The Clinical Relevance of Antimicrobial Susceptibility Testing : Ramblings of a Very Old Clinical Microbiologist
|
|
- Shannon Hicks
- 5 years ago
- Views:
Transcription
1 The Clinical Relevance of Antimicrobial Susceptibility Testing : Ramblings of a Very Old Clinical Microbiologist Gary V. Doern, Professor Emeritus University of Iowa College of Medicine
2 What is the defining paradigm in medicine today? Dennis G. Maki, M.D. Professor Emeritus Department of Medicine University of Wisconsin School of Medicine Advances in cancer care? The technology of medicine? The business of medicine? Evidenced-based clinical practice! Medical Grand Rounds, University of Iowa College of Medicine (February, 2012)
3 I don t see much sense in that said Rabbit. No, said Pooh humbly, there isn t. But there was going to be when I began it. It s just that something happened to it along the way. (A.A. Milne, Winnie-the-Pooh, 1926) In the absence of unbiased empirical data derived from systematic, objective investigations, the practice of clinical microbiology is little more than an expensive crap shoot (G.V. Doern, J Clin Microbiol, 2014)
4 I guess I need to be careful here Trump administration prohibits CDC from using the following words in all communications: - entitlement - evidence-based - diversity - fetus - science-based - transgender - vulnerable (J. Eilperin, Washington Post, Dec. 15, 2017)
5 It s deja vue, all over again! (Yogi Berra, 1978) (George Orwell, 1949)
6 Not the first time F*&%, C#%&, and
7 Survey CM laboratory directors 10 academic medical centers 5 acute care hospitals 5 state public health laboratories Parameters: - analytical precision - cost - laboratory impact - clinical impact Evidence scale: 1-3 (inadequate) (1-10) 4-7 (moderate) 8-10 (adequate)
8 Survey Results Method Automated BC systems Automated mycobacteriology Automated ID/AST Analytical precision Cost Laboratory impact Clinical impact MALDI-TOF MS NG sequencing Multiplex PCR POC molecular Evidence scale: 1-3 = inadequate 4-7 = some evidence 8-10 = adequate
9 Heaven, forbid some data! Survey of 15 clinical microbiology laboratory directors (2014) Identify the most important concepts, activities and/or procedures in current laboratory practice 71 different functions identified - CM blood culture incubation for 5 days CFU/ml = significant bacteriuria - No C. diff determinations on formed stool - AFB smears only on concentrated sputa - WB definitive diagnostic method for Lyme - Sputum GS directs w/u of sputum cultures - AST essential in directing antimicrobial Rx
10 So how are we doing? Survey of 15 clinical microbiology laboratory directors (2014) Identify the most important concepts, activities and/or procedures in current laboratory practice 71 different functions identified - 46 functions accessed - 16 functions (35%) evaluable data - 7/16 (44%) data supports practice - 54% - data contradicts practice
11 But the question before us is: What do the results of in vitro susceptibility tests mean from the perspective of patients with infection? Stated another way: What is the clinical predictive value of AST results?
12 Manual AST Systems
13 Automated Antimicrobial Susceptibility Testing Systems
14 Results of In Vitro Susceptibility Testing Quantitative procedures: Minimum inhibitory concentrations Qualitative procedures: Susceptible (S) Intermediate (I) Resistant (R)
15 Good things come in threes!
16 Interpretive Categories The Big Three: Susceptible Favorable outcome Intermediate Don t know Resistant Unfavorable outcome
17 How is Resistance Defined? MIC determinations represent the most refined means of measuring in vitro antibacterial activity The units of an MIC are: ug/ml MIC breakpoints (interpretive criteria) Susceptible (S) Intermediate (I) Resistant (R)
18 AST Results Interpretive Criteria Australian Clinical Diagnosis Society British Society for Antimicrobial Chemotherapy Clinical and Laboratory Standards Institute Deutches Institut fur Normung European Committee on Antimicrobial Susceptibility testing Societe Francaise de Microbiologie Swedish Reference Group for Antibiotics Werkgroep Richtijnen Gevoeligheidsbepaligen
19 The Clinical and Laboratory Standards Institute (CLSI) * AST method standards Quality control criteria Drug selection Interpretive criteria present *Formerly the National Committee for Clinical Laboratory Standards (NCCLS)
20 Establishing Interpretive Categories Four approaches: MIC frequency distribution analysis Correlation with known mechanisms of resistance Clinical correlation Pharmacodynamics
21 Establishing Interpretive Categories Four approaches: MIC frequency distribution analysis Correlation with known mechanisms of resistance Clinical correlation Pharmacodynamics
22 Number of isolates Penicillin MIC Frequency Distribution for S. pneumoniae 1925 isolates, 45 U.S. medical centers, Susc. Intermediate Resistant MIC (µg/ml)
23 Establishing Interpretive Categories Four approaches: MIC frequency distribution analysis Correlation with known mechanisms of resistance Clinical correlation Pharmacodynamics
24 Resistance Mechanisms That Drive Treatment Failure Certain β-lactamases: - staphylococcal penase - TEM-1, TEM-2, SHV-1 - derepressed ampc - Rob-1, CTX-M - metallo-β-lactamases meca-derived PBP 2a erm-derived ribosomal alterations Aminoglycoside modifying enzymes van A and van B-altered CW pentapeptides parc + gyra mutations
