Soft tissue and bone penetration abilities of daptomycin in diabetic patients with bacterial foot infections.
OBJECTIVE
In the attempt to overcome increasing glycopeptide- and methicillin-resistant soft tissue infections, daptomycin is presently considered as an attractive alternative to the class of glycopeptides. However, daptomycin dosing and its ability to penetrate into inflamed target tissues are still a matter of controversy. Thus, in the present investigation, we set out to evaluate daptomycin's ability to penetrate into inflamed subcutaneous adipose tissue and bone in diabetic patients presenting with severe bacterial foot infection.


METHODS
The microdialysis technique was utilized to collect interstitial space fluid from inflamed subcutaneous adipose tissue and metatarsal bone. Plasma and unaffected subcutaneous adipose tissue served as reference compartments. Serial sampling of specimens at steady-state was performed from 0 to 8 h post-dose in five patients (Group A) and from 8 to 16 h after study drug administration in another group of four patients (Group B). In all subjects, daptomycin was administered intravenously once daily at a dosage of 6 mg/kg body weight for 4 consecutive days at minimum.


RESULTS
Equilibrium between free tissue and plasma concentrations was achieved approximately 2 h post-infusion. Under steady-state conditions, the degree of tissue penetration was assessed by the calculation of the ratio of free (f) AUC of daptomycin in plasma to the fAUC in tissues. The mean ratios of the fAUC0-16 tissue to the fAUC0-16 plasma were 1.44, 0.98 and 1.08 for healthy tissue, inflamed subcutaneous adipose tissue and bone, respectively. The corresponding ratios of the fAUCs from 0 to 24 h were 1.54, 1.06 and 1.17, respectively.


CONCLUSIONS
With the reservation that pharmacokinetic-pharmacodynamic targets for daptomycin in tissues are currently not established, we conclude that daptomycin given at intravenous doses of 6 mg/kg body weight once daily may be considered an effective treatment regimen in diabetic patients suffering from bacterial foot infection and osteomyelitis.
Traunmüller
Friederike
F
Department of Surgery, Division of Plastic Surgery, Medical University of Graz, Auenbruggerplatz 29, A-8036 Graz, Austria.
Schintler
Michael V
MV
Metzler
Julia
J
Spendel
Stephan
S
Mauric
Oliver
O
Popovic
Martin
M
Konz
Karl Heinz
KH
Scharnagl
Erwin
E
Joukhadar
Christian
C
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001842:Bone and Bones / Q000737:chemistry*; D017576:Daptomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D017719:Diabetic Foot / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D040521:Subcutaneous Tissue / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D017576:Daptomycin