Antibiotic Resistance This page intentionally left blank Antibiotic Resistance Mechanisms and New Antimicrobial Approaches Kateryna Kon, MD, PhD Department of Microbiology, Virology, and Immunology Kharkiv National Medical University Kharkiv, Ukraine Mahendra Rai, PhD Biotechnology Department SGB Amravati University Maharashtra, India AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 125 London Wall, London EC2Y 5AS, UK 525 B Street, Suite 1800, San Diego, CA 92101-4495, USA 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, USA The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK Copyright r 2016 Elsevier Inc. All rights reserved. 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ISBN: 978-0-12-803642-6 For Information on all Academic Press publications visit our website at https://www.elsevier.com/ Publisher: Sara Tenney Acquisition Editor: Linda Versteeg-buschman Editorial Project Manager: Halima Williams Production Project Manager: Lucı´aPerez´ Designer: Victoria Pearson Typeset by MPS Limited, Chennai, India Contents List of Contributors ............................................................................................................................. xv Preface ................................................................................................................................................ xxi CHAPTER 1 Antimicrobial Stewardship: Hospital Strategies to Curb Antibiotic Resistance....................................................... 1 L. Hsieh and A. Amin Introduction .................................................................................................................1 Moving From Cost to Quality and Patient Safety......................................................3 Elements of ASPs........................................................................................................4 Antimicrobial Stewardship Team ..........................................................................4 Antimicrobial Stewardship Strategies for Acute Care Hospitals...............................4 Key Stewardship Interventions ..............................................................................4 Supplemental Interventions.........................................................................................6 Education................................................................................................................6 Pharmacy Strategies ...............................................................................................7 Incorporating IT .....................................................................................................7 Laboratory Strategies ..................................................................................................8 Penicillin Skin Testing..............................................................................................12 Antibiotic Cycling.....................................................................................................12 Facilitators and Barriers of ASPs .............................................................................13 Measurements and Benchmarks................................................................................13 References .................................................................................................................15 CHAPTER 2 Mechanisms of Antibacterial Resistance: Shedding Some Light on These Obscure Processes? .................................. 19 K. de Sousa Oliveira, L.A. de Lima, N.B. Cobacho, S.C. Dias and O.L. Franco Introduction ...............................................................................................................19 Discovering the First Antibiotics.........................................................................19 Bacterial Resistance .............................................................................................20 Infection Control ..................................................................................................22 Mechanisms of Antibacterial Resistance..................................................................23 Enzymatic Inhibition............................................................................................24 PBP Modifications ...............................................................................................24 Porin Modifications..............................................................................................25 Efflux Pumps........................................................................................................25 Molecular Modification of Antibiotic Targets ....................................................29 v vi Contents Concluding Remarks.................................................................................................30 Acknowledgments .....................................................................................................31 References .................................................................................................................31 CHAPTER 3 Signaling Pathways Sustaining Antibiotic Resistance: Lessons From Methicillin-Resistant Staphylococcus aureus......... 37 P.F. Seke Etet, A.H. Nwabo Kamdje, L. Vecchio, M. Farahna and M.F. Mahomoodally Introduction ...............................................................................................................37 Emergence of Antibiotic-Resistant Bacteria ............................................................38 Resistant Bacteria Are Common in Urban Environments ..................................38 High MRSA Prevalence Reported in Hospitals of Developing Countries: Is Low Hygiene the Major Culprit? ............................................39 Origin of Resistance: Long-Term Use of Antibiotics.........................................40 Clinical Importance of Methicillin and Vancomycin Resistance .......................41 MRSA Metabolism Changes and Antibiotic Resistance..........................................43 Metabolic Pathway Changes Favor S. aureus Resistance...................................43 Bacterial Persisters ...............................................................................................44 Small Colony Variants .........................................................................................46 MRSA and Persister Resistance to Oxidative Stress ..........................................47 Mechanism of Actions of Nonmetabolic Genes Pivotal for MRSA Resistance .....48 Examples of Major Antibiotic Resistance Genes: mecA and cfr........................48 Efflux Genes.........................................................................................................50 Conclusions ...............................................................................................................50 References .................................................................................................................51 CHAPTER 4 Trends in Antimicrobial Resistance Among Enteric Pathogens: A Global Concern..................................................... 63 M. Ballal Introduction ...............................................................................................................63 Key Problems of Resistance in Hospitals and Communities...................................64 Tracking................................................................................................................65 What Causes Drug Resistance? ...........................................................................65 Costs of Resistance ..............................................................................................66