25 Establishing Interpretive Categories Four approaches: MIC frequency distribution analysis Correlation with known mechanisms of resistance Pharmacodynamics Clinical correlation
26 Antibiotic Effect in Patients Potency a product of: antibacterial effect (MIC) drug delivery (PK) drug-bug interaction PHARMACODYNAMICS
27 PK/PD Analysis as a Means for Establishing MIC Breakpoints Advantages: Based on accessible data Arithmetic (ie. simple) Concepts based on empiric investigation Disadvantages: A broad averaging technique Merits dose specific breakpoints
28 Establishing Interpretive Categories Four approaches: MIC frequency distribution analysis Correlation with known mechanisms of resistance Pharmacodynamics Clinical correlation
29 Clinical Predictive Value? Focus: Single agents used parenterally to manage monomicrobic infections in non-immunocompromised hosts in which standard doses of agent reliably achieve typical concentrations at the site of infection
30 Correlation of Cefotaxime MICs and Disease Outcome Cefotaxime Percentage Percentage MIC (no.) cured or improved eradication 4 (1003) 94% 91% S 8 (273) 90% 86% 16 (151) 77% 75% I 32 (70) 84% 71% 64 (19) R 64% 50% [1506 patients total]
31 Correlation of Meropenem MICs and Disease Outcome Meropenem Percentage Percentage MIC (n) cured or improved eradication 2 (301) 94% 92% S 4 (89) 93% 92% 8 (29) I 86% 82% 16 (11) 65% 61% 32 (5) R 60% 60% [n = 435 patients total]
32 Clinical Correlation in Pneumococcal Pneumonia MIC No. of No. (%) who (µg/ml) patients failed therapy: Penicillin 0.06 (S) (19) (I) 24 5 (21) 2 (R) 10 2 (20) Cefotaxime 0.5 (S) (20) 1 (I) 4 1 (15) 2 (R) 1 0 (0) 21% 20% [Pallares et al, N Engl J Med, 1995]
33 Clinical Correlation in Gonococcal Genital Tract Infections Men and women with urethritis or cervicitis [Jaffe et al, N Engl J Med, 1976] Penicillin no. Failure MIC rate % % % % % 4.8 mu PCN + 1 g proben
34 Clinical Predictive Value Monomicrobic infections in immunocompetent patients treated with a single parenteral antibiotic Susceptible 90% 95% response Intermediate 65% 90% response Resistant 60% 65% response 23/100 patients
35 Clinical Predictive Value Monomicrobic infections in immunocompetent patients treated with a single parenteral antibiotic The higher the MIC, the worse the outcome The lower the MIC, the better the outcome
36 Everybody Else. Infections treated with oral or topical antibiotics, or combination agents Polymicrobial infections Infections in sites with diminished penetration or concentration of drug at the site Infections in immunocompromised patients
37 Oral Antimicrobials and Respiratory Tract Infections Haemophilus influenzae infections AOME (n=262), AS (n=237), AECB (n =270) Agent Resp # No. of isolates with each MIC (µg/ml): Loracarbef C/I R/F Amox/clav C/I R/F Doern et al, Am J Med, 1992
38 Multiple Antibiotics 143 of 200 patients with Pseudomonas aeruginosa bacteremia received combination therapy parenterally MICs of antimicrobial agents determined versus patient s infecting strains and correlated with outcome No Correlation! Hilf et al, Am J Med, 1989
39 Urinary Tract Infection 136 out-patient women with acute uncomplicated cystitis (DUF + PMNs) Positive urine cultures No previous antibiotics (6 months) Two TMP/SMX treatment groups: 2 g PO once vs. 500 mg q12h for 10 d Assess relationship between TMX MICs and outcome (ie. failure, relapse, recurrence) No Correlation! Schultz et al, Mayo Clin Proc, 1984
40 Urinary Tract Infection 618 women with DUF + pyuria 544 (88%) with positive urine cultures ALL treated with TMX 500 mg qd 5 d Period: No. responding/no. treated TMX S TMX R 1 week* 288/353 (86%) 64/151 (42%) 4 weeks* 265/285 (93%) 53/76 (70%) * P < Raz et al, Clin Infect Dis, 34:1165, 2002
41 Closed Space Anaerobic Infections 19 patients with intraabdominal infections ALL treated with cefoxitin (2 g q 8 h for 10 d) Medium (method): G.M. Cefoxitin MIC: Cured a Failed b Wilkins Chalgren (AD) Wilkins Chalgren (BMD) Commercial media (BMD) Brain heart infusion (BMD) a. n = 11 patients; b. n = 8 patients Snydman et al, Antimicrob Agents Chemother, 1992
42 Everybody Else. Infections treated with oral or topical antibiotics, or combination agents Polymicrobial infections Infections in sites with diminished penetration or concentration of drug at the site Infections in immunocompromised patients
43 The Predictive Value of In vitro Susceptibility Testing Response Rate ACTUAL IDEAL Susceptible Intermediate Resistant
44 Clinical Predictive Value 51 years of in vitro susceptibility testing
45 Clinical Correlation In vitro anti-tumor susceptibility test VS. Outcome in patients with hematologic malignancies DiSCA MTCS Number (%) MTCS Response 22 (18.5) > 55% 0% 31 (26.1) 31 55% 9% 36 (30.3) 5 30% 54% 30 (25.2) < 5% 79% (Bosanquet et al, Lancet, 1997)
46 Confounding Variables Fixed non-varying inoculum Constant ph; no protein binding Optimum growth conditions Fixed non-varying concentration of antimicrobial Host factors not considered
47 The Clinical Continuum AST results reporting Processing of information Exposure Incubation period Disease manefestations Performance of AST Specimen processing Specimen transport Intervention! Seek care Clinical evaluation Care plan Specimen collection Specimen ordering Implementation
