This issue of Clinics in Laboratory Medicine, guest edited by James E. Kirby, will focus on Advances and Trends in
Clinical Microbiology and take a look at the next 20 years. Topics include, but are not limited to, Rapid
susceptibility testing methods; Synergy testing; Serology testing re-imagined; Total Laboratory Automation in Clinical
Microbiology; MALDI-TOF; Superbugs of the Future, the Antimicrobial Laboratory Resistance Network, Partnerships between
Public Health and the clinical microbiology laboratory; Next generation sequencing, from identification to
susceptibility prediction; Distributed microbiology testing; Direct from Sample Identification; Biomarkers - predicting
viral versus bacterial infection; PK/PD in the era of emerging multidrug-resistance; Training the next generation of
clinical microbiologists; and Pictorial illustration of debate, developments, and controversy in clinical microbiology.
Author Information
Edited by James E. Kirby
Contents
Preface: Our Pathogens Are Not Standing Still and Neither Can We
Rapid Susceptibility Testing Methods
When One Drug Is Not Enough: Context, Methodology, and Future Prospects in Antibacterial Synergy Tes
Clinical Microbiology in Underresourced Settings
Total Laboratory Automation: What Is Gained, What Is Lost, and Who Can Afford It?
Matrix-Assisted Laser Desorption/Ionization Time-of-Flight: The Revolution in Progress
Next-Generation Sequencing in Clinical Microbiology: Are We There Yet?
Distributed Microbiology Testing: Bringing Infectious Disease Diagnostics to Point of Care
Direct-from-Specimen Pathogen Identification: Evolution of Syndromic Panels
Predicting Bacterial Versus Viral Infection, or None of the Above: Current and Future Prospects of B
What the Clinical Microbiologist Should Know About Pharmacokinetics/Pharmacodynamics in the Era of E
Mapping the Road to the Future: Training the Next Generation of Clinical Microbiologists, from Techn
We Cannot Do It Alone: The Intersection of Public Health, Public Policy, and Clinical Microbiology
Pictorial Illustration
What Is the Future of Clinical Microbiology?
CLINICS IN LABORATORY MEDICINE
FORTHCOMING ISSUES
December 2019
March 2020
RECENT ISSUES
June 2019
March 2019
Preface: Our Pathogens Are Not Standing Still and Neither Can We
REFERENCE
Rapid Susceptibility Testing Methods
Key points
INTRODUCTION
FROM REFERENCE TO COMMERCIAL METHODS: CURRENT STATE
WITH EMERGING ANTIMICROBIAL RESISTANCE, TIMELINESS BECOMES IMPORTANT
RAPID SUSCEPTIBILITY LANDSCAPE OVERVIEW
GENOTYPIC TESTING
THE GRAM-POSITIVE/NEGATIVE GENOTYPIC DIVIDE
CHALLENGES OF RAPID PHENOTYPIC ANTIMICROBIAL SUSCEPTIBILITY TESTING
MICROSCOPY-BASED RAPID PHENOTYPIC ANTIMICROBIAL SUSCEPTIBILITY TESTING
MICROSCOPY PLUS MICROFLUIDICS
ALTERNATIVE OPTICAL DETECTION METHODS
SPECTROMETRY-BASED DETECTION
SIGNAL AMPLIFICATION
DECISION SUPPORT MUST GO HAND IN HAND WITH RAPID ANTIMICROBIAL SUSCEPTIBILITY
SUMMARY
ACKNOWLEDGMENTS
REFERENCES
When One Drug Is Not Enough
Key points
INTRODUCTION
MECHANISMS OF COMBINATION ANTIBIOTIC ACTIVITY
Prevention of Resistance
Enhanced Activity
SYNERGY TESTING METHODS
Checkerboard Array
Diffusion-Based Methods
Time-Kill Assay
In Vitro Pharmacokinetic/Pharmacodynamic Models
Animal Models
SYNERGY TESTING IN THE CLINICAL MICROBIOLOGY LABORATORY
CLINICAL RELEVANCE OF IN VITRO SYNERGY TESTING RESULTS
THE FUTURE OF SYNERGY TESTING
Clinical Trials Incorporating In Vitro Synergy Data
Simpler Synergy Testing Methods
Maximizing the Usefulness of Synergy Data
SUMMARY
REFERENCES
Clinical Microbiology in Underresourced Settings
Key points
EXAMPLES OF PERSONNEL ISSUES
EXAMPLES OF SUPPLIES ISSUES
RISING TO THE CHALLENGE
Importance of Initial Assessment
Importance of Infrastructure
Utilization of Standard Operating Procedures and Other Written Materials
Working Within the Local, Regional, and National Health Care System
Being Patient
SUMMARY
REFERENCES
Total Laboratory Automation
Key points
AUTOMATED SYSTEMS: DEFINITIONS AND DIFFERENCES
WHY TOTAL AUTOMATION IN CLINICAL MICROBIOLOGY?
THE MICROBIOLOGY LABORATORY STAFF, WILL THEY ACCEPT AUTOMATION?
WHAT IS GAINED?
