Procalcitonin for Antibiotic Prescription in Chronic Obstructive Pulmonary Disease Exacerbations: Systematic Review, Meta-Analysis, and Clinical Perspective.
ABSTRACT: The 2020 Global Initiative for Obstructive Lung Disease report indicates that the blood biomarker procalcitonin (PCT) may assist in decision-making regarding the initiation of antibiotics for chronic obstructive pulmonary disease (COPD) exacerbations. PCT is an acute-phase reactant that increases in response to inflammation and infection, and has been studied in various bacterial infections for initiation and de-escalation of antibacterials. The purpose of this systematic review and meta-analysis was to evaluate the strength of the data on the use of PCT to guide antibiotic prescription in COPD exacerbations. Among the randomized clinical trials included in our meta-analysis, almost all of which were conducted exclusively in the hospital setting. PCT was found to decrease overall antibiotic exposure in COPD exacerbations by 2.01 days (p?=?0.04), while no apparent effects were found on clinical outcomes (length of hospital stay, p?=?0.88; treatment failure p?=?0.51; all-cause mortality p?=?0.28). However, the majority of blood PCT levels in COPD exacerbations were below the manufacturer-recommended cutoff for antibiotics, and the use of this marker was associated with worse outcomes in the intensive care setting. Further, based on additional sensitivity analysis excluding studies with high risk of bias or with converted outcome value, the effect of PCT on antibiotic duration in RCTs was no longer significant (MD?=?-1.88 days, 95% CI [-3.95, 0.19] days, p?=?0.08, and MD?=?-1.72 days, 95% CI [-4.28, 0.83] days, p?=?0.19, respectively). Our review and analysis does not support the use of PCT to guide antibiotic prescription in COPD exacerbations.
Project description:BACKGROUND:Antibiotics are often prescribed for hospitalized patients with chronic obstructive pulmonary disease (COPD) exacerbations. The use of procalcitonin (PCT) in the management of pneumonia has safely reduced antibiotic durations, but limited data on the impact of PCT guidance on the management of COPD exacerbations remain. OBJECTIVE:To determine the impact of PCT guidance on antibiotic utilization for hospitalized adults with exacerbations of COPD. DESIGN:A retrospective, pre-/post-intervention cohort study was conducted to compare the management of patients admitted with COPD exacerbations before and after implementation of PCT guidance. The pre-intervention period was March 1, 2014, through October 31, 2014, and the post-intervention period was March 1, 2015, through October 31, 2015. PARTICIPANTS:All patients with hospital admissions during the pre- and post-intervention period with COPD exacerbations were included. Patients with concomitant pneumonia were excluded. INTERVENTION:Availability of PCT laboratory values in tandem with a PCT guidance algorithm and education. MAIN MEASURES:The primary outcome was duration of antibiotic therapy for COPD. Secondary objectives included duration of inpatient length of stay (LOS) and 30-day readmission rates. KEY RESULTS:There were a total of 166 and 139 patients in the pre- and post-intervention cohorts, respectively. There were no differences in mean age (66.2 vs. 65.9; P = 0.82) or use of home oxygenation (34% vs. 39%; P = 0.42) in the pre- and post-intervention groups, respectively. PCT guidance was associated with a reduced number of antibiotic days (5.3 vs. 3.0; p = 0.01) and inpatient LOS (4.1 days vs. 2.9 days; P = 0.01). Respiratory-related 30-day readmission rates were unaffected (10.8% vs. 9.4%; P = 0.25). CONCLUSIONS:Utilizing PCT guidance in the management of COPD exacerbations was associated with a decreased total duration of antibiotic therapy and hospital LOS without negatively impacting hospital readmissions.
Project description:<h4>Rationale</h4>Randomized trials suggest that assessment of serum procalcitonin (PCT) levels can be used to safely limit antibiotic use among patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD).<h4>Objectives</h4>To determine the impact of PCT testing on antibiotic treatment of patients hospitalized for exacerbations of COPD in routine practice.<h4>Methods</h4>We conducted a series of cross-sectional and longitudinal multivariable analyses using data from 2009 to 2011 and 2013 to 2014 from a sample of 505 U.S. hospitals.<h4>Results</h4>Of 203,177 patients hospitalized for COPD exacerbation in 2013 to 2014, nearly 9 out of 10 were treated with antibiotics. Hospital PCT testing rates ranged from 0 to 83%. In cross-sectional analysis, there was a weak negative association between the rate of PCT testing and risk-adjusted rates of antibiotic initiation (Spearman correlation, -0.12; P?=?0.005); each 10-point increase in the percentage of patients undergoing PCT testing was associated with a 0.7% decline in risk-adjusted antibiotic use (P?=?0.001). There was no association between hospital rates of PCT testing and duration of antibiotic treatment. In a longitudinal analysis, comparing treatment patterns in 2009 to 2011 and 2013 to 2014, we did not observe a significant difference in the change in antibiotic treatment rates or duration of therapy between hospitals that had adopted PCT testing compared with those that had not.<h4>Conclusions</h4>As currently implemented, PCT testing appears to have had little impact on decisions to initiate antibiotic therapy or on duration of treatment for COPD exacerbations. Implementation research is necessary to translate the promising outcomes from PCT testing observed in randomized trials into clinical practice.
