Procalcitonin testing to guide antibiotic therapy for the treatment of sepsis in intensive care settings and for suspected bacterial infection in emergency department settings: a systematic review and cost-effectiveness analysis

M. Westwood, B. Ramaekers, P. Whiting, F. Tomini, M. Joore, N. Armstrong, S. Ryder, L. Stirk, J. Severens, J. Kleijnen

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Abstract

Background: Determination of the presence or absence of bacterial infection is important to guide appropriate therapy and reduce antibiotic exposure. Procalcitonin (PCT) is an inflammatory marker that has been suggested as a marker for bacterial infection.

Objectives: To assess the clinical effectiveness and cost-effectiveness of adding PCT testing to the information used to guide antibiotic therapy in adults and children (1) with confirmed or highly suspected sepsis in intensive care and (2) presenting to the emergency department (ED) with suspected bacterial infection.

Methods: Twelve databases were searched to June 2014. Randomised controlled trials were assessed for quality using the Cochrane Risk of Bias tool. Summary relative risks (RRs) and weighted mean differences (WMDs) were estimated using random-effects models. Heterogeneity was assessed visually using forest plots and statistically using the I-2 and Q statistics and investigated through subgroup analysis. The cost-effectiveness of PCT testing in addition to current clinical practice was compared with current clinical practice using a decision tree with a 6 months' time horizon.

Results: Eighteen studies (36 reports) were included in the systematic review. PCT algorithms were associated with reduced antibiotic duration [WMD -3.19 days, 95% confidence interval (CI)-5.44 to -0.95 days, I-2 = 95.2%; four studies], hospital stay (WMD-3.85 days, 95% CI -6.78 to -0.92 days, I-2 = 75.2%; four studies) and a trend towards reduced intensive care unit (ICU) stay (WMD -2.03 days, 95% CI -4.19 to 0.13 days, I-2 = 81.0%; four studies). There were no differences for adverse clinical outcomes. PCT algorithms were associated with a reduction in the proportion of adults (RR 0.77, 95% CI 0.68 to 0.87; seven studies) and children (RR 0.86, 95% CI 0.80 to 0.93) receiving antibiotics, reduced antibiotic duration (two studies). There were no differences for adverse clinical outcomes. All but one of the studies in the ED were conducted in people presenting with respiratory symptoms. Cost-effectiveness: the base-case analyses indicated that PCT testing was cost-saving for (1) adults with confirmed or highly suspected sepsis in an ICU setting; (2) adults with suspected bacterial infection presenting to the ED; and (3) children with suspected bacterial infection presenting to the ED. Cost-savings ranged from 368 pound to 3268 pound. Moreover, PCT-guided treatment resulted in a small quality-adjusted life-year (QALY) gain (ranging between = 84% of being cost-effective for all settings and populations considered (at willingness-to-pay thresholds of 20,000 pound and 30,000 pound per QALY).

Conclusions: The limited available data suggest that PCT testing may be effective and cost-effective when used to guide discontinuation of antibiotics in adults being treated for suspected or confirmed sepsis in ICU settings and initiation of antibiotics in adults presenting to the ED with respiratory symptoms and suspected bacterial infection. However, it is not clear that observed costs and effects are directly attributable to PCT testing, are generalisable outside people presenting with respiratory symptoms (for the ED setting) and would be reproducible in the UK NHS. Further studies are needed to assess the effectiveness of adding PCT algorithms to the information used to guide antibiotic treatment in children with suspected or confirmed sepsis in ICU settings. Additional research is needed to examine whether the outcomes presented in this report are fully generalisable to the UK.

Original languageEnglish
Pages (from-to)1
Number of pages238
JournalHealth Technology Assessment
Volume19
Issue number96
DOIs
Publication statusPublished - Nov 2015

Keywords

  • RESPIRATORY-TRACT INFECTIONS
  • C-REACTIVE PROTEIN
  • QUALITY-OF-LIFE
  • CRITICALLY-ILL PATIENTS
  • EARLY APPROPRIATE ANTIBIOTICS
  • INVESTIGATOR-INITIATED TRIAL
  • COMMUNITY-ACQUIRED PNEUMONIA
  • WHETHER DAILY MEASUREMENTS
  • SEVERE ACUTE-PANCREATITIS
  • IMPROVE SURVIVAL

