If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Procalcitonin (PCT)-guided antibiotic therapy failed to decrease the mortality in critically ill patients.
•
PCT-guided cessation of antibiotics decreased short-term mortality in patients, but not in those with a SOFA score of >8.
•
PCT-guided antibiotic therapy failed to shorten the ICU length of stay (LOS) and hospital LOS in critically ill patients.
•
PCT-guided antibiotic therapy shortened the antibiotic duration in critically ill patients.
Abstract
Background
Optimizing antibiotic therapy has an important impact on the management of critically ill patients. Procalcitonin (PCT) is considered to be of possible use in the guidance of antibiotic stewardship; however, its efficacy remains controversial. Thus, a meta-analysis was performed to determine the efficacy of PCT-guided antibiotic therapy in critically ill patients.
Methods
The relevant literature was searched in PubMed, Embase, Web of Science, and the Cochrane Library covering the period from 2004 to August 2018. Randomized controlled trials (RCTs) were included if critically ill patients were treated with PCT-guided antibiotic therapy or standard care. The primary outcome was short-term mortality; secondary endpoints were the duration of antibiotic treatment, intensive care unit (ICU) length of stay (LOS), and hospital LOS.
Results
Sixteen RCTs enrolling 6452 critically ill patients were included in this analysis. The pooled analysis demonstrated a comparable short-term mortality (rate ratio (RR) 0.90, 95% confidence interval (CI) 0.80–1.01; p = 0.07), ICU LOS (mean difference (MD) 0.38, 95% CI −0.05 to 0.81; p = 0.09), and hospital LOS (MD 0.19, 95% CI −1.56 to 1.95; p = 0.83) for PCT-guided antibiotic therapy and standard antibiotic therapy, and an antibiotic duration shorter by 0.99 days (95% CI −1.85 to −0.13 days; p = 0.02) for PCT-guided antibiotic therapy. In the subgroup analysis, patients with an average Sequential Organ Failure Assessment (SOFA) score of <8 in the PCT-guided cessation of antibiotics group had a lower short-term mortality compared with the standard care group (RR 0.81, 95% CI 0.66–0.99; p = 0.04), while no difference was found in the subgroup with an average SOFA score of >8 (RR 0.85, 95% CI 0.66–1.11; p = 0.23).
Conclusions
PCT-guided antibiotic therapy fails to decrease the mortality or LOS of critically ill patients with suspected or confirmed sepsis. PCT-guided cessation of antibiotic therapy could reduce the mortality in patients with an average SOFA score of <8, but not in those with an average SOFA score of >8.
), remains a major contributor to death in critically ill patients. The initiation of broad-spectrum antibiotics within the first hour of triage in the emergency department or presenting from another care institution, is an essential aspect of high-quality sepsis management (
). However, the incorrect use or abuse of antibiotics is considered to lead to an increased risk of opportunistic infection, antimicrobial resistance, and mortality, and increased healthcare costs (
). Optimizing the management of antibiotic therapy has a very important impact on the treatment of sepsis and management of multidrug-resistant bacteria.
An organized and systematic approach to delivering interventions with proven efficacy and the prompt institution of appropriate therapy are the most effective means for improving the prognosis in the intensive care setting (
Levy et al., 2018). The blood infection biomarker procalcitonin (PCT) has been approved and suggested for the guidance of antibiotic therapy in the context of acute infections and sepsis (
Clinical and economic impact of procalcitonin to shorten antimicrobial therapy in septic patients with proven bacterial infection in an intensive care setting.
Effect of sodium selenite administration and procalcitonin-guided therapy on mortality in patients with severe sepsis or septic shock: a randomized clinical trial.
Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial.
Development and validation of a diagnostic model for early differentiation of sepsis and non-infectious SIRS in critically ill children a data-driven approach using machine-learning algorithms.
). PCT is a calcitonin precursor produced by the epithelial cell in response to bacterial infections, and levels reduce rapidly during recovery. Therefore, as a representative marker of the host response to acute infection, PCT has been proposed to assist physicians in determining individual infection status and making individualized antibiotic therapy decisions.
However, the efficacy of PCT-guided antibiotic therapy in suspected or confirmed infection and sepsis has proved controversial over recent decades (
Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial.
Development and validation of a diagnostic model for early differentiation of sepsis and non-infectious SIRS in critically ill children a data-driven approach using machine-learning algorithms.
Development and validation of a diagnostic model for early differentiation of sepsis and non-infectious SIRS in critically ill children a data-driven approach using machine-learning algorithms.
