Table of Contents

Cover

PREFACE

ABOUT THE AUTHOR

IMPORTANT NOTICE

1 INTRODUCTION

1.1 GENERAL INTRODUCTION
1.2 DEFINITIONS
1.3 GENERAL MICROBIOLOGY
1.4 GENERAL CONSIDERATIONS
FURTHER READING

2 PHYSICAL DISINFECTION

2.1 INTRODUCTION
2.2 HEAT
2.3 COLD TEMPERATURES
2.4 RADIATION
2.5 FILTRATION
FURTHER READING

3 CHEMICAL DISINFECTION

3.1 INTRODUCTION
3.2 ACIDS AND ACID DERIVATIVES
3.3 ALKALIS (BASES)
3.4 ALDEHYDES
3.5 ALCOHOLS
3.6 ANILIDES
3.7 ANTIMICROBIAL DYES
3.8 BIGUANIDES
3.9 DIAMIDINES
3.10 ESSENTIAL OILS AND PLANT EXTRACTS
3.11 HALOGENS AND HALOGEN-RELEASING AGENTS
3.12 METALS
3.13 PEROXYGENS AND OTHER FORMS OF OXYGEN
3.14 PHENOLICS
3.15 ANTISEPTIC PHENOLICS
3.16 QACS AND OTHER SURFACTANTS
3.17 MISCELLANEOUS BIOCIDES OR APPLICATIONS
FURTHER READING

4 ANTISEPTICS AND ANTISEPSIS

4.1 INTRODUCTION
4.2 SOME DEFINITIONS SPECIFIC TO ANTISEPSIS
4.3 THE STRUCTURE OF SKIN
4.4 SKIN MICROBIOLOGY
4.5 ANTISEPTIC APPLICATIONS
4.6 BIOCIDES USED AS ANTISEPTICS
FURTHER READING

5 PHYSICAL STERILIZATION

5.1 INTRODUCTION
5.2 STEAM
5.3 DRY-HEAT STERILIZATION
5.4 RADIATION STERILIZATION
5.5 FILTRATION
5.6 DEVELOPING METHODS
FURTHER READING

6 CHEMICAL STERILIZATION

6.1 INTRODUCTION
6.2 EPOXIDES
6.3 LTSF
6.4 HIGH-TEMPERATURE FORMALDEHYDE-ALCOHOL
6.5 HYDROGEN PEROXIDE
6.6 OTHER OXIDIZING-AGENT-BASED PROCESSES
FURTHER READING

7 MECHANISMS OF ACTION

7.1 INTRODUCTION
7.2 ANTI-INFECTIVES
7.3 MACROMOLECULAR STRUCTURE
7.4 GENERAL MECHANISMS OF ACTION
FURTHER READING

8 MECHANISMS OF MICROBIAL RESISTANCE

8.1 INTRODUCTION
8.2 BIOCIDE-MICROORGANISM INTERACTION
8.3 INTRINSIC BACTERIAL RESISTANCE MECHANISMS
8.4 INTRINSIC RESISTANCE OF MYCOBACTERIA
8.5 INTRINSIC RESISTANCE OF OTHER GRAM-POSITIVE BACTERIA
8.6 INTRINSIC RESISTANCE OF GRAM-NEGATIVE BACTERIA
8.7 ACQUIRED BACTERIAL RESISTANCE MECHANISMS
8.8 MECHANISMS OF VIRAL RESISTANCE
8.9 MECHANISMS OF PRION RESISTANCE
8.10 MECHANISMS OF FUNGAL RESISTANCE
8.11 MECHANISMS OF RESISTANCE IN OTHER EUKARYOTIC MICROORGANISMS
FURTHER READING

