Once daily high dose tigecycline - pharmacokinetic/pharmacodynamic based dosing for optimal clinical effectiveness: dosing matters, revisited

ABSTRACT

Introduction: Tigecycline has emerged as first line therapy for serious systemic infections due to important pathogens (except P. aeruginosa and Proteus sp.), including multi-drug resistant (MDR) and Gram negative bacilli (GNB), including carbapenem resistant Enterobacteriae. Tigecycline has a ‘low resistance potential,’ is protective against C. difficile, and is often the only antibiotic effective against MDR GNB, e.g., Klebsiella sp.

Areas covered: Standard dose tigecycline therapy has been used for intra-abdominal infections, complicated skin/skin structure infections (cSSSIs), and CAP. Clinical experience with once daily high dose tigecycline (HDT), i.e., 200 – 400 mg (IV) x 1, then 100 – 200 mg (IV) q24 h, is reviewed. Optimal tigecycline efficacy is dependent on PK/PD based dosing. Suboptimal outcomes have been due to inappropriate use or suboptimal dosing.

Expert commentary: Tigecycline’s spectrum against nearly all important pathogens (including MSSA/MRSA, VSE/VRE, B. fragilis, C. difficile, MDR and GNB) assures tigecycline a critical place in the antibiotic armamentarium. Dosed optimally, HDT can be a cornerstone of antibiotic stewardship programs in preventing C. difficile, treating MDR GNB pathogens, and in preventing resistance. Properly used and optimally dosed, once daily HDT should be considered preferred therapy for severe systemic infections and those due to MDR GNB pathogens.

KEYWORDS:

• Relative resistance
• resistance breakpoints
• low resistance potential
• dose dependent susceptibility (DD-S)
• serious systemic infections
• MSSA
• MRSA
• VSE
• VRE
• klebsiella pneumoniae
• acinetobacter sp.
• stenotropomonas sp.
• MDR gram negative bacilli (GNB)
• XDR gram negative bacilli
• CRE
• C. difficile
• high volume of distribution (V_d)
• long serum half-life (t ½)
• once daily dosing
• loading dose
• concentration dependent kinetics
• post-antibiotic effect (PAE)
• antibiotic stewardship programs (ASP)

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.