Procalcitonin Algorithm Research Articles

Biomarker guided antibiotic stewardship in community acquired pneumonia: A randomized controlled trial.

In community-acquired pneumonia (CAP), the role of biomarkers to shorten duration of antibiotic treatment has not been firmly established. We assessed the effectiveness of active feedback of treatment algorithms based on procalcitonin (PCT) and C-reactive protein (CRP), compared to standard care, on the duration of antibiotic treatment in patients hospitalized with community-acquired pneumonia (CAP) in non-ICU wards. We performed a randomised, open label, parallel group, multi-centre trial in 3 Dutch teaching hospitals. Treatment was guided by a PCT algorithm, CRP algorithm or standard care. Participants were recruited by a member of the study team and randomised at day 2-3 of admission in a 1:1:1 ratio. Treatment was discontinued upon predefined thresholds of biomarkers that were assessed on admission, day 4 and days 5-7 if indicated. The primary outcome was total days on antibiotic treatment until day 30. In total 468 participants were included in this study. The median days on antibiotics (IQR) was 7 (IQR 7-10) in the control group, 4 (IQR 3-7) in the CRP group (rate ratio (RR) of 0.70, 95% CI 0.61-0.82 compared to standard care; p <0.001), and 5.5 (IQR 3-9) in the PCT group (RR of 0.78, 95% CI 0.68-0.89 compared to standard care; p <0.001). New antibiotics within the first 30 days were prescribed to 24, 23 and 35 patients in standard care, CRP and PCT groups, respectively. The hazard ratio for a new prescription in patients in the PCT group compared to standard care 1.63 (CI 0.97-2.75; p = 0.06). No difference in time to clinical stability or length of stay was found. A strategy of feedback of CRP-guided and PCT-guided treatment algorithms reduced the number of days on antibiotic in the first 30 days after hospital admission in non-ICU wards for CAP. The study was not powered to determine safety of shortening duration of antibiotic treatment. (NCT01964495).

The Role of Biomarkers in Influenza and COVID-19 Community-Acquired Pneumonia in Adults.

Pneumonia is a growing problem worldwide and remains an important cause of morbidity, hospitalizations, intensive care unit admission and mortality. Viruses are the causative agents in almost a fourth of cases of community-acquired pneumonia (CAP) in adults, with an important representation of influenza virus and SARS-CoV-2 pneumonia. Moreover, mixed viral and bacterial pneumonia is common and a risk factor for severity of disease. It is critical for clinicians the early identification of the pathogen causing infection to avoid inappropriate antibiotics, as well as to predict clinical outcomes. It has been extensively reported that biomarkers could be useful for these purposes. This review describe current evidence and provide recommendations about the use of biomarkers in influenza and SARS-CoV-2 pneumonia, focusing mainly on procalcitonin (PCT) and C-reactive protein (CRP). Evidence was based on a qualitative analysis of the available scientific literature (meta-analyses, randomized controlled trials, observational studies and clinical guidelines). Both PCT and CRP levels provide valuable information about the prognosis of influenza and SARS-CoV-2 pneumonia. Additionally, PCT levels, considered along with other clinical, radiological and laboratory data, are useful for early diagnosis of mixed viral and bacterial CAP, allowing the proper management of the disease and adequate antibiotics prescription. The authors propose a practical PCT algorithm for clinical decision-making to guide antibiotic initiation in cases of influenza and SARS-CoV-2 pneumonia. Further well-design studies are needed to validate PCT algorithm among these patients and to confirm whether other biomarkers are indeed useful as diagnostic or prognostic tools in viral pneumonia.

793. Procalcitonin-guided Antibiotic Stewardship Oversight Reduces Antibiotic Use and Adverse Outcomes for Patients Admitted with Pneumonia, Results from a Real-world Randomized Controlled Trial in US Hospitals