INDEX

End User License Agreement

List of Tables

Chapter 1

TABLE 1.1 Examples of various types of microorganisms
TABLE 1.2 Some advantages and disadvantages of microorganisms
TABLE 1.3 Comparison of general prokaryotic and eukaryotic structuresa
TABLE 1.4 Helminths associated with disease
TABLE 1.5 Examples of common fungi
TABLE 1.6 Classification of protozoa, based on their motility mechanisms and mic...
TABLE 1.7 Examples of pathogenic mycoplasmas
TABLE 1.8 General differentiation of types of bacteria based on their microscopi...
TABLE 1.9 Examples of gram-positive bacteria
TABLE 1.10 Examples of gram-negative bacteria
TABLE 1.11 Cell wall structures in mycobacteria and related organisms
TABLE 1.12 Examples of extremophile archaea
TABLE 1.13 Viral families, with examples of classifications, including size, pre...
TABLE 1.14 Examples of viral diseases
TABLE 1.15 Examples of bacterial, fungal, and algal toxins
TABLE 1.16 Common examples of bacterial exotoxins
TABLE 1.17 Examples of surrogate microorganisms used to test and verify antimicr...
TABLE 1.18 Examples of standardized suspension tests
TABLE 1.19 Examples of standardized carrier tests
TABLE 1.20 Examples of simulated-use and/or in-use tests and/or guidelinesa
TABLE 1.21 Bacterial-endospore species used to monitor and validate sterilizatio...
TABLE 1.22 Examples of biological-indicator standards
TABLE 1.23 A typical classification of chemical indicators
TABLE 1.24 Examples of chemical-indicator standards
TABLE 1.25 Examples of standards and guidelines for antisepsis, disinfection and...
TABLE 1.26 Various constituents of formulated biocidal products
TABLE 1.27 Examples of process variables in various disinfection/sterilization t...
TABLE 1.28 Various components of cleaning formulations
TABLE 1.29 Examples of common water contaminants and their effects

Chapter 2

TABLE 2.1 Examples of various standards and guidelines for heat disinfection
TABLE 2.2 Wavelengths and energies of types of electromagnetic radiation
TABLE 2.3 Types of UV radiation
TABLE 2.4 IR wavelength range
TABLE 2.5 Typical uses of filtration for liquid and gas applications
TABLE 2.6 Classification of clean rooms based on number of ≥0.5-μm particles det...
TABLE 2.7 Examples of standards and guidelines for disinfection and sterilizatio...

Chapter 3

TABLE 3.1 Examples of various guidelines and standards on the use and applicatio...
TABLE 3.2 Various types and sources of essential oils
TABLE 3.3 Other oxygen- and hydrogen peroxide-releasing compounds
TABLE 3.4 Comparison of sporicidal efficacies of liquid and gaseous hydrogen per...
TABLE 3.5 Hydrogen peroxide-based synergistic formulations and processes
TABLE 3.6 Various types of phenolic compounds
TABLE 3.7 Classification of surfactants
TABLE 3.8 Various biocides used on antimicrobial surfaces
TABLE 3.9 Various types of proteins, peptides, and enzymes used as biocides

Chapter 4

TABLE 4.1 Common or notable infections of the skin
TABLE 4.2 Examples of various guidelines and standards on the use and applicatio...
TABLE 4.3 Examples of biocides most widely used as skin antiseptics and washesa
TABLE 4.4 Miscellaneous biocides used as antiseptics and their applications

Chapter 5

TABLE 5.1 Common steam contaminants and their effects
TABLE 5.2 Typical qualities of WFI and “clean” steama
TABLE 5.3 Typical steam sterilization cycles
TABLE 5.4 Examples of standards and guidelines for steam sterilization applicati...
TABLE 5.5 Typical steam sterilization cycles recommended for TSE-associated deco...
TABLE 5.6 Examples of bacterial-spore resistance to dry heat at 160°C
TABLE 5.7 Materials disinfected and/or sterilized by radiation
TABLE 5.8 Typical doses of radiation for biocidal applications
TABLE 5.9 Examples of standards and guidelines for radiation sterilization appli...

Chapter 6

TABLE 6.1 Typical ethylene oxide sterilization process conditions, based on FDA-...
TABLE 6.2 Examples of standards and guidelines for EO sterilization applications
TABLE 6.3 Examples of standards and guidelines for LTSF sterilization applicatio...
TABLE 6.4 Comparison of STERRAD hydrogen peroxide gas-plasma sterilization syste...

Chapter 7

TABLE 7.1 Comparison of anti-infectives and biocides
TABLE 7.2 Widely used antibiotics (antibacterials) and their mechanisms of actio...
TABLE 7.3 Widely used antifungal drugs and mechanisms of action
TABLE 7.4 Widely used antiviral drugs and mechanisms of action
TABLE 7.5 Widely used antiparasitic drugs and mechanisms of action
TABLE 7.6 Biocides with an oxidizing-agent-based mode of action
TABLE 7.7 Examples of products observed on reaction of oxidizing agents with ami...
TABLE 7.8 Biocides with cross-linking- or coagulation-based modes of action
TABLE 7.9 Biocidal processes with transfer-ofenergy-based modes of action
TABLE 7.10 Biocides that act by disrupting the structures and functions of macro...

