title: Once daily high dose tigecycline - pharmacokinetic/pharmacodynamic based dosing for optimal clinical effectiveness: dosing matters, revisited.
abstract: 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.
authors.affiliation: a Infectious Disease Division , Winthrop-University Hospital , Mineola , NY , USA.|b State University of New York, School of Medicine, Stony Brook , New York , NY , USA.
authors.forename: Burke A
authors.initials: BA
authors.lastname: Cunha
authors.affiliation: c Pharmacy Department , Roswell Park Cancer Institute, Buffalo , New York , NY , USA.|d State University of New York, School of Medicine, Buffalo , New York , NY , USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Baron
authors.affiliation: e Infectious Disease Division , Rhode Island Hospital and The Miriam Hospital.|f Brown University Alpert School of Medicine , Providence , RI , USA.
authors.forename: Cheston B
authors.initials: CB
authors.lastname: Cunha
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006801:Humans; D059413:Intraabdominal Infections / Q000188:drug therapy; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline
keywords: C. difficile; CRE; MDR gram negative bacilli (GNB); MRSA; MSSA; Relative resistance; VRE; VSE; XDR gram negative bacilli; acinetobacter sp.; antibiotic stewardship programs (ASP); concentration dependent kinetics; dose dependent susceptibility (DD-S); high volume of distribution (Vd); klebsiella pneumoniae; loading dose; long serum half-life (t ½); low resistance potential; once daily dosing; post-antibiotic effect (PAE); resistance breakpoints; serious systemic infections; stenotropomonas sp.