A randomized trial of the efficacy and safety of sequential intravenous/oral moxifloxacin monotherapy versus intravenous piperacillin/tazobactam followed by oral amoxicillin/clavulanate for complicated skin and skin structure infections.

OBJECTIVES: The primary aim of the RELIEF study was to evaluate the efficacy and safety of two sequential intravenous (iv)/oral regimens: moxifloxacin iv/oral versus piperacillin/tazobactam (TZP) iv followed by oral amoxicillin/clavulanate (AMC). PATIENTS AND METHODS: The study had a prospective, randomized, double-dummy, double-blind, multicentre design. Patients ≥18 years were prospectively stratified according to complicated skin and skin structure infection (cSSSI) subtype/diagnosis (major abscess, diabetic foot infection, wound infection or infected ischaemic ulcer), surgical intervention and severity of illness. Diagnoses and disease severity were based on predetermined criteria, documented by repeated photographs, and confirmed by an independent data review committee. Patients were randomized to receive either 400 mg of moxifloxacin iv once daily followed by 400 mg of moxifloxacin orally once daily or 4.0/0.5 g of TZP iv thrice daily followed by 875/125 mg of AMC orally twice daily for 7-21 days. The primary efficacy variable was clinical response at test of cure (TOC) for the per-protocol (PP) population. Clinical efficacy was assessed by the data review committee based on repeated photographs and case descriptions. Clinical trials registry number: NCT 00402727. RESULTS: A total of 813 patients were randomized. Clinical success rates at TOC were similar for moxifloxacin and TZP-AMC in the PP [320/361 (88.6%) versus 275/307 (89.6%), respectively; P = 0.758] and intent-to-treat (ITT) [350/426 (82.2%) versus 305/377 (80.9%), respectively; P = 0.632] populations. Thus, moxifloxacin was non-inferior to TZP-AMC. Bacteriological success rates were high in both treatment arms [moxifloxacin: 432/497 (86.9%) versus TZP-AMC: 370/429 (86.2%), microbiologically valid (MBV) population]. Moxifloxacin was non-inferior to TZP-AMC at TOC in both the MBV and the ITT populations. Both treatments were well tolerated. CONCLUSIONS: Once-daily iv/oral moxifloxacin monotherapy was clinically and bacteriologically non-inferior to iv TZP thrice daily followed by oral AMC twice daily in patients with cSSSIs.

Cold-plasma coagulation in the treatment of malignant pleural mesothelioma: results of a combined approach.

Malignant pleural mesothelioma is on a continuous rise throughout the Western countries. It is associated with asbestos fibre exposition in the past. Surgical approaches include extrapleural pneumonectomy and pleurectomy/decortication (P/D). We investigated the feasability of the implementation of cold-plasma coagulation (CPC) on the pleura, pericardium and diaphragm into an established therapeutic algorithm consisting of P/D and hyperthermic intrathoracal chemoperfusion (HITHOC) therapy. The underlying rationale was the prevention of cardiotoxic effects during HITHOC as well as accidental translocation of malignant cells to the abdomen. CPC was done as part of a multimodal therapy in stage III mesothelioma patients. Histologic examinations of pleural excisates after CPC were done. The patients were followed up in three-month intervals. Neither parenchymal fistulas, nor cardiotoxic effects were observed. The histologic examination of the pleural excisates showed complete predictable necrosis. Moreover, until now (median time after operation 1 year) no relapse of the disease was observed. CPC proved to be a safe technique when used on the pleura, pericardium and diaphragm. We consider our trial as a pilot-study. To evaluate potential survival benefits using this technique larger trials are mandatory.