Chapter 8

TABLE 8.1 Examples of intrinsic and acquired mechanisms of resistance to biocide...
TABLE 8.2 Examples of bacterial responses to environmental stress
TABLE 8.3 Differences observed in the expression of proteins during the hydrogen...
TABLE 8.4 Classification of active-transporter systems
TABLE 8.5 Examples of bacterial efflux systems that have been shown to extrude b...
TABLE 8.6 Protective cell surface structures external to the bacterial cell wall
TABLE 8.7 Typical bacteria and fungi associated with biofilm formation
TABLE 8.8 Biofilms and microbial response to antimicrobial agents
TABLE 8.9 Examples of known extreme resistance to biocides and biocidal processe...
TABLE 8.10 Spore-forming bacteria and their significance
TABLE 8.11 Sporistatic and sporicidal concentrations of liquid biocidesa
TABLE 8.12 Structures, components, and activities of endospores and their vegeta...
TABLE 8.13 Examples of revival mechanisms that have been described following bio...
TABLE 8.14 Ranges of MICs and MBCs of chlorhexidine and triclosan against S. aur...
TABLE 8.15 MICs of various biocides (determined in test media) for gram-positive...
TABLE 8.16 Possible transport mechanisms of some biocides into gram-negative bac...
TABLE 8.17 Acquired mechanisms of resistance to antimicrobial drugs
TABLE 8.18 Examples of RND efflux pumps associated with biocide resistance in P....
TABLE 8.19 Examples of mutations causing increased sensitivity to biocides
TABLE 8.20 Identified and possible mechanisms of plasmid-encoded resistance to b...
TABLE 8.21 Examples of acquired (plasmid or transposon) resistance to mercury in...
TABLE 8.22 Examples of plasmid-mediated resistance to silver and copper in bacte...
TABLE 8.23 Plasmid-mediated resistance to various toxic metals in bacteria
TABLE 8.24 Examples of qac genes and susceptibilities of S. aureus strains to bi...
TABLE 8.25 qac genes and resistance to QACs and other biocides
TABLE 8.26 Viral classification and response to biocidesa
TABLE 8.27 Effects of various disinfection and sterilization methods on prions
TABLE 8.28 Possible mechanisms of fungal resistance to biocides
TABLE 8.29 Comparison of the relative resistances of bacteria and fungi to bioci...
TABLE 8.30 Fungicidal concentrations of biocides for yeasts and molds
TABLE 8.31 Various cell wall structures of fungi
TABLE 8.32 Parameters affecting the response of S. cerevisiae to chlorhexidine
TABLE 8.33 Examples of spores produced by fungi
TABLE 8.34 Minimum amoebicidal concentrations for Acanthamoeba trophozoites and ...

List of Illustrations

Chapter 1

FIGURE 1.1 A typical helminth life cycle (example: Enterobius vermicularis).
FIGURE 1.2 Typical fungal structures. (A) Filamentous fungus (mold). Hyphae are ...
FIGURE 1.3 Simplified fungal cell envelope. The cross-linked cell wall is linked...
FIGURE 1.4 Life cycle of Toxoplasma gondii.
FIGURE 1.5 Simple representation of a mycoplasma cell surface structure.
FIGURE 1.6 Basic structure of a bacterial cell, showing the cell surface in grea...
FIGURE 1.7 Bacterial cell wall structures. The cell membranes are similar struct...
FIGURE 1.8 Basic structure of peptidoglycan. Polysaccharides of repeating sugars...
FIGURE 1.9 Cells of Mycobacterium tuberculosis. Courtesy of Clifton Barry, NIAID...
FIGURE 1.10 Basic viral structure.
FIGURE 1.11 Typical viral life cycle. The stages include (1) attachment, (2) pen...
FIGURE 1.12 E. coli bacteriophages. The T-phages are complex DNA viruses; MS2 an...
FIGURE 1.13 Theory of prions as infectious proteins. PrPc is the normal form of ...
FIGURE 1.14 Representation of the proposed structural changes in PrP.
FIGURE 1.15 The general structure of lipopolysaccharide. The lipid A component i...
FIGURE 1.16 Typical fungal aflatoxin structure.
FIGURE 1.17 General microbial resistance to biocides and biocidal processes. Thi...
FIGURE 1.18 Typical time kill, or D-value, determination. A known concentration ...
FIGURE 1.19 Determination of the D value on microbial exposure to a biocide.
FIGURE 1.20 Typical survivor curves on biocide exposure. Curve 1 is concave down...
FIGURE 1.21 Qualitative and semiquantitative population determinations.
FIGURE 1.22 D-value estimation using most probable number estimations.
FIGURE 1.23 Example of a self-contained biological indicator. The 3M Attest 1292...
FIGURE 1.24 Example of a chemical-indicator color change.
FIGURE 1.25 Rate of microbial inactivation on exposure to sterilization processe...
FIGURE 1.26 Basic structures of surfactants and soaps and micelles (a water-in-o...
FIGURE 1.27 Examples of single (left)- and multiple (right)-chamber washer and w...
FIGURE 1.28 Various types of cleaning chemical formulations.