Abstract Background ProSAVE (NCT04158804) is the first prospective interventional RCT to address the effect of procalcitonin (PCT)-guidance in the setting of antimicrobial stewardship (ASP) oversight on clinical outcomes and antibiotics usage for patients admitted with pneumonia. Methods Analysis of the pilot cohort from a multicenter trial was conducted enrolling subjects admitted with pneumonia at three clinical sites (academic and community hospitals). Subjects meeting eligibility criteria were randomized 1:1 between the standard of care (SoC) versus PCT-guided ASP oversight (PCT arm); subjects were monitored daily by chart review for up to 30 days. An FDA-approved PCT algorithm was used to guide antimicrobial usage. 95 patients were enrolled as ITT of which 60 patients were assigned per-protocol who were adherent to the PCT algorithm (30 in SoC and 30 in the PCT arm). Primary study endpoints were antimicrobial usage and composite safety comprising readmission, death, intubation, septic shock, renal failure, and pneumonia complications such as empyema and abscess up to day 30. Results Baseline subject characteristics were similar between both arms; median age 73y (IQR: 62–86, heart disease (43% SoC vs. 40% PCT arm), and diabetes (23% SoC vs. 29% PCT arm). Early antimicrobial cessation by day 4 of hospitalization was achieved more often in the PCT arm as compared to SoC (ITT: SoC n=5, 11% vs. PCT arm n=14, 29%, p=0.045). In addition, antimicrobial prescription at discharge was lower in the intervention arm (ITT: SoC n=24, 51% vs. PCT arm n=15, 31%, p=0.08; similar and statistically significant efficacy for PP) (Fig 1, panel A). A substantial statistically significant improvement of safety was observed in the PCT arm compared to SoC (reduction by 18.3% (95%-CI: 2.3% – 36.3%) from 23.3% (11.9% – 41.1%, SoC) to 3.3% (0.8% – 16.7%, PCT arm) in PP, similar in ITT) (Fig 1, panel B). Readmission was the main driver for fewer safety events in the intervention arm (SoC 50% vs. PCT arm 33%). Conclusion In this pilot cohort of ProSAVE, the introduction of PCT-guided, ASP intervention to medical teams proved to be a successful aid for resourceful antibiotic management decisions resulting in shorter antibiotic durations and significantly lower adverse event rates. Disclosures Michael Mansour, MD, PhD, ThermoFisher Scientific: Grant/Research Support.

Procalcitonin: In diagnosis of paediatric infections

Although there are many diagnostic tests available for the diagnosis of infections, all have their own limitations with regard to time, sensitivity and specificity. As a result, there is an unnecessary and prolonged use of antibiotics, leading to multidrug resistance and antibiotic misuse. Increasing evidence supports the use of procalcitonin (PCT) in diagnosing bacterial infections as early as possible and titrating the antibiotics according to the dynamics of PCT value. PCT helps in the early diagnosis of the upper and lower respiratory tract infections, meningitis, post-operative cases, sepsis in intensive care units and the judicial use of antibiotics according to PCT algorithms. PCT is a reliable marker as compared to the other markers such as C-reactive protein, interleukin 1, 6, IF-gamma and tumour necrosis factor-alfa. PCT value is not affected by neutropenia, immunodeficiency disorders and with the use of steroid and non-steroid anti-inflammatory drugs. The aim of this review article is to summarise the current evidence for PCT in different infections and clinical settings and discusses the diagnostic and prognostic value of PCT in different types of infections, its limitations and the economics of usage of PCT.

Procalcitonin for sepsis management: Implementation within an antimicrobial stewardship program.

Clinical trials of procalcitonin (PCT)-based algorithms for antibacterial therapy have shown a reduction in antimicrobial use and improved survival. Translation of PCT algorithms to clinical settings has often been unsuccessful. We hypothesized that appropriate utilization of PCT could be improved by implementing an antimicrobial stewardship team (AST) approach to PCT testing. We completed a pre-post intervention evaluation of adult patients admitted to the intensive care unit with a diagnosis of sepsis. The standard PCT algorithm period (SPAP) cohort included patients enrolled before dedicated AST involvement. During the AST-supported PCT algorithm period (ASPAP), the AST reviewed and provided feedback for all appropriate patients. The primary outcome was adherence to the PCT algorithm. Thirty-five and 57 patients were evaluated in the SPAP and ASPAP cohorts, respectively. There were no differences in demographics or infection site between the groups. Baseline PCT assessment was ordered in a larger proportion of patients in the ASPAP cohort (90% vs 57%; P = 0.0006). Follow-up PCT measurement was performed in more patients in the ASPAP cohort (76% vs 23%; P < 0.0001). Antibiotics were discontinued per algorithm in more patients in the ASPAP cohort (25/57 [44%] vs 2/35 [7%]; P < 0.0001). Patients in the ASPAP cohort experienced a shorter total duration of antibiotics (5 vs 7 days; P = 0.02), with no significant difference in length of stay or 30-day readmission or mortality between the cohorts. A PCT algorithm successfully implemented by an AST was associated with a significant decrease in total antibiotic days with no differences in mortality or length of stay.

