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TABLE OF CONTENTS VOLUME I Section 4. Basic Principles of Infection Prevention Practice Acknowledgements Editors 27. Hand Hygiene Authors 28. Standard Precautions Reviewers 29. I solation Precautions (Transmission-based Production Staff Precautions) Declarations of Conflicts of Interest 30. Aseptic Technique Preface 31. Cleaning, Disinfection, and Sterilization 32. Reprocessing Single-use Devices Section 1. Overview of Infection Prevention Programs VOLUME II 1. Infection Prevention and Control Programs Section 5. Prevention Measures for Healthcare- 2. C ompetency and Certification of the Infection Associated Infections Preventionist 3. Education and Training 33. Urinary Tract Infection 4. Accrediting and Regulatory Agencies 34. Intravascular Device Infections 5. Infection Prevention and Behavioral Interventions 35. Infections in Indwelling Medical Devices 6. Healthcare Informatics and Information Technology 36. Pneumonia 7. Product Evaluation 37. Surgical Site Infection 8. Legal Issues 9. Staffing Section 6. Infection Prevention for Specialty Care Populations Section 2. Epidemiology, Surveillance, Performance, and Patient Safety Measures 38. Burns 39. Dialysis 10. General Principles of Epidemiology 40. Geriatrics 11. Surveillance 41. Neonates 12. Outbreak Investigations 42. Pediatrics 13. Use of Statistics in Infection Prevention 43. Perinatal Care 14. Process Control Charts 44. I nfection Prevention in Oncology and Other 15. Risk-adjusted Comparisons Immunocompromised Patients 16. Quality Concepts 45. Solid Organ Transplantation 17. Performance Measures 46. Hematopoietic Stem Cell Transplantation 18. Patient Safety 47. Nutrition and Immune Function 19. Qualitative Research Methods 20. Research Study Design Section 7. Infection Prevention for Practice Settings and Service-Specific Patient Care Areas Section 3. Microbiology and Risk Factors for Transmission 48. Ambulatory Care 49. Behavioral Health 21. R isk Factors Facilitating Transmission of Infectious 50. Cardiac Catheterization and Electrophysiology Agents 51. Correctional Facilities 22. Microbial Pathogenicity and Host Response 52. Child Care Services 23. The Immunocompromised Host 53. Dental Services 24. Microbiology Basics 54. Emergency and Other Pre-Hospital Medical Services 25. Laboratory Testing and Diagnostics 55. Endoscopy 26. Antimicrobials and Resistance v 56. Home Care 95. Tuberculosis and Other Mycobacteria 57. Hospice and Palliative Care 96. Viral Hemorrhagic Fevers 58. Imaging Services and Radiation Oncology 97. Viral Hepatitis 59. Intensive Care 98. West Nile Virus 60. Interventional Radiology 99. Parasites 61. Long-term Care 62. Long-term Acute Care 63. Ophthalmology Services Section 9. Infection Prevention for Occupational 64. Ambulatory Surgery Centers Health 65. Postmortem Care 66. Rehabilitation Services 100. Occupational Health 67. Respiratory Care Services 101. Occupational Exposure to Bloodborne Pathogens 68. Surgical Services 102. V olunteers, Contract Workers, and Other 69. Xenotransplantation Nonemployees Who Interact with Patients 103. Immunization of Healthcare Personnel 104. Pregnant Healthcare Personnel Volume III 105. Minimizing Exposure to Blood and Body Fluids Section 8. Healthcare-Associated Pathogens and Diseases Section 10. Infection Prevention for Support Services and the Care Environment 70. Biofilms 71. Bordetella pertussis 106. Sterile Processing 72. Clostridium difficile Infection and 107. Environmental Services Pseudomembranous Colitis 108. Laboratory Services 73. Creutzfeldt-Jakob Disease and other Prion Diseases 109. Nutrition Services 74. Central Nervous System Infection 110. Pharmacy Services 75. Enterobacteriaceae 111. Laundry, Patient Linens, Textiles, and Uniforms 76. Enterococci 112. Maintenance and Engineering 77. Environmental Gram-negative Bacilli 113. Waste Management 78. Fungi 114. Heating, Ventilation, and Air Conditioning 79. A. Diarrheal Diseases: Viral 115. W ater Systems Issues and Prevention of Waterborne B. Diarrheal Diseases: Bacterial Infectious Diseases in Healthcare Facilities C. Diarrheal Diseases: Parasitic 116. Construction and Renovation 80. Herpes Virus 81. HIV/AIDS Section 11. Community-based Infection Prevention 82. Influenza Practices 83. Foodborne Illnesses 84. Legionella pneumophila 85. Lyme Disease (Borrelia burgdorferi) 117. Public Health 86. Measles, Mumps, Rubella 118. Travel Health 87. Neisseria meningitidis 119. Emergency Management 88. Parvovirus 