Integrating Rapid Pathogen Identification and Antimicrobial Stewardship Significantly Decreases Hospital Costs
01 Sep 2013-Archives of Pathology & Laboratory Medicine (Arch Pathol Lab Med)-Vol. 137, Iss: 9, pp 1247-1254
TL;DR: In this article, an evidence-based intervention that integrated matrix-assisted laser desorption and ionization time-of-flight mass spectrometry, rapid antimicrobial susceptibility testing, and near-real-time antimicrobial stewardship practices was implemented.
Abstract: Context.—Early diagnosis of gram-negative bloodstream infections, prompt identification of the infecting organism, and appropriate antibiotic therapy improve patient care outcomes and decrease health care expenditures. In an era of increasing antimicrobial resistance, methods to acquire and rapidly translate critical results into timely therapies for gram-negative bloodstream infections are needed. Objective.—To determine whether mass spectrometry technology coupled with antimicrobial stewardship provides a substantially improved alternative to conventional laboratory methods. Design.—An evidence-based intervention that integrated matrix-assisted laser desorption and ionization time-of-flight mass spectrometry, rapid antimicrobial susceptibility testing, and near–real-time antimicrobial stewardship practices was implemented. Outcomes in patients hospitalized prior to initiation of the study intervention were compared to those in patients treated after implementation. Differences in length of hospitalizati...
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Cornell University1, Boston University2, Johns Hopkins University3, University of Miami4, University of California, San Francisco5, Texas A&M Health Science Center College of Medicine6, Centers for Disease Control and Prevention7, University of Washington8, Case Western Reserve University9, University of Pennsylvania10, Denver Health Medical Center11, University of Michigan12, University of California, Davis13, University of California, Los Angeles14, United States Department of Veterans Affairs15, Washington University in St. Louis16, Wake Forest University17, University of Utah18, Memorial Sloan Kettering Cancer Center19
TL;DR: These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.
Abstract: Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.
1,969 citations
Cites background from "Integrating Rapid Pathogen Identifi..."
...in time to initiation of appropriate antibiotic therapy [158– 162], rates of recurrent infection [159], mortality [159, 163], length of stay [159, 161], and hospital costs [160, 161]....
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Brown University1, Oregon Health & Science University2, Providence Portland Medical Center3, Hofstra University4, University of Utah5, George Washington University6, Johns Hopkins University7, National Institutes of Health8, CEPHEID9, Rutgers University10, Johns Hopkins University School of Medicine11, Harvard University12, Becton Dickinson13, Nova Southeastern University14, Duke University15, Infectious Diseases Society of America16
TL;DR: The current diagnostic landscape, including unmet needs and emerging technologies, and the challenges to the development and clinical integration of improved tests are reviewed, and recommendations that address a host of identified barriers are presented.
Abstract: 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.
491 citations
Additional excerpts
...reduction in reagent and labor costs [53, 57]....
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TL;DR: MALDI-TOF with AST intervention decreased time to organism identification and time to effective and optimal antibiotic therapy and acceptance of an AST intervention was associated with a trend toward reduced mortality on multivariable analysis.
Abstract: BACKGROUND Integration of rapid diagnostic testing via matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) with antimicrobial stewardship team (AST) intervention has the potential for early organism identification, customization of antibiotic therapy, and improvement in patient outcomes. The objective of this study was to assess the impact of this combined approach on clinical and antimicrobial therapy-related outcomes in patients with bloodstream infections. METHODS A pre-post quasi-experimental study was conducted to analyze the impact of MALDI-TOF with AST intervention in patients with bloodstream infections. The AST provided evidence-based antibiotic recommendations after receiving real-time notification following blood culture Gram stain, organism identification, and antimicrobial susceptibilities. Outcomes were compared to a historic control group. RESULTS A total of 501 patients with bacteremia or candidemia were included in the final analysis: 245 patients in the intervention group and 256 patients in the preintervention group. MALDI-TOF with AST intervention decreased time to organism identification (84.0 vs 55.9 hours, P < .001), and improved time to effective antibiotic therapy (30.1 vs 20.4 hours, P = .021) and optimal antibiotic therapy (90.3 vs 47.3 hours, P < .001). Mortality (20.3% vs 14.5%), length of intensive care unit stay (14.9 vs 8.3 days) and recurrent bacteremia (5.9% vs 2.0%) were lower in the intervention group on univariate analysis, and acceptance of an AST intervention was associated with a trend toward reduced mortality on multivariable analysis (odds ratio, 0.55, P = .075). CONCLUSION MALDI-TOF with AST intervention decreased time to organism identification and time to effective and optimal antibiotic therapy.
443 citations
Cites background from "Integrating Rapid Pathogen Identifi..."
...However, there are limited data evaluating the impact of MALDI-TOF implementation on patient outcomes [6]....
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...Previously published studies include 1 noncomparator observational study, 1 observational cohort study, and 1 quasi-experimental study with stewardship intervention [6, 12, 19]....
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...5 days compared to conventional methods [6, 11, 12]....
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...Finally, Perez and colleagues [6] conducted a pre–post quasiexperimental study integrating MALDI-TOF organism identification plus AST intervention, but limited the inclusion to patients with gram-negative bacteremia....
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TL;DR: A prospective randomized controlled trial evaluating outcomes associated with rapid multiplex PCR detection of bacteria, fungi, and resistance genes directly from positive BCBs found that rmPCR reported with templated comments reduced treatment of contaminants and use of broad-spectrum antimicrobials.
