Ertapenem versus piperacillin/tazobactam for diabetic foot infections (SIDESTEP): Prospective, randomised, controlled, double-blinded, multicentre trial

Benjamin A. Lipsky, David G Armstrong, Diane M. Citron, Alan D. Tice, David E. Morgenstern, Murray A. Abramson

Research output: Contribution to journalArticle

206 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1695-1703
Number of pages9
JournalThe Lancet
Volume366
Issue number9498
DOIs
StatePublished - Nov 12 2005
Externally publishedYes

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Diabetic Foot
Multicenter Studies
Infection
Anti-Bacterial Agents
Foot
Amoxicillin-Potassium Clavulanate Combination
Methicillin
Enterococcus
Vancomycin
Therapeutics
tazobactam drug combination piperacillin
ertapenem
Staphylococcus aureus
Research Personnel
Safety

ASJC Scopus subject areas

  • Medicine(all)

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Ertapenem versus piperacillin/tazobactam for diabetic foot infections (SIDESTEP) : Prospective, randomised, controlled, double-blinded, multicentre trial. / Lipsky, Benjamin A.; Armstrong, David G; Citron, Diane M.; Tice, Alan D.; Morgenstern, David E.; Abramson, Murray A.

In: The Lancet, Vol. 366, No. 9498, 12.11.2005, p. 1695-1703.

Research output: Contribution to journalArticle

Lipsky, Benjamin A. ; Armstrong, David G ; Citron, Diane M. ; Tice, Alan D. ; Morgenstern, David E. ; Abramson, Murray A. / Ertapenem versus piperacillin/tazobactam for diabetic foot infections (SIDESTEP) : Prospective, randomised, controlled, double-blinded, multicentre trial. In: The Lancet. 2005 ; Vol. 366, No. 9498. pp. 1695-1703.
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abstract = "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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AU - Morgenstern, David E.

AU - Abramson, Murray A.

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