48 What do these have in common?
49
50
51 Health Care Costs
52 We need to better. The distance between the clinical microbiology laboratory and the patient with infection is only as long as we choose to make it Linkage of AST results to: Patient parameters known to be associated with infection outcome: - age, gender, race, ethnicity - ± underlying disease - patient genotype - cytokine profiles - T-cell genotypes
53 For us you see my friends, it is not merely to endure, but rather to prevail Wm. Faulkner Stockholm, 1957
2016 Europe-Nordic-US Symposium New Frontiers in Antibacterial Resistance Research. Pharmacological Approaches to Address AR
2016 Europe-Nordic-US Symposium New Frontiers in Antibacterial Resistance Research Pharmacological Approaches to Address AR G.L. Drusano, M.D. Professor and Director Institute for Therapeutic Innovation
More informationNovel Approaches to Further Antibacterial Drug Development: New Approaches to the Clinical Development Program
Novel Approaches to Further Antibacterial Drug Development: New Approaches to the Clinical Development Program An industry view John H. Rex, Infection Clinical Vice President AstraZeneca Pharmaceuticals
More informationSetting Clinical Breakpoints/ECOFFS
23 rd August 2016 Setting Clinical Breakpoints/ECOFFS Robin A Howe Antimicrobial use in Primary Care An E. coli is grown from blood cultures Cefuroxime MIC 2mg/L Zone around CXM 30ug disc 27mm Is it sensitive?
More informationNovel Approaches to Further Antibacterial Drug Development: New Approaches to the Clinical Development Program
Novel Approaches to Further Antibacterial Drug Development: New Approaches to the Clinical Development Program An industry view John H. Rex, Infection Clinical Vice President AstraZeneca Pharmaceuticals
More informationPharmacokinetics as applied to in vitro and animal models
Pharmacokinetics as applied to in vitro and animal models Michael R. Jacobs, MD, PhD Case Western Reserve University University Hospitals of Cleveland Cleveland, OH Topics In vitro pharmacodynamic models
More informationUse of Molecular Assays for Resistance Detection
Use of Molecular Assays for Resistance Detection Antimicrobial resistance and susceptibility are complex, and current in vitro methods have been developed to predict a microorganism s response to antibacterial
More informationAre There Non-Carbapenem β-lactam Options for Treating ESBL Infections?
CIDEIM Are There Non-Carbapenem β-lactam Options for Treating ESBL Infections? Pranita D. Tamma, M.D., M.H.S. Assistant Professor, Pediatrics Director, Pediatric Antimicrobial Stewardship Program CIDEIM
More informationINNOVATIVE SCIENCE DRIVES ANTIBIOTIC LEADERSHIP. Corporate Presentation October 2018 Nasdaq: AKAO
INNOVATIVE SCIENCE DRIVES ANTIBIOTIC LEADERSHIP Corporate Presentation October 2018 Nasdaq: AKAO Forward Looking Statements This presentation contains forward-looking statements. All statements other than
More informationJohan W Mouton Canisius-Wilhelmina Hospital Nijmegen, The Netherlands
Can pk/pd replace clinical trials? Johan W Mouton Canisius-Wilhelmina Hospital Nijmegen, The Netherlands The Traditional Approach Phase Participants Research questions Number Characteristics I 10-50 Usually
More informationDisk Diffusion Method for Susceptibility Testing of
JOURNAL OF CLINICAL MICROBIOLOGY, Aug. 1991, p. 1604-1609 0095-1137/91/081604-06$02.00/0 Copyright 1991, American Society for Microbiology Vol. 29, No. 8 Disk Diffusion Method for Susceptibility Testing
More informationEMA Workshop Non-Clinical Models to Identify PK/PD Indices and PD Targets In Vitro
EMA Workshop Non-Clinical Models to Identify PK/PD Indices and PD Targets In Vitro G.L. Drusano, M.D. Professor and Director Institute for Therapeutic Innovation University of Florida In Vitro There are
More informationShionogi Presents Results of the First Clinical Efficacy Trial and In Vitro Data on Cefiderocol (S ), a Siderophore Cephalosporin
Shionogi Presents Results of the First Clinical Efficacy Trial and In Vitro Data on Cefiderocol (S-649266), a Siderophore Cephalosporin Osaka, Japan, April 22, 2017 - Shionogi & Co., Ltd. today announced
More informationBlood cultures: past, present and future. Dr Natalia Solomon MD, FRCPSC Medical Microbiologist DynaLIFE Dx
Blood cultures: past, present and future Dr Natalia Solomon MD, FRCPSC Medical Microbiologist DynaLIFE Dx Faculty/ Presenter Disclosure Faculty: Dr Natalia Solomon Relationships with commercial interests:
More informationNDA Requirements: Surveillance, Clinical Trial Data, Breakpoints
NDA Requirements: Surveillance, Clinical Trial Data, Breakpoints Kevin M. Krause Director Microbiology Achaogen, Inc. Presented at the ASM/ESCMID Conference on Drug Development to Meet the Challenge of
More informationBeta-lactamase inhibition: A potted history of beta lactamase and lessons from recent development of betalactamase inhibiter combinations