Abstract: Background. The value of rapid, panel-based molecular diagnostics for positive blood culture bottles (BCBs) has not been rigorously assessed. We performed a prospective randomized controlled trial evaluating outcomes associated with rapid multiplex PCR (rmPCR) detection of bacteria, fungi, and resistance genes directly from positive BCBs.
Methods. A total of 617 patients with positive BCBs underwent stratified randomization into 3 arms: standard BCB processing (control, n = 207), rmPCR reported with templated comments (rmPCR, n = 198), or rmPCR reported with templated comments and real-time audit and feedback of antimicrobial orders by an antimicrobial stewardship team (rmPCR/AS, n = 212). The primary outcome was antimicrobial therapy duration. Secondary outcomes were time to antimicrobial de-escalation or escalation, length of stay (LOS), mortality, and cost.
Results. Time from BCB Gram stain to microorganism identification was shorter in the intervention group (1.3 hours) vs control (22.3 hours) (P < .001). Compared to the control group, both intervention groups had decreased broad-spectrum piperacillin-tazobactam (control 56 hours, rmPCR 44 hours, rmPCR/AS 45 hours; P = .01) and increased narrow-spectrum β-lactam (control 42 hours, rmPCR 71 hours, rmPCR/AS 85 hours; P = .04) use, and less treatment of contaminants (control 25%, rmPCR 11%, rmPCR/AS 8%; P = .015). Time from Gram stain to appropriate antimicrobial de-escalation or escalation was shortest in the rmPCR/AS group (de-escalation: rmPCR/AS 21 hours, control 34 hours, rmPCR 38 hours, P < .001; escalation: rmPCR/AS 5 hours, control 24 hours, rmPCR 6 hours, P = .04). Groups did not differ in mortality, LOS, or cost.
Conclusions. rmPCR reported with templated comments reduced treatment of contaminants and use of broad-spectrum antimicrobials. Addition of antimicrobial stewardship enhanced antimicrobial de-escalation.
Clinical Trials Registration. {"type":"clinical-trial","attrs":{"text":"NCT01898208","term_id":"NCT01898208"}}NCT01898208.
364 citations
Cites background from "Integrating Rapid Pathogen Identifi..."
...However, these studies were limited by their retrospective designs, use of historical controls [5, 6, 10, 22], lack of randomization, and failure to match subjects by severity of illness [7]....
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TL;DR: Modern applications in the clinical microbiology laboratory are reviewed with a focus on the most recent publications in the field, and automated, high throughput, and applicable to a broad range of common as well as esoteric bacteria and fungi are discussed.
Abstract: BACKGROUND: First introduced into clinical microbiology laboratories in Europe, MALDI-TOF MS is being rapidly embraced by laboratories around the globe. Although it has multiple applications, its widespread adoption in clinical microbiology relates to its use as an inexpensive, easy, fast, and accurate method for identification of grown bacteria and fungi based on automated analysis of the mass distribution of bacterial proteins.
CONTENT: This review provides a historical perspective on this new technology. Modern applications in the clinical microbiology laboratory are reviewed with a focus on the most recent publications in the field. Identification of aerobic and anaerobic bacteria, mycobacteria, and fungi are discussed, as are applications for testing urine and positive blood culture bottles. The strengths and limitations of MALDI-TOF MS applications in clinical microbiology are also addressed.
SUMMARY: MALDI-TOF MS is a tool for rapid, accurate, and cost-effective identification of cultured bacteria and fungi in clinical microbiology. The technology is automated, high throughput, and applicable to a broad range of common as well as esoteric bacteria and fungi. MALDI-TOF MS is an incontrovertibly beneficial technology for the clinical microbiology laboratory.
346 citations
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TL;DR: The rate of sepsis due to fungal organisms increased by 207 percent, with gram-positive bacteria becoming the predominant pathogens after 1987, and the total in-hospital mortality rate fell, yet the total number of deaths continued to increase.
Abstract: Background Sepsis represents a substantial health care burden, and there is limited epidemiologic information about the demography of sepsis or about the temporal changes in its incidence and outcome. We investigated the epidemiology of sepsis in the United States, with specific examination of race and sex, causative organisms, the disposition of patients, and the incidence and outcome. Methods We analyzed the occurrence of sepsis from 1979 through 2000 using a nationally representative sample of all nonfederal acute care hospitals in the United States. Data on new cases were obtained from hospital discharge records coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Results Review of discharge data on approximately 750 million hospitalizations in the United States over the 22-year period identified 10,319,418 cases of sepsis. Sepsis was more common among men than among women (mean annual relative risk, 1.28 [95 percent confidence interval, 1.24 to 1.32]...
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4,692 citations
Tufts Medical Center1, University of California, San Diego2, Boston Children's Hospital3, University of California, Los Angeles4, Los Angeles Biomedical Research Institute5, Providence Portland Medical Center6, United States Department of Veterans Affairs7, Case Western Reserve University8, University of Virginia9, Johns Hopkins University School of Medicine10
TL;DR: An update on potentially effective antibacterial drugs in the late-stage development pipeline is provided, in the hope of encouraging collaboration between industry, academia, the National Institutes of Health, the Food and Drug Administration, and the Centers for Disease Control and Prevention work productively together.
Abstract: The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, “Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews,” and recently issued a “Call to Action” to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure—one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.
4,256 citations