Chapter 2

FIGURE 2.1 Typical microbial sensitivities to moist-heat disinfection.
FIGURE 2.2 Effect of temperature on microbial lethality and Z-value determinatio...
FIGURE 2.3 A pasteurizer for heat treatment of liquids. Courtesy of System Produ...
FIGURE 2.4 Moist-heat resistance of microorganisms.
FIGURE 2.5 Atomic structure and the source of radiation.
FIGURE 2.6 The electromagnetic spectrum. The range of wavelengths is shown on th...
FIGURE 2.7 A representation of a typical UV (low-pressure UV mercury) lamp and t...
FIGURE 2.8 Simple structure of a magnetron used for the production of microwaves...
FIGURE 2.9 A simple continuous-duty UV disinfection system for liquids. The UV l...
FIGURE 2.10 The theory of filtration. Various types of filtration processes are ...
FIGURE 2.11 The microscopic structures of the surfaces of three filter materials...
FIGURE 2.12 Examples of a variety of liquid filter types. Reproduced with permis...
FIGURE 2.13 An example of a rigid-walled isolator system, with glove access port...
FIGURE 2.14 Air pressure in environmentally controlled enclosed areas. (A) Rooms...
FIGURE 2.15 Biological safety class I, II, and III cabinets. Class I cabinets pr...
FIGURE 2.16 Range of filtration methods and reference size exclusion capabilitie...

Chapter 3

FIGURE 3.1 Dissociation of benzoic acid. As the pH increases, the dissociation o...
FIGURE 3.2 High-level disinfectants for medical-device disinfection based on 2.4...
FIGURE 3.3 Examples of formaldehyde-releasing agents.
FIGURE 3.4 Examples of an alcohol-based disinfectant (left) and an alcohol-based...
FIGURE 3.5 Aminoacridines commonly used as antiseptics.
FIGURE 3.6 Examples of chlorhexidine-based antiseptics and disinfectants. Courte...
FIGURE 3.7 An example of an essential-oilcontaining disinfectant.
FIGURE 3.8 Simplified chemistry of iodine in water, demonstrating those species ...
FIGURE 3.9 The structure of PVPI. The polymer consists of repeating units of the...
FIGURE 3.10 Various types of PVPI antiseptic products. Reproduced with permissio...
FIGURE 3.11 Simplified chemistry of chlorine in water, demonstrating those speci...
FIGURE 3.12 Examples of organic chloramines.
FIGURE 3.13 Typical bromine-releasing agents. PSHB is an example of a water-inso...
FIGURE 3.14 Sodium hypochlorite (bleach)-based disinfectant. A concentrate (whic...
FIGURE 3.15 Silver sulfadiazine.
FIGURE 3.16 A typical copper-silver ionization system. The electrode cell consis...
FIGURE 3.17 Structure of benzoyl peroxide.
FIGURE 3.18 Example of the generation of PAA from sodium perborate and acetylsal...
FIGURE 3.19 Examples of the production of chlorine dioxide from chlorine.
FIGURE 3.20 Examples of ozone generators. Courtesy of Absolute Systems (left) an...
FIGURE 3.21 Examples of vaporized hydrogen peroxide (VHP) generators. The exampl...
FIGURE 3.22 Typical room fumigation setup with a hydrogen peroxide gas generator...
FIGURE 3.23 A range of chlorine dioxide-based liquid formulations for medical-de...
FIGURE 3.24 A chlorine dioxide gas generator for liquid applications. Courtesy o...
FIGURE 3.25 A typical chlorine dioxide fumigation cycle. The biocide concentrati...
FIGURE 3.26 The effect of temperature on the sporicidal efficacy of PAA. The ave...
FIGURE 3.27 Phenolic-based disinfectants. Both are formulation concentrates (whi...
FIGURE 3.28 Typical bisphenolic structures.
FIGURE 3.29 The modes of action of triclosan and hexachloro phene against enoyl ...
FIGURE 3.30 Basic surfactant and micelle structures.
FIGURE 3.31 The basic structure of QACs.
FIGURE 3.32 QAC-based disinfectants. A readyto-use spray formulation and an exam...
FIGURE 3.33 Examples of chlorine-based N-halamines.
FIGURE 3.34 The enzymatic activity of lysozyme. The structure of peptidoglycan (...