Beta-lactamase inhibition: A potted history of beta lactamase and lessons from recent development of betalactamase inhibiter combinations Dr Shampa Das, Senior Lecturer, Molecular and Clinical Pharmacology,
More informationDisclosures. Shareholder: GlaxoSmithKline Spero Therapeutics. Consultant: Prokaryotics
Disclosures Shareholder: GlaxoSmithKline Spero Therapeutics Consultant: Prokaryotics The opinions expressed in this presentation are my own and are not necessarily shared by my industry colleagues Tomayko
More informationInvestigational New Drug - Groundwork for in vitro antimicrobial susceptibility testing
Investigational New Drug - Groundwork for in vitro antimicrobial susceptibility testing Erika Matuschek, Ph D Lead Scientist/Operational Manager EUCAST Development Laboratory (EDL) Växjö, Sweden ASM/ESCMID
More informationVerification of Disk Diffusion Tests
Verification of Disk Diffusion Tests Objectives 1. Describe disk diffusion tests 2. Describe process of FDA clearance of susceptibility tests 3. Discuss CLIA requirements for laboratory verification of
More informationCurriculum Vitae. Abbas Maleki, Ph.D. Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
Curriculum Vitae Abbas Maleki, Ph.D Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran E-mail: abbasmaleki_ilam@yahoo.com maleki-a@medilam.ac.ir Tel: +989187419401 Personal
More informationRapid Diagnostic Tests for Antimicrobial Resistance: Comparability of Results and Interpretation of Data
Rapid Diagnostic Tests for Antimicrobial Resistance: Comparability of Results and Interpretation of Data Christopher Teale, Animal and Plant Health Agency, UK. 12 th OIE One-Day Seminar, in association
More informationQuality Control and Quality Assurance for Antibiotic Testing
Quality assurance Quality Control and Quality Assurance for Antibiotic Testing 26 Sep 2013 Microbiology Technical Workshop Lily Ng Siew Yong practice of assessing performance in all steps of the process
More informationAntibiotic Susceptibility Testing (ABST/AST)
Antibiotic Susceptibility Testing (ABST/AST) Goal Offer guidance to physicians in selecting effective antibacterial therapy for a pathogen in a specific body site. Performed on bacteria isolated from clinical
More informationBiofilm Protocol Optimization For Pseudomonas aeruginosa. Introduction. Materials and Methods. Culture Media, Incubation Time, and Biofilm Measurement
Biofilm Protocol Optimization For Pseudomonas aeruginosa Culture Media, Incubation Time, and Biofilm Measurement Introduction In addition to the conventional arsenal of antibiotic resistance mechanisms
More informationMolecular susceptibility testing
Molecular susceptibility testing Dr Andrew Ginn Supervising Scientist Antimicrobial Resistance Reference Laboratory ICPMR, Westmead Hospital Resistance genes Gram negatives Transmissible; e.g. ESBLs, MBLs,
More informationAdvances in Medical Microbiology - Are the Patients Better Off?
Advances in Medical Microbiology - Are the Patients Better Off? R.P. Rennie Professor Emeritus. Laboratory Medicine and Pathology University of Alberta. Clinical Microbiology Consultant Alberta Health
More informationPERANAN MIKROBIOLOGI DALAM DIAGNOSIS PENYAKIT INFEKSI. dr. Agus Eka Darwinata, Ph.D.
PERANAN MIKROBIOLOGI DALAM DIAGNOSIS PENYAKIT INFEKSI dr. Agus Eka Darwinata, Ph.D. CLINICAL MICROBIOLOGY Clinical microbiology is the discipline of detection, characterization, and quantification of
More informationStandard Operating Procedure
Date of issue: 23 January 2018 Page 1 of 11 Standard Operating Procedure EUCAST SOP 3.2 23 January 2018 Date of issue: 23 January 2018 Page 2 of 11 SOP Number (number.version): 3.2 Date of issue: 23 January
More informationCRE Laboratory Testing and CRE Lab Testing Recommendations in-depth recommendations on CRE laboratory detection
December 2014 Dear Laboratory Director, The Illinois Department of Public Health (IDPH) amended the Control of Communicable Diseases Code (77 Ill. Adm. Code 690) to require reporting of Carbapenem-Resistant
More informationAntifungal PK/PD Made Simple. David Andes, MD University of Wisconsin
Antifungal PK/PD Made Simple David Andes, MD University of Wisconsin PK/PD Concept Serum Drug Concentration Peak:MIC AUC:MIC Ratio Time Above MIC MIC Time Hypothesis and Concept There is an optimal drug
More informationby author How to effectively report laboratory findings to clinicians (Breakpoints and Interpretation)
How to effectively report laboratory findings to clinicians (Breakpoints and Interpretation) A Vatopoulos National School of Public Health & Central Public Health Laboratory KEELPNO Antibiotic Activity
More informationIDSA is pleased to offer the following comments on specific priority areas identified by FDA:
October 31, 2018 Shashi Malhotra Office of Acquisitions & Grants Services (OAGS) Food and Drug Administration Telephone: 240-402-7592 Email: Shashi.Malhotra@fda.hhs.gov SUBJECT: NOT-FD-18-16: Development