Cite this

@article{ad2e741dccb8494cb02c21ac6cbbbb7c,
title = "Procalcitonin testing to guide antibiotic therapy for the treatment of sepsis in intensive care settings and for suspected bacterial infection in emergency department settings: a systematic review and cost-effectiveness analysis",
abstract = "Background: Determination of the presence or absence of bacterial infection is important to guide appropriate therapy and reduce antibiotic exposure. Procalcitonin (PCT) is an inflammatory marker that has been suggested as a marker for bacterial infection.Objectives: To assess the clinical effectiveness and cost-effectiveness of adding PCT testing to the information used to guide antibiotic therapy in adults and children (1) with confirmed or highly suspected sepsis in intensive care and (2) presenting to the emergency department (ED) with suspected bacterial infection.Methods: Twelve databases were searched to June 2014. Randomised controlled trials were assessed for quality using the Cochrane Risk of Bias tool. Summary relative risks (RRs) and weighted mean differences (WMDs) were estimated using random-effects models. Heterogeneity was assessed visually using forest plots and statistically using the I-2 and Q statistics and investigated through subgroup analysis. The cost-effectiveness of PCT testing in addition to current clinical practice was compared with current clinical practice using a decision tree with a 6 months' time horizon.Results: Eighteen studies (36 reports) were included in the systematic review. PCT algorithms were associated with reduced antibiotic duration [WMD -3.19 days, 95{\%} confidence interval (CI)-5.44 to -0.95 days, I-2 = 95.2{\%}; four studies], hospital stay (WMD-3.85 days, 95{\%} CI -6.78 to -0.92 days, I-2 = 75.2{\%}; four studies) and a trend towards reduced intensive care unit (ICU) stay (WMD -2.03 days, 95{\%} CI -4.19 to 0.13 days, I-2 = 81.0{\%}; four studies). There were no differences for adverse clinical outcomes. PCT algorithms were associated with a reduction in the proportion of adults (RR 0.77, 95{\%} CI 0.68 to 0.87; seven studies) and children (RR 0.86, 95{\%} CI 0.80 to 0.93) receiving antibiotics, reduced antibiotic duration (two studies). There were no differences for adverse clinical outcomes. All but one of the studies in the ED were conducted in people presenting with respiratory symptoms. Cost-effectiveness: the base-case analyses indicated that PCT testing was cost-saving for (1) adults with confirmed or highly suspected sepsis in an ICU setting; (2) adults with suspected bacterial infection presenting to the ED; and (3) children with suspected bacterial infection presenting to the ED. Cost-savings ranged from 368 pound to 3268 pound. Moreover, PCT-guided treatment resulted in a small quality-adjusted life-year (QALY) gain (ranging between = 84{\%} of being cost-effective for all settings and populations considered (at willingness-to-pay thresholds of 20,000 pound and 30,000 pound per QALY).Conclusions: The limited available data suggest that PCT testing may be effective and cost-effective when used to guide discontinuation of antibiotics in adults being treated for suspected or confirmed sepsis in ICU settings and initiation of antibiotics in adults presenting to the ED with respiratory symptoms and suspected bacterial infection. However, it is not clear that observed costs and effects are directly attributable to PCT testing, are generalisable outside people presenting with respiratory symptoms (for the ED setting) and would be reproducible in the UK NHS. Further studies are needed to assess the effectiveness of adding PCT algorithms to the information used to guide antibiotic treatment in children with suspected or confirmed sepsis in ICU settings. Additional research is needed to examine whether the outcomes presented in this report are fully generalisable to the UK.",
keywords = "RESPIRATORY-TRACT INFECTIONS, C-REACTIVE PROTEIN, QUALITY-OF-LIFE, CRITICALLY-ILL PATIENTS, EARLY APPROPRIATE ANTIBIOTICS, INVESTIGATOR-INITIATED TRIAL, COMMUNITY-ACQUIRED PNEUMONIA, WHETHER DAILY MEASUREMENTS, SEVERE ACUTE-PANCREATITIS, IMPROVE SURVIVAL",
author = "M. Westwood and B. Ramaekers and P. Whiting and F. Tomini and M. Joore and N. Armstrong and S. Ryder and L. Stirk and J. Severens and J. Kleijnen",
year = "2015",
month = "11",
doi = "10.3310/hta19960",
language = "English",
volume = "19",
pages = "1",
journal = "Health Technology Assessment",
issn = "1366-5278",
publisher = "National Coordinating Centre for Health Technology Assessment",
number = "96",

