Erwin Scharnagl

Soft tissue and bone penetration abilities of daptomycin in diabetic patients with bacterial foot infections

OBJECTIVES 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 daptomycins ability to penetrate into inflamed subcutaneous adipose tissue and bone in diabetic patients presenting with severe bacterial foot infection. PATIENTS AND 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.

High fosfomycin concentrations in bone and peripheral soft tissue in diabetic patients presenting with bacterial foot infection

OBJECTIVES Appropriate antimicrobial therapy and surgical intervention may be required in diabetic patients presenting with severe bacterial foot infection. Methicillin-resistant Staphylococcus aureus (MRSA) agents such as fosfomycin are increasingly in demand because of recent concern regarding vancomycin and daptomycin efficacy and constant use. Intravenous fosfomycin is approved for the therapy of severe soft tissue infections and is highly active against methicillin-susceptible S. aureus and MRSA. in the present study we investigated fosfomycins ability to penetrate bone tissue in diabetic patients suffering from severe bacterial foot infection. PATIENTS AND METHODS The well established microdialysis technique was utilized to determine fosfomycin concentrations in metatarsal bone in nine patients scheduled for partial bone resection due to bacterial foot infection and osteomyelitis. Plasma and unaffected subcutaneous adipose tissue served as reference compartments. RESULTS After a single intravenous dose of approximately 100 mg of fosfomycin per kg of body weight, the mean C(max), T(max) and AUC(0-6) for bone were 96.4 mg/L, 3.9 h and 330.0 mg x h/L, respectively. The degree of tissue penetration as determined by the ratios of the AUC(0-6) for bone to plasma and for subcutaneous adipose tissue to plasma were 0.43 +/- 0.04 and 0.76 +/- 0.05, respectively. CONCLUSIONS On the basis of relevant pharmacokinetic-pharmacodynamic indices, it seems that fosfomycin is an effective antibiotic for the treatment of deep-seated diabetic foot infections with osseous matrix involvement.

Treatment of painful neuroma by resection and nerve stump transplantation into a vein.

Twenty-three patients (14 men, 9 women) with 24 painful neuromas underwent resection of neuroma and transposition of the nerve stump into an adjacent vein. The neuromas resulted from amputations (N = 7), tumor excision (N = 5), laceration injuries (N = 4), different types of wrist surgery (N = 3), vein-stripping procedures (N = 2), open fracture of the radius (N = 1), and toe harvest for thumb reconstruction (N = 1). The duration of painful symptoms averaged 66.7 weeks at the time of operation. Average follow-up was 26.5 months. In 22 patients the symptoms improved permanently. Twelve patients experienced complete and permanent relief of pain; some mild degree of pain returned in 8 patients. Two patients experienced moderate pain, and pain recurred unchanged 2 months postoperatively in 1 patient. The results presented are consistent with results of animal experiments demonstrating that typical neuroma does not develop in nerve stumps transposed into veins. Further clinical use of this approach is encouraged.

Reconstruction of combined defects of the Achilles tendon and the overlying soft tissue with a fascia lata graft and a free fasciocutaneous lateral arm flap.

A new approach to reconstruction of the Achilles tendon and overlying soft tissue is presented. A fascia lata graft is used to reconstruct the tendon and is enwrapped by the fascia that is included in a fasciocutaneous lateral arm flap. Five patients were treated with this technique; three of them after surgical Achilles tendon repair, rerupture, and consecutive infection, one after a full-thickness burn with loss of the tendon and one with a history of ochronosis and necrosis of the whole tendon and overlying soft tissue. There were no anastomotic complications and all flaps healed primarily. Functional evaluation with the Cybex II dynamometer was done at least 49 months after reconstruction. A good functional and cosmetic result was obtained in all patients and donor site morbidity was acceptable. These results are well within the results of other surgical treatment options reported in the literature.