Project description:For decades, there is an unresolved debate about adequate prescription of antibiotics for patients suffering from exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this systematic review was to analyse randomised controlled trials investigating the clinical benefit of antibiotics for COPD exacerbations.We conducted a systematic review of randomised, placebo-controlled trials assessing the effects of antibiotics on clinically relevant outcomes in patients with an exacerbation. We searched bibliographic databases, scrutinized reference lists and conference proceedings and asked the pharmaceutical industry for unpublished data. We used fixed-effects models to pool results. The primary outcome was treatment failure of COPD exacerbation treatment.We included 13 trials (1557 patients) of moderate to good quality. For the effects of antibiotics on treatment failure there was much heterogeneity across all trials (I(2) = 75%) [corrected] Meta-regression revealed severity of exacerbation as significant explanation for this heterogeneity (p = 0.038) [corrected] Antibiotics did not reduce treatment failures in outpatients with mild to moderate exacerbations (pooled odds ratio 1.81, 95% CI 0.55-1.18, I(2) = 13%) [corrected] Inpatients with severe exacerbations had a substantial benefit on treatment failure rates (pooled odds ratio of 0.25, 95% CI 0.16-0.39, I2 = 0%; number-needed to treat of 4, 95% CI 3-5) and on mortality (pooled odds ratio of 0.20, 95% CI 0.06-0.62, I2 = 0%; number-needed to treat of 14, 95% CI 12-30).Antibiotics effectively reduce treatment failure and mortality rates in COPD patients with severe exacerbations. For patients with mild to moderate exacerbations, antibiotics may not be generally indicated and further research is needed to guide antibiotic prescription in these patients.
Project description:The duration of antibiotic treatment of exacerbations of COPD (ECOPD) is controversial. Serum procalcitonin (PCT) is a biomarker of bacterial infection used to identify the cause of ECOPD.We investigated whether a PCT-guided plan would allow a shorter duration of antibiotic treatment in patients with severe ECOPD. For this multicenter, randomized, non-inferiority trial, we enrolled 184 patients hospitalized with ECOPD from 18 hospitals in Italy. Patients were assigned to receive antibiotics for 10 days (standard group) or for either 3 or 10 days (PCT group). The primary outcome was the rate of ECOPD at 6 months. Having planned to recruit 400 patients, we randomized only 183: 93 in the PCT group and 90 in the standard group. Thus, the completed study was underpowered. The ECOPD rate at 6 months between PCT-guided and standard antibiotic treatment was not significant (% difference, 4.04; 90% confidence interval [CI], -7.23 to 15.31), but the CI included the non-inferiority margin of 15. In the PCT-guided group, about 50% of patients were treated for 3 days, and there was no difference in primary or secondary outcomes compared to patients treated for 10 days.Although the primary and secondary clinical outcomes were no different for patients treated for 3 or 10 days in the PCT group, the conclusion that antibiotics can be safely stopped after 3 days in patients with low serum PCT cannot be substantiated statistically. Thus, the results of this study are inconclusive regarding the noninferiority of the PCT-guided plan compared to the standard antibiotic treatment. The study was funded by Agenzia Italiana del Farmaco (AIFA-FARM58J2XH). Clinical trial registered with www.clinicaltrials.gov (NCT01125098).ClinicalTrials.gov NCT01125098.
