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.

Treatment with sequential intravenous or oral moxifloxacin was associated with faster clinical improvement than was standard therapy for hospitalized patients with community-acquired pneumonia who received initial parenteral therapy.

BACKGROUND: Although third-generation cephalosporins, such as ceftriaxone (CTRX), and pneumococcal fluoroquinolones, such as moxifloxacin (MXF), are currently recommended first-line antibiotics for empirical treatment of inpatients with community-acquired pneumonia, CTRX and MXF have never undergone a head-to-head comparison. We therefore compared the efficacy, safety, and speed and quality of defervescence of sequential intravenous or oral MXF and high-dose CTRX with or without erythromycin (CTRX+/-ERY) for patients with community-acquired pneumonia requiring parenteral therapy. METHODS: In this prospective, multicenter, randomized, controlled, nonblinded study, 397 patients were randomly assigned to receive either MXF (400 mg once daily intravenously, possibly followed by oral tablets) or CTRX (2 g intravenously once daily) with or without ERY (1 g intravenously every 6-8 h) for 7-14 days. RESULTS: Among 317 patients evaluable for efficacy and safety, 138 (85.7%) of 161 MXF-treated patients and 135 (86.5%) of 156 CTRX+/-ERY-treated patients (59 [37.8%] of whom received CTRX and ERY) achieved continued clinical resolution. Defervescence and relief of symptoms, such as chest pain, occurred significantly earlier in the MXF-treated group than in the CTRX+/-ERY-treated group. Both regimens were generally well tolerated. CONCLUSIONS: For adult patients hospitalized with community-acquired pneumonia, sequential MXF therapy was clinically equivalent to high-dose CTRX+/-ERY therapy but led to a faster clinical improvement.