococci, Clostridium difficile, Peptostreptococcus spp., and Corynebacterium jeikeium 1
- Activity is unaffected by methicillin resistance or beta-lactamase production 1
- No significant oral absorption; requires parenteral administration 1
Pharmacokinetics
The exceptionally long elimination half-life of approximately 60 hours enables once-daily dosing, a major advantage over vancomycin. 2, 4
- High protein binding (≥98%) results in slow tissue penetration, necessitating aggressive loading doses 5
- Can be administered by rapid intravenous bolus, intravenous infusion, or intramuscular injection 1, 2
- Intramuscular route offers reliable absorption for patients with limited venous access and facilitates outpatient therapy 3
Dosing Regimen
Standard Loading Doses
All patients require loading doses of 6 mg/kg IV every 12 hours for three doses (standard infections) or 12 mg/kg IV every 12 hours for three doses (severe infections), regardless of renal function. 5, 6
- Standard infections: 6 mg/kg IV q12h × 3 doses 5
- Severe infections (endocarditis, septic arthritis, complicated bacteremia, osteomyelitis): 12 mg/kg IV q12h × 3 doses 5, 7
- Loading doses depend on volume of distribution, not clearance, and must never be reduced in renal impairment 6, 8
- Critically ill patients with expanded extracellular volume from fluid resuscitation require full loading doses to achieve therapeutic levels rapidly 6
Maintenance Dosing by Renal Function
After loading, maintenance doses are 6 mg/kg daily (standard infections) or 12 mg/kg daily (severe infections), with interval extension based on GFR. 5
| GFR (mL/min) | Maintenance Interval |
|---|---|
| >50 | Every 24 hours [5,6] |
| 10–50 | Every 48 hours [5,6] |
| <10 | Every 72 hours [5,6] |
Special Populations
Hemodialysis: Loading dose 12 mg/kg, then 6 mg/kg on days 2 and 3, followed by 6 mg/kg once weekly 5, 6
Continuous renal replacement therapy (CAVH/CVVH): Follow GFR 10–50 mL/min schedule (every 48 hours) 5, 6
CAPD peritonitis:
- IV route: Follow GFR <10 mL/min schedule (every 72 hours) 5
- Intraperitoneal route: 20 mg/L in each bag (week 1), 20 mg/kg every other bag (week 2), 20 mg/kg in night bag only (week 3) 5
Pediatric patients: Loading dose 10 mg/kg IV q12h × 3 doses; maintenance 6–10 mg/kg every 24 hours 5
Infection-Specific Dosing and Duration
Endocarditis
Native valve: 12 mg/kg IV q12h × 3 doses, then 12 mg/kg once daily for 4–6 weeks 5
Prosthetic valve: 12 mg/kg IV q12h × 3 doses, then 12 mg/kg once daily for 6 weeks plus rifampin 300 mg IV/PO q8h plus gentamicin 1 mg/kg IV q8h 5
Bacteremia
Uncomplicated (negative follow-up cultures within 2–4 days, no prosthetic devices, no endocarditis, defervescence within 72 hours): 6–12 mg/kg IV q12h × 3 doses, then once daily for 2 weeks 5
Complicated (any bacteremia not meeting uncomplicated criteria): 6–12 mg/kg IV q12h × 3–6 doses, then 6–12 mg/kg once daily for 4–6 weeks 5
Osteomyelitis and Septic Arthritis
Osteomyelitis: 12 mg/kg IV q12h × 3 doses, then 12 mg/kg once daily for >6 weeks 5, 7
Septic arthritis: 12 mg/kg IV q12h × 3 doses, then 12 mg/kg once daily for 3–4 weeks 5, 7
Skin and Soft Tissue Infections
Uncomplicated: 6 mg/kg IV q12h × 3 doses, then once daily for 5–10 days 5
Complicated/inpatient: 6–12 mg/kg IV q12h × 3 doses, then once daily for 7–14 days 5
Fournier's gangrene: 12 mg/kg IV q12h × 3 doses, then 6 mg/kg q12h as part of combination therapy 5
Central Nervous System Infections
Meningitis: 14 days 5
Brain abscess, subdural empyema, spinal epidural abscess: 4–6 weeks 5
Pneumonia
Hospital-acquired/ventilator-associated: 7–21 days depending on clinical response and pathogen 5
Clostridium difficile Infection
Oral administration: 100–200 mg PO twice daily for ≥10 days 8
Therapeutic Drug Monitoring
Target Trough Concentrations
Standard infections: Trough ≥10 mg/L 5, 8
Severe infections (endocarditis, septic arthritis, osteomyelitis, complicated bacteremia): Trough ≥20 mg/L 5, 6, 7
- Achieving trough ≥20 mg/L in severe infections is associated with significantly higher clinical success (approximately 75% vs 50%, p=0.008) 5
- Therapeutic window is 15–30 mg/L for most infections; levels >60 mg/L are potentially toxic 6
Monitoring Indications
Routine monitoring is not required for standard infections, but is mandatory in the following situations: 5, 6
- S. aureus endocarditis or septic arthritis 5
- Major burns 5
- Intravenous drug users 5
- Rapidly changing renal function 5
- Immunocompromised patients 6
- Concurrent aminoglycoside therapy 5
- MRSA infections with high MIC values to glycopeptides 8
Monitoring Schedule
Check trough levels on day 4 after loading doses, repeat at steady state (days 7–11), and continue twice weekly throughout therapy. 5
Adverse Effects
Common Adverse Effects
Teicoplanin has a significantly better safety profile than vancomycin, with lower rates of nephrotoxicity, ototoxicity, and infusion-related reactions. 1, 3
- Local reactions: Pain at injection site (intramuscular administration) 1
- Hypersensitivity: Itching, drug fever, skin rash 1, 4
- Hematologic: Eosinophilia, neutropenia 4
- Hepatic: Transient elevation of serum aminotransferases 4
Serious Adverse Effects
Nephrotoxicity: Much lower incidence than vancomycin, especially when combined with aminoglycosides 1, 3
Ototoxicity: Potential exists but incidence is quite low when recommended serum concentrations are maintained 2, 4
Anaphylactoid reactions ("red man syndrome"): Seldom observed, in contrast to vancomycin 1
Critical Pitfalls to Avoid
Loading Dose Errors
The most common and serious error is failure to provide adequate loading doses, leading to subtherapeutic levels and treatment failure. 8
- Never omit loading doses in any renal function category 5
- Never reduce loading doses in renal impairment; only adjust maintenance intervals 5, 6
- Critically ill patients with increased volume of distribution require full loading doses despite altered pharmacokinetics 8
Maintenance Dosing Errors
Failure to extend dosing intervals in renal impairment leads to drug accumulation. 8
- Always adjust maintenance intervals based on GFR as outlined above 5, 6
- Do not use standard 24-hour intervals in patients with GFR <50 mL/min 5
Duration Errors
Do not use 2-week courses for complicated bacteremia; 4–6 weeks are required to prevent relapse and metastatic infection. 5
- Maintain parenteral therapy throughout the treatment course for complicated bacteremia 5
- Do not stop therapy based solely on symptom resolution; complete the full duration based on infection type 5
Monitoring Errors
Overlooking the need for therapeutic drug monitoring in high-risk situations or severe infections leads to suboptimal outcomes. 6, 8