Project description:Asthma and chronic obstructive pulmonary disease (COPD) cause significant morbidity and mortality worldwide, primarily through exacerbations. Exacerbations are often treated with antibiotics but their optimal course duration is uncertain. Reducing antibiotic duration may influence antimicrobial resistance but risks treatment failure. The objective of this article is to review published literature to investigate whether shorter antibiotic therapy duration affects clinical outcomes in the treatment of asthma and COPD exacerbations. We systematically searched electronic databases (MEDLINE, EMBASE, CINAHL, World Health Organisation International Clinical Trial Registry Platform, the Cochrane library, and ISRCTN) with no language, location, or time restrictions. We retrieved observational and controlled trials comparing different durations of the same oral antibiotic therapy in the treatment of acute exacerbations of asthma or COPD in adults. We found no applicable studies for asthma exacerbations. We included 10 randomized, placebo-controlled trials for COPD patients, all from high-income countries. The commonest studied antibiotic class was fluoroquinolones. Antibiotic courses shorter than 6 days were associated with significantly fewer overall adverse events (risk ratio (RR): 0.84, 95% confidence interval (CI): 0.75-0.93, p = 0.001) when compared with those of 7 or more days. There was no statistically significant difference for clinical success or bacteriological eradication in sputum (RR: 1.00, 95% CI: 0.88-1.13 and RR: 1.06, 95% CI: 0.79-1.44, respectively). Shorter durations of antibiotics for COPD exacerbations do not seem to confer a higher risk of treatment failure but are associated with fewer adverse events. This is in keeping with previous studies in community acquired pneumonia, but studies were heterogeneous and differed from usual clinical practice. Further observational and prospective work is needed to explore the significance of antibiotic duration in the treatment of asthma and COPD exacerbations.
Project description:PURPOSE:To compare the efficacy of an antibiotic protocol guided by serum procalcitonin (PCT) with that of standard antibiotic therapy in severe acute exacerbations of COPD (AECOPDs) admitted to the intensive care unit (ICU). METHODS:We conducted a multicenter, randomized trial in France. Patients experiencing severe AECOPDs were assigned to groups whose antibiotic therapy was guided by (1) a 5-day PCT algorithm with predefined cutoff values for the initiation or stoppage of antibiotics (PCT group) or (2) standard guidelines (control group). The primary endpoint was 3-month mortality. The predefined noninferiority margin was 12%. RESULTS:A total of 302 patients were randomized into the PCT (n = 151) and control (n = 151) groups. Thirty patients (20%) in the PCT group and 21 patients (14%) in the control group died within 3 months of admission (adjusted difference, 6.6%; 90% CI - 0.3 to 13.5%). Among patients without antibiotic therapy at baseline (n = 119), the use of PCT significantly increased 3-month mortality [19/61 (31%) vs. 7/58 (12%), p = 0.015]. The in-ICU and in-hospital antibiotic exposure durations, were similar between the PCT and control group (5.2 ± 6.5 days in the PCT group vs. 5.4 ± 4.4 days in the control group, p = 0.85 and 7.9 ± 8 days in the PCT group vs. 7.7 ± 5.7 days in the control group, p = 0.75, respectively). CONCLUSION:The PCT group failed to demonstrate non-inferiority with respect to 3-month mortality and failed to reduce in-ICU and in-hospital antibiotic exposure in AECOPDs admitted to the ICU.
Project description:Background:European trials using procalcitonin (PCT)-guided antibiotic therapy for patients with lower respiratory tract infections (LRTIs) have demonstrated significant reductions in antibiotic use without increasing adverse outcomes. Few studies have examined PCT for LRTIs in the United States. Methods:In this study, we evaluated whether a PCT algorithm would reduce antibiotic exposure in patients with LRTI in a US hospital. We conducted a controlled pre-post trial comparing an intervention group of PCT-guided antibiotic therapy to a control group of usual care. Consecutive patients admitted to medicine services and receiving antibiotics for LRTI were enrolled in the intervention. Providers were encouraged to discontinue antibiotics according to a PCT algorithm. Control patients were similar patients admitted before the intervention. Results:The primary endpoint was median antibiotic duration. Overall adverse outcomes at 30 days comprised death, transfer to an intensive care unit, antibiotic side effects, Clostridium difficile infection, disease-specific complications, and post-discharge antibiotic prescription for LRTI. One hundred seventy-four intervention patients and 200 controls were enrolled. Providers complied with the PCT algorithm in 75% of encounters. Procalcitonin-guided therapy reduced median antibiotic duration for pneumonia from 7 days to 6 (P = .045) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) from 4 days to 3 (P = .01). There was no difference in the rate of adverse outcomes in the PCT and control groups. Conclusions:A PCT-guided algorithm safely reduced the duration of antibiotics for treating LRTI. Utilization of a PCT algorithm may aid antibiotic stewardship efforts.This clinical trial was a single-center, controlled, pre-post study of PCT-guided antibiotic therapy for LRTI. The intervention (incorporation of PCT-guided algorithms) started on April 1, 2017: the preintervention (control group) comprised patients admitted from November 1, 2016 to April 16, 2017, and the postintervention group comprised patients admitted from April 17, 2017 to November 29, 2017 (Supplementary Figure 1). The study comprised patients admitted to the internal medicine services to a medical ward, the Medical Intensive Care Unit (MICU), the Cardiac Intensive Care Unit (CICU), or the Progressive Care Unit (PCU) "step down unit". The registration data for the trails are in the ClinicalTrials.gov database, number NCT0310910.
