Using Procalcitonin to Guide Antibiotic Therapy

Abstract Procalcitonin levels rise in response to systemic inflammation, especially of bacterial origin. Multiple randomized controlled trials have demonstrated that procalcitonin-based algorithms can safely reduce antibiotic use in 2 clinical scenarios. First, in stable, low-risk patients with respiratory infections, procalcitonin levels of <0.25 µg/L can guide the decision to withhold antibiotics or stop therapy early. Second, in critically ill patients with suspected sepsis, clinicians should not initially withhold antibiotics, but procalcitonin levels of <0.5 µg/L or levels that decrease by ≥80% from peak can guide discontinuation once patients stabilize. The recent stop antibiotics on procalcitonin guidance study (SAPS), the largest procalcitonin trial to date, demonstrated reduction in both antibiotic exposure and mortality in critically ill patients. Although procalcitonin is ready for routine use, future research should examine optimal strategies for implementation in hospitals, its real-world impact on clinical outcomes and costs, its applicability to immunocompromised patients, and the generalizability of trials to the US population

Prevalence, underlying causes, and preventability of sepsis-associated mortality in US acute care hospitals

Importance: Sepsis is present in many hospitalizations that culminate in death. The contribution of sepsis to these deaths, and the extent to which they are preventable, is unknown. Objective: To estimate the prevalence, underlying causes, and preventability of sepsis-associated mortality in acute care hospitals. Design, Setting, and Participants: Cohort study in which a retrospective medical record review was conducted of 568 randomly selected adults admitted to 6 US academic and community hospitals from January 1, 2014, to December 31, 2015, who died in the hospital or were discharged to hospice and not readmitted. Medical records were reviewed from January 1, 2017, to March 31, 2018. Main Outcomes and Measures: Clinicians reviewed cases for sepsis during hospitalization using Sepsis-3 criteria, hospice-qualifying criteria on admission, immediate and underlying causes of death, and suboptimal sepsis-related care such as inappropriate or delayed antibiotics, inadequate source control, or other medical errors. The preventability of each sepsis-associated death was rated on a 6-point Likert scale. Results: The study cohort included 568 patients (289 [50.9%] men; mean [SD] age, 70.5 [16.1] years) who died in the hospital or were discharged to hospice. Sepsis was present in 300 hospitalizations (52.8%; 95% CI, 48.6%-57.0%) and was the immediate cause of death in 198 cases (34.9%; 95% CI, 30.9%-38.9%). The next most common immediate causes of death were progressive cancer (92 [16.2%]) and heart failure (39 [6.9%]). The most common underlying causes of death in patients with sepsis were solid cancer (63 of 300 [21.0%]), chronic heart disease (46 of 300 [15.3%]), hematologic cancer (31 of 300 [10.3%]), dementia (29 of 300 [9.7%]), and chronic lung disease (27 of 300 [9.0%]). Hospice-qualifying conditions were present on admission in 121 of 300 sepsis-associated deaths (40.3%; 95% CI 34.7%-46.1%), most commonly end-stage cancer. Suboptimal care, most commonly delays in antibiotics, was identified in 68 of 300 sepsis-associated deaths (22.7%). However, only 11 sepsis-associated deaths (3.7%) were judged definitely or moderately likely preventable; another 25 sepsis-associated deaths (8.3%) were considered possibly preventable. Conclusions and Relevance: In this cohort from 6 US hospitals, sepsis was the most common immediate cause of death. However, most underlying causes of death were related to severe chronic comorbidities and most sepsis-associated deaths were unlikely to be preventable through better hospital-based care. Further innovations in the prevention and care of underlying conditions may be necessary before a major reduction in sepsis-associated deaths can be achieved

Improving documentation and coding for acute organ dysfunction biases estimates of changing sepsis severity and burden: a retrospective study

