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Antibiotic Resistance: Challenges and Opportunities, An Issue of Infectious Disease Clinics of North America, E-Book

Antibiotic Resistance: Challenges and Opportunities, An Issue of Infectious Disease Clinics of North America, E-Book

Robert A. Bonomo | Richard R. Watkins

(2016)

Additional Information

Abstract

For many years, physicians and the public assumed that the discovery of new antimicrobial agents would outpace the ability of bacteria to mutate and develop drug resistance. Yet the development of new antibiotics has not kept up with bacterial evolution, especially since the late 1990’s. At that time a multitude of pharmaceutical companies abandoned antibiotic research because of strong economic disincentives. For example, it is challenging for these companies to recuperate the investment (typically in the hundreds of millions of dollars) made in developing a new antibiotic, which is typically prescribed for a few days, compared to drugs that treat chronic conditions like heart disease or mental illness. This situation has led the U.S. federal government to take a more active lead in addressing antibiotic resistance. Recently, the White House announced an action plan that includes improving surveillance, developing better diagnostic tools, accelerating drug development, and improving global coordination of antibiotic resistance issues. Equally important is the $1.2 billion dollars that has been pledged to fund these efforts. While we await the implementation of new policies, this issue of Infectious Disease Clinics of North America brings together leading authorities in the field of antibiotic resistance who discuss current issues including antibiotic stewardship, the changing role of the microbiology laboratory in determining antibiotic resistance in gram-negative pathogens, the continuing spread of metallo-β-lactamases, ESBLs and KPCs, antibiotic options for treating resistant gram-negative infections such as colistin and tigecycline, resistance mechanisms and new treatment options for Mycobacterium tuberculosis, emerging resistance mechanisms in aminoglycosides, issues with antibiotic resistance in immunocompromised patients, new β-lactamase inhibitors in the clinic, and resistance in VRE and Staphylococcus aureus. Additionally, combination therapy for resistant gram-negative infections has been advocated by some authorities and the advantages and disadvantages of this strategy will be reviewed.

