Procalcitonin to Initiate or Discontinue Antibiotics in Acute Respiratory Tract Infections Daphne Stannard Crit Care Nurse 2014, 34:75-76. doi: 10.4037/ccn2014559 © 2014 American Association of Critical-Care Nurses Published online http://www.cconline.org
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Critical Care Nurse is the official peer-reviewed clinical journal of the American Association ofCritical-Care Nurses, published bi-monthly by The InnoVision Group 101 Columbia, Aliso Viejo, CA 92656. Telephone: (800) 899-1712, (949) 362-2050, ext. 532. Fax: (949) 362-2049. Copyright © 2011 by AACN. All rights reserved. Downloaded from http://ccn.aacnjournals.org/ at CLEMSON UNIVERSITY on November 10, 2014
Cochrane Review Summary A summary of findings from the Cochrane Library with implications for critical care nursing
Procalcitonin to Initiate or Discontinue Antibiotics in Acute Respiratory Tract Infections Daphne Stannard, RN, PhD, CCRN, CCNS
Review Question What is the safety and efficacy of using procalcitonin for starting or stopping antibiotics using individual patient data with varying severity of acute respiratory infections (ARIs) and from different clinical settings?
Relevance to Critical Care Nursing Significant morbidity and mortality worldwide are related to ARIs. These infections comprise a large and heterogeneous group of bacterial, viral, and other etiologies. Although the diagnostic gold standard for establishing the presence or absence of ARI has been the use of blood or sputum cultures, these tests lack both sensitivity and specificity, with only around 10% of patients with pneumonia having positive cultures (including some false positives).1 Procalcitonin, a prohormone of calcitonin, has emerged in recent years as a promising biomarker for the diagnosis of bacterial infections, as higher levels of procalcitonin are found in severe bacterial infections but remain fairly low in viral infections and nonspecific inflammatory diseases. Procalcitonin is released in multiple tissues in response to bacterial infections through direct stimulation of cytokines, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6. Conversely, procalcitonin production is blocked by interferon γ, a cytokine released in response to viral infections. As such, procalcitonin levels may be used
Contributing Editor Daphne Stannard, the contributing editor for the Cochrane Review Summary, is the chief nurse researcher and director of the Institute for Nursing Excellence at UCSF Medical Center, San Francisco, California. She is also the director of the UCSF JBI Centre. For questions related to this article, contact Daphne Stannard at daphne.stannard@ ucsfmedctr.org. ©2014 American Association of Critical-Care Nurses doi: http://dx.doi.org/10.4037/ccn2014559
www.ccnonline.org
to support tailored clinical decision making for the appropriate initiation and duration of antibiotic therapy in patients with a bacterial ARI.
Study Description and Results This summary is based on a Cochrane systematic review that included individual patient data from 14 randomized controlled trials (RCTs) with a total of 4211 participants. Inclusion criteria were adult patients with a clinical diagnosis of ARI, as well as patients with sepsis and suspected ARIs. The systematic review and individual patient data metaanalysis of RCTs was undertaken to compare the effects of using procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARIs to patients without procalcitonin measurements. The aim of the analysis was to assess the safety and efficacy of a procalitonin-guided approach to treatment over a large range of patients with varying severity of ARIs. Trials were excluded if they exclusively focused on pediatric participants or if they used procalcitonin to escalate antibiotic therapy. No
CriticalCareNurse
Vol 34, No. 2, APRIL 2014
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exclusion was made on the basis of language or clinical setting, and trials from primary care, the emergency department, and medical and surgical intensive care units (ICUs) were included. Primary outcomes included all-cause mortality after randomization up to a follow-up time of 30 days and setting-specific treatment failure. Secondary outcomes included the following: • Antibiotic use (initiation, duration, and total exposure [defined as the total amount of antibiotic days divided by the total number of patients]) • Length of hospital stay for hospitalized patients • Length of ICU stay for critically ill patients • Number of days with restricted activities within 14 days after randomization for primary care patients The overall quality of the evidence included in the review was moderate. There were 6 trials with concealed allocation and 5 trials with blinded outcome assessment. All trials achieved complete or near-complete follow-up for mortality. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate hierarchical logistic regression for the co-primary endpoints of mortality from any cause and treatment failure. Linear and logistic regression modeling was used for continuous and binary secondary endpoints, respectively. Multivariable hierarchical logistic regression was used to combine patient data from the different trials, and individual patient data were requested from the investigators of all eligible trials. In metaanalyses with aggregated trial data, summary ORs were calculated using
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a random-effects model and the Mantel-Haenszel statistical method in RevMan 2011 (Cochrane software, London, UK).