). Previous meta-analyses have generally reported a marked decrease in antibiotic exposure with PCT-guided antibiotic therapy, but not in mortality or intensive care unit (ICU) and hospital length of stay (LOS) (
Development and validation of a diagnostic model for early differentiation of sepsis and non-infectious SIRS in critically ill children a data-driven approach using machine-learning algorithms.
). Furthermore, a recent trial in France reported a comparable antibiotic exposure and mortality in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) admitted to the ICU in the PCT-guided antibiotic therapy group and standard care group (
The present study was performed to address this prominent drawback of conflicting meta-analysis results and to provide an updated meta-analysis on the efficacy of PCT-guided antibiotic therapy. It was sought to expand on the previous analyses by including studies published more recently in a meta-analysis on the efficacy of PCT-guided antibiotic therapy in critically ill patients.
Materials and methods
This meta-analysis was performed and reported according to a pre-specified protocol registered in the International Prospective Register of Systematic Reviews (
) (PROSPERO registration number: CRD42018109721) and was prepared in accordance with the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-analyses).
Literature search and data extraction
The PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials (RCTs) published between January 2004 and August 2018. The keywords (“Procalcitonin” OR “PCT”) and (“Anti-Bacterial Agents” OR “Antibiotics” OR “Antibacterial”) were searched to identify potentially relevant studies assessing PCT-guided antibiotic therapy among critically ill patients. No language restriction was imposed. (See Supplementary Material Table S1.)
Working in pairs, four reviewers screened citations and abstracts in duplicate and independently. The inclusion criteria encompassed PCT-guided antibiotic therapy compared with standard antibiotic therapy, critically ill adult patients, data reported for mortality, LOS, or duration of antibiotic use, and randomized controlled study design. Studies that did not use PCT to guide antibiotic clinical decision-making were excluded. Case reports, case series, observational or retrospective studies, systematic reviews, and meta-analyses were excluded. Research that was only available in abstract/poster format or that did not present original study data was also excluded. Trials performed before 2004 were not included in this review because the automated PCT immunoassay was only commercialized in that year. Discrepancies between the reviewers’ decisions regarding inclusion and exclusion were resolved through discussion.
Two reviewers independently extracted variables from the identified studies including publication details, country of origin, setting, study design, patient characteristics, PCT algorithm used, interventions, methodological quality, compliance with the algorithm, and outcomes. The PCT algorithm was defined as the serum PCT result dictating the medical decision and guiding the initiation, cessation, or both (mixed) of antibiotic therapy. In brief, ‘initiation of antibiotics’ referred to the clinician’s decision to start or not to start, or to escalate antibiotic therapy, and to intensify the diagnostic effort to identify uncontrolled sources of infection based on a PCT value. ‘Cessation of antibiotics’ referred to the clinician’s decision to de-escalate or not to de-escalate, or to stop antibiotic therapy according to a lower baseline value or the drop in PCT concentration. Confirmed infection was defined in a patient with symptoms, signs, and positive laboratory examinations, or a definite diagnosis of sepsis or septic shock. Low adherence to PCT algorithms was defined as <70%, in accordance with Schuetz et al. (
) showed that the initial Sequential Organ Failure Assessment (SOFA) score predicted the mortality of critically ill patients, with an area under the receiver operating characteristics curve (AUROC) of 0.79 (95% confidence interval (CI) 0.75–0.83) and optimal cut-off of 8 points. Thus, a SOFA score of 8 was chosen as the threshold to discriminate the more severely critically ill patients among the patients with sepsis. Discrepancies in data extraction were discussed with a senior researcher and finally resolved by consensus.
Risk of bias assessment
Two reviewers independently reviewed the included studies and evaluated the risk of bias using the Cochrane Collaboration tool (
). A value of high risk, unclear risk, or low risk was assigned to random sequence generation, allocation concealment, blinding of participants, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and other sources of bias. Discrepancies were resolved by discussion. A funnel plot was used to show the assessment of publication risk of bias.
Outcomes and analyses
The primary outcome was the short-term, all-cause mortality, which included mortality within approximately 28 days and ICU or hospital mortality. Secondary outcomes included the duration of antibiotics, hospital LOS, and ICU LOS. For each of the outcomes or subgroups, a meta-analysis was only performed if there were sufficient data and there were at least three studies in each subgroup, otherwise the studies were excluded from that analysis.
