Pharmacokinetics of linezolid in bone tissue investigated by in vivo microdialysis.

Pharmacokinetics of unbound anti-infectives in bone is difficult to characterize. The aim of this study was to assess the feasibility of the microdialysis technique to cancellous bone for single dose pharmacokinetic investigations of the anti-infective linezolid. Serial bone biopsies (left tibia) and microdialysate samples (right tibia: 2 catheters) as well as plasma and bone marrow samples were obtained from 10 pigs. The concentrations of linezolid reached bacteriostatic levels in plasma, bone marrow, bone biopsies and microdialysates. With the use of microdialysis we here present the first results for unbound linezolid bone penetration. Unbound linezolid concentrations in bone obtained by microdialysis were lower than might have been expected from previous bone biopsy studies. To achieve effective concentrations (24 h) for susceptible organisms the chosen dose of linezolid might not be sufficient.

Distribution of gentamicin from a Gentacoll sponge measured by in vivo microdialysis.

Microdialysis has produced valuable information concerning the distribution of antibiotics in peripheral tissue. The aim of this study was to measure the local distribution of gentamicin in cancellous bone tissue after the application of a Gentacoll sponge. Two microdialysis catheters were inserted into the cancellous bone of 9 pigs. After calibration of the microdialysis, a Gentacoll sponge was implanted, either dry or wet, into the bone marrow of the tibia. Serum and microdialysates were obtained over a period of 6 h. Data presented are median (range). A rank sum test was performed for statistical analysis. The peak concentration was 120 mg/l (33-585) (wet group) and 178 mg/l (60-1294) (dry group) (p=0.31). The AUC6 of the catheters placed 1 cm away from the implant was 24,431 mg*min/l (5155-152,855) and the AUC6 of the catheter placed 2 cm away from the implant was 13,759 mg*min/l (6351-74,573) (p=0.25). The study showed that peak concentrations and AUC6 did not differ between the wet- and dry-application group; neither did the distance from the sponge to the catheter have a significant impact on the distribution of gentamicin. It seems that microdialysis is capable to measure concentrations of locally applied antibiotics.

Application of microdialysis to cancellous bone tissue for measurement of gentamicin levels.

OBJECTIVES: Knowledge concerning the distribution of antibiotics in bone tissue is valuable for pharmacokinetic and clinical use. Unfortunately, appropriate techniques are difficult to apply. We introduced microdialysis catheters to cancellous bone tissue for the investigation of gentamicin levels and compared the pharmacokinetics measured with values obtained from bone samples. METHODS: After two microdialysis catheters had been inserted into cancellous bone, eight pigs received an intravenous bolus of 240 mg of gentamicin. Microdialysates and bone samples were obtained over a period of 6 h and drug concentrations were measured. RESULTS: The area under the curves of the two microdialysates and bone samples were 1569, 1721 and 1533 mg.min/L (ANOVA, P=0.81). Reproducibility of the measurements from the microdialysates was defined as the mean ratio of AUC6/catheter no. 1/AUC6/catheter no. 2. This ratio was 1.02. CONCLUSIONS: Microdialysis is a suitable, relatively non-invasive and reproducible technique for dynamic and quantitative measurement of gentamicin levels in experimental research.

The metabolism of the diabetic foot: in vivo investigation with microdialysis.

BACKGROUND: Many amputations might be delayed or prevented by more effective clinical supervision of the diabetic foot ulcer. The aim of this study was to measure the local metabolism on the edge of a diabetic ulcer and compare it to healthy subcutaneous tissue. PATIENTS AND METHODS: In 5 non-fasting diabetic patients, we inserted a microdialysis catheter into the edge of a diabetic ulcer and a reference catheter into healthy abdominal subcutaneous tissue, and recorded the local concentrations of glucose, lactate and glycerol during rest. RESULTS: The concentrations of glucose in the ulcers were 7.8 mM (SEM 1.9) and in the reference tissue 10.6 mM (SEM 1.8) (p = 0.4). The concentrations of lactate were 2.9 mM (SEM 0.7) and 2.1 mM (SEM 0.7) (p = 0.2), while those of glycerol were 290 microM (SEM 84) vs 98 microM (SEM 7.2) (p = 0.002). INTERPRETATION: This study shows that microdialysis can detect differences in dialysate concentrations of metabolites in diabetic ulcers and a reference tissue, providing valuable information concerning metabolites in the diabetic foot ulcer. Future studies should combine the technique with measurements of local blood flow.