More informationCase. Case. Case. Case. Reference lab AST. Nelesh Govender, NICD 2013/03/08. Candida species: Antifungal susceptibility testing in 2013
Nelesh Govender, NICD 13/3/8 se ndida species: Antifungal susceptibility testing in 13 Nelesh Govender National Institute for Communicable Diseases and University of the Witwatersrand, Johannesburg Elderly
More informationVerification of Gradient Diffusion Strips
Verification of Gradient Diffusion Strips Objectives 1. Describe gradient diffusion tests 2. Describe process of FDA clearance of susceptibility tests 3. Discuss CLIA requirements for laboratory verification
More informationINNOVATIVE SCIENCE DRIVES ANTIBIOTIC LEADERSHIP. Corporate Presentation June 2018 Nasdaq: AKAO
INNOVATIVE SCIENCE DRIVES ANTIBIOTIC LEADERSHIP Corporate Presentation June 2018 Nasdaq: AKAO Forward Looking Statements This presentation contains forward-looking statements. All statements other than
More informationCombatting AMR: diagnostics
Combatting AMR: diagnostics Professor Neil Woodford Antimicrobial Resistance & Healthcare Associated Infections (AMRHAI) Reference Unit Crown copyright Gonorrhoea: a paradigm for better diagnostics International
More informationDeveloping Novel Antibacterials to Treat Multi-drug Resistant Gram-negative Bacterial Infections. 13 th Needham Healthcare Conference April 8, 2014
Developing Novel Antibacterials to Treat Multi-drug Resistant Gram-negative Bacterial Infections 13 th Needham Healthcare Conference April 8, 2014 Forward Looking Statements Forward-Looking Statements
More informationCI-867, a New Semisynthetic Penicillin: In Vitro Studies
ANTIROBIAL AGENTS AND CHEMOTHERAPY, Dec. 19, p. 939-943 66-44//12-939/5$2./ Vol. 18, No. 6, a New Semisynthetic Penicillin: In Vitro Studies SUSANNE S. WEAVER AND GERALD P. BODEY* Department of Developmental
More informationSusceptibility Tests
JOURNAL OF CLINICAL MICROBIOLOGY, Aug. 1982, p. 213-217 Vol. 16, No. 2 0095-1137/82/080213-05$02.00/0 In Vitro Studies with Cefotaxime: Disk Diffusion Susceptibility Tests SMITH SHADOMY* AND EDWARD L.
More informationBATTLING BUGS: INROADS IN INFECTIOUS DISEASES
UW MEDICINE PATIENTS ARE FIRST BATTLING BUGS: INROADS IN INFECTIOUS DISEASES UW MINI-MEDICAL SCHOOL Brad T. Cookson M.D., Ph.D. February 11, 2014 FEVER: THE HOST RESPONDS Humanity has but three great enemies:
More informationA Verification Study for Implementing the Revised CLSI Breakpoints. Summary. Breakpoint Differences Cephalosporin Breakpoints for Enterobacteriaceae
A Verification Study for Implementing the Revised CLSI Breakpoints Jean B. Patel, PhD, D(ABMM) Deputy Director, Office of Antimicrobial Resistance National Center for Emerging and Zoonotic Infectious Disease
More informationA Verification Study for Implementing the Revised CLSI Breakpoints. Summary. Glossary CDC 1
A Verification Study for Implementing the Revised CLSI Breakpoints Jean B. Patel, PhD, D(ABMM) Deputy Director, Office of Antimicrobial Resistance National Center for Emerging and Zoonotic Infectious Disease
More informationCOMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP)
The European Agency for the Evaluation of Medicinal Products Evaluation of Medicines for Human Use London, 27 July 2000 CPMP/EWP/2655/99 COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) POINTS TO CONSIDER
More informationESBLs and KPCs: Impact of Revised CLSI Breakpoints on testing and Reporting Algorithms
ESBLs and KPCs: Impact of Revised CLSI Breakpoints on testing and Reporting Algorithms Stephen G. Jenkins, Ph.D. Director, Clinical Microbiology Laboratories New York/Presbyterian Hospital Weill Cornell
More informationDisruptive Technology to Guide Precision Antibiotic Therapy
Disruptive Technology to Guide Precision Antibiotic Therapy Company Presentation, October 2018 Forward Looking Statement This presentation includes statements relating to the company's Acuitas AMR Gene
More informationAdopting EUCAST breakpoints in countries currently on CLSI breakpoints
19th ECCMID 1 Adopting EUCAST breakpoints in countries currently on CLSI breakpoints and some personal thinking Paul M. Tulkens Representative of ISC to EUCAST Unité de pharmacologie cellulaire et moléculaire
More informationInfluence of therapy duration on suppression of emergence of resistance and influence of granulocytes on cell kill
Influence of therapy duration on suppression of emergence of resistance and influence of granulocytes on cell kill G.L. Drusano, M.D. Co-Director Ordway Research Institute Short Course Therapy Short Course
More informationDivision of Dockets Management (HFA 305) U.S. Food and Drug Administration 5630 Fishers Lane Room 1061 Rockville, MD 20852
May 24, 2012 Division of Dockets Management (HFA 305) U.S. Food and Drug Administration 5630 Fishers Lane Room 1061 Rockville, MD 20852 Re: Comments on Docket #FDA- 2012 D 0148; Draft Guidance for Industry
More informationCORPORATE PRESENTATION