Linezolid concentrations in infected soft tissue and bone following repetitive doses in diabetic patients with bacterial foot infections

The present study aimed at assessing unbound extracellular concentrations of linezolid in inflamed soft tissue and bone of diabetic patients suffering from severe bacterial foot infections. Linezolid was administered intravenously twice daily at a dosage of 600 mg. At steady-state conditions, the microdialysis technique was utilised to sample serially interstitial space fluid from inflamed subcutaneous adipose tissue and metatarsal bone from 0-8h post dose in three representative patients. Mean peak concentrations of free linezolid in plasma, healthy subcutis, inflamed subcutis and cancellous bone were 16.6+/-3.0, 15.5+/-2.5, 15.8+/-2.8 and 15.1+/-4.1mg/L, respectively. The degree of tissue penetration as expressed by the ratio of the area under the concentration-time curve of free linezolid from 0-12h (fAUC(0-12)) in tissue to the fAUC(0-12) in plasma was 1.32+/-0.09, 1.12+/-0.22 and 1.09+/-0.11 for healthy subcutis, inflamed subcutis and bone, respectively. Based on currently available pharmacokinetic/pharmacodynamic targets, we conclude that linezolid administered at 600 mg twice daily may be considered an effective treatment in diabetic patients suffering from bacterial foot infection complicated by osteomyelitis.

The lower trapezius musculocutaneous flap from pedicled to free flap: anatomical basis and clinical applications based on the dorsal scapular artery.

The pedicled lower trapezius musculocutaneous flap is a standard flap in head and neck reconstruction. A review of the literature showed that there is no uniform nomenclature for the branches of the subclavian artery and the vessels supplying the trapezius muscle and that the different opinions on the vessels supplying this flap lead to confusion and technical problems when this flap is harvested. This article attempts to clarify the anatomical nomenclature, to describe exactly how the flap is planned and harvested, and to discuss the clinical relevance of this flap as an island or free flap. The authors dissected both sides of the neck in 124 cadavers to examine the variations of the subclavian artery and its branches, the vessel diameter at different levels, the course of the pedicle, the arc of rotation, and the variation of the segmental intercostal branches to the lower part of the trapezius muscle. Clinically, the flap was used in five cases as an island skin and island muscle flap and once as a free flap. The anatomical findings and clinical applications proved that there is a constant and dependable blood supply through the dorsal scapular artery (synonym for the deep branch of the transverse cervical artery in the case of a common trunk with the superficial cervical artery) as the main vessel. Harvesting an island flap or a free flap is technically demanding but possible. Planning the skin island far distally permitted a very long pedicle and wide arc of rotation. The lower part of the trapezius muscle alone could be classified as a type V muscle according to Mathes and Nahai because of its potential use as a turnover flap supplied by segmental intercostal perforators. The lower trapezius flap is a thin and pliable musculocutaneous flap with a very long constant pedicle and minor donor-site morbidity, permitting safe flap elevation and the possibility of free-tissue transfer.

Management of an unfortunate triad after breast reconstruction: Pyoderma gangrenosum, full-thickness chest wall defect and Acinetobacter Baumannii Infection

If diagnosed late, post-surgical pyoderma gangrenosum (PSPG) is a rare, tricky and potentially life-threatening complication. Once diagnosed, immunosuppressive agents may provoke further complications. Well-intentioned extensive serial debridement may cause deep skin and soft-tissue defects, requiring skin grafting and possible flap surgery. The combination of necessary immunosuppressive treatment, protracted hospital stay and broad-spectrum systemic antimicrobial therapy may encourage serious acquired multidrug resistance (MDR). We report an unfortunate triad following breast reconstruction of PSPG, full-thickness chest wall defect and MDR with Acinetobacter baumannii infection. Interdisciplinary treatment using free flap surgery and negative-pressure wound therapy with instillation therapy (V.A.C.Instill(R) Wound Therapy) enabled survival and complete wound closure.

The Vascular Anatomy of the Tensor Fasciae Latae Perforator Flap

Background: The purpose of this study was to differentiate between musculocutaneous and septocutaneous perforators of the tensor fasciae latae perforator flap; to evaluate their number, size, and location; and to provide landmarks to facilitate flap dissection. An additional injection study estimated the skin area of the flap. Methods: The anatomical study was performed on 23 fixed and injected cadavers. The perforators of the tensor fasciae latae were identified and classified as septocutaneous or musculocutaneous. Diameter, location, and numbers were measured and the perforators were dissected up to their origin. The injection study was performed on 10 fresh cadavers. On one side, the ascending branch of the lateral circumflex femoral artery was injected with methylene blue; on the other side, the septocutaneous perforators were injected selectively. The size, location, and borders of the stained skin were measured. Results: Forty-five thighs were included in this study. All perforators emerged from the ascending branch of the lateral circumflex artery. The average number of musculocutaneous perforators was 2.3 (range, 0 to 5), the distance from the anterior superior iliac spine was 10.9 cm (range, 4.5 to 16.1 cm), and the diameter was 0.9 mm (range, 0.2 to 2 mm). Four specimens had no musculocutaneous perforator. The average number of septocutaneous perforators was 1.8 (range, 1 to 3), the distance from the anterior superior iliac spine was 10.9 cm (range, 6.2 to 15.7 cm), and the diameter was 1.5 mm (range, 0.5 to 3 mm). Seventy-six percent of the septocutaneous perforators emerged between 8 and 12 cm from the anterior superior iliac spine. The possible pedicle length of a flap based on these vessels is 8.1 cm (range, 6.5 to 10 cm). In the injection study, the average skin area stained with methylene blue was 19.4 × 13.4 cm (range, 10 to 24 cm × 7 to 17 cm) in the ascending branch group. In the perforator group, the average skin area was 19.2 × 13.7 cm (range, 15 to 22 cm × 12 to 16 cm). Conclusions: The authors could show that the number of septocutaneous perforators for the tensor fasciae latae flap is more constant and that their diameter is greater than that of musculocutaneous perforators. The location of these perforators on a line extending from the ilium to the greater trochanter facilitates planning and dissection of a flap.