In situ gentamicin concentrations in cortical bone: an experimental study using microdialysis in bone.

We used microdialysis to study gentamicin in cortical bone and compared these results to values obtained in bone specimens. 10 healthy pigs were given an intravenous bolus of 160 mg of gentamicin. We measured reproducibility by inserting two microdialysis catheters into the cortex of tibial diaphyses and by taking samples of serum, dialysates and bone specimens during 6 hours and measuring the concentrations of this antibiotic. The peak concentrations in the two microdialysis probes and bone specimens were 3 mg/L, 2.9 mg/L and 2.6 mg/L (Anova, p = 0.3). Similarly, the areas under the curve from 0 to 6 hours (AUC6h) were 704 mg/min/L, 661 mg/min/L and 569 mg/min/L (Anova, p = 0.07). The reproducibility of the measurements of the microdialysates was evaluated with the mean AUC(6h/catheter no.1)/AUC(6h/catheter no. 2) ratio, which was 1.12. It seems that microdialysis is a suitable method for making dynamic and quantitative measurements of gentamicin in bone.

The diagnostic value of digital subtraction arthrography and radionuclide bone scan in revision hip arthroplasty.

A prospective analysis of plain serial radigraphs (PSR), digital subtraction arthrography (DSA), and radionuclide bone scans (RBS) was performed in 56 cemented total hip arthroplasties to evaluate the efficacy and usefulness of each study in the diagnosis of loosening. To avoid selection bias in the evaluation of DSA and RBS, the decision to perform repeat surgery was based exclusively on the clinical history and PSR. Results of each study were compared with intraoperative assessment of the status of components and expressed in terms of sensitivity, specificity, and accuracy. Overall accuracy for the acetabular component by PSR was 66%; by DSA, 93%; by RBS, 46%. Overall accuracy for the femoral component by PSR was 79%; by DSA, 93%; RBS, 50%. Our results indicate that DSA can be recommended as a further analysis in cases with a painful hip prosthesis and no or inconclusive findings on PSR. RBS did not give any useful information and cannot be recommended routinely.

Poor results with the Shuttle Stop: resorbable versus nonresorbable intramedullar cement restrictor in a prospective and randomized study with a 2-year follow-up.

In a randomized prospective study we compared 2 femoral plugs as regards probable migration of the restrictor, cement leakage and possible early aseptic loosening. In group I, the femoral canal was plugged with a resorbable Shuttle Stop (HC Implants, BV. Leiden, The Netherlands). In group II, a nonresorbable restrictor of polyethylene was used (De Puy, UK). Both groups were identical as regards age, gender and primary disease. All patients were followed for at least 2 years after surgery. Postoperatively, we found more failures with displacement of the femoral plug and cement leakage in group I than in group II. At the 2-year follow-up, we found no differences in stem loosening or grade of radiolucent lines in the cement-bone interface. We can not recommend the Shuttle Stop for femoral canal sealing in total hip replacememt.

[Staphylococcus aureus infections--the clinical picture and treatment]. / Infektioner med Staphylococcus aureus--klinik og behandling.

Infections caused by Staphylococcus aureus comprise relatively benign local skin infections, as well as serious generalised conditions. In Denmark, more than 85% of all S. aureus isolates are found resistant to penicillin, whereas resistance to methicillin is rare (< 1%) and therefore one of the penicillinase-stable penicillins is still the drug of choice. Dicloxacillin is usually chosen, because of its superior penicillinase stability. Infections caused by methicillin resistant strains may be treated with different combinations of macrolides, fusidic acid, aminoglycosides, fluoroquinolones, and rifampicin, but vancomycin is generally used. Newer drugs like the oxazolidinones and streptogramins are effective against methicillin-resistant strains and will be available in Denmark within a short time. Antibiotic treatment, however, is most often only a supplement to surgical intervention. This paper deals with the clinical picture and treatment of some common S. aureus infections.