Topical Antimicrobials Testing and Evaluation

194 Pages·2014·24.96 MB·English

by  Daryl S. Paulson

General Chemistry P
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SECOND EDITION
Topical Antimicrobials Testing and Evaluation
A range of factors must be considered when developing a topical T
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antimicrobial for use in a healthcare personnel handwash, surgical scrub, P
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or preoperative skin preparation. Antimicrobial effectiveness, low skin C
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irritation, ease of use, and pleasing aesthetics are all essential if the L

product is to succeed. In addition, all facets of the product must comply A
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with stringent regulatory requirements. With updated protocols and T
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research, Topical Antimicrobials Testing and Evaluation, M S E C O N D E D ITI O N
Second Edition comprehensively presents and reviews the latest IC
techniques for testing antimicrobial compounds for effectiveness and R
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regulatory compliance. B
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Topics include L
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• The anatomical structure of the skin and skin microbiology E
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relevant to product testing T Testing Evaluation
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• Use of antimicrobial products against specific microorganisms N
such as Staphylococcus and Streptococcus species G and

• Measurement of antimicrobial action of topical antimicrobials A
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from experimental design, microbiological, biostatistical, and D

marketplace perspectives E
• Various aspects of the topical antimicrobial products currently in VA Daryl S. Paulson
common use in medical, food service, and consumer markets L
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• Statistical analysis and specific statistical designs for clinical trials A
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• Epistemological requirements in evaluating the effects of specific I
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treatments N
• Evaluation strategies and sample working protocols for hand
and body soaps, food-handler antimicrobial products, and S
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medical/healthcare industry antimicrobial products C
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The book is designed to inform industry and academia on the require- E
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ments to get products approved by the FDA and to market while also ITIO
providing critical insight on ways to best service expanding markets. N
K10678
ISBN: 978-1-4398-1322-5
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9 781439 813225