CORPORATE PRESENTATION March 2018 1 Forward Looking Statement This presentation includes statements relating to the company's Acuitas MDRO and Acuitas Lighthouse clinical laboratory services, FDA cleared
More informationReceived 5 October 2014; returned 4 November 2014; revised 9 November 2014; accepted 8 December 2014
J Antimicrob Chemother 2015; 70: 1547 1551 doi:10.1093/jac/dku548 Advance Access publication 27 January 2015 Risk factors for ambulatory urinary tract infections caused by high-mic fluoroquinolone-susceptible
More informationCHAPTER 24. Immunology
CHAPTER 24 Diagnostic i Microbiology and Immunology Growth-Dependent Diagnostic Methods Isolation of Pathogens from Clinical Specimens Proper sampling and culture of a suspected pathogen is the most reliable
More informationAbstract. Introduction
ORIGINAL ARTICLE 10.1111/j.1469-0691.2009.02893.x Comparative assessment of inoculum effects on the antimicrobial activity of amoxycillin clavulanate and piperacillin tazobactam with extended-spectrum
More informationRegulatory hurdles and opportunities
Regulatory hurdles and opportunities Professor Roger Finch Nottingham University Hospitals & University of Nottingham, UK Drug licensing and regulation Mandatory for market authorisation Supports the public
More informationChapman University Digital Commons. Chapman University. George G. Zhanel University of Manitoba. Kate Parkinson University of Manitoba
Chapman University Chapman University Digital Commons Pharmacy Faculty Articles and Research School of Pharmacy 4-23-2017 Pharmacodynamic Activity of Fosfomycin Simulating Urinary Concentrations Achieved
More informationESCMID Online Lecture Library. by author
Eric DANNAOUI ESCMID Postgraduate Education Course 20-22 June 2013, Sibiu Antifungal susceptibility testing and detection of resistance: principles and practices Unité de Parasitologie-Mycologie, Laboratoire
More informationWake Forest Baptist Medical Center Guideline for Use of Ribavirin in the Treatment of Respiratory Syncytial Virus (RSV) Infection
Wake Forest Baptist Medical Center Guideline for Use of Ribavirin in the Treatment of Respiratory Syncytial Virus (RSV) Infection General Information Aerosolized ribavirin has been shown in limited clinical
More informationWake Forest Baptist Medical Center Guideline for Use of Ribavirin in the Treatment of Respiratory Syncytial Virus (RSV) Infection
Wake Forest Baptist Medical Center Guideline for Use of Ribavirin in the Treatment of Respiratory Syncytial Virus (RSV) Infection General Information Aerosolized ribavirin has been shown in limited clinical
More informationDr. Rukumani Devi Velayuthan Mycology Unit Co-ordinator PPUM
Antifungal sensitivity testing using VITEK 2 Dr. Rukumani Devi Velayuthan Mycology Unit Co-ordinator PPUM VITEK 2 Systems The VITEK 2 System is intended for the automated identification and susceptibility
More informationLaboratory Testing for Diagnosis and Treatment of TB
Laboratory Testing for Diagnosis and Treatment of TB Jennifer Rakeman, PhD Associate Director and Microbiology Manager Public Health Laboratory NYC Department of Health and Mental Hygiene Laboratory diagnosis
More informationNational Center for Emerging and Zoonotic Infectious Diseases The Role of Breakpoint Committees for New Drugs Perspectives from the United States
National Center for Emerging and Zoonotic Infectious Diseases The Role of Breakpoint Committees for New Drugs Perspectives from the United States Jean B. Patel, PhD, D(ABMM) Science Lead, Antibiotic Resistance
More informationValidation of 2 nd line drug susceptibility testing. Ed Desmond California Dept. of Public Health
Validation of 2 nd line drug susceptibility testing Ed Desmond California Dept. of Public Health XDRTB!!! KwaZulu-Natal outbreak, 2006 53 HIV-infected patients, 52 deaths Average survival from specimen
More informationMASTER PROTOCOLS IN COLLABORATIVE RESEARCH
MASTER PROTOCOLS IN COLLABORATIVE RESEARCH Lisa LaVange, PhD Professor and Associate Chair ASA Biopharmaceutical Section/ Industry/Regulatory Workshop Washington, DC September 13-14, 2018 Outline Precision
More informationAntibiotic Susceptibility Testing and Data Interpretation
Antibiotic Susceptibility Testing and Data Interpretation Dr Shabbir Simjee Microbiologist Co-Chair CLSI VAST Basingstoke England Bangkok, 7-8 October 2014 For clarity, these are solely my personal views/opinions
More informationSetting and Revising Antibacterial Susceptibility Breakpoints
CLINICAL MICROBIOLOGY REVIEWS, July 2007, p. 391 408 Vol. 20, No. 3 0893-8512/07/$08.00 0 doi:10.1128/cmr.00047-06 Copyright 2007, American Society for Microbiology. All Rights Reserved. Setting and Revising
More informationThe general concept of pharmacodynamics
Asian PK/PD Educational Workshop The general concept of pharmacodynamics modeling the antibacterial effects relations PK / PD This part uses material from presentations of H. Derendorf (Gainesville, Fla.)