Table of Contents

Section Title Page Action Price
Front Cover Cover
Antibiotic Resistance:Challenges and Opportunities\r i
Copyright\r ii
Contributors iii
CONSULTING EDITOR iii
EDITORS iii
AUTHORS iii
Contents vii
Preface: Antibiotic Resistance in the Twenty-First Century: Current Concepts and Future Directions\r vii
Overview: Global and Local Impact of Antibiotic Resistance\r vii
The Changing Role of the Clinical Microbiology Laboratory in Defining Resistance in Gram-negatives\r vii
The Continuing Plague of Extended-spectrum β-lactamase–producing Enterobacteriaceae Infections\r vii
Multidrug-Resistant Bacteria in the Community: Trends and Lessons Learned\r viii
Agents of Last Resort: Polymyxin Resistance\r viii
Vancomycin-Resistant Enterococci: Therapeutic Challenges in the 21st Century\r viii
New β-Lactamase Inhibitors in the Clinic\r viii
Antibiotic-Resistant Infections and Treatment Challenges in the Immunocompromised Host\r ix
Bacteremia due to Methicillin-Resistant Staphylococcus aureus: New Therapeutic Approaches\r ix
Drug-Resistant Tuberculosis: Challenges and Progress\r ix
Aminoglycoside Resistance: The Emergence of Acquired 16S Ribosomal RNA Methyltransferases\r ix
The Evolving Role of Antimicrobial Stewardship in Management of Multidrug Resistant Infections\r x
INFECTIOUS DISEASE CLINICS\rOF NORTH AMERICA\r xi
FORTHCOMING ISSUES xi
September 2016 xi
December 2016 xi
March 2017 xi
RECENT ISSUES xi
March 2016 xi
December 2015 xi
September 2015 xi
Preface: Antibiotic Resistance in the Twenty-First Century: Current Concepts and Future Directions\r xiii
Overview: Global and Local Impact of Antibiotic Resistance 313
Key points 313
INTRODUCTION 313
EVOLUTION OF ANTIBIOTIC RESISTANCE 314
ANTIBIOTICS AND AGRICULTURE 317
SOCIETAL BURDEN OF ANTIBIOTIC RESISTANCE 318
WHAT CAN BE DONE TO AVERT A POSTANTIBIOTIC ERA? 319
SUMMARY 319
REFERENCES 320
The Changing Role of the Clinical Microbiology Laboratory in Defining Resistance in Gram-negatives 323
Key points 323
INTRODUCTION 323
AVAILABLE METHODS 324
Standard Antimicrobial Susceptibility Test Methods 324
Rapid Biochemical Tests to Detect Extended-spectrum β-Lactamase and Carbapenemase Producers 325
Single and Multiplex Endpoint Polymerase Chain Reactions 325
Single and Multiplex Real-time Polymerase Chain Reactions 326
Loop-mediated Isothermal Amplification 327
Next-generation Sequencing 328
Whole-genome Sequencing 328
Microarrays 329
Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectroscopy 330
PROMISING TECHNOLOGIES IN DEVELOPMENT 330
Rapid Antimicrobial Susceptibility Testing 330
Microfluidics and Nanotechnology 331
Fluorescence In Situ Hybridization 332
FilmArray 332
Rapid Whole-genome Sequencing 332
Polymerase Chain Reaction/Electrospray Ionization Mass Spectrometry 332
DISCUSSION 333
REFERENCES 333
The Continuing Plague of Extended-spectrum β-lactamase–producing Enterobacteriaceae Infections 347
Key points 347
INTRODUCTION 348
THE EMERGENCE OF EXTENDED-SPECTRUM β-LACTAMASES 348
WORLDWIDE PREVALENCE OF EXTENDED-SPECTRUM β-LACTAMASES 349
LACTAMASES–PRODUCING ENTEROBACTERIACEAE INFECTIONS 349
OUTBREAK IN NONHOSPITAL SETTINGS 350
STRAIN IN THE COMMUNITY 352
WHAT ARE THE PREDICTORS FOR EXTENDED-SPECTRUM β-LACTAMASES–PRODUCING ENTEROBACTERIACEAE INFECTIONS ACQUIRED OUTSIDE OF THE ... 353
WHAT IS THE ISOLATED IMPACT OF EXTENDED-SPECTRUM β-LACTAMASE ACQUISITION ON PATIENTS' CLINICAL OUTCOMES? 355
