Procalcitonin algorithm to guide initial antibiotic therapy in acute exacerbations of COPD admitted to the ICU: a randomized multicenter study.
ABSTRACT: 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:The objective of this study was to establish the efficacy and safety of procalcitonin (PCT)-guided antibiotic discontinuation in critically ill patients with sepsis in a country with a high prevalence of antimicrobial resistance and a national health insurance system. METHODS:In a multi-center randomized controlled trial, patients were randomly assigned to a PCT group (stopping antibiotics based on a predefined cut-off range of PCT) or a control group. The primary end-point was antibiotic duration. We also performed a cost-minimization analysis of PCT-guided antibiotic discontinuation. RESULTS:The two groups (23 in the PCT group and 29 in the control group) had similar demographic and clinical characteristics except for need for renal replacement therapy on ICU admission (46% vs. 14%; P = 0.010). In the per-protocol analysis, the median duration of antibiotic treatment for sepsis was 4 days shorter in the PCT group than the control group (8 days; interquartile range [IQR], 6-10 days vs. 14 days; IQR, 12-21 days; P = 0.001). However, main secondary outcomes, such as clinical cure, 28-day mortality, hospital mortality, and ICU and hospital stays were not different between the two groups. In cost evaluation, PCT-guided therapy decreased antibiotic costs by USD 30 (USD 241 in the PCT group vs. USD 270 in the control group). The results of the intention-to-treat analysis were similar to those obtained for the per-protocol analysis. CONCLUSION:PCT-guided antibiotic discontinuation in critically ill patients with sepsis could reduce the duration of antibiotic use and its costs with no apparent adverse outcomes. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02202941.
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:Viral lower respiratory tract illness (LRTI) frequently causes adult hospitalization and is linked to antibiotic overuse. European studies suggest that the serum procalcitonin (PCT) level may be used to guide antibiotic therapy. We conducted a trial assessing the feasibility of using PCT algorithms with viral testing to guide antibiotic use in a US hospital.Three hundred patients hospitalized with nonpneumonic LRTI during October 2013-April 2014 were randomly assigned at a ratio of 1:1 to receive standard care or PCT-guided care and viral PCR testing. The primary outcome was antibiotic exposure, and safety was assessed at 1 and 3 months.Among the 151 patients in the intervention group, viruses were identified in 42% (63), and 83% (126) had PCT values of <0.25 µg/mL. There were no significant differences in antibiotic use or adverse events between intervention patients and those in the nonintervention group. Subgroup analyses revealed fewer subjects with positive results of viral testing and low PCT values who were discharged receiving antibiotics (20% vs 45%; P = .002) and shorter antibiotic durations among algorithm-adherent intervention patients versus nonintervention patients (2.0 vs 4.0 days; P = .004). Compared with historical controls (from 2008-2011), antibiotic duration in nonintervention patients decreased by 2 days (6.0 vs 4.0 days; P < .001), suggesting a study effect.Although antibiotic use was similar in the 2 arms, subgroup analyses of intervention patients suggest that physicians responded to viral and biomarker data. These data can inform the design of future US studies.NCT01907659.
Project description:There is a growing use of procalcitonin (PCT) to facilitate the diagnosis and management of severe sepsis. We investigated the impact of one to two PCT determinations on ICU day 1 on health-care utilization and cost in a large research database.A retrospective, propensity score-matched multivariable analysis was performed on the Premier Healthcare Database for patients admitted to the ICU with one to two PCT evaluations on day 1 of ICU admission vs patients who did not have PCT testing.A total of 33,569 PCT-managed patients were compared with 98,543 propensity score-matched non-PCT patients. In multivariable regression analysis, PCT utilization was associated with significantly decreased total length of stay (11.6 days [95% CI, 11.4 to 11.7] vs 12.7 days [95% CI, 12.6 to 12.8]; 95% CI for difference, 1 to 1.3; P < .001) and ICU length of stay (5.1 days [95% CI, 5.1 to 5.2] vs 5.3 days [95% CI, 5.3 to 5.4]; 95% CI for difference, 0.1 to 0.3; P < .03), and lower hospital costs ($30,454 [95% CI, 29,968 to 31,033] vs $33,213 [95% CI, 32,964 to 33,556); 95% CI for difference, 2,159 to 3,321; P < .001). There was significantly less total antibiotic exposure (16.2 days [95% CI, 16.1 to 16.5] vs 16.9 days [95% CI, 16.8 to 17.1]; 95% CI for difference, -0.9 to 0.4; P = .006) in PCT-managed patients. Patients in the PCT group were more likely to be discharged to home (44.1% [95% CI, 43.7 to 44.6] vs 41.3% [95% CI, 41 to 41.6]; 95% CI for difference, 2.3 to 3.3; P = .006). Mortality was not different in an analysis including the 96% of patients who had an independent measure of mortality risk available (19.1% [95% CI, 18.7 to 19.4] vs 19.1% [95% CI, 18.9 to 19.3]; 95% CI for difference, -0.5 to 0.4; P = .93).Use of PCT testing on the first day of ICU admission was associated with significantly lower hospital and ICU lengths of stay, as well as decreased total, ICU, and pharmacy cost of care. Further elucidation of clinical outcomes requires additional data.