More informationLauren A. Darling1#, Ann M. Evans1, Kathleen A. Stellrecht1,2, Seela M. Nattanmai1,
JCM Accepted Manuscript Posted Online 20 September 2017 J. Clin. Microbiol. doi:10.1128/jcm.01185-17 Copyright 2017 American Society for Microbiology. All Rights Reserved. 1 JCM Letter to the Editor Submission
More informationFLUCONAZOLE SUSCEPTIBILITY TESTING OF CANDIDA SPECIES BY DISC DIFFUSION AND AGAR DILUTION METHOD
FLUCONAZOLE SUSCEPTIBILITY TESTING OF CANDIDA SPECIES BY DISC DIFFUSION AND AGAR DILUTION METHOD Supriya Tankhiwale, Sunita Gajbhiye, Rajaram Powar 1. Associate Professor, Department of Microbiology, Government
More informationVITEK 2. Microbiology with Confidence
VITEK 2 Microbiology with Confidence RESULTS YOU CAN TRUST AUTOMATED VALIDATION OF EVERY RESULT VITEK 2 technology represents a smarter way to automate ID/AST testing. It provides rapid, automatic, standardized
More informationIdentification of the In Vivo Pharmacokinetics and Pharmacodynamic Drivers of Iclaprim
AAC Accepted Manuscript Posted Online 29 January 2018 Antimicrob. Agents Chemother. doi:10.1128/aac.02550-17 Copyright 2018 American Society for Microbiology. All Rights Reserved. 1 Identification of the
More informationPK-PD TARGET SELECTION It s All About the Goal
PK-PD TARGET SELECTION It s All About the Goal Paul G. Ambrose, Pharm.D. Chair, USCAST Executive Committee President, Institute for Clinical Pharmacodynamics It s All About the Goal The choice of a rational
More informationOutline. Introduction. Broth and Agar testing methods Automated susceptibility testing. Aims of antimicrobial susceptibility testing:
Outline Microbiology Technical Workshop Broth and Agar testing methods Automated susceptibility testing Dr Tan Yen Ee Registrar Singapore General Hospital 25th Sept 2013 Introduction Broth testing methods
More informationABC. Methods for Determining Bactericidal Activity of Antimicrobial Agents; Approved Guideline. Volume 19 Number 18
M26-A ISBN 1-56238-384-1 September 1999 ISSN 0273-3099 Methods for Determining Bactericidal Activity of Antimicrobial Agents; Approved Guideline Volume 19 Number 18 Arthur L. Barry, Ph.D. William A. Craig,
More informationForecast diagnostics for antimicrobial resistance (AMR)
Forecast diagnostics for antimicrobial resistance (AMR) Authors: Ann Van den Bruel, Philip Turner NIHR Diagnostic Evidence Cooperative Oxford, University of Oxford Context When asked to make forecasts
More informationAntibiotics to Treat Multidrug-Resistant Bacterial Infections
Antibiotics to Treat Multidrug-Resistant Bacterial Infections Copyright 2017 Tetraphase Pharmaceuticals, Inc. C O M P A N Y P R E S E N T A T I O N A p r i l 2 0 1 7 TTPH Forward-Looking Statements and
More informationComparative in-vitro activity of cefaclor against urinary tract isolates of Escherichia coli
Journal of Antimicrobial Chemotherapy (1996) 38, 59-66 Comparative in-vitro activity of cefaclor against urinary tract isolates of Escherichia coli C. A. Webster,. Curran and K. J. Towner* Department of
More information[[Page 63034]] ======================================================================= DEPARTMENT OF HEALTH AND HUMAN SERVICES
[Federal Register Volume 79, Number 204 (Wednesday, October 22, 2014)] [Rules and Regulations] [Pages 63034-63036] From the Federal Register Online via the Government Printing Office [www.gpo.gov] [FR
More informationCME/SAM. Clinical Laboratory Detection of AmpC β-lactamase Does It Affect Patient Outcome?
Microbiology and Infectious Disease / Laboratory Detection of AmpC β-lactamase Clinical Laboratory Detection of AmpC β-lactamase Does It Affect Patient Outcome? Kenneth H. Rand, MD, 1 Bradley Turner, MD,
More informationThe biomérieux solution. VITEK2 : A challenge with ESBL ESBL. Karen Bush
International Newsletter n 4 December 2003 Through the IDENTIFYING RESISTANCE Newsletter, biomérieux s ambition is to contribute to the awareness and progress in the field of resistance to antibiotics.
More informationThe Cat s Out of the Bag: Microbiological Investigations of Acute Transfusion Reactions.
The Cat s Out of the Bag: Microbiological Investigations of Acute Transfusion Reactions. Philippe Lagacé-Wiens, MD FRCPC, DTM&H plagacewiens@sharedhealthmb.ca COI declaration I have no conflicts, real
More informationNCCLS Standards for Antimicrobial Susceptibility Tests
CE Update Microbiology III NCCLS Standards for Antimicrobial Susceptibility Tests Clyde Thornsberry, PhD T he most requested test of the clinical microbiology laboratory today is probably t h e antimicrobial
More informationCERTIFICATE OF ACCREDITATION
CERTIFICATE OF ACCREDITATION In terms of section 22(2) (b) of the Accreditation for Conformity Assessment, Calibration and Good Laboratory Practice Act, 2006 (Act 19 of 2006), read with sections 23(1),
More informationNasdaq: AKAO. Cowen Health Care Conference March 3, 2015
Nasdaq: AKAO Cowen Health Care Conference March 3, 2015 Forward Looking Statements Forward-Looking Statements This presentation contains forward-looking statements. All statements other than statements
More informationPharmacodynamics of Ampicillin-Sulbactam in an In Vitro Infection Model against Escherichia coli Strains with Various Levels of Resistance
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Feb. 1998, p. 231 235 Vol. 42, No. 2 0066-4804/98/$04.00 0 Copyright 1998, American Society for Microbiology Pharmacodynamics of Ampicillin-Sulbactam in an In Vitro
More informationGuideline on the evaluation of medicinal products indicated for treatment of bacterial infections, Rev. 3 Draft
