Hugo and Russell's Pharmaceutical Microbiology

Cover
Title Page
Copyright Page
Contents
Notes on Contributors
Preface to the First Edition
Prefaceto the Ninth Edition
About the Companion Website
Part 1 Introducing Pharmaceutical Microbiology
	Chapter 1 Introduction to Pharmaceutical Microbiology
		1.1 Pharmaceutical Microbiology: Microorganisms and Medicines
			1.1.1 The Discipline of Pharmaceutical Microbiology
			1.1.2 Microorganisms and Medicines
		1.2 Scope and Content of the Book
Part 2 Biology of Microorganisms
	Chapter 2 Fundamental Features of Microbiology
		2.1 Introduction
			2.1.1 Viruses, Viroids and Prions
			2.1.2 Prokaryotes and Eukaryotes
		2.2 Naming of Microorganisms
		2.3 Microbial Metabolism
		2.4 Microbial Cultivation
			2.4.1 Culture Media
			2.4.2 Cultivation Methods
			2.4.3 Planktonic and Sessile (Biofilm) Growth
		2.5 Enumeration of Microorganisms
		2.6 Microbial Genetics
			2.6.1 Bacteria
			2.6.2 Eukaryotes
			2.6.3 Genetic Variation and Gene Expression
		2.7 Pharmaceutical Importance of the Major Categories of Microorganisms
		2.8 Preservation of Microorganisms
	Chapter 3 Bacteria
		3.1 Introduction
			3.1.1 Bacterial Diversity and Ubiquity
		3.2 Bacterial Ultrastructure
			3.2.1 Cell Size and Shape
			3.2.2 Cellular Components
			3.2.3 Cell Surface Components
		3.3 Biofilms
		3.4 Bacterial Sporulation
			3.4.1 Endospore Structure
			3.4.2 Endospore Formation
			3.4.3 Endospore Germination
		3.5 Bacterial Toxins
		3.6 Bacterial Reproduction and Growth Kinetics
			3.6.1 Multiplication and Division Cycle
			3.6.2 Population Growth
			3.6.3 Growth and Genetic Exchange
		3.7 Environmental Factors that Influence Growth and Survival
			3.7.1 Physicochemical Factors that Affect Growth and Survival of Bacteria
			3.7.2 Nutrition and Growth
		3.8 Detection, Identification and Characterisation of Organisms of Pharmaceutical and Medical Significance
			3.8.1 Culture Techniques
			3.8.2 Microscopy
			3.8.3 Biochemical Testing and Rapid Identification
			3.8.4 Molecular Approaches to Identification
			3.8.5 Pharmaceutically and Medically Relevant Microorganisms
		References
		Further Reading
	Chapter 4 Fungi
		4.1 What Are Fungi?
		4.2 Structure of the Fungal Cell
		4.3 Medical Significance of Fungi
		4.4 Antifungal Therapy
			4.4.1 Polyene Antifungals
			4.4.2 Azole Antifungals
			4.4.3 Echinocandins
			4.4.4 Synthetic Antifungal Agents
		4.5 Medically Important Fungal Pathogens of Humans
			4.5.1 Candida albicans
			4.5.2 Aspergillus fumigatus
			4.5.3 Histoplasma capsulatum
			4.5.4 Cryptococcus neoformans
			4.5.5 Dermatophytes
		4.6 Emerging Fungal Pathogens
			4.6.1 Saccharomyces cerevisiae
			4.6.2 Non-albicans Candida Species
			4.6.3 Penicillium marneffei
		4.7 Antibiotic Production by Fungi
		Further Reading
	Chapter 5 Viruses and Other Acellular Infectious Agents: Characteristics and Control
		5.1 Introduction
		5.2 General Structure of Viruses
			5.2.1 Viral Nucleic Acid
			5.2.2 Viral Capsid
			5.2.3 Viral Envelope
			5.2.4 Viral Envelope-associated Proteins
		5.3 Virus–Host Cell Interactions
			5.3.1 Coronaviruses
			5.3.2 Human Immunodeficiency Virus (HIV)
			5.3.3 Oncogenic Viruses
		5.4 Multiplication of Human Viruses
			5.4.1 Attachment to the Host Cell
			5.4.2 Penetration of the Viral Particle