Summary of Main Results • Overall, there was no difference in all-cause mortality in procalcitonin-treated patients compared to control patients (5.7% vs 6.3%, adjusted OR 0.94, 95% CI 0.71 to 1.23; 14 trials). This was consistent across clinical settings and ARI diagnoses. • A significantly lower risk for treatment failure was found in the procalcitonin-treated patients compared to control patients (19.1% vs 21.9%, adjusted OR 0.82, 95% CI 0.71 to 0.97; 14 trials). • Procalcitonin-treated patients had a lower antibiotic exposure overall (adjusted difference in days, -3.47, 95% CI -3.78 to -3.17; 14 trials) in all clinical settings and across ARI diagnoses. • There was no significant difference in the length of stay for emergency department and ICU patients.
be noted that most of the trials were conducted in Europe and China and additional high-quality research is needed to confirm the safety of this approach for nonEuropean countries (including the United States).2 CCN Financial Disclosures None reported.
References 1. Muller F, Christ-Crain M, Bregenzer T, et al. Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial. Chest. 2010;138(1):121-129. 2. Schuetz P, Müller B, Christ-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2012;9: CD007498. doi: 10.1002/14651858 .CD007498.pub2. http://onlinelibrary .wiley.com/doi/10.1002/14651858.CD007 498.pub2/abstract. Accessed February 3, 2014.
Nursing Implications This systematic review and metaanalysis of individual patient data from 14 RCTs found no increased risk for mortality or treatment failure when procalcitonin was used to guide initiation and duration of antibiotic treatment in patients with ARIs compared to control patients. In relation to efficacy, procalcitoninguided patients had a consistent reduction of antibiotic use. It should
Vol 34, No. 2, APRIL 2014
Downloaded from http://ccn.aacnjournals.org/ at CLEMSON UNIVERSITY on November 10, 2014
www.ccnonline.org
Downloaded from http://ccn.aacnjournals.org/ at CLEMSON UNIVERSITY on November 10, 2014
Subscription Information http://ccn.aacnjournals.org/subscriptions Information for authors http://ccn.aacnjournals.org/misc/ifora.xhtml
Submit Manuscript www.editorialmanager.com/ccn
E-mail alerts http://ccn.aacnjournals.org/subscriptions/etoc.xhtml
Critical Care Nurse is the official peer-reviewed clinical journal of the American Association ofCritical-Care Nurses, published bi-monthly by The InnoVision Group 101 Columbia, Aliso Viejo, CA 92656. Telephone: (800) 899-1712, (949) 362-2050, ext. 532. Fax: (949) 362-2049. Copyright © 2011 by AACN. All rights reserved. Downloaded from http://ccn.aacnjournals.org/ at CLEMSON UNIVERSITY on November 10, 2014
Cochrane Review Summary A summary of findings from the Cochrane Library with implications for critical care nursing
Procalcitonin to Initiate or Discontinue Antibiotics in Acute Respiratory Tract Infections Daphne Stannard, RN, PhD, CCRN, CCNS
Review Question What is the safety and efficacy of using procalcitonin for starting or stopping antibiotics using individual patient data with varying severity of acute respiratory infections (ARIs) and from different clinical settings?
Relevance to Critical Care Nursing Significant morbidity and mortality worldwide are related to ARIs. These infections comprise a large and heterogeneous group of bacterial, viral, and other etiologies. Although the diagnostic gold standard for establishing the presence or absence of ARI has been the use of blood or sputum cultures, these tests lack both sensitivity and specificity, with only around 10% of patients with pneumonia having positive cultures (including some false positives).1 Procalcitonin, a prohormone of calcitonin, has emerged in recent years as a promising biomarker for the diagnosis of bacterial infections, as higher levels of procalcitonin are found in severe bacterial infections but remain fairly low in viral infections and nonspecific inflammatory diseases. Procalcitonin is released in multiple tissues in response to bacterial infections through direct stimulation of cytokines, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6. Conversely, procalcitonin production is blocked by interferon γ, a cytokine released in response to viral infections. As such, procalcitonin levels may be used
Contributing Editor Daphne Stannard, the contributing editor for the Cochrane Review Summary, is the chief nurse researcher and director of the Institute for Nursing Excellence at UCSF Medical Center, San Francisco, California. She is also the director of the UCSF JBI Centre. For questions related to this article, contact Daphne Stannard at daphne.stannard@ ucsfmedctr.org. ©2014 American Association of Critical-Care Nurses doi: http://dx.doi.org/10.4037/ccn2014559
www.ccnonline.org
to support tailored clinical decision making for the appropriate initiation and duration of antibiotic therapy in patients with a bacterial ARI.
