Systematic Review and Meta-analysis of Procalcitonin-Guidance Versus Usual Care for Antimicrobial Management in Critically Ill Patients

Focus on Subgroups Based on Antibiotic Initiation, Cessation, or Mixed Strategies

Simon W. Lam, PharmD, FCCM, BCCCP; Seth R. Bauer, PharmD, FCCM, FCCP; Robert Fowler, MDCM, MS; Abhijit Duggal, MD, MPH, MSc

Disclosures

Crit Care Med. 2018;46(5):684-690. 

In This Article

Abstract and Introduction

Abstract

Objective: Numerous studies have evaluated the use of procalcitonin guidance during different phases of antibiotics management (initiation, cessation, or a combination of both) in patients admitted to ICUs. Several meta-analyses have attempted to generate an overall effect of procalcitonin-guidance on patient outcomes. However, combining studies from different phases of antibiotics management may not be appropriate due to the risk of clinical heterogeneity. The purpose of this systematic review and meta-analysis was to evaluate the effect of procalcitonin-guided strategies in different phases of antibiotics use.

Data Sources: We searched MEDLINE and EMBASE from inception until November 1, 2017.

Study Selection: We included randomized controlled trials that evaluated procalcitonin guidance compared with usual care for management of antibiotics in critically ill adult patients.

Data Extraction: We extracted study details, patient characteristics, procalcitonin algorithm, and outcomes.

Data Synthesis: We included 15 studies, from 1,624 abstracts identified based on our search strategy (three initiation, nine cessation, and three mixed). The pooled risk ratio for short-term mortality for the initiation, cessation, and mixed procalcitonin strategies were 1.00 (95% CI, 0.86–1.15,;p = 0.91), 0.87 (95% CI, 0.77–0.98; p = 0.02), and 1.01 (95% CI, 0.80–1.29; p = 0.93), respectively. Procalcitonin for cessation and mixed strategies was associated with decrease antibiotics duration (–1.26 d [p < 0.001] and –3.10 d [p =0.04], respectively). No differences were observed in other outcome measures.

Conclusion: When evaluating all studies of procalcitonin-guided antibiotics management in critically ill patients, no difference in short-term mortality was observed. However, when only examining procalcitonin-guided cessation of antibiotics, lower mortality was detected. Future studies should focus specifically on procalcitonin for the cessation of antibiotics in critically ill patients.

Introduction

Early adequate empiric antibiotics is associated with improved survival for patients with sepsis; however, the failure to de-escalate or continuing antibiotics beyond recommended durations contribute to 50% of antibiotics prescribed in hospital settings being unnecessary or inappropriate.[1] This may contribute to increasing rates of resistant organisms and unwarranted adverse effects associated with antimicrobials. The Surviving Sepsis Campaign (SSC) guidelines suggest that biomarkers such as procalcitonin may be used to shorten the duration of antimicrobial use in patients with sepsis.[2] Numerous trials have evaluated the effects of procalcitonin-guided strategies on antimicrobial use and clinical outcomes in critically ill patients admitted to the ICU.[3–18]

Several systematic reviews and meta-analyses have attempted to summarize the available literature and generate an overall effect size of procalcitonin-guided strategies on outcomes such as antibiotic exposure, mortality, and hospital and ICU length of stay (LOS).[19–26] In general, the previous meta-analyses demonstrated a statistically significant decrease in antibiotics exposure (weighted mean difference in antibiotics days ranging from 2.05 to 4.19 d) with procalcitonin-guided therapy compared with standard care, but did not detect a difference in mortality, ICU LOS, or hospital LOS between strategies. However, many of these studies suffer from the limitation of combining studies that evaluated procalcitonin-guided strategies in different phases of antimicrobial use (initiation, cessation, or mixed) to provide an average effect size.[27] The combination of studies from different phases of antimicrobial use with meta-analytic methods may not be appropriate due to substantial clinical heterogeneity. This is also evident when evaluating the magnitude of statistical heterogeneity observed in available meta-analyses.[22–25] Furthermore, since the publication of the previous systematic reviews, two additional large randomized control studies evaluating procalcitonin-guided strategies have been published.[14,15] Therefore, we performed a systematic review and meta-analysis to 1) evaluate the true effect size of procalcitonin-guided strategies in different phases of antimicrobial use; and 2) incorporate the findings from the most up-to-date clinical studies.

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