			5.4.3 Uncoating of the Viral Particle
			5.4.4 Replication of Viral Nucleic Acids and Translation of the Genome
			5.4.5 Maturation or Assembly of Virions
			5.4.6 Release of Virions into the Surrounding Environment
		5.5 Cultivation of Human Viruses
			5.5.1 Cell Culture
			5.5.2 The Chick Embryo
			5.5.3 Animal Inoculation
		5.6 Viral Epidemics and Pandemics
		5.7 Control of Viruses
			5.7.1 Antiviral Chemotherapy
			5.7.2 Vaccination
			5.7.3 Viricidal Effects of Chemical and Physical Agents on Viruses
			5.7.4 Control of Viruses in Pharmaceutical Products
		5.8 Biotechnological Applications of Viruses
		5.9 Bacterial Viruses
			5.9.1 Overview
			5.9.2 Bacteriophages and Their Products as Antibacterial Agents
			5.9.3 Other Applications of Bacteriophages
		5.10 Subviral Infectious Agents and Prions
		Further Reading
	Chapter 6 Protozoa
		6.1 Introduction
			6.1.1 Protozoa
			6.1.2 Parasitism
			6.1.3 Habitats
			6.1.4 Physiology of Parasitic Protozoa
		6.2 Blood and Tissue Parasites
			6.2.1 Malaria
			6.2.2 Trypanosomatids
			6.2.3 Toxoplasma gondii
		6.3 Intestinal Parasites
			6.3.1 Giardia lamblia (syn. intestinalis, duodenalis)
			6.3.2 Entamoeba histolytica
			6.3.3 Cryptosporidium parvum
		6.4 Trichomonas and Free-living Amoebae
			6.4.1 Trichomonas Vaginalis
			6.4.2 Free-living Opportunist Amoebae
		6.5 Host Response to Infection
			6.5.1 Immune Response
			6.5.2 Immune Pathology
			6.5.3 Immune Evasion
		6.6 Detection of Parasites
			6.6.1 Methods of Detection
			6.6.2 Analysis of Samples
		6.7 Control of Protozoan Parasites
			6.7.1 Chemotherapy
			6.7.2 Other Approaches to Control
		Acknowledgement
		References
		Further Reading
Part 3 Pathogens and Host Response
	Chapter 7 Principles of Microbial Pathogenicity and Epidemiology
		7.1 Introduction
		7.2 The Human Microbiome
		7.3 Portals of Entry
			7.3.1 Skin
			7.3.2 Respiratory Tract
			7.3.3 Intestinal Tract
			7.3.4 Urogenital Tract
			7.3.5 Conjunctiva
		7.4 Consolidation
			7.4.1 Nutrient Acquisition
			7.4.2 Biofilms
			7.4.3 Resistance to Host Defences
		7.5 Manifestation of Disease
			7.5.1 Non-invasive Pathogens
			7.5.2 Partially Invasive Pathogens
			7.5.3 Fully Invasive Pathogens
		7.6 Damage to Tissues
			7.6.1 Direct Damage
			7.6.2 Indirect Damage
		7.7 Recovery from Infection: the Exit of Microorganisms
		7.8 Epidemiology of Infectious Disease
		Further Reading
	Chapter 8 Microbial Biofilms: Consequences for Health
		8.1 Introduction
		8.2 Biofilms
			8.2.1 Biofilms in Nature and the Consequences for Health
			8.2.2 Biofilms in the Food Industry
			8.2.3 Biofilms in the Pharmaceutical Industry
			8.2.4 Biofilms in Healthcare Facilities
			8.2.5 Biofilms and Medical Devices
		8.3 Tolerance of Biofilms to Antimicrobials
		8.4 Mechanisms of Biofilm Tolerance
			8.4.1 Biofilm Structure
			8.4.2 Biofilm Physiology
			8.4.3 Cellular Signalling and Biofilm Resistance
			8.4.4 Plasticity of Biofilms
		8.5 Treatment of Chronic Biofilm Infections
			8.5.1 New Biofilm Assays
			8.5.2 Better Use of Existing Antimicrobials
			8.5.3 Next-generation Antimicrobials
		Acknowledgements
		References
		Further Reading
	Chapter 9 Immunology
		9.1 Introduction
			9.1.1 Historical Perspective and Scope of Immunology
			9.1.2 Definitions and Outline Structure of the Immune System
