Improving Sepsis Outcomes in the Era of Pay-for-Performance and Electronic Quality Measures: A Joint IDSA/ACEP/PIDS/SHEA/SHM/SIDP Position Paper.

The Centers for Medicare & Medicaid Services (CMS) introduced the Severe Sepsis/Septic Shock Management Bundle (SEP-1) as a pay-for-reporting measure in 2015 and is now planning to make it a pay-for-performance measure by incorporating it into the Hospital Value-Based Purchasing Program. This joint IDSA/ACEP/PIDS/SHEA/SHM/SIPD position paper highlights concerns with this change. Multiple studies indicate that SEP-1 implementation was associated with increased broad-spectrum antibiotic use, lactate measurements, and aggressive fluid resuscitation for patients with suspected sepsis but not with decreased mortality rates. Increased focus on SEP-1 risks further diverting attention and resources from more effective measures and comprehensive sepsis care. We recommend retiring SEP-1 rather than using it in a payment model and shifting instead to new sepsis metrics that focus on patient outcomes. CMS is developing a community-onset sepsis 30-day mortality electronic clinical quality measure (eCQM) that is an important step in this direction. The eCQM preliminarily identifies sepsis using systemic inflammatory response syndrome (SIRS) criteria, antibiotic administrations or diagnosis codes for infection or sepsis, and clinical indicators of acute organ dysfunction. We support the eCQM but recommend removing SIRS criteria and diagnosis codes to streamline implementation, decrease variability between hospitals, maintain vigilance for patients with sepsis but without SIRS, and avoid promoting antibiotic use in uninfected patients with SIRS. We further advocate for CMS to harmonize the eCQM with the Centers for Disease Control and Prevention's (CDC) Adult Sepsis Event surveillance metric to promote unity in federal measures, decrease reporting burden for hospitals, and facilitate shared prevention initiatives. These steps will result in a more robust measure that will encourage hospitals to pay more attention to the full breadth of sepsis care, stimulate new innovations in diagnosis and treatment, and ultimately bring us closer to our shared goal of improving outcomes for patients.

Infectious Diseases Society of America Position Paper: Recommended Revisions to the National Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) Sepsis Quality Measure.

The Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1's potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1's complex "time zero" definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA's core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics.

Neglected Variables in the Interpretation of Serum Procalcitonin Levels in Patients With Septic Shock.

The interpretation of serum procalcitonin (PCT) levels in septic patients is facilitated by reviewing the known stimuli that activate the PCT family of genes. Herein we describe 7 pathways that, alone or in combination, can increase serum PCT levels. As a marker of activation of innate immunity, high PCT levels affect clinical diagnosis, can be trended as a measure of "source" control, and can guide duration of antibacterial therapy in septic patients. Low PCT levels reflect little to no activation of an innate immune response, influence the differential diagnosis, and support the discontinuation of empiric antibiotic therapy. Understanding the pathways that result in elevated serum PCT levels is necessary for interpretation and subsequent clinical management.

Novel approaches are needed to develop tomorrow's antibacterial therapies.

Society faces a crisis of rising antibiotic resistance even as the pipeline of new antibiotics has been drying up. Antibiotics are a public trust; every individual's use of antibiotics affects their efficacy for everyone else. As such, responses to the antibiotic crisis must take a societal perspective. The market failure of antibiotics is due to a combination of scientific challenges to discovering and developing new antibiotics, unfavorable economics, and a hostile regulatory environment. Scientific solutions include changing the way we screen for new antibiotics. More transformationally, developing new treatments that seek to disarm pathogens without killing them, or that modulate the host inflammatory response to infection, will reduce selective pressure and hence minimize resistance emergence. Economic transformation will require new business models to support antibiotic development. Finally, regulatory reform is needed so that clinical development programs are feasible, rigorous, and clinically relevant. Pulmonary and critical care specialists can have tremendous impact on the continued availability of effective antibiotics. Encouraging use of molecular diagnostic tests to allow pathogen-targeted, narrow-spectrum antibiotic therapy, using short rather than unnecessarily long course therapy, reducing inappropriate antibiotic use for probable viral infections, and reducing infection rates will help preserve the antibiotics we have for future generations.

The future of antibiotics and resistance: a tribute to a career of leadership by John Bartlett.

The ways we have developed, used, and protected antibiotics have led, predictably, to our current crisis of rising antibiotic resistance and declining new treatments. If we want to stave off a postantibiotic era, we need to fundamentally change our approach. We need to challenge long-standing assumptions and cherished beliefs. We need to push through the reflexive resistance and excuses (eg, "that's not how we do things" and "that can't be done") that result from challenging established ways. Excuses abound. Action is needed. Ultimately, we need a coordinated national action plan to combat resistance. Herein we discuss 7 tasks and 3 common themes that cut across those tasks, which are necessary to achieve long-term success in dealing with antibiotics and resistance. These principles derive from many years of dialogue with Dr John Bartlett. The field of infectious diseases, and indeed medicine in general, has benefited immeasurably from his remarkable leadership.

Seven ways to preserve the miracle of antibiotics.