Procalcitonin-Guided Antibiotic Prescribing for Acute Exacerbations of Chronic Obstructive Pulmonary Disease in the Emergency Department.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) can be caused by viral, bacterial, or environmental factors. Recent studies have suggested that procalcitonin serum levels may help reduce unnecessary antibiotic use without statistically significant differences in rates of treatment failure for AECOPD. The purpose of this quality improvement project was to create a procalcitonin-based algorithm to aid emergency department (ED) clinicians in the management of patients with AECOPD who do not require hospitalization and to evaluate its efficacy and practicality. The primary outcome of this project was the rate of antibiotic prescriptions before and after the initiation of the algorithm. This study used an observational, retrospective, pre-and posteducation/intervention design. Clinicians were educated individually on the use of procalcitonin, and a copy of the algorithm was made available to each clinician and posted in the ED. Patients who were discharged from the ED with a diagnosis of an AECOPD were identified using International Classification of Diseases, Tenth Revision codes. Patient charts were reviewed from November 2018 to March 2019 for the preimplementation period and November 2019 to March 2020 for the postimplementation period. The rate of antibiotic prescriptions and the number of procalcitonin tests ordered before and after the introduction of the algorithm were analyzed. In addition, information on COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) grouping and 30-, 60-, and 90-day reexacerbation rates were collected. It was estimated that a sample size of 146 patients (73 patients/group) would provide 80% power to detect a between-group difference of 10% in the percentage of patients who were prescribed antibiotics. Categorical variables were expressed using estimates of their frequency and percentages. Percentages were compared using Fisher exact tests. For all tests, the significance level was set at 0.05. Seventy-three patients were included in the preintervention group, and 77 patients were included in the postintervention group. Patients in the preintervention and postintervention groups had similar representation in GOLD categories: 52% and 51% for D, 17.8% and 23.4% for C, 21.9% and 16.8% for B, and 8.2% and 7.8% for A, respectively. The rate of antibiotic prescriptions decreased by 20% after implementation from 83.6% before to 63.6% after implementation (P = .01). The differences in reexacerbation rates between the preintervention and postintervention groups were similar: 19.2% vs 23.4% at 30 days, 12.3% vs 11.7% at 60 days, and 4.1% vs 9.1% at 90 days, respectively. Prior to education and introduction of the procalcitonin algorithm, procalcitonin was ordered for 1.4% of AECOPD cases. Postimplementation, procalcitonin was ordered for 28.6% of AECOPD cases and used in clinical decision making 81.8% of the time. In this study of the implementation of a treatment algorithm for patients with mild and moderate AECOPD who present to the ED, procalcitonin was shown to reduce the rate of antibiotic prescriptions without an observable difference in reexacerbation rates 30, 60, and 90 days after presentation.

Procalcitonin to Reduce Antibiotic Exposure during Acute Chest Syndrome in Adult Patients with Sickle-Cell Disease.

Acute chest syndrome (ACS) is a major complication of sickle-cell disease. Bacterial infection is one cause of ACS, so current guidelines recommend the routine use of antibiotics. We performed a prospective before–after study in medical wards and an intensive-care unit (ICU). During the control phase, clinicians were blinded to procalcitonin concentration results. We built an algorithm using the obtained measurements to hasten antibiotic cessation after three days of treatment if bacterial infection was not documented, and procalcitonin concentrations were all <0.5 μg/L. During the intervention period, the procalcitonin algorithm was suggested to physicians as a guide for antibiotic therapy. The primary endpoint was the number of days alive without antibiotics at Day 21. One-hundred patients were analyzed (103 ACS episodes, 60 in intervention phase). Possible or proven lung infection was diagnosed during 13% of all ACS episodes. The number of days alive without antibiotics at Day 21 was higher during the intervention phase: 15 [14–18] vs. 13 [13,14] days (p = 0.001). More patients had a short (≤3 days) antibiotic course during intervention phase: 31% vs 9% (p = 0.01). There was neither infection relapse nor pulmonary superinfection in the entire cohort. A procalcitonin-guided strategy to prescribe antibiotics in patients with ACS may reduce antibiotic exposure with no apparent adverse outcomes.