			9.1.3 Cells of the Immune System
		9.2 The Innate Immune System
			9.2.1 Innate Barriers at Epidermal and Mucosal Surfaces
			9.2.2 Innate Defence Once Epidermal or Mucosal Barriers Have Been Compromised
			9.2.2.1 Mononuclear Phagocytic Cells
		9.3 The Humoral Adaptive Immune System
			9.3.1 B-Lymphocyte Antigens
			9.3.2 Basic Structure of Antibody Molecules
			9.3.3 Clonal Selection and Expansion
			9.3.4 Humoral Immune Effector Functions
		9.4 Cell-mediated Adaptive Immune System
			9.4.1 T-Lymphocyte Antigen Recognition and MHC Proteins
			9.4.2 Processing of Proteins to Allow Peptide Presentation by MHC Molecules
			9.4.3 More on T-lymphocyte Subpopulations
		9.5 Some Clinical Perspectives
			9.5.1 Transplantation Rejection
			9.5.2 Hypersensitivity
			9.5.3 Autoimmunity
			9.5.4 Therapeutic Monoclonal Antibodies
			9.5.5 Immunosuppressants
		9.6 Summary
		Dedication
		Reference
		Further Reading
	Chapter 10 Vaccination and Immunisation
		10.1 Introduction
		10.2 Spread of Infection
			10.2.1 Common-source Infections
			10.2.2 Propagated-source Infections
		10.3 Objectives of a Vaccine/Immunisation Programme
			10.3.1 Disease Severity
			10.3.2 Vaccine Effectiveness
			10.3.3 Safety
			10.3.4 Public Perception
			10.3.5 Cost
			10.3.6 Longevity of Immunity
		10.4 Classes of Immunity
			10.4.1 Passive Immunity
			10.4.2 Active Immunity
		10.5 Types of Vaccine
			10.5.1 Live Vaccines
			10.5.2 Inactivated (Killed) and Component Vaccines
			10.5.3 DNA Vaccines
			10.5.4 mRNA Vaccines
			10.5.5 Viral Vector Vaccines
		10.6 Routine Immunisation against Infectious Disease
			10.6.1 Poliomyelitis Vaccination
			10.6.2 Measles, Mumps and Rubella Vaccination
			10.6.3 Tuberculosis
			10.6.4 Diphtheria, Tetanus and Acellular Pertussis (DTaP) Immunisation
			10.6.5 Immunisation against Bacteria Associated with Meningitis
			10.6.6 Human Papillomavirus Vaccination
			10.6.7 COVID-19 Vaccination
		10.7 The UK Routine Childhood Immunisation Programme
		10.8 Immunisation of the Over 65s and Other Risk Groups
		Acknowledgements
		Further Reading
Part 4 Prescribing Therapeutics and Infection Control
	Chapter 11 Antibiotics and Synthetic Antimicrobial Agents: Their Properties and Uses
		11.1 Antibiotic Development, Past and Present
			11.1.1 Antibiotic Usage
		11.2 β-Lactam Antibiotics
			11.2.1 Penicillins
			11.2.2 Cephalosporins
			11.2.3 β-Lactamase Inhibitors
			11.2.4 Carbapenems and Monobactams
			11.2.5 Hypersensitivity
		11.3 Tetracyclines
		11.4 Macrolides
		11.5 Sulphonamides and Trimethoprim
		11.6 Quinolones
		11.7 Aminoglycosides
		11.8 Glycopeptides
		11.9 Antitubercular Drugs
		11.10 Newer Antibiotics for MRSA and Other Gram-positive Cocci Infections
		11.11 Miscellaneous Antibacterial Antibiotics
			11.11.1 Clindamycin
			11.11.2 Fusidic Acid
			11.11.3 Mupirocin
			11.11.4 Colistin
			11.11.5 Chloramphenicol
			11.11.6 Metronidazole and Other Nitroimidazoles
			11.11.7 Nitrofurantoin
		11.12 Antifungal antibiotics
			11.12.1 Azoles
			11.12.2 Polyenes
			11.12.3 Echinocandins
			11.12.4 Other Antifungal Agents
		11.13 Antiviral Drugs
			11.13.1 Human Immunodeficiency Virus
			11.13.2 Herpes and Cytomegalovirus Infections
			11.13.3 Viral Hepatitis
			11.13.4 Influenza and Respiratory Syncytial Virus
		Acknowledgements
		References