Project description:Serum procalcitonin (PCT) concentration is used to guide antibiotic decisions in choice, timing, and duration of anti-infection therapy to avoid antibiotic overuse. Thus, we performed a systematic review and meta-analysis to seek evidence of different PCT-guided antimicrobial strategies for critically ill patients in terms of predefined clinical outcomes.We searched for relevant studies in PubMed, Embase, Web of Knowledge, and the Cochrane Library up to 25 February 2017. Randomized controlled trials (RCTs) were included if they reported data on any of the predefined outcomes in adult ICU patients managed with a PCT-guided algorithm or according to standard care. Results were expressed as risk ratio (RR) or mean difference (MD) with accompanying 95% confidence interval (CI).We included 13 trials enrolling 5136 patients. These studies used PCT in three clinical strategies: initiation, discontinuation, or combination of antibiotic initiation and discontinuation strategies. Pooled analysis showed a PCT-guided antibiotic discontinuation strategy had fewer total days with antibiotics (MD - 1.66 days; 95% CI - 2.36 to - 0.96 days), longer antibiotic-free days (MD 2.26 days; 95% CI 1.40-3.12 days), and lower short-term mortality (RR 0.87; 95% CI 0.76-0.98), without adversely affecting other outcomes. Only few studies reported data on other PCT-guided strategies for antibiotic therapies, and the pooled results showed no benefit in the predefined outcomes.Our meta-analysis produced evidence that among all the PCT-based strategies, only using PCT for antibiotic discontinuation can reduce both antibiotic exposure and short-term mortality in a critical care setting.
Project description:Appropriate use of antibiotics in the management of hospitalised patients with COPD exacerbations is defined within the GOLD strategy. This paper analyses the factors associated with antibiotic prescribing in patients to better understand how prescribing may be improved.The European COPD audit was a study of clinical care in 384 hospitals from 13 European countries between 2010 and 2011 enrolling 16018 patients. Those admitted to hospital due to a clinician-made diagnosis of exacerbation of COPD at the time of discharge were audited. We defined antibiotic prescribing compliance as consistent with the GOLD 2010 recommendations. Two different multivariate models were used to evaluate factors associated with the prescription of antibiotics and the guideline-compliant prescriptions.Overall 86% of admissions were given antibiotics but only 61.4% cases met the GOLD recommendations. Antibiotics were more likely to be given in hospital and at discharge if received prior to admission. Antibiotic prescription was more likely in patients who met the GOLD recommendations and in those with radiological consolidation but there was also a significant use of antibiotics in patients who did not meet either criterion. Patients cared for on a Respiratory Ward were more likely to receive GOLD compliant antibiotic management.The present study describes the audited in-hospital antibiotic prescription for COPD exacerbation across different European countries. In general, there is an apparent overuse of antibiotics likely to be associated with both patient and practice-related variables.
Project description:Context: The incidence of early-onset neonatal infection has greatly decreased, but a new diagnostic approach is needed to avoid overdiagnosis and overtreatment. The aim of this study was to assess the potential impact of an algorithm incorporating umbilical-cord-blood procalcitonin (PCT) level on neonatal antibiotics prescription rate as compared with current practice. Material and methods: We conducted a prospective study in three maternity wards in France. All term and preterm neonates with the usual risk factors for neonatal group B Streptococcus infection were eligible for umbilical-cord-blood PCT testing. We compared the proportion of neonates who were exposed early to antibiotics (before 6 days of life) to that of neonates for whom antibiotics prescription would be indicated according to the PCT-based algorithm. Results: Among the 3,080 neonates included, 1 neonate presented with certain infection and 38 neonates with probable infection. The global antibiotics prescription rate was 4.6% [95% confidence interval (CI), 4.1-5]. With the PCT-based algorithm, the potential decrease in prescription rate would be 1.8% (95% CI, 1.3-2.3), corresponding to a 39% (95% CI, 37.3-40.7) relative reduction in antibiotics exposure (p < 0.05). Conclusion: These results suggest that the umbilical-cord-blood PCT-based algorithm could significantly help the clinicians in their antibiotic prescription decision to decrease neonatal antibiotics exposure as compared with current practice. If validated in a larger interventional randomized study, this approach could help clinicians stratify the risk of early-onset neonatal infection and initiate early antibiotics treatment in newborns at high risk of infection while limiting the deleterious effects of useless prescriptions in non-infected newborns.