Procalcitonin and lung ultrasound algorithm to diagnose severe pneumonia in critical paediatric patients (PROLUSP study). A randomised clinical trial

BackgroundLung ultrasound (LUS) in combination with a biomarker has not yet been studied. We propose a clinical trial where the primary aims are: 1. To assess whether an algorithm with LUS and procalcitonin (PCT) may be useful for diagnosing bacterial pneumonia; 2. To analyse the sensitivity and specificity of LUS vs chest X-ray (CXR).Methods/designA 3-year clinical trial. Inclusion criteria: children younger than 18 years old with suspected pneumonia in a Paediatric Intensive Care Unit. Patients will be randomised into two groups: Experimental Group: LUS will be performed as first lung image. Control Group: CXR will be performed as first pulmonary image. Patients will be classified according to the image and the PCT: a) PCT < 1 ng/mL and LUS/CXR are not suggestive of bacterial pneumonia (BN), no antibiotic will be prescribed; b) LUS/CXR are suggestive of BN, regardless of the PCT, antibiotic therapy is recommended; c) LUS/CXR is not suggestive of BN and PCT > 1 ng/mL, antibiotic therapy is recommended.ConclusionThis algorithm will help us to diagnose bacterial pneumonia and to prescribe the correct antibiotic treatment. A reduction of antibiotics per patient, of the treatment length, and of the exposure to ionizing radiation and in costs is expected.Trial registrationNCT04217980.

Hospital physicians\u2019 experiences with procalcitonin \u2013 implications for antimicrobial stewardship; a qualitative study

BackgroundProcalcitonin is an inflammatory biomarker that is sensitive for bacterial infections and a promising clinical decision aid in antimicrobial stewardship programs. However, there are few studies of physicians’ experiences concerning the use of PCT. The objective of this study was to investigate whether hospital physicians’ experience with procalcitonin after 18 months of use can inform the PCT implementation in antimicrobial stewardship programs.Materials/methodsWe deployed a qualitative approach using semi-structured interviews with 14 hospital physicians who had experience with procalcitonin in clinical practice. Interviews were audio-taped, transcribed verbatim and analysed using thematic analysis.ResultsPhysicians reported a knowledge gap, which made them uncertain about the appropriate procalcitonin use, interpretation, and trustworthiness. Simultaneously, the physicians experienced procalcitonin as a useful clinical decision aid but emphasised that their clinical evaluation of the patient was the most important factor when deciding on antibiotic treatment.ConclusionsProcalcitonin was regarded a helpful clinical tool, but the physicians called for more knowledge about its appropriate uses. Active implementation of unambiguous procalcitonin algorithms and physician education may enhance the utility of the test as an antimicrobial stewardship adjunct.

Impact of Pharmacist-Directed Simplified Procalcitonin Algorithm on Antibiotic Therapy in Critically Ill Patients With Sepsis.

The purpose was to determine whether a simplified procalcitonin (PCT) algorithm guided by pharmacist recommendations reduces antibiotic duration of therapy in critically ill patients with suspected sepsis. This was a single-centered pre-post study conducted at a 1368-bed community teaching hospital in the United States. A prospective cohort with pharmacist intervention utilizing a simplified PCT algorithm was compared with a retrospective historical cohort with standard therapy. Adult patients admitted to the intensive care unit (ICU) with suspected sepsis who received intravenous antibiotics were included. A pharmacist recommended continuation or discontinuation of antibiotics based on the PCT level per our algorithm and full clinical assessment of the patient. Primary outcome was total duration of antibiotic therapy. Secondary outcomes were ICU and hospital length of stay (LOS), reinitiation of antibiotic therapy within 72 hours of discontinuation, and 28-day in-hospital mortality. From September 2017 to May 2018, 360 patients were screened for eligibility. Of these, 26 patients were included in the PCT group and 26 patients in the standard therapy group. Baseline characteristics were similar between groups. A significant difference in duration of antibiotic therapy was detected with a median of 9 days in the PCT group versus 12 days in the standard therapy group (P = .02). There were no significant differences in secondary endpoints of ICU and hospital LOS, reinitiation of antibiotics at 72 hours, or 28-day mortality. Use of a simplified PCT algorithm with pharmacist-guided recommendations significantly reduced the duration of antibiotic therapy in critically ill patients with sepsis.