		Further Reading
	Chapter 12 Mechanisms of Action of Antibiotics and Synthetic Anti-infective Agents
		12.1 Introduction
		12.2 The Microbial Cell Wall
			12.2.1 Peptidoglycan Biosynthesis in Bacteria and Its Inhibition
			12.2.2 Mycolic acid and Arabinogalactan Biosynthesis in Mycobacteria
			12.2.3 Echinocandins – Caspofungin, Anidulafungin and Micafungin
		12.3 Protein Synthesis
			12.3.1 Protein Synthesis and Its Selective Inhibition
			12.3.2 Aminoglycoside–Aminocyclitol Antibiotics
			12.3.3 Tetracyclines
			12.3.4 Chloramphenicol
			12.3.5 Macrolides and Azalides
			12.3.6 Clindamycin
			12.3.7 Streptogramins – Quinupristin and Dalfopristin
			12.3.8 Oxazolidinones – Linezolid and Tedizolid Phosphate
			12.3.9 Mupirocin
			12.3.10 Fusidic Acid
			12.3.11 Pleuromutilins – Retapamulin and Lefamulin
		12.4 Chromosome Function and Replication
			12.4.1 Basis for the Selective Inhibition of Chromosome Replication and Function
			12.4.2 Fluoroquinolones
			12.4.3 Nitroimidazoles (Metronidazole, Tinidazole) and Nitrofurans (Nitrofurantoin)
			12.4.4 Semi-synthetic Rifamycins (Rifampicin, Rifabutin, Rifaximin, Rifapentine) and Fidaxomicin
			12.4.5 5-Fluorocytosine
		12.5 Folate Antagonists
			12.5.1 Folate Metabolism in Microbial and Mammalian Cells
			12.5.2 Sulphonamides
			12.5.3 DHFR Inhibitors – Trimethoprim, Pyrimethamine, Proguanil and Trimetrexate
		12.6 The Cytoplasmic Membrane
			12.6.1 Composition and Susceptibility of Membranes to Selective Disruption
			12.6.2 Polymyxins
			12.6.3 Daptomycin
			12.6.4 Polyenes
			12.6.5 Imidazoles and Triazoles
			12.6.6 Terbinafine and Amorolfine
		Further Reading
	Chapter 13 Bacterial Resistance to Antibiotics
		13.1 Introduction
		13.2 The Origins of Resistance
		13.3 Mechanisms of Resistance
		13.4 Resistance to β-Lactam Antibiotics
			13.4.1 β-Lactamases
			13.4.2 β-Lactamase Inhibitors
			13.4.3 Altered Penicillin-binding Proteins and Methicillin-resistant Staphylococcus aureus
		13.5 Resistance to Glycopeptide Antibiotics
			13.5.1 MRSA and Reduced Glycopeptide Susceptibility
		13.6 Resistance to Aminoglycoside Antibiotics
		13.7 Resistance to Tetracycline Antibiotics
		13.8 Resistance to Fluoroquinolone Antibiotics
		13.9 Resistance to Macrolide, Lincosamide and Streptogramin Antibiotics
		13.10 Resistance to Chloramphenicol
		13.11 Resistance to Oxazolidinone Antibiotics
		13.12 Resistance to Trimethoprim
		13.13 Resistance to Mupirocin
		13.14 Resistance to the Polymyxin Antibiotic Colistin (Polymyxin E)
		13.15 Resistance to the Lipopeptide Antibiotic Daptomycin
		13.16 Resistance to Antimycobacterial Therapy
		13.17 Multiple Drug Resistance
			13.17.1 R-Plasmids
			13.17.2 Mobile Gene Cassettes and Integrons
			13.17.3 Chromosomal Multiple Antibiotic Resistance (mar) Locus
			13.17.4 Multidrug Efflux Pumps
		13.18 Clinical Resistance, MICs, Breakpoints, Phenotypic Resistance and Outcome
		13.19 Conclusion
		Acknowledgement
		References
		Further Reading
	Chapter 14 Clinical Uses of Antimicrobial Drugs
		14.1 Introduction
		14.2 Principles of Use of Antimicrobial Drugs
			14.2.1 Susceptibility of Infecting Organisms
			14.2.2 Host Factors
			14.2.3 Pharmacological Factors
			14.2.4 Drug Resistance
			14.2.5 Drug Combinations
			14.2.6 Adverse Reactions
			14.2.7 Superinfection
