TY - JOUR
T1 - Ertapenem versus piperacillin/tazobactam for diabetic foot infections (SIDESTEP)
T2 - Prospective, randomised, controlled, double-blinded, multicentre trial
AU - Lipsky, Benjamin A.
AU - Armstrong, David G.
AU - Citron, Diane M.
AU - Tice, Alan D.
AU - Morgenstern, David E.
AU - Abramson, Murray A.
N1 - Funding Information:
We thank the following Merck and Co employees: Karen Beck for data review, Norman Bohidar for statistical analysis and study design, Karen Coryell-Moore, Carolyn Urban, Frank LaBarbera, and Courtney Martin for data coordination, Tara Erb and Adam Polis for statistical analysis, Jennifer Ferro for manuscript preparation, Richard Gesser for manuscript review, Patricia Hoover for data review, Tom King for writing assistance, Carissa Mazurick for statistical programming, and Sandy Rawlins and Helene Wilson for their help with the study and its administration. We also thank Gabriel Halperin for participating in discussions on the manuscript. This study was sponsored by Merck and Co, West Point, PA, USA.
PY - 2005/11/12
Y1 - 2005/11/12
N2 - Background: Diabetic foot infections are a common and serious problem, yet few randomised trials of adequate quality have compared the efficacy of the various antibiotic regimens available for their treatment. Our aim was to assess the efficacy and safety of ertapenem versus piperacillin/tazobactam for foot infections. Methods: We did a randomised, double-blinded, multicentre trial in adults (n=586) with diabetes and a foot infection classified as moderate-to-severe and requiring intravenous antibiotics. We assigned patients intravenous ertapenem (1 g daily; n=295) or piperacillin/tazobactam (3·375 g every 6 h; n=291) given for a minimum of 5 days, after which oral amoxicillin/clavulanic acid (875/125 mg every 12 h) could be given for up to 23 days. Investigators retained the option to administer vancomycin to patients in either group to ensure adequate coverage for potentially antibiotic resistant Enterococcus spp and meticillin-resistant Staphylococcus aureus (MRSA). Our primary outcome was the proportion of patients with a favourable clinical response (cure or improvement) on the day that intravenous antibiotic was discontinued. Analyses were by an evaluable-patient only approach. This study is registered with ClinicalTrials.gov, number NCT00229112. Findings: Of the 576 patients treated, 445 were available for assessment at the end of intravenous therapy. Both baseline characteristics and favourable clinical response rates were similar for the 226 who received ertapenem and the 219 who received piperacillin/tazobactam (94% vs 92%, respectively; between treatment difference 1·9%, 95% CI -2·9 to 6·9). Rates of favourable microbiological responses (eradication rates and clinical outcomes, by pathogen) and adverse events did not differ between groups. Interpretation: Clinical and microbiological outcomes for patients treated with ertapenem were equivalent to those for patients treated with piperacillin/tazobactam, suggesting that this once-daily antibiotic should be considered for parenteral therapy of diabetic foot infections, when deemed appropriate.
AB - Background: Diabetic foot infections are a common and serious problem, yet few randomised trials of adequate quality have compared the efficacy of the various antibiotic regimens available for their treatment. Our aim was to assess the efficacy and safety of ertapenem versus piperacillin/tazobactam for foot infections. Methods: We did a randomised, double-blinded, multicentre trial in adults (n=586) with diabetes and a foot infection classified as moderate-to-severe and requiring intravenous antibiotics. We assigned patients intravenous ertapenem (1 g daily; n=295) or piperacillin/tazobactam (3·375 g every 6 h; n=291) given for a minimum of 5 days, after which oral amoxicillin/clavulanic acid (875/125 mg every 12 h) could be given for up to 23 days. Investigators retained the option to administer vancomycin to patients in either group to ensure adequate coverage for potentially antibiotic resistant Enterococcus spp and meticillin-resistant Staphylococcus aureus (MRSA). Our primary outcome was the proportion of patients with a favourable clinical response (cure or improvement) on the day that intravenous antibiotic was discontinued. Analyses were by an evaluable-patient only approach. This study is registered with ClinicalTrials.gov, number NCT00229112. Findings: Of the 576 patients treated, 445 were available for assessment at the end of intravenous therapy. Both baseline characteristics and favourable clinical response rates were similar for the 226 who received ertapenem and the 219 who received piperacillin/tazobactam (94% vs 92%, respectively; between treatment difference 1·9%, 95% CI -2·9 to 6·9). Rates of favourable microbiological responses (eradication rates and clinical outcomes, by pathogen) and adverse events did not differ between groups. Interpretation: Clinical and microbiological outcomes for patients treated with ertapenem were equivalent to those for patients treated with piperacillin/tazobactam, suggesting that this once-daily antibiotic should be considered for parenteral therapy of diabetic foot infections, when deemed appropriate.
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U2 - 10.1016/S0140-6736(05)67694-5
DO - 10.1016/S0140-6736(05)67694-5
M3 - Article
C2 - 16291062
AN - SCOPUS:27744552117
SN - 0140-6736
VL - 366
SP - 1695
EP - 1703
JO - Lancet
JF - Lancet
IS - 9498
ER -