Chapter 4

FIGURE 4.1 Cross section of skin structure. Illustration by Patrick Lane, ScEYEn...
FIGURE 4.2 Examples of various types of antiseptic products.
FIGURE 4.3 Examples of biocide-impregnated materials for skin application.
FIGURE 4.4 A representation of the penetration of chlorhexidine into the skin ep...

Chapter 5

FIGURE 5.1 The relationship between saturated steam temperature and pressure.
FIGURE 5.2 A steam sterilizer. Sterilizers are available in a variety of sizes a...
FIGURE 5.3 The basic design of an upward-displacement steam sterilizer.
FIGURE 5.4 The basic design of a downward-displacement steam sterilizer.
FIGURE 5.5 The basic design of a prevacuum steam sterilizer.
FIGURE 5.6 Typical steam sterilization cycles, showing different mechanisms of a...
FIGURE 5.7 The Bowie-Dick test, a method of testing the steam penetration and ai...
FIGURE 5.8 Typical water pretreatment systems for the production of steam.
FIGURE 5.9 Effect of temperature on the lethality of a G. stearothermophilus spo...
FIGURE 5.10 An industrial dry-heat sterilizer, which is used for depyrogenation....
FIGURE 5.11 Representative effects of humidity/water content on the dry-heat res...
FIGURE 5.12 Generation and decay of 60Co.
FIGURE 5.13 The generation of X rays. Electrons are shown being generated from t...
FIGURE 5.14 A simplified linear high-energy E-beam generator.
FIGURE 5.15 A typical γ-irradiator sterilizer.
FIGURE 5.16 A typical exposure rack containing 60Co as a γ-radiation source with...
FIGURE 5.17 A typical E-beam sterilizer. An X-ray sterilizer may be in a similar...
FIGURE 5.18 Example of plasma generation with oxygen gas (O2).
FIGURE 5.19 An example of a pulsed-light sterilizer. Courtesy of Xenon Corporati...
FIGURE 5.20 The relationship between solid, liquid, gas, and supercritical fluid...

Chapter 6

FIGURE 6.1 An example of a small EO sterilizer, showing the front-loading steril...
FIGURE 6.2 A typical EO sterilizer.
FIGURE 6.3 Typical EO sterilization processes. Vacuum processes (top), in which ...
FIGURE 6.4 The sporicidal (B. atrophaeus) effects of EO concentrations at 60% re...
FIGURE 6.5 A representation of a typical LTSF sterilization system.
FIGURE 6.6 A typical LTSF sterilization cycle.
FIGURE 6.7 An LTSF sterilizer. The sterilizer (with the door open) is shown on t...
FIGURE 6.8 An example of the effect of the hydrogen peroxide gas concentration o...
FIGURE 6.9 A typical hydrogen peroxide gas sterilizer.
FIGURE 6.10 STERRAD hydrogen peroxide gas-plasma sterilizers. (Reprinted with pe...
FIGURE 6.11 Typical hydrogen peroxide gas sterilization processes. In the cycle ...
FIGURE 6.12 A SYSTEM 1 processor with STERIS 20 sterilant. (Reprinted with permi...
FIGURE 6.13 Electrolyzed water. (A) A typical electrolyzed-water generator. (B) ...
FIGURE 6.14 Examples of electrolyzed-water generators. Courtesy of Sterilox Tech...
FIGURE 6.15 A 125-liter ozone sterilizer. (Reprinted with permission from TSO3.)