Project description:Procalcitonin (PCT)-based algorithms have been used to guide antibiotic therapy in several clinical settings. However, evidence supporting PCT-based algorithms for secondary peritonitis after emergency surgery is scanty. In this study, we aimed to investigate whether a PCT-based algorithm could safely reduce antibiotic exposure in this population.From April 2012 to March 2013, patients that had secondary peritonitis diagnosed at the emergency department and underwent emergency surgery were screened for eligibility. PCT levels were obtained pre-operatively, on post-operative days 1, 3, 5, and 7, and on subsequent days if needed. Antibiotics were discontinued if PCT was <1.0 ng/mL or decreased by 80% versus day 1, with resolution of clinical signs. Primary endpoints were time to discontinuation of intravenous antibiotics for the first episode and adverse events. Historical controls were retrieved for propensity score matching. After matching, 30 patients in the PCT group and 60 in the control were included for analysis. The median duration of antibiotic exposure in PCT group was 3.4 days (interquartile range [IQR] 2.2 days), while 6.1 days (IQR 3.2 days) in control (p < 0.001). The PCT algorithm significantly improves time to antibiotic discontinuation (p < 0.001, log-rank test). The rates of adverse events were comparable between 2 groups. Multivariate-adjusted extended Cox model demonstrated that the PCT-based algorithm was significantly associated with a 87% reduction in hazard of antibiotic exposure within 7 days (hazard ratio [HR] 0.13, 95% CI 0.07-0.21, p < 0.001), and a 68% reduction in hazard after 7 days (adjusted HR 0.32, 95% CI 0.11-0.99, p ?=? 0.047). Advanced age, coexisting pulmonary diseases, and higher severity of illness were significantly associated with longer durations of antibiotic use.The PCT-based algorithm safely reduces antibiotic exposure in this study. Further randomized trials are needed to confirm our findings and incorporate cost-effectiveness analysis.Australian New Zealand Clinical Trials Registry ACTRN12612000601831.
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:Procalcitonin (PCT) biomarker is suggested to tailor antibiotic therapy in the medical intensive care unit (ICU) but studies in perioperative medicine are scarce. The aim of this study was to determine whether PCT reported thresholds are associated with the initial treatment response in perioperative septic shock secondary to intra-abdominal infection.This single ICU, observational study included patients with perioperative septic shocks secondary to intra-abdominal infection. Demographics, PCT at days 0, 1, 3, 5, treatment response and outcome were collected. Treatment failure included death related to the initial infection, second source control treatment or a new onset intra-abdominal infection. The primary endpoint was to assess whether PCT thresholds (0.5 ng/ml or a drop from the peak of at least 80%) predict the initial treatment response.We included 101 consecutive cases. Initial treatment failed in 36 patients with a subsequent mortality of 75%. Upon admission, PCT was doubled when treatment ultimately failed (21.7 ng/ml ± 38.7 vs. 41.7 ng/ml ± 75.7; P = 0.04). Although 95% of the patients in whom PCT dropped down below 0.5 ng/ml responded to treatment, 50% of the patients in whom PCT remained above 0.5 ng/ml also responded successfully to treatment. Moreover, despite a PCT drop of at least 80%, 40% of patients had treatment failure.In perioperative intra-abdominal infections with shock, PCT decrease to 0.5 ng/ml lacked sensitivity to predict treatment response and its decrease of at least 80% from its peak failed to accurately predict treatment response. Studies in perioperative severe infections are needed before using PCT to tailor antibiotic use in this population.