120. I nfectious Disease Disasters: Bioterrorism, Emerging 89. Rabies Infections, and Pandemics 90. Respiratory Syncytial Virus 121. Animal Research and Diagnostics 91. Sexually Transmitted Diseases 122. Animals Visiting Healthcare Facilities 92. Skin and Soft Tissue Infections 123. Body Piercing, Tattoos, and Electrolysis 93. Staphylococci 94. Streptococci Index vi APIC Text of Infection Control and Epidemiology Preface When I was asked to be the clinical editor for the 4th edition the Infection Preventionist, Chapter 28 Standard Precautions, of the APIC Text of Infection Control and Epidemiology, I Chapter 62 Long-Term Acute Care, and Chapter 64 Ambula- could not imagine a greater honor nor could I imagine a greater tory Surgery Centers. challenge! After more than 25 years of a very active infection prevention practice, I was being offered this great opportunity The 4th edition of the APIC Text is printed in three volumes to lead the revision of the most prominent infection prevention to make reading and handling easier, and the chapters have and control reference book. When I accepted this offer, I began been arranged into sections so that information on programs to sense that this opportunity was not as much a call to lead, or specialty areas, for example, are presented together. Addi- as it was a call to serve—a call to serve the APIC organization, tionally, each chapter contains international perspectives and as well as you the consumer of the APIC Text. Admittedly, in future trends. some ways the task ahead was intimidating as I realized that the consumer would be you, the infection preventionist, each with As you open the pages of the APIC Text, 4th edition, you will your own knowledge and experiences—your own expertise. find within its contents the most up-to-date information to meet your everyday needs in the work setting. Infection prevention- Although the work has been challenging, the rewards have ists now more than ever have a major role in the protection been much greater. I have had the opportunity to work with and safety of healthcare personnel and patients in both tradi- 12 accomplished, committed section editors and more than tional, as well as nontraditional settings. Having access to the 150 authors—all leaders and experts in infection prevention. Text—whether in hard copy or electronically via the APIC Text They have all worked diligently to produce a quality reference to Online—is essential to your practice. It has been my pleasure help you make informed, effective, and timely decisions in your to work for you in order to publish the newest edition of the infection prevention program. APIC Text. Let me share a few points about the 4th edition. All the chap- Finally, I would be remiss if I did not acknowledge the efforts of ters have been revised and updated to reflect current practices those who built the foundation for this fourth edition. Without and guidelines at the time of publication. Because much of them, especially Dr. Ruth Carrico, who served as the editor of healthcare is rapidly moving outside the acute care setting, the first three editions of the APIC Text, this work could not have particular attention has been focused on infection prevention been as comprehensive, and of the quality, it is. practices in alternative healthcare settings such as rehabilitation, ambulatory care centers and long-term acute care settings. In Regards, fact, four new chapters have been added to address current trends and issues: Chapter 2 Competency and Certification of Patti G. Grota, PhD, RN, CNS-M-S, CIC Patti G. Grota, PhD, RN, CNS-M-S, CIC, has been active in tion prevention and other healthcare-associated adverse events. infection prevention and patient safety for more than 20 years. She was awarded the APIC 2011 New Investigator Award at From 1988 to 2012, Dr. Grota worked in infection control in the 38th Annual Educational Conference and International the South Texas Veterans Healthcare System Infection Control Meeting for her research in patient factors associated with in San Antonio and Kerrville, Texas, and served as deputy chief adverse events of hospitalized veterans in infection control of the program. She is currently an Assistant Professor of Nurs- isolation. ing at Schreiner University in Kerrville, Texas. In addition, she is a member of the Association for Professionals in Infection Con- Dr. Grota received a Bachelor of Science in Nursing from trol and Epidemiology (APIC) and has served as the President of