The effect of diabetes and severe ischaemia on the penetration of ceftazidime into tissues of the limb.
OBJECTIVE
To determine the effect of diabetes and of different degrees of ischaemia on the penetration of ceftazidime into different tissues.


METHODS
Sixteen patients (10 with diabetes mellitus) undergoing lower extremity amputation for severe ischaemia (in 12 in combination with infection), received 2000 mg ceftazidime intravenously as a bolus 30 min prior to the operation. Skin perfusion was determined by transcutaneous oxygen pressure measurements (TcPO2) on the dorsal side of the midfoot. After amputation bone, skin and muscle samples were obtained from the forefoot, midfoot and proximal tibia. Tissue and plasma concentrations were determined by HPLC. The tissue concentrations were corrected for blood contamination.


RESULTS
No differences were observed in skin, muscle or bone ceftazidime levels between diabetic and non-diabetic patients. Multiple regression analysis suggested that tissue perfusion was a major determinant of skin and bone ceftazidime concentrations, predicting 40-47% of the ceftazidime concentrations at several biopsy sites.


CONCLUSIONS
The present study suggests that tissue perfusion is the major determinant of the penetration of a third generation cephalosporin into the tissues of the ischaemic (diabetic) foot. Diabetes alone however, has no major effects upon this penetration.
Raymakers
J T
JT
Department of Surgery, University Hospital Maastricht, The Netherlands. jraymakers@wish.net
Houben
A J
AJ
van der Heyden
J J
JJ
Tordoir
J H
JH
Kitslaar
P J
PJ
Schaper
N C
NC
D000368:Aged; D000671:Amputation, Surgical; D002442:Ceftazidime / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000493:pharmacokinetics*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D005260:Female; D005734:Gangrene / Q000601:surgery; D006801:Humans; D007511:Ischemia / Q000503:physiopathology*; D007866:Leg / Q000098:blood supply* / Q000601:surgery; D008297:Male; D016491:Peripheral Vascular Diseases / Q000503:physiopathology / Q000601:surgery*; D014018:Tissue Distribution
D002511:Cephalosporins; D002442:Ceftazidime