}

Procalcitonin testing to guide antibiotic therapy for the treatment of sepsis in intensive care settings and for suspected bacterial infection in emergency department settings: a systematic review and cost-effectiveness analysis. / Westwood, M.; Ramaekers, B.; Whiting, P.; Tomini, F.; Joore, M.; Armstrong, N.; Ryder, S.; Stirk, L.; Severens, J.; Kleijnen, J.

In: Health Technology Assessment, Vol. 19, No. 96, 11.2015, p. 1.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Procalcitonin testing to guide antibiotic therapy for the treatment of sepsis in intensive care settings and for suspected bacterial infection in emergency department settings: a systematic review and cost-effectiveness analysis

AU - Westwood, M.

AU - Ramaekers, B.

AU - Whiting, P.

AU - Tomini, F.

AU - Joore, M.

AU - Armstrong, N.

AU - Ryder, S.

AU - Stirk, L.

AU - Severens, J.

AU - Kleijnen, J.

PY - 2015/11

Y1 - 2015/11

N2 - Background: Determination of the presence or absence of bacterial infection is important to guide appropriate therapy and reduce antibiotic exposure. Procalcitonin (PCT) is an inflammatory marker that has been suggested as a marker for bacterial infection.Objectives: To assess the clinical effectiveness and cost-effectiveness of adding PCT testing to the information used to guide antibiotic therapy in adults and children (1) with confirmed or highly suspected sepsis in intensive care and (2) presenting to the emergency department (ED) with suspected bacterial infection.Methods: Twelve databases were searched to June 2014. Randomised controlled trials were assessed for quality using the Cochrane Risk of Bias tool. Summary relative risks (RRs) and weighted mean differences (WMDs) were estimated using random-effects models. Heterogeneity was assessed visually using forest plots and statistically using the I-2 and Q statistics and investigated through subgroup analysis. The cost-effectiveness of PCT testing in addition to current clinical practice was compared with current clinical practice using a decision tree with a 6 months' time horizon.Results: Eighteen studies (36 reports) were included in the systematic review. PCT algorithms were associated with reduced antibiotic duration [WMD -3.19 days, 95% confidence interval (CI)-5.44 to -0.95 days, I-2 = 95.2%; four studies], hospital stay (WMD-3.85 days, 95% CI -6.78 to -0.92 days, I-2 = 75.2%; four studies) and a trend towards reduced intensive care unit (ICU) stay (WMD -2.03 days, 95% CI -4.19 to 0.13 days, I-2 = 81.0%; four studies). There were no differences for adverse clinical outcomes. PCT algorithms were associated with a reduction in the proportion of adults (RR 0.77, 95% CI 0.68 to 0.87; seven studies) and children (RR 0.86, 95% CI 0.80 to 0.93) receiving antibiotics, reduced antibiotic duration (two studies). There were no differences for adverse clinical outcomes. All but one of the studies in the ED were conducted in people presenting with respiratory symptoms. Cost-effectiveness: the base-case analyses indicated that PCT testing was cost-saving for (1) adults with confirmed or highly suspected sepsis in an ICU setting; (2) adults with suspected bacterial infection presenting to the ED; and (3) children with suspected bacterial infection presenting to the ED. Cost-savings ranged from 368 pound to 3268 pound. Moreover, PCT-guided treatment resulted in a small quality-adjusted life-year (QALY) gain (ranging between = 84% of being cost-effective for all settings and populations considered (at willingness-to-pay thresholds of 20,000 pound and 30,000 pound per QALY).Conclusions: The limited available data suggest that PCT testing may be effective and cost-effective when used to guide discontinuation of antibiotics in adults being treated for suspected or confirmed sepsis in ICU settings and initiation of antibiotics in adults presenting to the ED with respiratory symptoms and suspected bacterial infection. However, it is not clear that observed costs and effects are directly attributable to PCT testing, are generalisable outside people presenting with respiratory symptoms (for the ED setting) and would be reproducible in the UK NHS. Further studies are needed to assess the effectiveness of adding PCT algorithms to the information used to guide antibiotic treatment in children with suspected or confirmed sepsis in ICU settings. Additional research is needed to examine whether the outcomes presented in this report are fully generalisable to the UK.

