Therapeutic serum concentrations of daptomycin after intraperitoneal administration in a patient with peritoneal dialysis-associated peritonitis.

902) and tigecycline has not been studied for UTI treatment besides case series. 3 A follow-up letter suggested that use of a higher than recommended dose may be effective for MDR Klebsiella pneumoniae or Acinetobacter baumannii urosepsis. 4 Moreover, the author provided 'estimates' of serum and urinary concentrations following 100, 200 and 400 mg loading doses, and 50 mg every 12 h, 100 mg every 12 h and 200 mg every 24 h maintenance doses, respectively. 3,4 Urine concentration was assumed to be 0.3, 0.6 or 1.2 mg/L depending on the dosing schedule at an unstated time post-dose based on a serum concentration of 1.5, 3.0 or 6.0 mg/L, respectively. 4 A linear relationship between dose and plasma/urine concentration was assumed and urine concentrations were calculated to be 20% of serum concentrations. Neither of these claims has a pharmacokinetic basis or considered varying dosing intervals. The assumption of linearity also contradicted a statement made in the letter about tigecycline kinetics resembling doxycycline's concentration-dependent kinetics at high doses. 4 If one accepts that 15% –22% of tigecycline is excreted unchanged in the urine with standard dosing of 50 mg every 12 h, then the amount excreted would be 100 mg/dayÂ0.15 – 0.22 (i.e. 15 –22 mg/day). Typical urine output is generally ,2 L/day; thus, urinary concentrations should average 7.5 – 11 mg/L or greater. In a clinical pharmacology review, 14.8% of a 50 mg dose was claimed to be excreted as tigecycline epimer and 2.0% was claimed to be excreted as unchanged drug. 5 The tigecycline epimer was described as pharmacologically inactive. However, tracing these data to the original published report revealed that the percentages were reversed. 6 Unchanged tigecycline urine excretion of 14.8% rather than 2.0% is consistent with the low-end percentage excreted range reported in the literature. Average tigecycline urine concentrations are expected to exceed the MIC for Gram-negative isolates reported as susceptible by several-fold; however, there is concern over whether serum concentrations would also exceed the MIC in bacteraemic patients. Nothing has been published about the activity of tigecy-cline in urine and the extent that activity depends on urine pH or metal cation concentrations. Tigecycline should not be used for UTI when other therapies including aminoglycosides, carba-penems and colistin are options; however, in rare situations, tige-cycline may be considered. Current data do not support the need for or safety of high-dose tigecycline as suggested by Cunha et al. …