The Shapiro–Procalcitonin algorithm (SPA) as a decision tool for blood culture sampling: validation in a prospective cohort study

Blood cultures (BC) are the gold standard for bacteremia detection despite a relatively low diagnostic yield and high costs. A retrospective study reported high predictive values for BC positivity when combining the clinical Shapiro score with procalcitonin (PCT). Single-center, prospective cohort study between 01/2016 and 02/2017 to validate SPA algorithm, including a modified Shapiro score ≥ 3 points (S) PLUS admission PCT > 0.25µg/l (P), or presence of overruling safety criteria (A) in patients with systemic inflammatory response syndrome. The diagnostic yield of SPA compared to non-standardized clinical judgment in predicting BC positivity was calculated and results presented as odds ratios (OR) with 95% confidence intervals. Of 1438 patients with BC sampling, 215 (15%) had positive BC which increased to 31% (173/555) in patients fulfilling SP criteria (OR for BC positivity 9.07 [6.34-12.97]). When adding 194 patients with overruling safety criteria (i.e., SPA), OR increased to 11.12 (6.99-17.69), although BC positivity slightly decreased to 26%. With an area under the receiver operating curve of 0.742, SPA indicated better diagnostic performance than its individual components. Positive BC in 689 patients not fulfilling SPA (sampling according to non-standardized clinical judgment) were rare (3%; OR for BC positivity 0.09 [0.06-0.14]). Eight out of 21 missed pathogens were still identified by sampling the primary infection focus. This study validates the high predictive value of SPA for bacteremia, increasing true BC positivity from 15 to 26%. Restricting BC sampling to SPA would have reduced BC sampling by 48%, while still detecting 194/215 organisms (90%), which makes SPA a valuable diagnosticstewardship tool.

Procalcitonin (PCT)-guided antibiotic stewardship in Asia-Pacific countries: adaptation based on an expert consensus meeting

Introduction Recently, an expert consensus on optimal use of procalcitonin (PCT)-guided antibiotic stewardship was published focusing mainly on Europe and the United States. However, for Asia-Pacific countries, recommendations may need adaptation due to differences in types of infections, available resources and standard of clinical care. Methods Practical experience with PCT-guided antibiotic stewardship was discussed among experts from different countries, reflecting on the applicability of the proposed Berlin consensus algorithms for Asia-Pacific. Using a Delphi process, the group reached consensus on two PCT algorithms for the critically ill and the non-critically ill patient populations. Results The group agreed that the existing evidence for PCT-guided antibiotic stewardship in patients with acute respiratory infections and sepsis is generally valid also for Asia-Pacific countries, in regard to proposed PCT cut-offs, emphasis on diagnosis, prognosis and antibiotic stewardship, overruling criteria and inevitable adaptations to clinical settings. However, the group noted an insufficient database on patients with tropical diseases currently limiting the clinical utility in these patients. Also, due to lower resource availabilities, biomarker levels may be measured less frequently and only when changes in treatment are highly likely. Conclusions Use of PCT to guide antibiotic stewardship in conjunction with continuous education and regular feedback to all stakeholders has high potential to improve the utilization of antibiotic treatment also in Asia-Pacific countries. However, there is need for adaptations of existing algorithms due to differences in types of infections and routine clinical care. Further research is needed to understand the optimal use of PCT in patients with tropical diseases.

2005. Successful Implementation of a Procalcitonin Algorithm Associated with Reduction in Antibiotic Days

BackgroundRandomized controlled trials of procalcitonin (PCT)-based algorithms for antibacterial therapy have been shown to reduce antimicrobial use and improve survival. Translation of PCT algorithms to clinical settings has often been unsuccessful.MethodsWe implemented a PCT algorithm, supported by focus groups prior to introduction of the PCT test in April 2016 and clinician training on the PCT algorithm for testing and antimicrobial management after test roll-out. The standard PCT algorithm period (SPAP) was defined as October 1, 2017 to March 31, 2018. The antimicrobial stewardship team (AST) initiated an AST-supported PCT algorithm (ASPA) in August 2018. The AST prospectively evaluated patients admitted to ICU for sepsis and ordered PCT per algorithm if the primary medical team had not ordered them. The ASPA period was defined as October 1, 2018–March 31, 2019. The AST conducted concurrent review and feedback for all antibiotic orders during both periods, using PCT result when available. We compared patient characteristics and outcomes between the two periods. The primary outcome was adherence to the PCT algorithm, with subcomponents of appropriate PCT orders and antimicrobial discontinuation. Secondary outcomes were total antibiotic days, excess antibiotic days avoided, ICU and hospital length of stay (LOS), 30-day readmission and mortality. Continuous variables were analyzed with Student t-test. Categorical variables were analyzed with chi-square or Mann–Whitney test, as appropriate.ResultsThere were 35 cases in the SPAP cohort and 57 cases in the ASPA cohort. There were no differences in demographics or infection site (Table 1). Baseline PCT was ordered in 57% of the SPAP cohort and 90% of the ASPA cohort (P = 0.0006) (Table 2). Follow-up PCT was performed in 23% of SPAP and 76% of ASPA (P < 0.0001). Antibiotics were discontinued per algorithm in 2/35 (7%) in the SPAP cohort and 25/57 (44%) in the ASPA cohort (P < 0.0001). Total antibiotic days was 7 (IQR 4–10) in the SPAP cohort and 5 (IQR 2–7) in the ASPA cohort (P = 0.02). There was no significant difference in LOS, ICU LOS, 30-day readmission, or mortality (Table 4).ConclusionA PCT algorithm successfully implemented by an AST was associated with a significant decrease in total antibiotic days. There were no differences in mortality or LOS. Disclosures All authors: No reported disclosures.