			14.2.8 Chemoprophylaxis
		14.3 Clinical Use
			14.3.1 Respiratory Tract Infections
			14.3.2 Urinary Tract Infections
			14.3.3 Gastrointestinal Infections
			14.3.4 Skin and Soft Tissue Infections
			14.3.5 Central Nervous System Infections
			14.3.6 Fungal Infections
			14.3.7 Medical device-associated Infections
		14.4 Antibiotic Policies
			14.4.1 Rationale
			14.4.2 Types of Antibiotic Policies
		Acknowledgements
		References
		Further Reading
	Chapter 15 Antibiotic Prescribing and Antimicrobial Stewardship
		15.1 The Need for Antimicrobial Stewardship
			15.1.1 The Problem of Antibiotic Resistance
			15.1.2 The Challenge of New Antibiotic Development
			15.1.3 The Need for Alternative Approaches to Antibiotic Use
		15.2 Antibiotic Consumption
			15.2.1 Relationship between Antibiotic Consumption and Bacterial Resistance
			15.2.2 Global Antibiotic Consumption
			15.2.3 Non-prescription Access to Antibiotics
			15.2.4 Non-human Antibiotic Use
		15.3 Antimicrobial Stewardship Programmes
			15.3.1 Definition and Aims of Antimicrobial Stewardship
			15.3.2 Components of an ASP
			15.3.3 ASP Interventions and their Evidence
			15.3.4 Antimicrobial Stewardship in Primary and Community Care
			15.3.5 ASPs and Infection Prevention and Control Strategies
			15.3.6 The Experience of ASPs during a Pandemic
		15.4 Monitoring Antimicrobial Stewardship Programmes
			15.4.1 Electronic Surveillance of Antibiotic Use and Resistance
		References
		Further Reading
	Chapter 16 Infection Prevention and Control: Healthcare-associated Infection
		16.1 Introduction
		16.2 Defining Healthcare-associated Infections
			16.2.1 Surgical Site Infections
			16.2.2 Bloodstream Infections
			16.2.3 Urinary Tract Infections
			16.2.4 Ventilator-associated Pneumonia
		16.3 Microorganisms Implicated in Healthcare-associated Infection
			16.3.1 Gram-positive Bacteria
			16.3.2 Gram-negative Bacteria
			16.3.3 Viruses
			16.3.4 Clinically Relevant Fungi
		16.4 Standard IPC Interventions for the Management and Prevention of HCAI
			16.4.1 Standard Precautions
			16.4.2 Hand Hygiene
			16.4.3 Infection Precautions (Contact Precaution and Droplet Precautions)
			16.4.4 Isolation Precautions
			16.4.5 Cohorting
			16.4.6 Cleaning and Disinfection
			16.4.7 Active Surveillance
			16.4.8 Clinical Protocol-driven Responses
			16.4.9 Antimicrobial Stewardship
		16.5 Impact of the Clinical Setting on Infection Prevention and Control
			16.5.1 Outbreaks and IPC Interventions
		16.6 Measuring Impact and Success
		16.7 Professional Support for Infection Prevention and Control
		References
		Further Reading
Part 5 Contamination and Contamination Control
	Chapter 17 Microbial Spoilage, Infection Risk and Contamination Control
		17.1 Introduction
		17.2 Spoilage: Chemical and Physicochemical Deterioration of Pharmaceuticals
			17.2.1 Pharmaceutical Ingredients Susceptible to Microbial Attack
			17.2.2 Observable Effects of Microbial Attack on Pharmaceutical Products
			17.2.3 Factors Affecting Microbial Spoilage of Pharmaceutical Products
		17.3 Hazard to Health
			17.3.1 Microbial Toxins
		17.4 Sources and Control of Contamination
			17.4.1 In Manufacture
			17.4.2 In Use
		17.5 The Extent of Microbial Contamination
			17.5.1 In Manufacture
			17.5.2 In Use
		17.6 Factors Determining the Outcome of a Medicament-borne Infection