TREATMENT OPTIONS FOR EXTENDED-SPECTRUM β-LACTAMASES–PRODUCING ENTEROBACTERIACEAE INFECTIONS IN HOSPITAL SETTINGS 355
Carbapenems 355
Cephalosporins 356
Fluoroquinolones 356
Cephamycins 357
β-Lactam–β-lactamase Inhibitors Combinations 357
Aminoglycosides 358
Tigecycline and Polymyxins 359
TREATING EXTENDED-SPECTRUM β-LACTAMASE INFECTIONS IN AMBULATORY SETTINGS 359
FUTURE PERSPECTIVE 360
REFERENCES 360
Multidrug-Resistant Bacteria in the Community 377
Key points 377
INTRODUCTION 377
COMMUNITY-ASSOCIATED, HEALTH CARE–ASSOCIATED, AND NOSOCOMIAL INFECTIONS 378
REQUIREMENTS FOR TRANSITION FROM NOSOCOMIAL PATHOGEN TO COMMUNITY-ASSOCIATED PATHOGEN 379
METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS 380
VANCOMYCIN-RESISTANT ENTEROCOCCI 380
CARBAPENEM-RESISTANT ACINETOBACTER BAUMANNII 381
MULTIDRUG-RESISTANT PSEUDOMONAS AERUGINOSA 382
ENTEROBACTERIACEAE THAT PRODUCE EXTENDED SPECTRUM β-LACTAMASES 383
CARBAPENEMASE-PRODUCING ENTEROBACTERIACEAE 384
PREVENTION 384
SUMMARY 385
REFERENCES 385
Agents of Last Resort 391
Key points 391
INTRODUCTION 391
MECHANISM OF ACTION 393
MECHANISMS OF RESISTANCE 393
CLINICAL EPIDEMIOLOGY OF POLYMYXIN-RESISTANT GRAM-NEGATIVE BACILLI 395
STRATEGIES TO MINIMIZE POLYMYXIN RESISTANCE 398
OPTIMIZING DOSING REGIMENS 398
COMBINATION THERAPY 401
PREVENTION OF POLYMYXIN RESISTANCE 404
Infection Control 404
Antimicrobial Stewardship 404
SUMMARY 405
REFERENCES 405
Vancomycin-Resistant Enterococci 415
Key points 415
INTRODUCTION: A REPORT FROM THE FRONT LINES 416
PROFILE OF AN OPPORTUNISTIC PATHOGEN 416
From the Iron Age to the Antibiotic Age 416
Enterococcal Infections: A Tale of Two Species 417
MASTER OF SURVIVAL 418
Host Colonization—Preamble to Infection 418
Virulence Factors 419
Antibiotic Resistance—Beyond Vancomycin 421
Daptomycin 421
Oxazolidinones 423
Lipoglycopeptides 424
Streptogramins 424
Glycylcyclines 425
COMBINED ARMS—THERAPEUTIC STRATEGIES FOR THE TREATMENT OF VANCOMYCIN-RESISTANT ENTEROCOCCI 425
Dual β-lactam Combinations 427
Daptomycin Combinations 427
Other Combinations 428
Therapeutic Approach 428
SUMMARY—NEW MILLENNIUM, NEW STRATEGIES 429
REFERENCES 430
New β-Lactamase Inhibitors in the Clinic 441
Key points 441
WHAT TRANSPIRED? THE FALL OF THE CURRENT CLINICALLY AVAILABLE β-LACTAM-β-LACTAMASE INHIBITOR COMBINATIONS 441
MAJOR OBSTACLES IN β-LACTAMASE INHIBITOR DEVELOPMENT 442
CHANGING THE β-LACTAM PARTNER: CEFTOLOZANE-TAZOBACTAM 443
DIAZABICYCLOOCTANONES, THE “FUTURE” OF β-LACTAMASE INHIBITOR MEDICINAL CHEMISTRY 445
AVIBACTAM, THE “PIONEER” DIAZABICYCLOOCTANONE IN THE CLINIC 445
RESISTANCE TO β-LACTAM-AVIBACTAM COMBINATIONS 447
DIAZABICYCLOOCTANONES, RELEBACTAM AND OP0595, ON THE HORIZON 448
DIAZABICYCLOOCTANONES IN PRECLINICAL DEVELOPMENT 448
BORONIC ACID β-LACTAMASE INHIBITORS ARE MAKING GREAT STRIDES 448
BORONIC ACIDS IN PRECLINICAL DEVELOPMENT 449
NOVEL SULFONES AND CLAVAMS IN PRECLINICAL DEVELOPMENT 452
PHOSPHONATES IN PRECLINICAL DEVELOPMENT 453
MONOBACTAMS ARE PROMISING β-LACTAMASE INHIBITORS OR EVADE β-LACTAMASE ACTIVITY 453
MONOBACTAMS AND DERIVATIVES IN PRECLINICAL DEVELOPMENT 455
A NEW SIDEROPHORE CEPHALOSPORIN IN CLINICAL DEVELOPMENT 455
NOVEL 3′-THIOBENZOYL CEPHALOSPORINS IN PRECLINICAL DEVELOPMENT 456
AND FSI-1686 456
LACTAMASE-SPECIFIC INHIBITORS IN PRECLINICAL DEVELOPMENT: BISTHIAZOLIDINES AND ME1071 457