1 2 3 19 December 2018 EMA/844951/2018 Rev. 3 Committee for Human Medicinal Products (CHMP) 4 5 6 7 8 9 10 11 12 13 14 15 Guideline on the evaluation of medicinal products indicated for treatment of bacterial,
More information6/21/2012 Speaker Hannah Wexler, PhD, Objectives Continuing Education Credit program and evaluation by 07/21/ an Archived Program 612an
Anaerobic Bacteria Susceptibility Testing 6/21/2012 Speaker Hannah Wexler, PhD, Adjunct Professor, Department of Medicine UCLA School of Medicine, Los Angeles, CA Dr. Hannah Wexler is an Adjunct Professor
More informationANTIMICROBIAL SUSCEPTIBILITY TESTING: ADVANCED
ANTIMICROBIAL SUSCEPTIBILITY TESTING: ADVANCED Romney Humphries, Ph.D., DABMM Section Chief, Clinical Microbiology University of California Los Angeles Lost Angeles, CA Susan E. Sharp, Ph.D., DABMM, FAAM
More informationFOCUS ON MRSA/SA SSTI ASSAY FAILURE IN PROSTHETIC JOINT. Institute of Microbiology, Lille University Hospital, F Lille, France
JCM Accepted Manuscript Posted Online 16 November 2016 J. Clin. Microbiol. doi:10.1128/jcm.01658-16 Copyright 2016, American Society for Microbiology. All Rights Reserved. FOCUS ON MRSA/SA SSTI ASSAY FAILURE
More informationAntimicrobial Drugs. Antimicrobial Drugs. The dawn of antibiotics. Alexander Fleming. Chain and Florey. Antibiotics
Antimicrobial Drugs Antimicrobial Drugs Chemotherapy: The use of drugs to treat a disease Antimicrobial drugs: Interfere with the growth of microbes within a host Antibiotic: Substance produced by a microbe
More informationAntimicrobial Susceptibility Testing Paradigms: Current Status and Future Directions
Antimicrobial Susceptibility Testing Paradigms: Current Status and Future Directions Robert J. Tibbetts Department of Pathology, Henry Ford Health System, Detroit, MI 48202. Corresponding Author Robert
More informationVoriconazole and Aspergillus spp. Rationale for the EUCAST clinical breakpoints, version May 2012
Voriconazole and Aspergillus spp. Rationale for the EUCAST clinical breakpoints, version 1.0 20 May 2012 Foreword EUCAST The European Committee on Antimicrobial Susceptibility Testing (EUCAST) is organised
More informationFrequency of MecA Gene in the Clinical Isolates of Staphylococcus epidermidis in Isfahan, Iran. Shabnam Shamansouri, Vajihe Karbasizade *
Frequency of MecA Gene in the Clinical Isolates of Staphylococcus epidermidis in Isfahan, Iran Shabnam Shamansouri, Vajihe Karbasizade * Department of Microbiology, Falavarjan Branch, Islamic Azad University,
More informationGuest Forum. Clinical Examinations and Treatment of Infections. The Screening Committee Lecture for the First Dr. Masao Horiba s Award
Guest Forum The Screening Committee Lecture for the First Dr. Masao Horiba s Award Clinical Examinations and Treatment of Infections Satoshi Ichiyama Kyoto University Graduate School of Medicine Department
More informationFactors Influencing Detection of Tolerance in Staphylococcus aureus
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Sept. 1982, p. 364-368 Vol. 22, No. 3 0066-4804/82/090364-0$02.00/0 Copyright 1982, American Society for Microbiology Factors Influencing Detection of Tolerance in
More informationActivity of meropenem and other antimicrobial agents against uncommon Gram-negative organisms
Journal of Antimicrobial Chemotherapy (993) 3, 33-37 Activity of and other antimicrobial agents against uncommon Gram-negative organisms Richard B. Clark and Suzanne E. Joyce Department of Pathology, Crozer-Chester
More informationEvaluation of the Carba NP Test for the Detection of Carbapenemase Activity in Bacteroides Species
Polish Journal of Microbiology 2018, Vol. 67, No 1, 97 101 SHORT COMMUNICATION Evaluation of the Carba NP Test for the Detection of Carbapenemase Activity in Bacteroides Species ISIN AKYAR 1, 2, *, MELTEM
More informationTeicoplanin has not yet been evaluated, but we expect it will perform like vancomycin.
Detection of VISA, GISA, hvisa, VRE, Staphylococci Daptomycin Resistant, and Acinetobacter/Pseudomonas Colistin Resistant, using the Neo Sensitabs prediffusion method. S. aureus CB 182, Susceptible strain.
More informationComparison of BD Phoenix to Vitek 2, MicroScan MICroSTREP, and Etest for Antimicrobial Susceptibility Testing of Streptococcus pneumoniae
JOURNAL OF CLINICAL MICROBIOLOGY, Nov. 2009, p. 3557 3561 Vol. 47, No. 11 0095-1137/09/$12.00 doi:10.1128/jcm.01137-09 Copyright 2009, American Society for Microbiology. All Rights Reserved. Comparison
More informationTime for Precision: A World Without Susceptibility Breakpoints
Open Forum Infectious Diseases PERSPECTIVES Time for Precision: A World Without Susceptibility Breakpoints Justin C. Bader, 1 Elizabeth A. Lakota, 1 David R. Andes, 2 Christopher M. Rubino, 1 Paul G. Ambrose,
More informationtesting for the daily routine?
What is the role of in vitro antifungal susceptibility testing for the daily routine? ESCMID, Rome 2010 Cornelia Lass-Flörl Medical University Innsbruck Faculty disclosure Invited speaker: Pfizer, Gilead,
More informationScreening for Resistant Organisms and Infection Control
Screening for Resistant Organisms and Infection Control Dr Sonal Saxena Professor Department of Microbiology Lady Hardinge Medical College New Delhi 1 MDRO The proportion of K. pneumoniae and E. coli with
More informationIncorporating New TB Diagnostics into RePORT
Incorporating New TB Diagnostics into RePORT Susan Dorman Johns Hopkins University School of Medicine REPORT MEETING, DURBAN, JULY 2016 MACS designed to: 1. Elucidate the natural history of the infection
More information