S E C O N D E D ITI O N
Topical Antimicrobials
Testing Evaluation
and

S E C O N D E D ITI O N
Topical Antimicrobials
Testing Evaluation
and
Daryl S. Paulson
BIOSCIENCES LABORATORIES, INC.
BOZEMAN, MONTANA, USA
Boca Raton London New York
CRC Press is an imprint of the
Taylor & Francis Group, an informa business
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© 2015 by Taylor & Francis Group, LLC
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Version Date: 20141029
International Standard Book Number-13: 978-1-4398-1323-2 (eBook - PDF)
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Contents
Preface.......................................................................................................................xi
Acknowledgments ..................................................................................................xiii
About the Author .....................................................................................................xv
Chapter 1 General Approach to Developing Topical Antimicrobials ...................1
I. Business .......................................................................................1
II. Quality Assurance .......................................................................4
A. Inspection of the Laboratory/Personnel Performing the Work ...5
III. Moving Quality Control Outward ...............................................5
A. During the Study: Control .....................................................8
B. The Fishbone Checklist (Cause and Effect) ..........................8
C. Quality Improvement: After the Study Has Been Completed ...9
IV. A Tighter Approach to Delivering a Useful Product ...................9
V. The Quadrant Model ...................................................................9
A. Social Requirements ..............................................................9
B. Cultural Requirements ........................................................11
C. Science .................................................................................11
D. Psychology ...........................................................................12
VI. A Recurring Problem: Reductionism ........................................12
A. Product Categories...............................................................13
1. Preoperative Skin-Prepping Formulations .......................13
2. Surgical Scrub Formulations and Hand Antiseptics ........15
3. Healthcare Personnel Handwash Formulations
and Hand Antiseptics ...........................................................17
4. Food-Handler Handwash Formulations
and Hand Sanitizers .............................................................18
5. Antimicrobial Handwash and Bodywash Formulations .....21
VII. Conclusion .................................................................................22
Chapter 2 Skin Properties ...................................................................................23
I. Structure ....................................................................................23
II. Epidermis...................................................................................25
III. Dermis .......................................................................................27
IV. Dermal Vascularization .............................................................28
A. Subcutaneous Tissue............................................................29
B. Hairs ....................................................................................29
C. Sebaceous Glands ................................................................29
D. Sweat Glands .......................................................................30
V. The Tissue Fluids ......................................................................30
v
vi Contents
Chapter 3 Skin Microbiology ..............................................................................31
I. Etiology of Infectious Diseases .................................................31
A. Encounter and Entry ............................................................31
B. Spread ..................................................................................32
C. Multiplication ......................................................................33
D. Immune System ...................................................................33
1. Microbial Nutrition ..........................................................34
2. Physical Factors ...............................................................35
3. Endogenous Microorganisms of the Body ......................35
II. Bacterial Cell .............................................................................36
A. Bacterial Cell Structures .....................................................37
1. Bacterial Size and Form ..................................................37
B. Cell Envelope .......................................................................38
1. Capsules and Slime Layers ..............................................38
2. Constitution of Capsular Substances ...............................39
3. Membrane Components ...................................................45
4. Bacterial Endospores .......................................................47
C. Biofilms ...............................................................................49
1. Biofilm Genesis ...............................................................49
2. Perioperative Implications ...............................................53
3. Vascular Catheterization ..................................................53
4. Orthopedics ......................................................................54
5. Endotracheal Tubes..........................................................54
D. Are Topical Antimicrobials Effective? ................................54
III. Mycology (Fungi) ......................................................................55
A. Yeasts ...................................................................................55
B. Molds ...................................................................................55
C. Dimorphism .........................................................................56
1. Cell Structure ...................................................................56
2. Capsule ............................................................................56
3. Cell Wall ..........................................................................57
Chapter 4 Specific Microorganisms ....................................................................59
I. Staphylococcus ..........................................................................59
II. Streptococcus ............................................................................59
A. Antigenic Structure .............................................................60
III. Other Microorganisms ..............................................................60
A. Mycobacteria .......................................................................60
B. Enterobacteriaceae ..............................................................60
C. Escherichia coli ...................................................................60
1. Surface Antigens ..............................................................61
2. Enterotoxins .....................................................................61
D. Klebsiella .............................................................................61
E. Serratia ................................................................................61
Contents vii
F. Proteus Bacterium ...............................................................62
G. Salmonella ...........................................................................62
H. Shigella ................................................................................62
1. Toxins ..............................................................................63
IV. Fungi ..........................................................................................63
A. Dimorphism .........................................................................63
B. Candida ...............................................................................63
C. Aspergillus ...........................................................................63
D. Histoplasma .........................................................................63
1. Cytoplasmic Membrane ...................................................64
2. Cytoplasmic Content .......................................................64
V. Viruses .......................................................................................64
A. Complex Viruses .................................................................66
Chapter 5 Measurement of Antimicrobial Action of Topical Antimicrobials ....67
I. General Performance Characteristics ........................................67
A. Description of the Study’s Purpose .....................................68
1. Exploratory Data Analysis ...............................................69
2. Standard Deviation ..........................................................69
3. Proper Randomization .....................................................69
4. Control Product(s) ...........................................................69
B. Description of the Experimental Strategy ...........................69
1. Statistical Conclusion Validity .........................................70
2. Internal Validity ...............................................................71
3. Construct Validity ............................................................72
4. External Validity ..............................................................73
5. Is the Study Biased? ........................................................75
6. Hawthorne Effect .............................................................76
7. John Henry Effect ............................................................77
8. Pygmalion Effect .............................................................78
C. Microbiological Methodology .............................................78
D. Statistical Methods Used to Evaluate the Study ..................79
E. New Product Development Applications .............................79
1. Marketing Concerns ........................................................81
2. Other Considerations .......................................................82
II. Conclusion .................................................................................83
Chapter 6 Current Topical Antimicrobials .........................................................85
I. Iodine Complexes ......................................................................85
A. Range of Action ...................................................................86
II. Chlorhexidine Gluconate ...........................................................87
A. Antimicrobial Action ...........................................................88
III. Tinctures of CHG and Alcohol .................................................89
IV. Parachlorometaxylenol ..............................................................89
viii Contents
V. Alcohols .....................................................................................90
VI. Triclosan ....................................................................................91
VII. Quaternary Ammonium Compounds ........................................91
Chapter 7 General Statistics ................................................................................93
I. Sample Size Determination .......................................................93
II. What Type of Analysis Should I Use to Ensure the Study
Has Been Done Correctly? ........................................................98
A. Exploratory Data Analysis (EDA) .......................................98
B. Covariance or Analysis of Variance Statistics:
Which Is the Correct Way? ...............................................100
1. Studies to Replace a Component (Toweling, Wraps, etc.) ...101
2. 95% Responder Rate .....................................................102
3. Computation ..................................................................103
4. Once the Data Are Examined, What Shall I Do
with Them? ........................................................................106
Chapter 8 Specific Statistical Designs for Clinical Trials....................................109
I. Preoperative Skin Preparation .................................................109
A. Statistical Model ................................................................110
B. Analysis of Means .............................................................111
Chapter 9 Epistemological Requirements in Evaluating the Effects
of Specific Treatments ......................................................................115
I. Experimental Strategy .............................................................115
II. Choice of Qualitative or Quantitative Methods.......................115
III. Statistical Models ....................................................................116
IV. Statistical Model-Building and Analysis: Exploratory Phase ...118
V. Statistical Model Selection ......................................................119
VI. Parametric Statistics ................................................................120
A. ANOVA .............................................................................121
VII. Nonparametric Statistics .........................................................121
VIII. Qualitative Research Designs ..................................................122
IX. Phenomenological Designs ......................................................123
X. Heuristic Designs ....................................................................124
XI. Historical Research Design .....................................................124
XII. Evaluative Research Design ....................................................125
XIII. Conclusion ...............................................................................125
Chapter 10 Evaluation Strategies and Sample Working Protocols .....................127
I. Consumer Antimicrobial Products ..........................................127
A. Evaluating Consumer Antimicrobial Handwash Products ...127