Quality: Automated Barcoding
Quality: Automated Plate Inoculation and Streaking
Efficiency: General
Efficiency: Decreased Incubation Time Required for the Detection of Organism Growth
Efficiency: 24/7 Automated Plate Inoculations and Incubation
Efficiency: Labor Savings
Efficiency: Work Flow
Measuring Efficiency
Accessibility of Culture Images
Safety
WHAT IS LOST?
Technical Knowledge and Skills
Pride and Ownership Associated with Conventional Workflow
Day Shift-Only Plate Reading
Automation Downtime
WHO CAN AFFORD AUTOMATION?
Return on Investment
Total Automation Occupies Less Space
Can You Afford Not to Automate?
THE FUTURE AND ADDITIONAL GAINS OF AUTOMATION IN MICROBIOLOGY
REFERENCES
Matrix-Assisted Laser Desorption/Ionization Time-of-Flight
Key points
INTRODUCTION
ADVANCES IN ORGANISM IDENTIFICATION
Identification of Mycobacteria
Filamentous Fungi
ADVANCES IN ANTIMICROBIAL SUSCEPTIBILITY TESTING
Detection of Staphylococcal Methicillin Resistance
Detection of Reduced Vancomycin Susceptibility in Staphylococcus aureus
Growth-Based Susceptibility Testing of Bacteria
Stable Isotope Susceptibility Testing
Direct-on-Target Microdroplet Growth Assay
Growth-Based Susceptibility Testing of Fungi
Growth-Based Susceptibility Testing of Mycobacteria
ADVANCES IN ORGANISM IDENTIFICATION FROM CLINICAL SPECIMENS
Direct Organism Identification from Positive Blood Cultures
Short-Incubation Matrix-assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry
Organism Identification Directly from Positive Blood Culture Broth
RAPID URINE MATRIX-ASSISTED LASER DESORPTION/IONIZATION TIME-OF-FLIGHT MASS SPECTROMETRY
SUMMARY
REFERENCES
Next-Generation Sequencing in Clinical Microbiology
Key points
INTRODUCTION
Whole-Genome Sequencing
Targeted Next-Generation Sequencing
Metagenomic Next-Generation Sequencing
Use of Next-Generation Sequencing for Clinical Care: Where Are We at Now?
What Does the Future Hold for Next-Generation Sequencing in Clinical Microbiology Laboratories
REFERENCES
Distributed Microbiology Testing
Key points
CONTEXT: POINT-OF-CARE TESTING, WHAT, WHERE, WHO, AND WHY?
POINT-OF-CARE TESTING IN THE NEAR FUTURE: STRENGTHS, WEAKNESSES, OPPORTUNITIES, AND THREATS
INFORMATICS AT THE POINT OF CARE
THE FAR FUTURE: THERANOS, BUT NOT SO STUPID
REFERENCES
Direct-from-Specimen Pathogen Identification
Key points
INTRODUCTION
RESPIRATORY TRACT SYNDROMIC PANELS
Upper Respiratory Tract Panels
Future target consideration
Surveillance potential for novel pathogens
Simple, rapid, and near point-of-care testing
GASTROINTESTINAL SYNDROMIC PANELS
Modular Panels
Comprehensive Panel
Existing Gaps
Targets of unclear or unestablished significance
Targets with clinical relevance but not universally included
Clostridioides difficile testing without clinical indication
Host response targeting
Demographic and region-specific testing
Detection of antimicrobial resistance
Gastrointestinal Panel Future Needs Summary
BLOODSTREAM SYNDROMIC PANELS
Future Directions and Considerations
Target wish list
Direct from whole blood testing
Antimicrobial susceptibility needs
CENTRAL NERVOUS SYSTEM SYNDROMIC PANELS
Existing Gaps
Acute versus chronic central nervous system infections
Shunt infections
Testing in cases of mosquito exposure
Syndromic testing paired with cytokine profiling
Antimicrobial susceptibility
SUMMARY
REFERENCES
Predicting Bacterial Versus Viral Infection, or None of the Above
Key points
INTRODUCTION
THE ROLE OF BIOMARKERS IN DIAGNOSIS AND MANAGEMENT OF INFECTIOUS DISEASES
The Role of Biomarkers for the Diagnosis and Management of Sepsis
C-reactive Protein
Pentraxin-3
Procalcitonin
Proadrenomedullin
Additional Biomarkers for Sepsis
The Role of Biomarkers for the Diagnosis and Management of Pneumonia
FUTURE DIRECTIONS FOR THE ROLE OF BIOMARKERS IN DIAGNOSIS OF INFECTIOUS DISEASES
SUMMARY
REFERENCES
What the Clinical Microbiologist Should Know About Pharmacokinetics/Pharmacodynamics in the Era of E
Key points
INTRODUCTION
LACTAMASE-MEDIATED RESISTANCE
PHARMACOLOGY OF ?LACTAMASE INHIBITION
EFFICACY OF LACTAM-LACTAMASE INHIBITOR COMBINATIONS
LIMITATIONS IN CURRENT PRACTICE WITH LACTAM-LACTAMASE INHIBITOR COMBINATIONS
Fixed Agent Pairings
Fixed Dose Ratio Pairings
Current Approaches to Susceptibility Testing
Conventional Pharmacokinetic/Pharmacodynamic Characterization of Combinations
ALTERNATIVE STRATEGIES FOR PAIRING AND ASSESSING LACTAM-LACTAMASE INHIBITOR