Chapter 7

FIGURE 7.1 Primary bacterial targets of key antibiotics.
FIGURE 7.2 The structures of amino acids and peptide bonding. Representations ar...
FIGURE 7.3 Examples of sugars, polysaccharides, and glycosidic bonds. The polysa...
FIGURE 7.4 The basic structures of fatty acids. The numbers of carbons in the fa...
FIGURE 7.5 Examples of various types of lipids. The general structures of a trig...
FIGURE 7.6 The basic structures of nucleotides. The structure consists of a suga...
FIGURE 7.7 Nucleotide structures. ATP (top left) is a mononucleotide, while DNA ...
FIGURE 7.8 The major target sites for oxidizing agents on the structure of DNA (...
FIGURE 7.9 Reaction of ethylene oxide with guanine.
FIGURE 7.10 Reaction of ethylene oxide with amino acid side chains.
FIGURE 7.11 Amino acids, showing free amine groups (circled), susceptible to cro...
FIGURE 7.12 A typical cross-linking reaction with formaldehyde between a lysine ...
FIGURE 7.13 A typical cross-linked reaction by glutaraldehyde between two amino ...
FIGURE 7.14 Heat denaturation of DNA (above) and protein (below). As the tempera...
FIGURE 7.15 The effects of ionizing and nonionizing radiation on a target atom. ...
FIGURE 7.16 The production of thymine dimers between adjacent thymine bases in D...
FIGURE 7.17 The mode of action of acridine dyes. The acridine molecule shown (pr...
FIGURE 7.18 The reaction of metal ions on exposed sulfhydryl groups on cysteine ...
FIGURE 7.19 The effects of biocides on cytoplasmic membranes. The biocide can ha...

Chapter 8

FIGURE 8.1 General microbial resistance to biocides and biocidal processes.
FIGURE 8.2 The initial sequence of events in biocide-microorganism interaction.
FIGURE 8.3 A typical bacterial growth curve, showing the four phases of growth.
FIGURE 8.4 The activation and deactivation of the OxyR protein, as an activator ...
FIGURE 8.5 The functions of various enzymes induced during oxidative stress.
FIGURE 8.6 Transport systems in bacteria across a typical cell membrane.
FIGURE 8.7 Establishment of the PMF.
FIGURE 8.8 Summary of the various types of efflux pumps associated with antimicr...
FIGURE 8.9 Intrinsic mechanisms of microbial resistance to heavy metals. The hea...
FIGURE 8.10 A P. aeruginosa biofilm on a surface. Individual rod-shaped bacteria...
FIGURE 8.11 The development of a biofilm. Initial attachment (adsorption) of a m...
FIGURE 8.12 An example of D. radiodurans survival of radiation. The survival of ...
FIGURE 8.13 Micrograph of D. radiodurans cells in a typical tetrad formation.
FIGURE 8.14 Microbial growth and optimum temperature conditions. Examples of var...
FIGURE 8.15 Microbial growth and optimum pH conditions. Examples of various micr...
FIGURE 8.16 Microbial growth and optimum salt conditions. Examples of various mi...
FIGURE 8.17 The basic life cycle of gram-positive endospore-forming rods. The ve...
FIGURE 8.18 Typical bacterial-endospore structure. An actual micrograph of endos...
FIGURE 8.19 A representation of a typical sporulation process, with the key stag...
FIGURE 8.20 The development of resistance of bacterial endospores to biocides an...
FIGURE 8.21 Loss of resistance to various biocides and heat during bacterial-end...
FIGURE 8.22 Typical life cycle of Streptomyces. A desiccated spore, under the ri...
FIGURE 8.23 The revival of microorganisms after biocidal treatment. On exposure,...
FIGURE 8.24 A representation of the mycobacterial cell wall structure.
FIGURE 8.25 A representation of a typical gram-positive bacterial cell wall stru...
FIGURE 8.26 A representation of a typical gram-negative bacterial cell wall stru...
FIGURE 8.27 The primary mechanisms of action of penicillin and of bacterial resi...
FIGURE 8.28 The modes of bacterial tolerance of triclosan due to acquired mutati...
FIGURE 8.29 Demonstration of the resistance of M. chelonae glutaraldehyde-resist...
FIGURE 8.30 The simplified structure of a typical mercury resistance operon in g...
FIGURE 8.31 Mechanisms of resistance to mercury.
FIGURE 8.32 pSK41, an example of a multidrug resistance plasmid in staphylococci...
FIGURE 8.33 Mechanisms of viral resistance to biocides. The typical structure of...
FIGURE 8.34 Mechanisms of resistance of prions to biocides and modes of action o...
FIGURE 8.35 Scanning electron micrograph of an encapsulated C. neoformans strain...
FIGURE 8.36 Typical growth of a fungus on a medium surface. Shown are 7-day-old ...
FIGURE 8.37 Fungal life cycle (ascomycota). The life cycle shown is typical of a...
FIGURE 8.38 Examples of various types of fungal spores and spore-bearing structu...
FIGURE 8.39 Representation of the structure of a helminth (Ascaris) egg.
FIGURE 8.40 C. parvum oocysts and sporozoites.
FIGURE 8.41 An Acanthamoeba cyst. Reprinted with permission of the U. S. Armed F...