1336. Impact of Procalcitonin-Guided Antibiotic Management in Chronic Obstructive Pulmonary Disease Exacerbation and Community-Acquired Pneumonia

BackgroundChronic obstructive pulmonary disease (COPD) exacerbation and community-acquired pneumonia (CAP) are major drivers of antibiotic overuse, primarily due to challenges in pathogen identification. Procalcitonin is a serum biomarker that assists in distinguishing bacterial infection from other causes. The purpose of this study was to determine whether the use of a procalcitonin (PCT) guided algorithm in patients diagnosed with COPD exacerbation and/or CAP can reduce antibiotic exposure without negatively impacting clinical outcomes.MethodsThis was a quasi-experimental study conducted at Mercy Medical Center in Canton, Ohio. The patient data for the retrospective cohort (control group) was collected from the months of September 2017 through January 2018. The prospective phase (PCT group) took place during the months of September 2018 through January 2019. Physicians utilized a procalcitonin guided algorithm to determine appropriate initiation and duration of antibiotic use in patients admitted with a primary diagnosis of COPD exacerbation and/or CAP. The primary outcome was the duration of antibiotic therapy, measured in days. Secondary outcomes included all-cause hospital readmission within 30 days of discharge, respiratory-related hospital readmission within 30 days of discharge, 30-day mortality, hospital length of stay, and adverse events to antibiotics.ResultsA total of 76 patients were included in the study, 43 in the control group and 33 in the PCT group. Baseline characteristics were similar between groups. The use of a PCT algorithm significantly decreased duration of antibiotics by 2.7 days in comparison to the control group (2.6 [n = 33] vs. 5.3 [n = 43] days; P < 0.001; 95% CI). Secondary safety outcomes between the PCT and control group were similar, including all-cause hospital readmission within 30 days of discharge (30.3% vs. 25.6%; P = 0.648), respiratory-related hospital readmission within 30 days of discharge (80.0% [n = 10] vs. 81.8% [n = 11]; P = 0.731), and 30-day mortality (no incidence in either group).ConclusionThe use of a PCT algorithm significantly reduced duration of antibiotics by 2.7 days without negatively impacting clinical outcomes in patients being treated for COPD exacerbation and/or CAP. Disclosures All authors: No reported disclosures.

Cost-Effectiveness Analysis of a Procalcitonin-Guided Decision Algorithm for Antibiotic Stewardship Using Real-World U.S. Hospital Data.

Medical decision-making is revolutionizing with the introduction of artificial intelligence and machine learning. Yet, traditional algorithms using biomarkers to optimize drug treatment continue to be important and necessary. In this context, early diagnosis and rational antimicrobial therapy of sepsis and lower respiratory tract infections (LRTI) are vital to prevent morbidity and mortality. In this study we report an original cost-effectiveness analysis (CEA) of using a procalcitonin (PCT)-based decision algorithm to guide antibiotic prescription for hospitalized sepsis and LRTI patients versus standard care. We conducted a CEA using a decision-tree model before and after the implementation of PCT-guided antibiotic stewardship (ABS) using real-world U.S. hospital-specific data. The CEA included societal and hospital perspectives with the time horizon covering the length of hospital stay. The main outcomes were average total costs per patient, and numbers of patients with Clostridium difficile and antibiotic resistance (ABR) infections. We found that health care with the PCT decision algorithm for hospitalized sepsis and LRTI patients resulted in shorter length of stay, reduced antibiotic use, fewer mechanical ventilation days, and lower numbers of patients with C. difficile and ABR infections. The PCT-guided health care resulted in cost savings of $25,611 (49% reduction from standard care) for sepsis and $3630 (23% reduction) for LRTI, on average per patient. In conclusion, the PCT decision algorithm for ABS in sepsis and LRTI might offer cost savings in comparison with standard care in a U.S. hospital context. To the best of our knowledge, this is the first health economic analysis on PCT implementation using U.S. real-world data. We suggest that future CEA studies in other U.S. and worldwide settings are warranted in the current age when PCT and other decision algorithms are increasingly deployed in precision therapeutics and evidence-based medicine.

PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP): study protocol for a randomised controlled trial

BackgroundDifferentiating infection from inflammation in acute pancreatitis is difficult, leading to overuse of antibiotics. Procalcitonin (PCT) measurement is a means of distinguishing infection from inflammation as levels rise rapidly in response to a pro-inflammatory stimulus of bacterial origin and normally fall after successful treatment. Algorithms based on PCT measurement can differentiate bacterial sepsis from a systemic inflammatory response. The PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP) trial tests the hypothesis that a PCT-based algorithm to guide initiation, continuation and discontinuation of antibiotics will lead to reduced antibiotic use in patients with acute pancreatitis and without an adverse effect on outcome.MethodsThis is a single-centre, randomised, controlled, single-blind, two-arm pragmatic clinical and cost-effectiveness trial. Patients with a clinical diagnosis of acute pancreatitis will be allocated on a 1:1 basis to intervention or standard care. Intervention will involve the use of a PCT-based algorithm to guide antibiotic use. The primary outcome measure will be the binary outcome of antibiotic use during index admission. Secondary outcome measures include: safety non-inferiority endpoint all-cause mortality; days of antibiotic use; clinical infections; new isolates of multiresistant bacteria; duration of inpatient stay; episode-related mortality and cause; quality of life (EuroQol EQ-5D); and cost analysis. A 20% absolute change in antibiotic use would be a clinically important difference. A study with 80% power and 5% significance (two-sided) would require 97 patients in each arm (194 patients in total): the study will aim to recruit 200 patients. Analysis will follow intention-to-treat principles.DiscussionWhen complete, PROCAP will be the largest randomised trial of the use of a PCT algorithm to guide initiation, continuation and cessation of antibiotics in acute pancreatitis. PROCAP is the only randomised trial to date to compare standard care of acute pancreatitis as defined by the International Association of Pancreatology/American Pancreatic Association guidelines to patients having standard care but with all antibiotic prescribing decisions based on PCT measurement.Trial registrationInternational Standard Randomised Controlled Trial Number, ISRCTN50584992. Registered on 7 February 2018.

Method Verification Shows a Negative Bias between 2 Procalcitonin Methods at Medical Decision Concentrations.

Procalcitonin (PCT) concentration increases as a result of systemic inflammation owing to bacterial infection. Many PCT algorithms and medical decision concentrations (MDCs) have been clinically validated using the B·R·A·H·M·S PCT™ sensitive Kryptor™ assay. Alternative PCT assays have recently been approved by the Food and Drug Administration for clinical use in the US and require method verification before clinical implementation. Precision, sensitivity, linearity, reportable range, and reference intervals were verified for the Architect B·R·A·H·M·S PCT assay. Accuracy of the Architect B·R·A·H·M·S PCT assay was evaluated by comparison with the B·R·A·H·M·S PCT sensitive Kryptor assay. The Architect B·R·A·H·M·S PCT assay was found to be precise (CV, ≤4.6%), sensitive (limit of blank, 0.001 ng/mL; limit of quantitation, ≤0.01 ng/mL), and linear according to the manufacturer's claims. The analytical measurement range (0.20-100.00 ng/mL) and the reference interval (≤0.07 ng/mL) were also verified. Patient result comparisons indicated high agreement at 0.10 ng/mL and 0.25 ng/mL and reduced positive agreement at 0.50 ng/mL and 2.00 ng/mL MDCs owing to negative bias compared with the B·R·A·H·M·S PCT sensitive Kryptor assay. The Architect B·R·A·H·M·S PCT assay meets most performance specifications claimed by the manufacturer; however, negative bias at 0.50 ng/mL and 2.00 ng/mL PCT concentrations is evident.