			17.6.1 Type and Degree of Microbial Contamination
			17.6.2 Route of Administration
			17.6.3 Resistance of the Patient
		17.7 Preservation of Medicines Using Antimicrobial Agents: Basic Principles
			17.7.1 Introduction
			17.7.2 Effect of Preservative Concentration, Temperature and Size of Inoculum
			17.7.3 Factors Affecting the ‘Availability’ of Preservatives
		17.8 Quality Assurance and the Control of Microbial Risk in Medicines
			17.8.1 Introduction
			17.8.2 Quality Assurance in Formulation Design and Development
			17.8.3 Good Pharmaceutical Manufacturing Practice
			17.8.4 Quality Control Procedures
			17.8.5 Post-market Surveillance
		17.9 Overview
		References
		Further Reading
	Chapter 18 Chemical Disinfectants, Antiseptics and Preservatives
		18.1 Introduction
			18.1.1 European Union Regulation
			18.1.2 Definitions
			18.1.3 Economic Aspects
		18.2 Factors Affecting Choice of Antimicrobial Agent
			18.2.1 Properties of the Chemical Agent
			18.2.2 Microbiological Challenge
			18.2.3 Intended Application
			18.2.4 Environmental Factors
			18.2.5 Toxicity of the Agent
		18.3 Types of Compound
			18.3.1 Acids and Esters
			18.3.2 Alcohols
			18.3.3 Aldehydes
			18.3.4 Biguanides
			18.3.5 Halogens
			18.3.6 Heavy Metals
			18.3.7 Hydrogen Peroxide and Peroxygen Compounds
			18.3.8 Phenols
			18.3.9 Surface-active Agents
			18.3.10 Other Antimicrobials
			18.3.11 Antimicrobial Combinations and Systems
		18.4 Disinfection Policies
		References
		Further Reading
	Chapter 19 Laboratory Evaluation of Antimicrobial Agents
		19.1 Introduction
			19.1.1 Definitions
		19.2 Factors Affecting the Antimicrobial Activity of Disinfectants
			19.2.1 Innate (Natural) Resistance of Microorganisms
			19.2.2 Microbial Density
			19.2.3 Disinfectant Concentration and Exposure Time
			19.2.4 Physical and Chemical Factors
			19.2.5 Presence of Extraneous Organic Material
		19.3 Evaluation of Liquid Disinfectants
			19.3.1 General
			19.3.2 Antibacterial Disinfectant Efficacy Tests
			19.3.3 Other Microbe Disinfectant Tests
		19.4 Evaluation of Solid Disinfectants
		19.5 Evaluation of Air Disinfectants
		19.6 Evaluation of Preservatives
		19.7 Rapid Evaluation Procedures
		19.8 Evaluation of Potential Chemotherapeutic Antimicrobials
			19.8.1 Tests for Bacteriostatic Activity
			19.8.2 Tests for Bactericidal Activity
			19.8.3 Tests for Fungistatic and Fungicidal Activities
			19.8.4 Evaluation of Possible Synergistic Antimicrobial Combinations
		19.9 Tests for Biofilm Susceptibility
			19.9.1 Synergy Biofilm Assays
		Acknowledgement
		References
		Further Reading
	Chapter 20 Microbicides: Mode of Action and Resistance
		20.1 Introduction
		20.2 Mechanisms of Interaction
		20.3 Antimicrobial Effects
		20.4 Mechanisms of Action
			20.4.1 Oxidation Reactions
			20.4.2 Cross-linking Reactions
			20.4.3 Coagulation
			20.4.4 Disruption of Functional Structures
		20.5 Enhancing Activity
		20.6 Mechanisms of Resistance to Microbicides
			20.6.1 General Mechanisms
			20.6.2 Induction of Resistance
			20.6.3 Dissemination of Resistance
			20.6.4 Bacterial Endospores
			20.6.5 Bacterial Biofilms
			20.6.6 Misuse and Abuse of Microbicides
		20.7 Viricidal Activity of Microbicides
		20.8 Microbicides and Protozoa