Antibiotic resistance is a well-acknowledged crisis with no clearly defined comprehensive, national corrective plan. We propose a number of interventions that, collectively, could make a large difference. These include collection of data to inform decisions, efforts to reduce antibiotic abuse in people and animals, great emphasis on antibiotic stewardship, performance incentives, optimal use of newer diagnostics, better support for clinical and basic resistance-related research, and novel methods to foster new antibiotic development.

Better tests, better care: improved diagnostics for infectious diseases.

In this IDSA policy paper, we review the current diagnostic landscape, including unmet needs and emerging technologies, and assess the challenges to the development and clinical integration of improved tests. To fulfill the promise of emerging diagnostics, IDSA presents recommendations that address a host of identified barriers. Achieving these goals will require the engagement and coordination of a number of stakeholders, including Congress, funding and regulatory bodies, public health agencies, the diagnostics industry, healthcare systems, professional societies, and individual clinicians.

Prevalence of diabetes mellitus in biopsy-positive giant cell arteritis.

BACKGROUND: We tested the hypothesis that patients with diabetes mellitus (DM) develop biopsy-positive giant cell arteritis (GCA) significantly less frequently than nondiabetic patients. METHODS: We compared the prevalence of DM in patients with positive temporal artery biopsy (TAB) with that in patients with negative TAB via a retrospective study of 215 patients who underwent TAB. Patients were classified as having biopsy-positive GCA if microscopic examination disclosed active or healed arteritis. Patients were classified as having DM if they had a diagnosis of diabetes in their medical history or were taking oral hypoglycemic medications and/or insulin at or before the time of biopsy. In addition, we performed a meta-analysis of 8 previously published articles with a total of 1,401 additional biopsy-proven cases of GCA in patients whose status was recorded as diabetic or nondiabetic. RESULTS: Of 44 cases with biopsy-positive GCA in our patient cohort, only 4 (9.1%) were diabetic at or before the time of biopsy. Of 171 patients with negative TAB, 61 (35.7%) had DM (P = 0.0006). The prevalence of DM among recorded cases of biopsy-positive GCA ranged from 0% to 13.8% in the 8 studies included in our meta-analysis, with a combined frequency of 89 diabetic patients in a total of 1,401 cases (6.35%). CONCLUSION: The low frequency of a positive TAB in diabetic GCA suspects should be considered when formulating an index of suspicion in the evaluation of patients with possible GCA. More research is needed to delineate the nature of the interaction between DM and GCA.

Procalcitonin as a biomarker in respiratory tract infection.

Serum procalcitonin (PCT) levels rapidly increase in patients with invasive bacterial disease. PCT levels increase faster than do C-reactive protein levels. Furthermore, a rapid decrease in the PCT level is supporting evidence that the source of the bacterial infection is responding to clinical management. In patients with community-acquired bacterial pneumonia, sequential PCT levels are useful as a guide to shorter courses of antimicrobial therapy. With use of emerging multiplex real-time polymerase chain reaction platforms for the detection of viral and bacterial respiratory pathogens, it should be possible to critically assess whether an elevated serum PCT level is a valid biomarker of invasive bacterial infection.

Enhanced Detection of Community-Acquired Pneumonia Pathogens With the BioFire® Pneumonia FilmArray® Panel.

BACKGROUND: Although most observational studies identify viral or bacterial pathogens in 50% or less of patients hospitalized with community-acquired pneumonia (CAP), we previously demonstrated that a multi-test bundle (MTB) detected a potential pathogen in 73% of patients. This study compares detection rates for potential pathogens with the MTB versus the Biofire® Pneumonia FilmArray® panel (BPFA) multiplex PCR platform and presents an approach for integrating BPFA results as a foundation for subsequent antibiotic stewardship (AS) activities. METHODS: Between January 2017 to March 2018, all patients admitted for CAP were enrolled. Patients were considered evaluable if all elements of the MTB and the BPFA were completed, and they met other a priori inclusion criteria. The primary endpoint was the percentage of potential pathogens detected using the MTB (8 viral and 6 bacterial targets) versus the BPFA (8 viral and 18 bacterial targets). Blood and sputum cultures were performed on all patients. Two or more procalcitonin (PCT) levels assisted clinical assessments as to whether detected bacteria were invading or colonizing. RESULTS: Of 585 enrolled patients, 274 were evaluable. A potential viral pathogen was detected in 40.5% with MTB versus 60.9% of patients with BPFA with an odds ratio (95% CI) of 9.00 (4.12 to 23.30) p<0.01. A potential bacterial pathogen was identified in 66.4% with the MTB vs 75.5% with the BPFA odds ratio (95% CI) of 2.09 (1.24 to 3.59), p 0.003). Low PCT levels helped identify detected bacteria as colonizers.

Scenario 1: a patient with hospital-acquired bacterial pneumonia--introduction to clinical trial design issues.

A prototypical patient is presented to introduce important design issues for clinical trials of antibacterials in the treatment of hospital-acquired bacterial pneumonia.

Scenario 2: A patient with ventilator-associated bacterial pneumonia--introduction to clinical trial design issues.

A prototypical patient is presented to introduce important design issues for clinical trials of antibacterials in the treatment of ventilator-associated bacterial pneumonia.