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

Abstract

ObjectivesThe 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 methodsThe 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.ResultsA 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.ConclusionsOnce-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.

Moxifloxacin in Complicated Skin and Skin Structure Infections (cSSSIs): A Prospective, International, Non-Interventional, Observational Study

“…DFI was the most frequent diagnosis in the Asia–Pacific region and patients there had longer response times in comparison with the other regions. Data from randomized clinical trials have shown that moxifloxacin achieves clinical cure in 79–82% of patients with cSSSIs [16–18, 24], rates that are comparable with the results obtained in the ARTOS study. As mentioned above, the majority of investigators in the ARTOS study have rated the overall effectiveness of moxifloxacin as ‘very good’ or ‘good.’ Based on the type of diagnosis it was found ‘very good’ or ‘good’ in 82.6% of DFI and 86.4% of infected ulcer patients, while the effectiveness was rated similarly for a higher proportion of patients with abscesses (94.5%) or wound infections (92–96.1%).…”

“…When comorbidities were taken into account regarding DFI patients, which may influence the length of therapy and clinical outcome, we have observed a similar result to that for the DFI patients enrolled in the RELIEF trial which was a randomized, double-blind study [18, 24]. Thus, comparing patients enrolled in the RELIEF and ARTOS studies regarding specific comorbidities of DFI patients, the proportion of patients with peripheral vascular disease (>65.5 vs 55.7%, respectively), peripheral neuropathy (49.5 vs 63.5%, respectively), or osteomyelitis (20 vs 28.8%, respectively) were rather similar.…”

“…Moxifloxacin achieves good penetration into muscle, subcutaneous adipose tissue, and inflammatory blister fluid, suggesting that adequate tissue concentrations can be achieved in cSSSIs [15]. Evidence for its clinical efficacy in cSSSIs has been demonstrated in a series of randomized, Phase III controlled trials [16–18]. …”

Efficacy and safety of IV/PO moxifloxacin and IV piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid in the treatment of diabetic foot infections: results of the RELIEF study

“…The rationale of the RELIEF study was to provide additional data on the efficacy and safety of MXF in four specific cSSSI diagnoses (major abscess, DFI, wound infection, infected ischemic ulcer) [22]; the present paper reports on the efficacy and safety of MXF versus a β-lactam/β-lactamase inhibitor combination in the subgroup of patients with DFI. The RELIEF study is unique in that it addresses the limitations of previous studies by stratification at inclusion, according to the severity of cSSSI and baseline surgery.…”

Delafloxacin: design, development and potential place in therapy

“…These features are especially needed in DFI. There is evidence of MXL utility in the treatment of DFI, with similar results to piperacillin–tazobactam followed by amoxicillin–clavulanate, even in patients with major vascular involvement (ischemic) or structural (large or profound ulcers),60–62 because it keeps antimicrobial concentrations in the perinecrotic tissue above the MIC 63. DLX provides over MXL the activity against MRSA and its diffusion in acid mediums, as is frequent in diabetic foot ischemia.…”