Project description:Antibiotics are overused in children and adolescents with lower respiratory tract infection (LRTI). Serum-procalcitonin (PCT) can be used to guide treatment when bacterial infection is suspected. Its role in pediatric LRTI is unclear.Between 01/2009 and 02/2010 we randomized previously healthy patients 1 month to 18 years old presenting with LRTI to the emergency departments of two pediatric hospitals in Switzerland to receive antibiotics either according to a PCT guidance algorithm established for adult LRTI or standard care clinical guidelines. In intention-to-treat analyses, antibiotic prescribing rate, duration of antibiotic treatment, and number of days with impairment of daily activities within 14 days of randomization were compared between the two groups.In total 337 children, mean age 3.8 years (range 0.1-18), were included. Antibiotic prescribing rates were not significantly different in PCT guided patients compared to controls (OR 1.26; 95% CI 0.81, 1.95). Mean duration of antibiotic exposure was reduced from 6.3 to 4.5 days under PCT guidance (-1.8 days; 95% CI -3.1, -0.5; P = 0.039) for all LRTI and from 9.1 to 5.7 days for pneumonia (-3.4 days 95% CI -4.9, -1.7; P<0.001). There was no apparent difference in impairment of daily activities between PCT guided and control patients.PCT guidance reduced antibiotic exposure by reducing the duration of antibiotic treatment, while not affecting the antibiotic prescribing rate. The latter may be explained by the low baseline prescribing rate in Switzerland for pediatric LRTI and the choice of an inappropriately low PCT cut-off level for this population.Controlled-Trials.com ISRCTN17057980 http://www.controlled-trials.com/ISRCTN17057980.
Project description:Pneumonia is among the most common acute complications after stroke and is associated with poor long-term outcome. Biomarkers may help identifying stroke patients at high risk for developing stroke-associated pneumonia (SAP) and to guide early treatment.This trial investigated whether procalcitonin (PCT) ultrasensitive (PCTus)-guided antibiotic treatment of SAP can improve functional outcome after stroke.In this international, multicenter, randomized, controlled clinical trial with blinded assessment of outcomes, patients with severe ischemic stroke in the middle cerebral artery territory were randomly assigned within 40 h after symptom onset to PCTus-based antibiotic therapy guidance in addition to stroke unit care or standard stroke unit care alone. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale (mRS) and dichotomized as acceptable (≤4) or unacceptable (≥5). Secondary endpoints included usage of antibiotics, infection rates, days of fever, and mortality. The trial was registered with http://ClinicalTrials.gov (Identifier NCT01264549).In the intention-to-treat-analysis based on 227 patients (112 in PCT and 115 in control group), 197 patients completed the 3-month follow-up. Adherence to PCT guidance was 65%. PCT-guided therapy did not improve functional outcome as measured by mRS (odds ratio 0.79; 95% confidence interval 0.45-1.35, p = 0.47). Pneumonia rate and mortality were similar in both groups. Days with fever tended to be lower (p = 0.055), whereas total number of days treated with antibiotics were higher (p = 0.004) in PCT compared to control group. A post hoc analysis including all PCT values in the intention-to-treat population demonstrated a significant increase on the first day of infection in patients with pneumonia and sepsis compared to patients with urinary tract infections or without infections (p < 0.0001).PCTus-guided antibiotic therapy did not improve functional outcome at 3 months after severe ischemic stroke. PCT is a promising biomarker for early detection of pneumonia and sepsis in acute stroke patients.
Project description:In randomised controlled trials, procalcitonin (PCT)-guided antibiotic treatment has been proven to significantly reduce length of antibiotic therapy in intensive care unit (ICU) patients. However, concern was raised on low protocol adherence and high rates of overruling, and thus the value of PCT-guided treatment in real clinical life outside study conditions remains unclear. In this study, adherence to a PCT protocol to guide antibiotic treatment in patients with severe sepsis and septic shock was analysed.From 2012 to 2014, surgical ICU patients with severe sepsis or septic shock were retrospectively screened for PCT measurement series appropriate to make treatment decisions on antibiotic therapy. We compared (1) patients with appropriate PCT measurement series to patients without appropriate series; (2) patients who reached the antibiotic stopping advice threshold (PCT?<?0.5 ng/mL and/or decrease to 10% of peak level) to patients who did not reach a stopping advice threshold; and (3) patients who were treated adherently to the PCT protocol to non-adherently treated patients. The groups were compared in terms of antibiotic treatment duration, PCT kinetics, and other clinical outcomes.Of 81 patients with severe sepsis or septic shock, 14 were excluded due to treatment restriction or short course in the ICU. The final analysis was performed on 67 patients. Forty-two patients (62.7%) had appropriate PCT measurement series. In patients with appropriate PCT series, median initial PCT (p?=?0.001) and peak PCT levels (p?<?0.001) were significantly higher compared to those with non-appropriate series. In 26 patients with appropriate series, PCT levels reached an antibiotic stopping advice. In 8 of 26 patients with stopping advice, antibiotics were discontinued adherently to the PCT protocol (30.8%). Patients with adherently discontinued antibiotics had a shorter antibiotic treatment (7d [IQR 6-9] vs. 12d [IQR 9-16]; p?=?0.002). No differences were seen in terms of other clinical outcomes.In patients with severe sepsis and septic shock, procalcitonin testing was irregular and adherence to a local PCT protocol was low in real clinical life. However, adherently treated patients had a shorter duration of antibiotic treatment without negative clinical outcomes. Procalcitonin peak values and kinetics had a clear impact on the regularity of PCT testing.