Oklahoma Baptist University, Shawnee, Oklahoma, in 1976; a APIC Chapter 71, San Antonio, Texas. Master of Science in Nursing in 1981 from Oklahoma Univer- sity Health Science Center; and a PhD in Nursing in 2010 from Dr. Grota has published numerous manuscripts and abstracts the University of Texas Health Science Center, San Antonio, and has lectured across the country on topics related to infec- Texas. xxiii 26 CHAPTER Antimicrobials and Resistance Forest W. Arnold, DO, MSc, FIDSA BACKGROUND Assistant Professor, Division of Infectious Diseases University of Louisville Epidemiological forces responsible for clinically important types Hospital Epidemiologist of resistance include (1) the selective pressure produced by University of Louisville Hospital antimicrobial use and (2) the transmission of resistance between Louisville, KY microbes and between or among their human and animal hosts. Although most resistance can be traced to the human behaviors ABSTRACT that lie behind these forces, the development and spread of resis- tance also are greatly affected by certain microbial characteristics, Although infection prevention traditionally has approached such as the ease by which an organism can develop or acquire the problem of resistance primarily from the aspect of resistance traits. Infection prevention, by its very nature, tradition- preventing transmission, more needs to be done to control ally has been concerned with preventing the transmission of re- how antimicrobials are commonly used. Antimicrobial use sistant organisms between human hosts in the healthcare setting. is the main selective pressure responsible for the increasing This chapter discusses available human antimicrobial agents, how drug resistance seen in hospitals. Patients come to possess they are used, antimicrobial resistance, and the management of a resistant pathogen by either having their bacteria acquire antimicrobial use as a means to control resistance. a gene that codes for resistance or by transmitting bacteria that already have the resistance gene in place. The former This chapter reviews all major antimicrobial categories with takes days to weeks to develop, whereas the latter merely re- special mention of agents that have been released since the quires a handshake. To have an impact on antimicrobial use last edition of this book. Characteristics and indications for use so as to reduce resistance, infection preventionists need a particularly for drugs commonly used among inpatients, the de- working knowledge of available antimicrobials, principles for termination and interpretation of antimicrobial susceptibility test their appropriate use, the mechanisms by which these drugs results, and various factors influencing successful antimicrobial inhibit microbial growth, and the mechanisms by which therapy are reviewed. The chapter also reviews microbial mech- microorganisms develop resistance. In addition, infection anisms responsible for antimicrobial resistance and methods to preventionists need to understand promising new strategies monitor and improve antimicrobial use. to improve antimicrobial use and how members of the infec- tion prevention community can become more involved. BASIC PRINCIPLES KEY CONCEPTS Characteristics of Antimicrobial Agents Definition • Although infection prevention traditionally has approached An antimicrobial is a substance that inhibits or kills microbes (vi- the problem of resistance primarily from the aspect of pre- ruses, bacteria, fungi, parasites), whereas an antibiotic is a type venting transmission, more needs to be done to control how of antimicrobial that is synthesized by a living microorganism, antimicrobials are commonly used. usually a fungus. Trimethoprim is technically an antimicrobial • Antimicrobial stewardship is the best investment for prevent- but not an antibiotic because a microorganism does not synthe- ing the proliferation of multidrug-resistant pathogens and the size trimethoprim. Many newly marketed agents are chemically adverse events associated with the drugs used to treat such modified from products synthesized by a microorganism. pathogens. • An antibiogram is a useful tool for infection preventionists to Administration determine the status of strategies in place to reduce multi- Most antimicrobials are administered by intravenous (IV) or oral drug-resistant pathogens. routes. Less common routes of administration include intra- • A multidisciplinary approach involving infection