Address editorial correspondence to ASM Press, 1752 N St. NW, Washington, DC 20036-2904, USA

Send orders to ASM Press, P.O. Box 605, Herndon, VA 20172, USA

Phone: (800) 546-2416 or (703) 661-1593

Fax: (703) 661-1501

E-mail: books@asmusa.org

Online: estore.asm.org

American Society for Microbiology

1752 N St. NW

Washington, DC 20036-2904

Library of Congress Cataloging-in-Publication Data

McDonnell, Gerald E.

Antisepsis, disinfection, and sterilization : types, action, and resistance / Gerald E. McDonnell.

p. ; cm.

Includes bibliographical references and index.

ISBN-13: 978-1-55581-392-5 (hardcover)

ISBN-10: 1-55581-392-5 (hardcover)

1. Sterilization. 2. Asepsis and antisepsis. 3. Disinfection and disinfectants. I. Title. [DNLM: 1. Antisepsis. 2. Disinfection. 3. Sterilization. WA 240 M478a 2007]

QR69.S75M33 2007

614.4′8—dc22 2006031854

Cover photo: Scanning electron micrograph of a mixed biofilm of yeast and bacteria on an indwelling silicone rubber voice prosthesis after 3 to 4 months in a laryngectomized patient. Courtesy of Henny C. van der Mei and Henk J. Busscher (Department of Biomedical Engineering, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands).

PREFACE

The control of microorganisms and microbial growth is an important consideration in medical, veterinary, dental, industrial, pharmaceutical, environmental, and food processing settings. This book has been developed to provide a basic understanding of the various chemical and physical antisepsis, disinfection, and sterilization methods used for infection prevention and contamination control. Disinfection and sterilization technologies are used for the control of microorganisms on surfaces, in products, or in air, while antisepsis is particularly associated with microbial reduction on the skin or mucous membranes. These varied applications play important roles in our daily lives, including the provision of safe drinking water, production and preservation of products, sterilization of medical devices, and decontamination of surfaces. The benefits of microbial control have been appreciated since ancient times—for example, in the use of heating, salts, and metals for preservation and wound treatment—despite the absence of any pure understanding of microbiology. Over the last 200 years, we have gained a greater appreciation of microorganisms and their roles in contamination and infection. In parallel, various chemical (referred to as “biocidal”) and physical antisepsis, disinfection, and sterilization methods have been developed and are widely used to render surfaces and products safe for use. Despite these advancements, microbial control issues continue to challenge us. Recent examples include the aftermath of the bioterrorism attacks in the United States; the alarming spread of viral and reemerging bacterial infections such as influenza viruses and tuberculosis, respectively; the more recent identification of newer infectious agents (notably prions and viroids); and the continuing concern of anti-infective (including antibiotic)-resistant microorganisms in hospitals and the general community.

As a background to this subject, an introduction to microbiology is provided, including a discussion of the spectrum of action, determination of efficacy, and common variables that affect the performance of antisepsis, disinfection, and sterilization methods. Disinfection and sterilization are considered as either chemical (biocide) or physical technologies. Chemical biocides include aldehydes, halogens, and phenolics, while physical processes include the use of heat, filtration, and radiation. For each biocide class or process, the various types are discussed, along with their applications, spectrum of activity, advantages, and disadvantages and a brief description of their modes of action. A wider range of methods is used for disinfection and antisepsis applications. Many of these are required to reduce the number of microorganisms, or even the number of certain types of microorganisms, to an acceptable level. In contrast, only a limited number of technologies are utilized for sterilization, which has the ultimate goal of rendering a surface, area, or substance free of all viable microbial contamination. For this reason, disinfection and sterilization methods are considered separately, with a specific chapter dedicated to the various biocides used as antiseptics and in antisepsis applications.

The current understanding of the mechanisms of biocidal action on microorganisms is considered. In most cases, the modes of action of biocides are quite distinct from the more specific mechanisms of action described for anti-infective agents such as antibiotics and antiviral agents. Most biocides demonstrate a wider range of antimicrobial activity, generally corresponding to nonspecific and varied modes of action. The mechanisms of action of biocides are considered in four general categories: oxidizing agents, cross-linking agents, agents that act by transfer of energy, and other structure-disrupting agents. Despite these general mechanisms, some biocides have been shown to have primary targets similar to those of certain antibiotics, and a better understanding of their mechanisms of action is of interest in the development of the next generation of anti-infectives.