It was planned to assess four subgroups for short-term mortality based upon the following: the strategies of PCT-guided antibiotics, average SOFA score >8 or <8, suspected or confirmed sepsis, and adherence >70% or <70%.
Statistical analysis
For the primary endpoint, short-term mortality was expressed as a risk ratio (RR) and 95% CI; a weighted pooled RR was calculated among included studies using a fixed-effects model for data without heterogeneity and a random-effects model for data with significant heterogeneity. Duration of antibiotics, hospital LOS, and ICU LOS were summarized using the mean difference (MD). The median, interquartile range (IQR), and range in the studies were used to estimate the mean and standard deviation (SD) (
). Analyses were done following the intention-to-treat principle, analyzing patients according to the groups to which they were randomly assigned. Heterogeneity was tested by Cochran Q test and I2. A p-value of <0.10 and I2 > 50% was considered to indicate significant heterogeneity.
Further meta-regression that focused on strategies of PCT-guided antibiotics, suspected or confirmed infection, SOFA score, and adherence was performed if there was significant clinical heterogeneity. Covariate meta-regression analysis was used to identify the source of heterogeneity and the subgroups. A pre-specified sensitivity analysis was done for short-term mortality and antibiotic duration by influence analysis to evaluate the consistency of the results. A two-sided p < 0.05 was accepted to indicate statistical significance.
A trial sequential analysis (TSA) was conducted for the primary outcome to assess the risk of random errors and to calculate the required number of participants (required information size, RIS). The RIS of the TSA was based on 5% risk of a type 1 error and 20% risk of a type 2 error (power of 80%). Analyses were performed using Review Manager (RevMan version 5.3), Stata (version 15), and TSA (version 0.9.5.10).
Results
Study selection
A total of 838 records were identified in the literature databases according to the search strategy (285 in PubMed, 151 in Embase, 284 in Web of Science, and 118 in Cochrane). Of these, 737 potentially eligible articles were reviewed after excluding 101 duplicates. A further 639 were excluded after reading the title or abstract as they were not relevant to the theme. At the full-text stage, 46 were excluded for having no original data, 16 for not using PCT in the antibiotic decision, and 20 for enrolling patients who were not critically ill. Finally, 16 articles involving 6452 participants were included in this review (
Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study.
Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial.
The comparison of procalcitonin guidance administer antibiotics with empiric antibiotic therapy in critically ill patients admitted in intensive care unit.
Effect of sodium selenite administration and procalcitonin-guided therapy on mortality in patients with severe sepsis or septic shock: a randomized clinical trial.
Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial.
Acute exacerbations of chronic obstructive pulmonary disease with low serum procalcitonin values do not benefit from antibiotic treatment: a prospective randomized controlled trial.
Clinical and economic impact of procalcitonin to shorten antimicrobial therapy in septic patients with proven bacterial infection in an intensive care setting.
reported comparison arms of PCT- versus C-reactive protein (CRP)-guided antimicrobial therapy. Three RCTs reported PCT-guided initiation of antibiotic therapy, 10 reported the cessation of antibiotics, and three reported mixed initiation and cessation of antibiotic therapy. Nine trials included patients with an average SOFA score of <8 and five trials included patients with an average SOFA score of >8;
Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial.
Acute exacerbations of chronic obstructive pulmonary disease with low serum procalcitonin values do not benefit from antibiotic treatment: a prospective randomized controlled trial.
did not report SOFA scores. Six studies included patients with confirmed infections, whereas the remaining 10 RCTs included patients with suspected infections. Adherence to PCT algorithms varied, ranging from 47% to 97%. A detailed description of the eligible studies is presented in Table 1.
Effect of sodium selenite administration and procalcitonin-guided therapy on mortality in patients with severe sepsis or septic shock: a randomized clinical trial.
Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial.
Clinical and economic impact of procalcitonin to shorten antimicrobial therapy in septic patients with proven bacterial infection in an intensive care setting.
Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial.
The comparison of procalcitonin guidance administer antibiotics with empiric antibiotic therapy in critically ill patients admitted in intensive care unit.
Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study.
Acute exacerbations of chronic obstructive pulmonary disease with low serum procalcitonin values do not benefit from antibiotic treatment: a prospective randomized controlled trial.
The quality of the trials was appraised according to the Cochrane Collaboration tool: the risk of bias was in high in four trials, moderate in nine trials, and low in three trials (Supplementary Material Figure S1). The funnel plot did not show any obvious publication bias, with a relatively uniform distribution either side of the line of unity (Supplementary Material Figure S2).