Adhering to the procalcitonin algorithm allows antibiotic therapy to be shortened in patients with ventilator-associated pneumonia

PurposeVentilator-associated pneumonia (VAP) increases exposure to antibiotics. Physicians are however reluctant to shorten treatment, arguing this could lead to failures and worse outcome. Monitoring procalcitonin (PCT) has proven effective for decreasing exposure to antibiotics in randomized controlled trials, but additional “real-life” studies are needed. Materials and methodsAll patients with VAP in whom ABT was stopped before death or discharge were included in this 5-year prospective cohort study. Patients in whom ABT was stopped in accordance with the algorithm (“PCT-guided” group: ABT withdrawal strongly encouraged if PCT < 0.5 ng/mL or < 80% peak value) were compared to those with ABT continuation despite PCT decrease (“not PCT-guided” group). The primary endpoint was ABT duration. The secondary endpoint was unfavorable VAP outcome (i.e. death or relapse). ResultsWe included 157 of the 316 patients with microbiologically-proven VAP. The algorithm was overruled in 81 patients (51.6%). ABT duration was significantly longer in these patients than in the PCT-guided group (9.5 vs. 8.0 days; p = .02), although baseline and VAP characteristics did not differ. The rate of unfavorable outcomes was comparable (46.9% vs. 51.3%; p = .69). ConclusionsPCT-guided ABT adherence appears safe for patients with VAP and is likely to reduce exposure to antibiotics.

Guideline-Based Clinical Assessment Versus Procalcitonin-Guided Antibiotic Use in Pneumonia: A Pragmatic Randomized Trial

Efforts to reduce unnecessary and unnecessarily long antibiotic treatment for community-acquired pneumonia have been attempted through use of procalcitonin and through guidelines based on serial clinical assessment. Our aim is to compare guideline-based clinical assessment- and procalcitonin algorithm-guided antibiotic use among patients with community-acquired pneumonia. We performed a pragmatic, randomized, multicenter trial from November 2012 to April 2015 at 12 French hospitals. We included emergency department (ED) patients older than 18 years with community-acquired pneumonia. Patients were randomly assigned to either the procalcitonin-guided or clinical assessment group. In accordance with past studies, we hypothesized that serial clinical assessment would be superior to procalcitonin-guided care. The primary outcome was antibiotic duration, and secondary outcomes included rates of antibiotic duration less than or equal to 5 days, and clinical success and combined serious adverse outcomes at 30 days in the intention-to-treat population. Of 370 eligible patients, 285 (77%) were randomly assigned to either clinical assessment- (n=143) or procalcitonin-guided care (n=142). Median age was 67 years (range 18 to 93 years) and 40% of patients were deemed to have Pneumonia Severity Index class IV or V. Procalcitonin algorithm adherence was 76%. Antibiotic duration was not significantly different between clinical assessment- and procalcitonin-guided groups (median 9 versus 10 days, respectively). Clinical success rate was 92% in each group and serious adverse outcome rates were similar (15% versus 20%, respectively). Guideline-based serial clinical assessment did not reduce antibiotic exposure compared with procalcitonin-guided care among ED patients with community-acquired pneumonia. The strategies were similar in terms of duration of antibiotic use and clinical outcomes.

Procalcitonin (PCT)-guided antibiotic stewardship: an international experts consensus on optimized clinical use.

Background Procalcitonin (PCT)-guided antibiotic stewardship (ABS) has been shown to reduce antibiotics (ABxs), with lower side-effects and an improvement in clinical outcomes. The aim of this experts workshop was to derive a PCT algorithm ABS for easier implementation into clinical routine across different clinical settings. Methods Clinical evidence and practical experience with PCT-guided ABS was analyzed and discussed, with a focus on optimal PCT use in the clinical context and increased adherence to PCT protocols. Using a Delphi process, the experts group reached consensus on different PCT algorithms based on clinical severity of the patient and probability of bacterial infection. Results The group agreed that there is strong evidence that PCT-guided ABS supports individual decisions on initiation and duration of ABx treatment in patients with acute respiratory infections and sepsis from any source, thereby reducing overall ABx exposure and associated side effects, and improving clinical outcomes. To simplify practical application, the expert group refined the established PCT algorithms by incorporating severity of illness and probability of bacterial infection and reducing the fixed cut-offs to only one for mild to moderate and one for severe disease (0.25 μg/L and 0.5 μg/L, respectively). Further, guidance on interpretation of PCT results to initiate, withhold or discontinue ABx treatment was included. Conclusions A combination of clinical patient assessment with PCT levels in well-defined ABS algorithms, in context with continuous education and regular feedback to all ABS stakeholders, has the potential to improve the diagnostic and therapeutic management of patients suspected of bacterial infection, thereby improving ABS effectiveness.