Microorganisms demonstrate various natural (intrinsic) and acquired mechanisms to resist the biocidal effects of chemical and physical processes. These mechanisms are also discussed and are important to consider in order to ensure the safe and effective use of biocides and biocidal processes. This topic has been particularly highlighted with the development of resistance to widely used anti-infectives (notably antibiotic-resistant bacteria), but similar mechanisms in microbial resistance to biocides and biocidal processes have been described. Biocide resistance in bacteria has been studied in some detail, with many examples of intrinsic and acquired mechanisms of resistance. Intrinsic mechanisms include biofilm formation and the development of dormant endospores. Acquired resistance mechanisms due to mutations and the acquisition of plasmids, not unlike those described for antibiotics, have also been described. Although many of these mechanisms allow for tolerance in the presence of biocides only at normally inhibitory levels, other mechanisms have been shown to dramatically change the response of a microorganism to biocides and to enable it to survive highly toxic conditions. Although less studied, specific mechanisms of resistance in viruses, prions, and fungi and other eukaryotes are also described.

Overall, it is intended that this book will give a basic understanding of and reference for the various types, modes of action, and mechanisms of resistance of antiseptics, disinfectants, and sterilants for students of microbiology, chemistry, infection control, contamination control, public health, and manufacturing. A greater understanding and appreciation of these technologies will ensure their long-term safe and effective use in contamination and infection prevention.

Acknowledgments

I greatly appreciate the many colleagues and friends who reviewed selected chapters of this book, as well as my wife, Lesley, for her encouragement.

GERALD E. MCDONNELL
Basingstoke, Hampshire, United Kingdom

ABOUT THE AUTHOR

Gerald E. McDonnell received a B.Sc. degree in medical laboratory sciences from the University of Ulster (1989) and a Ph.D. in microbial genetics at the Department of Genetics, Trinity College, University of Dublin (1992). His graduate work involved studies on the control of gene expression in Bacillus subtilis. He spent 3 years at the Mycobacterial Research Laboratories, Colorado State University, investigating the mechanisms of antibiotic resistance and cell wall biosynthesis in mycobacteria. In 1995 he joined the St. Louis, Mo., operations of ConvaTec, a division of Bristol-Myers Squibb, as a group leader in microbiology in the research and development of skin care, hard surface disinfection, and cleaning chemistries. He then joined STERIS Corporation and has worked for STERIS for more than 10 years in the United States and in the company’s European, Middle East, and Africa (EMEA) region on the development, research, and support of infection and contamination prevention products and services, including cleaning, antisepsis, disinfection, and sterilization. Dr. McDonnell is currently the vice president of research and EMEA affairs for STERIS, based at its facility in Basingstoke, United Kingdom. He is responsible for the development and support of decontamination processes and services, and he provides training on various aspects of decontamination and contamination control. His basic research interests include infection prevention, decontamination microbiology, emerging pathogens, and modes of action and resistance to biocides. His work also includes the development and implementation of international and national guidance and standards in decontamination. He has published widely in peer-reviewed journals and books, has been granted patents in decontamination technologies, and frequently gives presentations on various aspects of his work at scientific meetings around the world.

IMPORTANT NOTICE

The author has taken great care to confirm the accuracy of the information presented in this book, based on peer-reviewed publications at the time of preparation. However, the author and publisher make no warranty, expressed or implied, that the information in this book is accurate or appropriate for any particular facility, environment, or individual situation, and they are not responsible for any consequences of application of any of the information in this book by any reader. The inclusion of specific products, instruments, reagents, or methods does not represent any endorsement by the American Society for Microbiology, ASM Press, or the author. Nor does the inclusion or inadvertent exclusion of any product, instrument, reagent, or method reflect a preference for any product over other similar competitive products. The comments included in this book are strictly those of the author and do not necessarily reflect the views of his employer. Some of the products, tests, methods, and applications discussed in this book have particular U.S. Food and Drug Administration (FDA) and Environmental Protection Agency (EPA) approval for selective uses; further specific approvals or exclusions may also apply to other international regulatory agencies within specific geographic areas or countries. It is the responsibility of the reader to ensure the necessary local approval status of any product or process that is considered for use in his or her particular hospital, industrial, environmental, or private setting or practice.

ANTISEPSIS, DISINFECTION, AND STERILIZATION

TYPES, ACTION, AND RESISTANCE

PREFACE

Acknowledgments

ABOUT THE AUTHOR

IMPORTANT NOTICE