		20.9 Microbicides and Fungi
		20.10 Inactivation of Prions
		20.11 Conclusion
		References
		Further Reading
	Chapter 21 Sterilisation Procedures and Sterility Assurance
		21.1 Introduction
		21.2 Sensitivity of Microorganisms
			21.2.1 Survivor Curves
			21.2.2 Expressions of Resistance
			21.2.3 Sterility Assurance
		21.3 Sterilisation Methods
		21.4 Heat Sterilisation
			21.4.1 Sterilisation Processes
			21.4.2 Moist Heat Sterilisation
			21.4.3 Dry Heat Sterilisation
		21.5 Gaseous Sterilisation
			21.5.1 Ethylene Oxide
			21.5.2 Formaldehyde
			21.5.3 Peroxygen Compounds
		21.6 Radiation Sterilisation
			21.6.1 Steriliser Design and Operation
		21.7 Filtration Sterilisation
			21.7.1 Filtration Sterilisation of Liquids
			21.7.2 Filtration Sterilisation of Gases
		21.8 Newer Sterilisation Technologies
			21.8.1 High-intensity Light
			21.8.2 Low-temperature Plasma
		21.9 Sterilisation Control and Sterility Assurance
		21.10 Bioburden Determinations
		21.11 Environmental Monitoring
		21.12 Validation and In-process Monitoring of Sterilisation Procedures
			21.12.1 Physical Indicators
			21.12.2 Chemical Indicators
			21.12.3 Biological Indicators
		21.13 Sterility Testing
			21.13.1 Sterility Testing Methods
			21.13.2 Antimicrobial Agents
			21.13.3 Positive Controls
			21.13.4 Specific Cases
			21.13.5 Sampling
			21.13.6 Retests
			21.13.7 The Role of Sterility Testing
		References
		Further Reading
Part 6 Pharmaceutical Production
	Chapter 22 Sterile Pharmaceutical Products and Principles of Good Manufacturing Practice
		22.1 Introduction
		22.2 Defining Sterility
		22.3 Sterilisation Methods
			22.3.1 Factors Affecting Sterilisation
		22.4 Demonstrating Sterility
		22.5 Types of Sterile Product
			22.5.1 Injections
			22.5.2 Non-injectable Sterile Fluids
			22.5.3 Ophthalmic Preparations
			22.5.4 Dressings
			22.5.5 Implants
			22.5.6 Absorbable Haemostats
			22.5.7 Surgical Ligatures and Sutures
			22.5.8 Instruments and Equipment
			22.5.9 General Considerations
		22.6 Good Manufacturing Practices for Sterile Products
			22.6.1 Regulatory Framework
			22.6.2 In-process Controls and Quality Control (QC)
		22.7 Sterility Assurance and the Manufacture of Sterile Products
		22.8 Terminal Sterilisation and Aseptic Processing
		22.9 Cleanrooms and Facility Design
			22.9.1 Design of Premises
			22.9.2 Internal Surfaces, Fittings and Floors
			22.9.3 Services
			22.9.4 Air Supply
		22.10 Operating Principles for Aseptic Processing
			22.10.1 Sterile Filtration
			22.10.2 Managing Aseptic Assembly, Connections and Interventions
			22.10.3 Transfer of Materials into and out of Aseptic Processing Areas
		22.11 Minimising Human Intervention
			22.11.1 Blow–Fill–Seal Technology
			22.11.2 Restricted Access Barrier Systems
			22.11.3 Isolators
			22.11.4 Single-use Sterile Disposable Technology
		22.12 Personnel
		22.13 Media Simulation Trials
		22.14 Quality Risk Management
		22.15 Environmental Monitoring
		22.16 Release of Sterile Products
			22.16.1 Assessments of Sterility
			22.16.2 Assessments of Pyrogenicity
			22.16.3 Visible Particulates
		22.17 Summary
		Acknowledgements
		Reference
		Further Reading
	Chapter 23 The Manufacture and Quality Control of Immunological Products
		23.1 Introduction
		23.2 Vaccines
			23.2.1 Types of Vaccines