AB - Background: Determination of the presence or absence of bacterial infection is important to guide appropriate therapy and reduce antibiotic exposure. Procalcitonin (PCT) is an inflammatory marker that has been suggested as a marker for bacterial infection.Objectives: To assess the clinical effectiveness and cost-effectiveness of adding PCT testing to the information used to guide antibiotic therapy in adults and children (1) with confirmed or highly suspected sepsis in intensive care and (2) presenting to the emergency department (ED) with suspected bacterial infection.Methods: Twelve databases were searched to June 2014. Randomised controlled trials were assessed for quality using the Cochrane Risk of Bias tool. Summary relative risks (RRs) and weighted mean differences (WMDs) were estimated using random-effects models. Heterogeneity was assessed visually using forest plots and statistically using the I-2 and Q statistics and investigated through subgroup analysis. The cost-effectiveness of PCT testing in addition to current clinical practice was compared with current clinical practice using a decision tree with a 6 months' time horizon.Results: Eighteen studies (36 reports) were included in the systematic review. PCT algorithms were associated with reduced antibiotic duration [WMD -3.19 days, 95% confidence interval (CI)-5.44 to -0.95 days, I-2 = 95.2%; four studies], hospital stay (WMD-3.85 days, 95% CI -6.78 to -0.92 days, I-2 = 75.2%; four studies) and a trend towards reduced intensive care unit (ICU) stay (WMD -2.03 days, 95% CI -4.19 to 0.13 days, I-2 = 81.0%; four studies). There were no differences for adverse clinical outcomes. PCT algorithms were associated with a reduction in the proportion of adults (RR 0.77, 95% CI 0.68 to 0.87; seven studies) and children (RR 0.86, 95% CI 0.80 to 0.93) receiving antibiotics, reduced antibiotic duration (two studies). There were no differences for adverse clinical outcomes. All but one of the studies in the ED were conducted in people presenting with respiratory symptoms. Cost-effectiveness: the base-case analyses indicated that PCT testing was cost-saving for (1) adults with confirmed or highly suspected sepsis in an ICU setting; (2) adults with suspected bacterial infection presenting to the ED; and (3) children with suspected bacterial infection presenting to the ED. Cost-savings ranged from 368 pound to 3268 pound. Moreover, PCT-guided treatment resulted in a small quality-adjusted life-year (QALY) gain (ranging between = 84% of being cost-effective for all settings and populations considered (at willingness-to-pay thresholds of 20,000 pound and 30,000 pound per QALY).Conclusions: The limited available data suggest that PCT testing may be effective and cost-effective when used to guide discontinuation of antibiotics in adults being treated for suspected or confirmed sepsis in ICU settings and initiation of antibiotics in adults presenting to the ED with respiratory symptoms and suspected bacterial infection. However, it is not clear that observed costs and effects are directly attributable to PCT testing, are generalisable outside people presenting with respiratory symptoms (for the ED setting) and would be reproducible in the UK NHS. Further studies are needed to assess the effectiveness of adding PCT algorithms to the information used to guide antibiotic treatment in children with suspected or confirmed sepsis in ICU settings. Additional research is needed to examine whether the outcomes presented in this report are fully generalisable to the UK.

KW - RESPIRATORY-TRACT INFECTIONS

KW - C-REACTIVE PROTEIN

KW - QUALITY-OF-LIFE

KW - CRITICALLY-ILL PATIENTS

KW - EARLY APPROPRIATE ANTIBIOTICS

KW - INVESTIGATOR-INITIATED TRIAL

KW - COMMUNITY-ACQUIRED PNEUMONIA

KW - WHETHER DAILY MEASUREMENTS

KW - SEVERE ACUTE-PANCREATITIS

KW - IMPROVE SURVIVAL

U2 - 10.3310/hta19960

DO - 10.3310/hta19960

M3 - Article

VL - 19

SP - 1

JO - Health Technology Assessment

JF - Health Technology Assessment

SN - 1366-5278

IS - 96

ER -