Primary outcome
A total of 16 RCTs (6452 participants) were included in the primary analysis of short-term mortality. The combined estimate of the pooled RR for all studies based on the fixed-effects model for short-term mortality was 0.90 (95% CI 0.80–1.01; p = 0.07), with no statistically significant difference observed between PCT-guided antibiotic therapy and standard antibiotic therapy (Figure 2). The test for heterogeneity was not significant (p = 0.88; I2 = 0%), as shown in the sensitivity analysis (Supplementary Material Figure S3). On analysis of each PCT strategy subgroup, PCT-guided cessation of antibiotics decreased the short-term mortality of patients in the PCT-guided group compared with those in the standard care group (RR 0.82, 95% CI 0.70–0.96; p = 0.01), while no difference was found for the subgroups of initiation strategy (RR 0.99, 95% CI 0.81–1.22; p = 0.96) or mixed strategy (RR 1.02, 95% CI 0.73–1.41; p = 0.92). No significant subgroup heterogeneity was observed (p > 0.50; I2 = 0%).
Figure 2Forest plot of the effects of PCT-guided antibiotic strategies on short-term mortality.
With regard to the PCT cessation strategy, patients with an average SOFA score of <8 in the PCT-guided group had lower short-term mortality compared with the standard care group in the subgroup analysis (RR 0.81, 95% CI 0.66–0.99; p = 0.04; Table 2), while no difference was found in the subgroup with a SOFA score >8 (RR 0.85, 95% CI 0.66–1.11; p = 0.23). There was no indication of heterogeneity (p > 0.50; I2 = 0%). In the subgroup analysis, patients with suspected sepsis or lower algorithm adherence in the PCT-guided group had lower short-term mortality compared with those in the standard care group, while no difference was found in the subgroups of confirmed sepsis or higher algorithm adherence.
Table 2Subgroups of PCT-guided cessation of antibiotic therapy.
Subgroups
Number of trials
Mortality: PCT vs. SC
Pooled OR
95% CI
p-Value
Heterogeneity: I2; p-value
Cessation
10
373/1852 vs. 432/1847
0.82
0.70–0.96
0.01
0%; 0.83
SOFA score
9
371/1756 vs. 427/1752
0.83
0.70–0.97
0.02
0%; 0.84
SOFA >8
3
151/612 vs. 164/592
0.85
0.66–1.11
0.23
0%; 0.75
SOFA <8
6
220/1144 vs. 263/1160
0.81
0.66–0.99
0.04
0%; 0.62
Diagnosis
10
373/1852 vs. 432/1847
0.82
0.70–0.96
0.01
0%; 0.83
Suspected
4
196/1110 vs. 241/1131
0.79
0.64–98
0.03
13%; 0.33
Confirmed
6
177/742 vs. 191/716
0.86
0.68–1.09
0.21
0%; 0.93
Adherence
10
373/1852 vs. 432/1847
0.95
0.85–1.07
0.01
0%; 0.83
Adherence >70%
4
56/380 vs. 54/378
1.03
0.68–1.56
0.90
0%; 0.65
Adherence <70%
6
317/1472 vs. 378/1469
0.79
0.67–0.94
0.007
0%; 0.84
CI, confidence interval; OR, odds ratio; PCT, procalcitonin-guided antibiotic therapy; SC, standard care; SOFA, Sequential Organ Failure Assessment.
A post hoc TSA for mortality at short-term mortality with included trials showed a TSA-adjusted RR of 0.91 (95% CI 0.80–1.02; p = 0.0988; I2 = 0%; diversity (D2) = 0%). The cumulative did not cross the Z-curve, the conventional boundary, or the trial sequential monitoring boundary (Figure 3; Supplementary Material Figure S4), indicating the urgent need for larger well-designed RCTs.
Figure 3Post hoc trial sequential analysis (TSA) for mortality at short-term mortality with included trials with no events.
*A post hoc TSA for mortality at short-term mortality with included trials with no events, type 1 error of 5%, and power of 80%, revealed a TSA-adjusted RR of 0.91 (95% CI 0.80–1.02; p = 0.0988; Q = 9.5, I2 = 0%; diversity (D2) = 0%; Figure 3 and Supplementary Material Figure S3). On the basis of a mortality incidence of 23.8% in the control arm and risk reduction of 10.00%, the required information size (RIS) is 10 135.