SUMMARY 458
REFERENCES 459
Antibiotic-Resistant Infections and Treatment Challenges in the Immunocompromised Host 465
Key points 465
INTRODUCTION 465
THE IMMUNE SYSTEM AND HOST SUSCEPTIBILITY TO BACTERIAL PATHOGENS 466
SOLID ORGAN TRANSPLANTATION 466
Prevalence of Pathogens in Solid Organ Transplant 467
Risks for Multidrug-resistant Organisms 467
Inappropriate Empiric Antibiotics 471
Morbidity and Mortality Associated with Multidrug-resistant Organisms 471
Mortality Risks 472
THE NEUTROPENIC HOST 472
Prevalence of Multidrug-resistant Organisms in Cancer Patients with Neutropenic Fever 473
Risks for Multidrug-resistant Organisms in the Febrile Neutropenic Patient 475
Inappropriate Empiric Antibiotics 476
Morbidity and Mortality Associated with Multidrug-resistant Organisms 477
Mortality Risks and Multidrug-resistant Organisms 477
HUMAN IMMUNODEFICIENCY VIRUS INFECTION AND AIDS 478
Incidence and Risks for Methicillin-resistant Staphylococcus aureus Colonization and Infection in Human Immunodeficiency Vi ... 479
Antibiotic Resistance in Streptococcus pneumoniae in Patients with Human Immunodeficiency Virus Infection 480
Antibiotic Resistance in Enterococcus spp. Among Human Immunodeficiency Virus-infected Patients 480
Does Trimethoprim–Sulfamethoxazole Prophylaxis Cause Resistance? 481
Other Antibiotic Resistance Among Gram-negative Pathogens, Including Extended Spectrum β-Lacatamase, Among Human Immunodefi ... 481
SUMMARY 481
REFERENCES 482
Bacteremia due to Methicillin-Resistant Staphylococcus aureus 491
Key points 491
INTRODUCTION 491
GLYCOPEPTIDES AND SEMISYNTHETIC LIPOGLYCOPEPTIDES 492
Vancomycin 492
Semisynthetic Lipoglycopeptides 493
Oritavancin 493
Dalbavancin 496
Telavancin 496
DAPTOMYCIN 496
FIFTH-GENERATION CEPHALOSPORINS: CEFTAROLINE 497
OXAZOLIDINONES 498
TIGECYCLINE 499
COMBINATION THERAPY 499
Combinations with Vancomycin 499
Combinations with Daptomycin 500
Daptomycin plus β-lactams 500
Daptomycin plus trimethoprim-sulfamethoxazole 501
Daptomycin plus either ceftaroline or trimethoprim-sulfamethoxazole: A comparison 501
Trimethoprim-sulfamethoxazole plus ceftaroline 501
Combinations with Fosfomycin 503
SUMMARY 503
REFERENCES 503
Drug-Resistant Tuberculosis 509
Key points 509
BACKGROUND 509
RESISTANCE MECHANISMS AND CURRENT APPROACHES TO TREATMENT 510
Standard Therapy for Drug-Susceptible Tuberculosis: Mechanisms and Resistance 511
Current Treatment Regimen for Multidrug-Resistant Tuberculosis: Second-Line Agents 511
CLINICAL TRIALS 513
Alternative Approaches to Drug-Resistant Tuberculosis Clinical Drug Development 515
SUMMARY 517
REFERENCES 517
Aminoglycoside Resistance 523
Key points 523
INTRODUCTION 523
MECHANISMS OF AMINOGLYCOSIDE RESISTANCE 524
BACTERIA 526
ArmA 527
RmtA 529
RmtB 529
RmtC 530
RmtD 530
RmtE 530
RmtF 530
RmtG 531
RmtH 531
NpmA 531
PREVALENCE OF 16S RIBOSOMAL RNA METHYLTRANSFERASES 531
CLINICAL IMPLICATIONS 531
SUMMARY 532
REFERENCES 532
The Evolving Role of Antimicrobial Stewardship in Management of Multidrug Resistant Infections 539
Key points 539
INTRODUCTION 539
RESISTANCE AND THE NEED FOR ANTIMICROBIAL STEWARDSHIP 540
COLLABORATE FOR SUCCESS 541
COST OF RESISTANCE AND IMPACT OF ANTIMICROBIAL STEWARDSHIP PROGRAMS 542
EVIDENCE OF STEWARDSHIP ON THE IMPACT OF ANTIMICROBIAL RESISTANCE 543
USE OF NEW ANTIMICROBIALS 548
SUMMARY 548
REFERENCES 549
Index 553