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.

Clinical use of [TIMP-2]•[IGFBP7] biomarker testing to assess risk of acute kidney injury in critical care: guidance from an expert panel.

BACKGROUND: The first FDA-approved test to assess risk for acute kidney injury (AKI), [TIMP-2]•[IGFBP7], is clinically available in many parts of the world, including the USA and Europe. We sought to understand how the test is currently being used clinically. METHODS: We invited a group of experts knowledgeable on the utility of this test for kidney injury to a panel discussion regarding the appropriate use of the test. Specifically, we wanted to identify which patients would be appropriate for testing, how the results are interpreted, and what actions would be taken based on the results of the test. We used a modified Delphi method to prioritize specific populations for testing and actions based on biomarker test results. No attempt was made to evaluate the evidence in support of various actions however. RESULTS: Our results indicate that clinical experts have developed similar practice patterns for use of the [TIMP-2]•[IGFBP7] test in Europe and North America. Patients undergoing major surgery (both cardiac and non-cardiac), those who were hemodynamically unstable, or those with sepsis appear to be priority patient populations for testing kidney stress. It was agreed that, in patients who tested positive, management of potentially nephrotoxic drugs and fluids would be a priority. Patients who tested negative may be candidates for "fast-track" protocols. CONCLUSION: In the experience of our expert panel, biomarker testing has been a priority after major surgery, hemodynamic instability, or sepsis. Our panel members reported that a positive test prompts management of nephrotoxic drugs as well as fluids, while patients with negative results are considered to be excellent candidates for "fast-track" protocols.

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.

Real-world use of procalcitonin and other biomarkers among sepsis hospitalizations in the United States: A retrospective, observational study.

BACKGROUND: Sepsis management guidelines endorse use of biomarkers to support clinical assessment and treatment decisions in septic patients. The impact of biomarkers on improving patient outcomes remains uncertain. METHODS: Retrospective observational study of adult sepsis discharges between January 1, 2012, and December 31, 2015, from Premier Healthcare Database hospitals. Sepsis was defined by an All Patients Refined Diagnosis-Related Group code of 720 (septicemia and disseminated infections). Use of four biomarker strategies was evaluated based on hospital records: (i) >1 procalcitonin (PCT), (ii) 1 PCT, (iii) no PCT but ≥1 C-reactive protein (CRP) and/or lactate and (iv) no sepsis biomarkers. Associations between biomarker use and clinical and cost outcomes were examined. The primary outcome was impact of biomarker strategy on hospital costs per day. RESULTS: Among 933,591 adult sepsis discharges during the study period, 731,392 (78%) had biomarker tests ordered. In multivariable analyses, discharges with >1 PCT had higher hospital costs per day ($1,904; 95% confidence interval [CI] $1,896-$1,911) compared with discharges with no sepsis biomarkers ($1,606; 95% CI $1,658-$1,664). Discharges with >1 PCT also had greater illness severity and antimicrobial exposure compared with other biomarker-use groups. The adjusted odds of dying during hospital stay compared with being discharged were significantly lower for sepsis discharges with >1 PCT (0.64; 95% CI 0.61-0.67) and 1 PCT (0.88; 95% CI 0.85-0.91) compared with no sepsis biomarker use. The proportion of discharges with ≥1 PCT increased almost six-fold during the study; use of other biomarkers remained constant. CONCLUSIONS: Between 2012 and 2015, PCT use among sepsis discharges increased six-fold while lactate and CRP use remained unchanged. PCT use was associated with decreased odds of in-hospital mortality but increased hospital costs per day. Serial biomarker monitoring may be associated with improved patient outcomes in the most critically ill septic patients.

Procalcitonin decrease over 72 hours in US critical care units predicts fatal outcome in sepsis patients.

INTRODUCTION: Close monitoring and repeated risk assessment of sepsis patients in the intensive care unit (ICU) is important for decisions regarding care intensification or early discharge to the ward. We studied whether considering plasma kinetics of procalcitonin, a biomarker of systemic bacterial infection, over the first 72 critical care hours improved mortality prognostication of septic patients from two US settings. METHODS: This retrospective analysis included consecutively treated eligible adults with a diagnosis of sepsis from critical care units in two independent institutions in Clearwater, FL and Chicago, IL. Cohorts were used for derivation or validation to study the association between procalcitonin change over the first 72 critical care hours and mortality. RESULTS: ICU/in-hospital mortality rates were 29.2%/31.8% in the derivation cohort (n=154) and 17.6%/29.4% in the validation cohort (n=102). In logistic regression analysis of both cohorts, procalcitonin change was strongly associated with ICU and in-hospital mortality independent of clinical risk scores (Acute Physiology, Age and Chronic Health Evaluation IV or Simplified Acute Physiology Score II), with area under the curve (AUC) from 0.67 to 0.71. When procalcitonin decreased by at least 80%, the negative predictive value for ICU/in-hospital mortality was 90%/90% in the derivation cohort, and 91%/79% in the validation cohort. When procalcitonin showed no decrease or increased, the respective positive predictive values were 48%/48% and 36%/52%. DISCUSSION: In septic patients, procalcitonin kinetics over the first 72 critical care hours provide prognostic information beyond that available from clinical risk scores. If these observations are confirmed, procalcitonin monitoring may assist physician decision-making regarding care intensification or early transfer from the ICU to the floor.

Success of a comprehensive school-based asthma intervention on clinical markers and resource utilization for inner-city children with asthma in Chicago: the Mobile C.A.R.E. Foundation's asthma management program.

Children with asthma in low-income households in Chicago were participants in a school-based mobile van clinic, Mobile C.A.R.E. Our objective was to investigate whether long-term follow-up changed clinical markers and resource utilization. Children were evaluated by a pediatrician in a mobile allergy clinic and classified and treated based on National Asthma Education and Prevention Program (NAEPP) guidelines. Intervention consisted of assessment of allergic environment with avoidance recommendations, institution of appropriate controller therapy and inhaler technique, education on asthma and asthma management, and expectations for asthma control. Over 20,000 children were screened, 2041 were examined at least once, and 677 children had four follow-up visits. With follow-up, there was a decrease in hospitalizations and emergency room visits. Symptomatic markers (daytime and nighttime cough, wheezing, and dyspnea symptoms), frequency of rescue inhaler use, and a quality-of-life score improved from baseline. These findings suggest that ongoing school interventions may reduce resource utilization and improve clinical symptoms. Primary care physicians may be able to deliver specialized care to large numbers of inner-city children with asthma.

Discussing life-sustaining treatments: an overview and communications guide for primary care physicians.

Physicians must be skilled communicators with patients, families, and multidisciplinary health care teams to meet ethical decision-making challenges arising in end-stage disease care. We offer practical suggestions for collaborative communication in the "perfect storm" of contemporary critical care settings.