Eight trials assessed 28-day mortality and no statistically significant difference was observed between the two groups (p = 0.05). Furthermore, there was no statistically significant difference between the groups for ICU mortality (reported in five trials; p = 0.86) or hospital mortality (assessed in nine trials; p = 0.52) (Table 3).
Antibiotic duration was assessed in 14 trials, with 10 in the cessation subgroup and three in the mixed subgroup, and one in the initiation subgroup. Two studies (
The comparison of procalcitonin guidance administer antibiotics with empiric antibiotic therapy in critically ill patients admitted in intensive care unit.
) were excluded because their measurement of antibiotic duration differed from that in the other studies. The overall mean antibiotic duration was 0.99 days shorter (95% CI −1.85 to −0.13 days; p = 0.02; Figure 4) in the PCT-guided group compared with that in the standard care group using a random-effects model. Significant heterogeneity between the pooled trials was observed (p < 0.001; I2 = 90%; Supplementary Material Figures S5 and S6). On analysis of each PCT strategy subgroup, the duration was 1.34 days shorter (95% CI −2.08 to −0.60 days; p = 0.02) for the patients in the cessation subgroup of the PCT-guided group, while the duration was not significantly shorter in the mixed subgroup patients (95% CI −3.1 to 1.71; p = 0.57). The tests for subgroup heterogeneity were significant (p < 0.001, I2 = 76% and p < 0.001, I2 = 92%, respectively).
Figure 4Forest plot of effects of PCT-guided antibiotic strategies on antibiotic duration.
Data on the ICU LOS were assessed in 14 trials. A significant reduction was demonstrated in the mixed PCT strategy subgroup. The ICU LOS in the PCT-guided groups was reduced by 2.01 days (95% CI 0.18–3.85 days; p = 0.03; Supplementary Material Figure S7) compared with that in the standard care groups, without heterogeneity (p = 0.50; I2 = 0%). However, there was no statistically significant difference in the cessation PCT strategy subgroup analysis or the whole pooled meta-analysis (MD 0.13, 95% CI −0.47 to 0.73; p = 0.67 and MD 0.38, 95% CI −0.05 to 0.81; p = 0.09), with moderate heterogeneity (p = 0.04, I2 = 44% and p = 0.04, I2 = 53%, respectively).
Among the 14 trials included in the meta-analysis for hospital LOS, both the random- and fixed-effects models could not demonstrate a significant reduction in the PCT-guided group compared with the standard care group (MD 0.19, 95% CI −1.56 to 1.95; p = 0.83; Supplementary Material Figure S8). Moderate heterogeneity was observed (I2 = 56%; p = 0.009). Furthermore, there was no statistically significant difference in the subgroup analysis of the PCT strategy subgroups or SOFA score subgroups (all p > 0.10), with moderate heterogeneity.
Discussion
The use of PCT-guided antibiotic therapy to optimize antibiotic treatment has been controversial over the past decades. This meta-analysis of 16 studies, including 6452 patients with infections treated in ICUs, revealed that PCT-guided antibiotic therapy did not lead to a decrease in mortality (a robust effect) and that PCT-guided initiation or mixed strategies of antibiotic therapy did not decrease the short-term mortality of critically ill patients with sepsis. Although the subgroup analysis of PCT-guided cessation of antibiotics revealed a lower short-term mortality in the PCT-guided groups and in those patients with a mean SOFA score of <8, the short-term mortality was comparable in the two groups in the SOFA score >8 subgroup and in those in the confirmed sepsis subgroup.
There are several possible explanations for this result. Firstly, sepsis is a heterogeneous syndrome developing from different possible infected organs and with different clinical presentations based on severity (
). Appropriate antibiotic therapy and close monitoring remain the cornerstone of sepsis care, but not all. Starting antibiotic treatment in the ambulance when the patient is suspected of suffering from an infection was found not to lead to improved survival (
). The severity of infection is often associated with the development of multidrug-resistant bacterial pathogens, which is detrimental to the patient outcome (
). It is possible that PCT-guided antibiotic therapy is more suitable for patients without multiple organ failure in the emergency department or general ward setting.
Secondly, PCT levels have been shown to increase in the event of systemic inflammatory response syndrome (SIRS) or organ dysfunction attributable to the presence of various non-infectious causes, such as trauma or ischemic conditions (
). Furthermore, PCT levels and PCT guidance failed to identify the response to antibiotic therapy or prevent potential adverse events, such as a toxic effect or bacterial resistance (
). In addition, the stewardship and movement towards shorter courses of antibiotic treatment may contribute to a further reduction in antibiotic exposure (
Comparing the outcomes of adults with enterobacteriaceae bacteremia receiving short-course versus prolonged-course antibiotic therapy in a multicenter, propensity score-matched cohort.