Introduction: Claims-based analyses report that the incidence of sepsis-associated organ dysfunction is increasing. We examined whether coding practices for acute organ dysfunction are changing over time and if so, whether this is biasing estimates of rising severe sepsis incidence and severity. Methods: We assessed trends from 2005 to 2013 in the annual sensitivity and incidence of discharge ICD-9-CM codes for organ dysfunction (shock, respiratory failure, acute kidney failure, acidosis, hepatitis, coagulopathy, and thrombocytopenia) relative to standardized clinical criteria (use of vasopressors/inotropes, mechanical ventilation for ≥2 consecutive days, rise in baseline creatinine, low pH, elevated transaminases or bilirubin, abnormal international normalized ratio or low fibrinogen, and decline in platelets). We studied all adult patients with suspected infection (defined by ≥1 blood culture order) at two US academic hospitals. Results: Acute organ dysfunction codes were present in 57,273 of 191,695 (29.9 %) hospitalizations with suspected infection, most commonly acute kidney failure (60.2 % of cases) and respiratory failure (28.9 %). The sensitivity of all organ dysfunction codes except thrombocytopenia increased significantly over time. This was most pronounced for acute kidney failure codes, which increased in sensitivity from 59.3 % in 2005 to 87.5 % in 2013 relative to a fixed definition for changes in creatinine (p = 0.019 for linear trend). Acute kidney failure codes were increasingly assigned to patients with smaller creatinine changes: the average peak creatinine change associated with a code was 1.99 mg/dL in 2005 versus 1.49 mg/dL in 2013 (p <0.001 for linear decline). The mean number of dysfunctional organs in patients with suspected infection increased from 0.32 to 0.59 using discharge codes versus 0.69 to 0.79 using clinical criteria (p <0.001 for both trends and comparison of the two trends). The annual incidence of hospitalizations with suspected infection and any dysfunctional organ rose an average of 5.9 % per year (95 % CI 4.3, 7.4 %) using discharge codes versus only 1.1 % (95 % CI 0.1, 2.0 %) using clinical criteria. Conclusions: Coding for acute organ dysfunction is becoming increasingly sensitive and the clinical threshold to code patients for certain kinds of organ dysfunction is decreasing. This accounts for much of the apparent rise in severe sepsis incidence and severity imputed from claims

Frequency and Types of Healthcare Encounters in the Week Preceding a Sepsis Hospitalization: A Systematic Review

OBJECTIVES: Early recognition and treatment are critical to improving sepsis outcomes. We sought to identify the frequency and types of encounters that patients have with the healthcare system in the week prior to a sepsis hospitalization. DATA SOURCES: PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, and the Cochrane Library. STUDY SELECTION: Observational cohort studies of patients hospitalized with sepsis or septic shock that were assessed for an outpatient or emergency department encounter with the healthcare system in the week prior to hospital admission. DATA EXTRACTION: The primary outcome was the proportion of patients with a healthcare encounter in the time period assessed (up to 1 week) prior to a hospitalization with sepsis. DATA SYNTHESIS: Six retrospective observational studies encompassing 6,785,728 sepsis admissions were included for evaluation, ranging from a 263-patient single-center cohort to a large database evaluating 6,731,827 sepsis admissions. The average (unweighted) proportion of patients having an encounter with the healthcare system in the week prior to a sepsis hospitalization was 32.7% and ranged from 10.3% to 52.9%. These encounters commonly involved presentation or potential symptoms of infectious diseases, antibiotic prescriptions, and appeared to increase in frequency closer to a sepsis hospitalization admission. No consistent factors were identified that distinguished a healthcare encounter as more or less likely to precede a sepsis hospitalization in the subsequent week. CONCLUSIONS: Patients that present to the hospital with sepsis are frequently evaluated in the healthcare system in the week prior to admission. Further research is necessary to understand if these encounters offer earlier opportunities for intervention to prevent the transition from infection to sepsis, whether they merely reflect the comorbidities of sepsis patients with a high baseline rate of healthcare encounters, or the declining trajectory of a patient\u27s overall health in response to infection

A modified Delphi approach to develop a trial protocol for antibiotic de-escalation in patients with suspected sepsis

Background: Early administration of antibiotics in sepsis is associated with improved patient outcomes, but safe and generalizable approaches to de-escalate or discontinue antibiotics after suspected sepsis events are unknown. Methods: We used a modified Delphi approach to identify safety criteria for an opt-out protocol to guide de-escalation or discontinuation of antibiotic therapy after 72 hours in non-ICU patients with suspected sepsis. An expert panel with expertise in antimicrobial stewardship and hospital epidemiology rated 48 unique criteria across 3 electronic survey rating tools. Criteria were rated primarily based on their impact on patient safety and feasibility for extraction from electronic health record review. The 48 unique criteria were rated by anonymous electronic survey tools, and the results were fed back to the expert panel participants. Consensus was achieved to either retain or remove each criterion. Results: After 3 rounds, 22 unique criteria remained as part of the opt-out safety checklist. These criteria included high-risk comorbidities, signs of severe illness, lack of cultures during sepsis work-up or antibiotic use prior to blood cultures, or ongoing signs and symptoms of infection. Conclusions: The modified Delphi approach is a useful method to achieve expert-level consensus in the absence of evidence suifficient to provide validated guidance. The Delphi approach allowed for flexibility in development of an opt-out trial protocol for sepsis antibiotic de-escalation. The utility of this protocol should be evaluated in a randomized controlled trial