[Osseous Tuberculosis - interdisciplinary treatment from diagnostics to microsurgical defect reconstruction - Case report and review of the literature and proposal of a therapeutic algorithm]. / Knochentuberkulose ­ interdisziplinäre Therapie von der Diagnosestellung bis zur plastisch- chirurgischen Deckung.

Tuberculosis is a central global health problem with an incidence of 10 million new cases per year and more than one million deaths per year. Contrary to this, osseous tuberculosis represents an extremely rare entity of tuberculosis. Osseous tuberculosis is challenging beginning with the correct diagnosis, adequate surgical as well infectiological treatment as well as extremity reconstruction. Facing increased migration and therefore increasing numbers of cases of tuberculosis in western countries, the question of a reliable diagnosis, therapy and protective measures in dealing with those patients is becoming increasingly important for Central Europe.In the present case, a 49-year-old female patient from Pakistan, the first presented to our institution with a clinical picture of an exanthema at the level of the upper ankle joint with radiological signs of osteolysis. Pathological and molecular pathological diagnostics revealed the presence of an infection caused by Mycobacteria tuberculosis complex. In the initial phase over 6 weeks, a 4-fold therapy with isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA) and ethambutol (EMB) was administered in accordance with the WHO guidelines, followed by 2-fold therapy with INH and RMP for 12 months in the subsequent continuity phase.14 months later, the patient was re-admitted to hospital because of a recurrent abscess. Therefore tuberculostatic therapy as a quadruple combination of INH, RMP, PZA and EMB was initiated for 6 weeks and as a double combination of INH and RMP for a total of one year.After the abscess had been eradicated, the joint was immobilized by ankle arthrodesis and the deep necrosis of the right ankle was finally reconstructed with allergenic bone grafts and a free microvascular M. gracilis flap.In the case presented here, successful treatment was possible via an interdisciplinary treatment consisiting of infectiology, orthopaedic surgery as well as plastic surgery specialists. Osseous tuberculosis could be eradicated and the bony defect could be reconstructed together with resulting soft tissue defect ultimately preserving of the extremity. In the context of this case study, a comprehensive overview of the current literature is described and a therapy algorithm is proposed due to the increasing relevance of this entity.

Efficacy of posaconazole and amphotericin B in experimental invasive pulmonary aspergillosis in dexamethasone immunosuppressed rats.

OBJECTIVES: Invasive pulmonary aspergillosis is associated with high mortality. To assess new antifungal therapy options, animal models have to be developed to assess, in an appropriate setting, the activity of new drugs. METHODS: Male albino CD rats (125-150 g) were fed with a protein-free diet and received dexamethasone thrice weekly subcutaneously during the whole experiment. After 2 weeks, an inoculum of 10(6) conidia of Aspergillus fumigatus (H11-20) was injected intratracheally. Antifungal treatment was initiated and continued for a total of 7 days. Animals were grouped in numbers of 10. One group of animals served as untreated control, whereas the others were treated with amphotericin B intraperitoneally (2 and 4 mg/kg) and posaconazole via gavage (2, 4, 10 and 20 mg/kg). Survival and log(10) cfu/g of the lungs were the endpoints. The strain H11-20 was tested for susceptibility in vitro to amphotericin B and posaconazole, respectively. Fungal burden of the lungs was expressed as log(10) cfu/g. Survival analysis was performed by the Kaplan-Meier method. Differences in fungal burden were assessed by the Mann-Whitney test. RESULTS: All untreated animals died within a week. Amphotericin B and posaconazole at 2 mg/kg demonstrated survival benefits over control (P = 0.01 and P = 0.04). Dosages of 4 mg/kg were superior to 2 mg/kg for amphotericin B (P = 0.02) and posaconazole (P < 0.05), respectively. No further survival benefits were demonstrated beyond dosages of 10 mg/kg. Rats treated with 20 mg/kg posaconazole, however, had a lower fungal burden than all the other treatment groups (P = 0.0002). CONCLUSIONS: Posaconazole and amphotericin B are effective in a dosage-dependent manner in this pulmonary aspergillosis model in immunocompromised rats.