			23.2.2 The Seed Lot System
			23.2.3 Production of the Bacteria and the Cellular Components of Bacterial Vaccines
			23.2.4 Fermentation
			23.2.5 Production of the Viruses and the Components of Viral Vaccines
			23.2.6 Blending
			23.2.7 Filling and Drying
			23.2.8 Quality Control
		23.3 In Vivo Diagnostics
			23.3.1 Preparation
			23.3.2 Quality Control
		23.4 Immune Sera
			23.4.1 Preparation
			23.4.2 Quality Control
		23.5 Human Immunoglobulins
			23.5.1 Source Material
			23.5.2 Fractionation
			23.5.3 Quality Control
		23.6 Monoclonal Antibodies
			23.6.1 Preparation
			23.6.2 Quality Control
		23.7 Acknowledgements
		References
		Further Reading
	Chapter 24 Recombinant DNA Technology
		24.1 Introduction: Biotechnology in the Pharmaceutical Sciences
		24.2 Enabling Techniques
			24.2.1 Cutting and Joining DNA Molecules
			24.2.2 Cloning Vectors
			24.2.3 Introduction of Vector into Hosts
			24.2.4 Construction of Genomic Libraries
			24.2.5 Screening of Genomic Libraries
			24.2.6 Optimising Expression of Recombinant Genes
			24.2.7 Amplifying DNA: the Polymerase Chain Reaction
			24.2.8 Genome Editing Using CRISPR–Cas9 Endonuclease
		24.3 Biotechnology in the Pharmaceutical Industry
			24.3.1 Recombinant Human Insulin
			24.3.2 Recombinant Somatostatin
			24.3.3 Recombinant Somatotropin
			24.3.4 Recombinant Hepatitis B Vaccine
			24.3.5 Recombinant Influenza and Coronavirus Vaccines
			24.3.6 Production of Recombinant Antibiotics
		24.4 New Diagnostics Using Recombinant DNA Technology
			24.4.1 Diagnosis of Infectious Diseases
			24.4.2 Diagnosis of Genetic Disorders
		Further Reading
Part 7 Current Trends and New Directions
	Chapter 25 The Wider Contribution of Microbiology to the Pharmaceutical Sciences
		25.1 Introduction
			25.1.1 Early Treatment of Human Disease
			25.1.2 Present-day Exploitation
		25.2 Pharmaceuticals Produced by Microorganisms
			25.2.1 Dextrans
			25.2.2 Vitamins, Amino Acids and Organic Acids
			25.2.3 Iron-chelating Agents
			25.2.4 Enzymes
		25.3 Applications of Microorganisms in the Partial Synthesis of Pharmaceuticals
			25.3.1 Production of Antibiotics
			25.3.2 Steroid Biotransformations
			25.3.3 Chiral Inversion
		25.4 Applications of Microorganisms in the Discovery of Pharmaceuticals
			25.4.1 Phage Display
		25.5 Use of Microorganisms and Their Products in Assays
			25.5.1 Antibiotic Bioassays
			25.5.2 Vitamin and Amino Acid Bioassays
			25.5.3 Phenylketonuria Testing
			25.5.4 Carcinogen and Mutagen Testing
			25.5.5 Use of Microbial Enzymes in Sterility Testing
			25.5.6 Immobilised Enzyme Technology
		25.6 Use of Microorganisms as Models of Mammalian Drug Metabolism
		25.7 Microorganisms as Therapy
			25.7.1 Bacteriophages
			25.7.2 Probiotics
			25.7.3 Toxins
		25.8 Insecticides
		25.9 Bioterrorism
		25.10 Concluding Remarks
		Further Reading
	Chapter 26 Alternative Strategies to Antibiotics: Priorities for Development
		26.1 Introduction
		26.2 Bacteriophage Therapy
		26.3 Bacteriophage Lysins
		26.4 Vaccines and Immunotherapies
			26.4.1 Vaccines for Bacterial Infections
			26.4.2 Immunotherapies
		26.5 Probiotics
			26.5.1 Gastrointestinal Conditions
			26.5.2 Recurrent Vaginitis
		26.6 Antimicrobial Peptides
		26.7 Conclusion
		Acknowledgements
		References
		Further Reading
Index
EULA