). Further research is necessary to assess the effect of combined PCT testing with other management of sepsis.
Thirdly, compliance varied in the included trials, and lower compliance with PCT-guided antibiotic therapy was associated with a shorter antibiotic duration (Table 2). Finally, the interventions used in the control groups and the randomization in the included trials are debatable (
). Clear initiation or cessation rules for antibiotic duration based on strict guidelines would make the control group more compatible with the PCT-guided group (
) and could lead to a better evaluation of the effect of PCT guidance.
The strengths of this meta-analysis include the large number of subjects enrolled and the variety of study characteristics. Moreover, focus was placed on the severity of sequential organ failure and whether infection was confirmed in the critically ill patients. However, this meta-analysis has several limitations. Firstly, the average SOFA score, which indicates severity of the enrolled population, was not feasible to explicitly evaluate the severity of critically ill. We used average SOFA scores for grouping, so the two subgroups of patients may have over-lapping SOFA scores, which might bring heterogeneity to analysis. Secondly, the small number of trials in the subgroup of PCT-guided initiation or mixed strategies of antibiotic therapy may have led to an underestimation of the effect of PCT guidance. Thirdly, the diagnostic criteria of sepsis varied between the included studies.
In conclusion, this meta-analysis demonstrated that PCT-guided cessation of antibiotic therapy decreased the short-term mortality of sepsis patients, but that PCT-guided initiation of antibiotics or mixed cessation and initiation strategies did not decrease the short-term mortality and that PCT-guided antibiotics did not decrease other term mortality. PCT-guided antibiotic therapy decreased the duration of antibiotics in the overall meta-analysis and the cessation of antibiotics subgroup analysis; however, this was in contrast to the subgroup of the mixed strategies and a SOFA score >8. Furthermore, PCT-guided antibiotic therapy did not reveal any benefit in the length of ICU or hospital stay. Taken together, it is deemed that the study findings can be attributed to the fact that the PCT-based prescribing guidelines provide fewer opportunities to change antibiotic decisions.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Consent for publication
Not applicable.
Ethical approval and consent to participate
Not applicable.
Funding
This work was supported in part by grants from the National Science and Technology Major Project for Control and Prevention of Major Infectious Diseases of China (Grant No. 2017ZX10103004), National Natural Science Foundation of China (Grant No. 81671892), Jiangsu Province Key Discipline/Laboratory of Medicine (Grant No. ZDXKA2016025), Jiangsu Province Key Provincial Talents Program (Grant No. ZDRCA2016082), and Postgraduate Research & Practice Innovation Program of Jiangsu Province (Grant No. KYCX18_0181).
Conflict of interest
The authors declare that they have no competing interests.
Author contributions: FP and YY studied the design; FP, WC, JFX, and QS conducted the study; FP and WC analyzed the data; FP, WC, JFX, and YY were involved in the data interpretation; FP, WC, HBQ, and YY wrote and revised the paper. All authors read and approved the final manuscript.
Appendix A. Supplementary data
The following is Supplementary data to this article:
Effect of sodium selenite administration and procalcitonin-guided therapy on mortality in patients with severe sepsis or septic shock: a randomized clinical trial.
Comparing the outcomes of adults with enterobacteriaceae bacteremia receiving short-course versus prolonged-course antibiotic therapy in a multicenter, propensity score-matched cohort.
Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial.
Clinical and economic impact of procalcitonin to shorten antimicrobial therapy in septic patients with proven bacterial infection in an intensive care setting.
Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial.
Development and validation of a diagnostic model for early differentiation of sepsis and non-infectious SIRS in critically ill children a data-driven approach using machine-learning algorithms.
The comparison of procalcitonin guidance administer antibiotics with empiric antibiotic therapy in critically ill patients admitted in intensive care unit.
Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study.
Acute exacerbations of chronic obstructive pulmonary disease with low serum procalcitonin values do not benefit from antibiotic treatment: a prospective randomized controlled trial.
30242-5&id=gr1.jpg){kind=link}
30242-5&id=gr2.jpg){kind=link}
30242-5&id=gr3.jpg){kind=link}
30242-5&id=gr4.jpg){kind=link}