Accidental perforating bone injury using the EpiPen® autoinjection device

Epinephrine is the drug of choice for the treatment of acute anaphylactic reactions (1). EpiPen (DEY, Napa, CA, USA) is widely prescribed by dermatologists and allergists for self-treatment of patients with lifethreatening allergic reactions (2). The pen works as an autoinjector device and contains 0.3 mg of epinephrine. Simultaneous accidental injections into fingers and palmar surface have been observed upon improper use. Until now, perforating bone injuries using an autoinjection device have not been reported in the literature. Because of its rapid effect on the important pathophysiologic events in an anaphylactic reaction, this drug is recommended for self-application to patients at risk from anaphylactic reactions, such as individuals with a history of anaphylaxis following hymenopteran stings or ingestion of certain foods (3). EpiPen is a disposable drug delivery system with a spring-activated concealed needle intended for intramuscular application. The EpiPen is designed as an emergency supportive therapy only and is not a substitute for immediate medical care. Initially, this autoinjector design was developed for the military to deliver antidotes in the event of a poison gas attack. It was ideal because of the need for a fast, convenient method of giving life-saving medication in a high-stress situation. Subsequently, the same autoinjector system was used with other drugs as part of the NASA Manned Space Flight Program. The EpiPen autoinjector resulted from the realization that patients experiencing serious allergic reactions may also be fearful of injecting themselves with life-saving medication or incapable of using a conventional syringe. We report about a 37-year-old woman who suffered an accidental autoinjection injury. While preparing the EpiPen autoinjection device for her mother, who got stung by an insect, she sustained a perforating injury of the index finger, with the needle entering the palmar side, going through the distal phalanx, and exiting through the dorsal side. On clinical examination, the index finger presented a rose color and appeared to be well perfused and warm. We found two tiny puncture wounds, one on the palmar side of the fingertip and the other one dorsal, proximal to the nail. There were no signs of ischemia. The patient developed pain after applying pressure on her index fingertip, but reported no loss of sensation. To exclude any inoculation of a foreign body in the fingertip, an X-ray was performed. We could not find any foreign body but discovered discrete signs of bone perforation in the distal phalanx in the anterior–posterior as well as in lateral view (Fig. 1). The patient was concerned about the needle having caused an inoculation of AL LERGY 2 0 0 5 : 6 0 : 2 5 9 – 2 6 7 • COPYRIGHT a 2005 BLACKWELL MUNKSGAARD • ALL R IGHTS RESERVED • CONTRIBUT IONS TO THIS SECT ION WILL NOT UNDERGO PEER REVIEW, BUT WILL BE REV IEWED BY THE ASSOCIATE EDITORS •

Influence of nerve stump transplantation into a vein on neuroma formation.

The objective of this animal study was to investigate the influence of nerve stump transposition into a vein on neuroma formation. In 24 rats the femoral nerve was severed and the proximal nerve stump was transposed into the lumen of the femoral vein on one side. On the other side, the nerve was severed and left in place. The distal nerve stump was shortened to knee level on both sides. In group 1, the bloodstream was released; in group 2, the segment of the femoral vein containing the nerve stump was excluded from circulation. Histological assessment was performed 8 months later. There were significant differences between the treatment and control sides with respect to neuroma size, endoneural architecture, neural–tissue-to-connective–tissue ratio, and myelination of axons. These data suggest that nerve transposition into a vein could inhibit the formation of classic neuroma.