Can Tigecycline (tigecycline) and Targocid (teicoplanin) be combined for antibiotic therapy in an adult patient with a hospital-acquired infection or complicated skin and soft tissue infection caused by resistant bacteria, including MRSA (methicillin-resistant Staphylococcus aureus)?

Can Tigecycline and Teicoplanin Be Combined for Antibiotic Therapy?

Yes, tigecycline and teicoplanin (Targocid) can be combined for antibiotic therapy in patients with hospital-acquired infections or complicated skin and soft tissue infections caused by resistant bacteria including MRSA, particularly when treating polymicrobial infections involving both Gram-positive and Gram-negative multidrug-resistant organisms.

Clinical Rationale for Combination Therapy

Complementary Antimicrobial Spectrum

• Tigecycline provides broad coverage against vancomycin-resistant enterococci (VRE), MRSA, and many multidrug-resistant Gram-negative bacteria including ESBL producers 1
• Teicoplanin offers reliable Gram-positive coverage including MRSA, with dosing at 6-12 mg/kg IV every 12 hours for 3 doses, then 6-12 mg/kg IV daily (high dose of 12 mg/kg should be used in severe disease or when MIC values are relatively high) 2
• This combination addresses polymicrobial infections where both resistant Gram-positive and Gram-negative pathogens are present 3

Evidence Supporting Combination Regimens

• In documented MRB infections, tigecycline combination therapy achieved 88% clinical success rates across various infection types 3
• For severe infections caused by carbapenem-resistant Enterobacterales (CRE) susceptible only to limited agents, treatment with more than one drug active in vitro is recommended 2
• Tigecycline-based combination therapy demonstrated superior outcomes compared to tigecycline monotherapy for CRE bloodstream infections (OR 2.73 for mortality with monotherapy vs. combination) 2

Critical Limitations and Contraindications

Tigecycline Restrictions

• Do NOT use tigecycline for bloodstream infections or hospital-acquired/ventilator-associated pneumonia as primary therapy 2
• If necessary for pneumonia, high-dose tigecycline (loading dose 200 mg, maintenance 100 mg every 12 hours) may be considered, though evidence remains limited 2
• Tigecycline has poor serum and urinary concentrations, limiting its role in bacteremia and urinary tract infections 2
• The FDA issued a boxed warning regarding increased all-cause mortality with tigecycline compared to controls; infectious disease consultation is recommended 2, 4

When Combination is Most Appropriate

• Severe infections caused by CRE carrying metallo-β-lactamases resistant to newer agents 2
• Polymicrobial complicated intra-abdominal infections with documented MRSA and resistant Gram-negatives 3
• Complicated skin and soft tissue infections in critically ill patients with high APACHE II scores (>15) and polymicrobial resistant pathogens 5
• Hospital-acquired infections where both VRE and ESBL-producing organisms are isolated 3

Dosing and Administration

Tigecycline Dosing

• Standard dose: Loading dose 100 mg IV, then 50 mg IV every 12 hours 3
• High-dose regimen (for critically ill with CRE): Loading dose 200 mg IV, then 100 mg IV every 12 hours 2
• Mean treatment duration in clinical practice: 12-13 days 5, 6

Teicoplanin Dosing

• Loading: 6-12 mg/kg IV every 12 hours for 3 doses 2
• Maintenance: 6-12 mg/kg IV once daily 2
• Use 12 mg/kg for severe disease, concomitant deep-seated infection, or settings with high MRSA MIC values 2

Monitoring and Expected Outcomes

Clinical Success Rates

• Overall clinical success with tigecycline monotherapy for MRB infections: 94% 3
• Combination therapy success for MRB infections: 88% 3
• Intra-abdominal infections with combination: 93% success 3
• Skin/soft tissue infections with combination: 100% success 3

Common Pitfalls to Avoid

• Do not use this combination for primary treatment of bacteremia—tigecycline's low serum levels make it inappropriate 2
• Avoid tigecycline monotherapy for CRE bloodstream infections—combination is essential 2
• Do not use for urinary tract infections—tigecycline has inadequate urinary concentrations 2
• Monitor for superinfection, particularly with Pseudomonas aeruginosa (occurs in approximately 30% of tigecycline-treated patients) 7
• Expect higher mortality in critically ill patients with SOFA scores ≥7 despite combination therapy 5

When to Avoid This Combination

• Non-severe infections or low-risk infections where monotherapy with older agents is appropriate based on susceptibility 2
• Infections caused by 3rd-generation cephalosporin-resistant Enterobacterales without carbapenem resistance (tigecycline not recommended) 2
• When newer β-lactam/β-lactamase inhibitors (ceftazidime-avibactam, meropenem-vaborbactam) are available and active in vitro 2
• Carbapenem-resistant Pseudomonas aeruginosa infections (insufficient evidence for tigecycline) 2