Effect of algorithm-based therapy vs usual care on clinical success and serious adverse events in patients with staphylococcal bacteremia a randomized clinical trial

the Staphylococcal Bacteremia Investigators

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

IMPORTANCE The appropriate duration of antibiotics for staphylococcal bacteremia is unknown. OBJECTIVE To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events. DESIGN, SETTING, AND PARTICIPANTS A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization. INTERVENTIONS Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care. MAIN OUTCOMES AND MEASURES Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia. RESULTS Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, −6.2% to ]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, −3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, −1.8 days [95% CI, −3.1 to −0.6]). CONCLUSIONS AND RELEVANCE Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm.

Original languageEnglish (US)
Pages (from-to)1249-1258
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume320
Issue number12
DOIs
StatePublished - Sep 25 2018

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Bacteremia
Randomized Controlled Trials
Therapeutics
Anti-Bacterial Agents
Coagulase
Standard of Care
Random Allocation
Staphylococcus
Spain
Staphylococcus aureus
Outcome Assessment (Health Care)
Confidence Intervals

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of algorithm-based therapy vs usual care on clinical success and serious adverse events in patients with staphylococcal bacteremia a randomized clinical trial. / the Staphylococcal Bacteremia Investigators.

In: JAMA - Journal of the American Medical Association, Vol. 320, No. 12, 25.09.2018, p. 1249-1258.

Research output: Contribution to journalArticle

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title = "Effect of algorithm-based therapy vs usual care on clinical success and serious adverse events in patients with staphylococcal bacteremia a randomized clinical trial",
abstract = "IMPORTANCE The appropriate duration of antibiotics for staphylococcal bacteremia is unknown. OBJECTIVE To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events. DESIGN, SETTING, AND PARTICIPANTS A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization. INTERVENTIONS Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care. MAIN OUTCOMES AND MEASURES Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15{\%} margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia. RESULTS Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4{\%}] women), 480 (94.3{\%}) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0{\%} vs 81.5{\%}; difference, 0.5{\%} [1-sided 97.5{\%} CI, −6.2{\%} to ]). Serious adverse events were reported in 32.5{\%} of algorithm-based therapy patients and 28.3{\%} of usual practice patients (difference, 4.2{\%} [95{\%} CI, −3.8{\%} to 12.2{\%}]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, −1.8 days [95{\%} CI, −3.1 to −0.6]). CONCLUSIONS AND RELEVANCE Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm.",
author = "{the Staphylococcal Bacteremia Investigators} and Holland, {Thomas L.} and Issam Raad and Boucher, {Helen W.} and Anderson, {Deverick J.} and Cosgrove, {Sara E.} and {Suzanne Aycock}, P. and Baddley, {John W.} and Chaftari, {Anne Marie} and Chow, {Shein Chung} and Chu, {Vivian H.} and Manuela Carugati and Paul Cook and {Ralph Corey}, G. and Crowley, {Anna Lisa} and Jennifer Daly and Jiezhun Gu and Ray Hachem and James Horton and Jenkins, {Timothy C.} and Donald Levine and Miro, {Jose M.} and Pericas, {Juan M.} and Riska, {Paul F.} and Zachary Rubin and Rupp, {Mark E.} and John Schrank and Matthew Sims and Dannah Wray and Marcus Zervos and Fowler, {Vance G.}",
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T1 - Effect of algorithm-based therapy vs usual care on clinical success and serious adverse events in patients with staphylococcal bacteremia a randomized clinical trial

AU - the Staphylococcal Bacteremia Investigators

AU - Holland, Thomas L.

AU - Raad, Issam

AU - Boucher, Helen W.

AU - Anderson, Deverick J.

AU - Cosgrove, Sara E.

AU - Suzanne Aycock, P.

AU - Baddley, John W.

AU - Chaftari, Anne Marie

AU - Chow, Shein Chung

AU - Chu, Vivian H.

AU - Carugati, Manuela

AU - Cook, Paul

AU - Ralph Corey, G.

AU - Crowley, Anna Lisa

AU - Daly, Jennifer

AU - Gu, Jiezhun

AU - Hachem, Ray

AU - Horton, James

AU - Jenkins, Timothy C.

AU - Levine, Donald

AU - Miro, Jose M.

AU - Pericas, Juan M.

AU - Riska, Paul F.

AU - Rubin, Zachary

AU - Rupp, Mark E.

AU - Schrank, John

AU - Sims, Matthew

AU - Wray, Dannah

AU - Zervos, Marcus

AU - Fowler, Vance G.

PY - 2018/9/25

Y1 - 2018/9/25

N2 - IMPORTANCE The appropriate duration of antibiotics for staphylococcal bacteremia is unknown. OBJECTIVE To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events. DESIGN, SETTING, AND PARTICIPANTS A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization. INTERVENTIONS Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care. MAIN OUTCOMES AND MEASURES Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia. RESULTS Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, −6.2% to ]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, −3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, −1.8 days [95% CI, −3.1 to −0.6]). CONCLUSIONS AND RELEVANCE Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm.

AB - IMPORTANCE The appropriate duration of antibiotics for staphylococcal bacteremia is unknown. OBJECTIVE To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events. DESIGN, SETTING, AND PARTICIPANTS A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization. INTERVENTIONS Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care. MAIN OUTCOMES AND MEASURES Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia. RESULTS Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, −6.2% to ]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, −3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, −1.8 days [95% CI, −3.1 to −0.6]). CONCLUSIONS AND RELEVANCE Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm.

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