Study Description and Results This summary is based on a Cochrane systematic review that included individual patient data from 14 randomized controlled trials (RCTs) with a total of 4211 participants. Inclusion criteria were adult patients with a clinical diagnosis of ARI, as well as patients with sepsis and suspected ARIs. The systematic review and individual patient data metaanalysis of RCTs was undertaken to compare the effects of using procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARIs to patients without procalcitonin measurements. The aim of the analysis was to assess the safety and efficacy of a procalitonin-guided approach to treatment over a large range of patients with varying severity of ARIs. Trials were excluded if they exclusively focused on pediatric participants or if they used procalcitonin to escalate antibiotic therapy. No
CriticalCareNurse
Vol 34, No. 2, APRIL 2014
Downloaded from http://ccn.aacnjournals.org/ at CLEMSON UNIVERSITY on November 10, 2014
75
exclusion was made on the basis of language or clinical setting, and trials from primary care, the emergency department, and medical and surgical intensive care units (ICUs) were included. Primary outcomes included all-cause mortality after randomization up to a follow-up time of 30 days and setting-specific treatment failure. Secondary outcomes included the following: • Antibiotic use (initiation, duration, and total exposure [defined as the total amount of antibiotic days divided by the total number of patients]) • Length of hospital stay for hospitalized patients • Length of ICU stay for critically ill patients • Number of days with restricted activities within 14 days after randomization for primary care patients The overall quality of the evidence included in the review was moderate. There were 6 trials with concealed allocation and 5 trials with blinded outcome assessment. All trials achieved complete or near-complete follow-up for mortality. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate hierarchical logistic regression for the co-primary endpoints of mortality from any cause and treatment failure. Linear and logistic regression modeling was used for continuous and binary secondary endpoints, respectively. Multivariable hierarchical logistic regression was used to combine patient data from the different trials, and individual patient data were requested from the investigators of all eligible trials. In metaanalyses with aggregated trial data, summary ORs were calculated using
76
CriticalCareNurse
a random-effects model and the Mantel-Haenszel statistical method in RevMan 2011 (Cochrane software, London, UK).
Summary of Main Results • Overall, there was no difference in all-cause mortality in procalcitonin-treated patients compared to control patients (5.7% vs 6.3%, adjusted OR 0.94, 95% CI 0.71 to 1.23; 14 trials). This was consistent across clinical settings and ARI diagnoses. • A significantly lower risk for treatment failure was found in the procalcitonin-treated patients compared to control patients (19.1% vs 21.9%, adjusted OR 0.82, 95% CI 0.71 to 0.97; 14 trials). • Procalcitonin-treated patients had a lower antibiotic exposure overall (adjusted difference in days, -3.47, 95% CI -3.78 to -3.17; 14 trials) in all clinical settings and across ARI diagnoses. • There was no significant difference in the length of stay for emergency department and ICU patients.
be noted that most of the trials were conducted in Europe and China and additional high-quality research is needed to confirm the safety of this approach for nonEuropean countries (including the United States).2 CCN Financial Disclosures None reported.
References 1. Muller F, Christ-Crain M, Bregenzer T, et al. Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial. Chest. 2010;138(1):121-129. 2. Schuetz P, Müller B, Christ-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2012;9: CD007498. doi: 10.1002/14651858 .CD007498.pub2. http://onlinelibrary .wiley.com/doi/10.1002/14651858.CD007 498.pub2/abstract. Accessed February 3, 2014.
Nursing Implications This systematic review and metaanalysis of individual patient data from 14 RCTs found no increased risk for mortality or treatment failure when procalcitonin was used to guide initiation and duration of antibiotic treatment in patients with ARIs compared to control patients. In relation to efficacy, procalcitoninguided patients had a consistent reduction of antibiotic use. It should
Vol 34, No. 2, APRIL 2014
Downloaded from http://ccn.aacnjournals.org/ at CLEMSON UNIVERSITY on November 10, 2014
www.ccnonline.org
Downloaded from http://ccn.aacnjournals.org/ at CLEMSON UNIVERSITY on November 10, 2014