prevention- muscular, rectal, topical, intrathecal, intraventricular, inhalation, ists; the departments of infectious diseases, microbiology, and intraperitoneal, surgically implanted antimicrobial devices (e.g., pharmacy; and others is necessary to confront antimicrobial orthopedic hardware or beads), and antimicrobial-coated de- resistance issues in healthcare settings. vices (e.g., endotracheal tubes or urinary catheters). Antimicrobials and Resistance 26-1 Mechanisms of Action In order to explain why this is not the case for every antimi- crobial, the concept of half-life should be understood. Half-life Antimicrobials may be bactericidal or fungicidal if they actively is a term used to quantify how long the body takes to metab- kill organisms, or they may be bacteriostatic or fungistatic if olize half of a drug, an antimicrobial in this case. Drugs such they merely arrest the growth of organisms and assist the host’s as aminoglycosides and fluoroquinolones are said to manifest immune system in clearing the infection. Whether a drug exerts concentration-dependent activity. In the case of these drugs, “-cidal” versus “-static” activity can depend on the concentra- achieving a higher concentration in the blood over a short tion to which an organism is exposed, but for most drugs the time is thought to be more effective at eliminating infection safely achieved concentrations in the human body are limited than maintaining a lower concentration over a longer period to a narrow enough range that this distinction is determined (Figure 26-1). One characteristic of these drugs is that they more by the underlying mechanism by which the drug inhibits usually have a prolonged post-antibiotic effect; that is, they microbial growth. continue to suppress microbial growth long after drug concen- tration has declined. The goal with these drugs is to maximize There are several mechanisms by which antimicrobials act on serum or tissue drug concentrations, which often allows for microorganisms (Table 26-1). All β-lactam drugs (e.g., penicillins, once-daily dosing. cephalosporins, monobactams, and carbapenems); the glyco- peptide vancomycin; and the echinocandins (e.g., caspofungin) In contrast, the activity of the β-lactams depends on maintain- inhibit cell wall synthesis. Cell membrane inhibitors include ing drug concentrations in the body above the MIC. Drugs daptomycin, colistimethate, and the imidazole antifungal agents, that have such time-dependent (above the MIC) activity are such as fluconazole, which inhibits an enzyme responsible for a best dosed with lower doses at an increased frequency (Figure crucial component of the cell membrane. Aminoglycosides (e.g., 26-2). This understanding has led to drugs such as the natural gentamicin and tobramycin), macrolides (e.g., azithromycin), penicillins and ampicillin being increasingly dosed as a contin- tetracyclines, and the oxazolidinone, linezolid, all inhibit protein uous infusion, rather than less frequent dosing, in the manage- synthesis in the bacterial ribosome. Another mechanism inhibits ment of serious infection. Notice that in Figure 26-1, there is a the production of metabolites essential for cell function (e.g., longer period of time between the end of the half-life and the trimethoprim-sulfamethoxazole and ethambutol). Finally, several next dose of the concentration-dependent drug compared to drugs, including the fluoroquinolones (e.g., ciprofloxacin, levo- the time-dependent drug in Figure 26-2. Also notice that the floxacin, and moxifloxacin), the antifungal flucytosine, and many concentration curve in Figure 26-1 goes below that MIC level of the antivirals (e.g., acyclovir) inhibit nucleic acid synthesis. while it stays above the level in Figure 26-2. Pharmacodynamic Factors Side Effects The effectiveness of antimicrobials can be optimized by under- Two major types of side effects are allergic and gastrointesti- standing what effect varying the concentration of a drug over nal reactions. Allergic reactions, including those manifested by time in relation to the minimal inhibitory concentration (MIC) rash, fever, and rare anaphylaxis, are undesirable effects that has on eliminating infection from the human body.1 The MIC is may occur with virtually any antimicrobial. Common gastroin- the lowest concentration of drug that still can inhibit microbial testinal disturbances include nausea and vomiting and, because growth. The logical assumption would be that for all drugs you virtually all antimicrobials inhibit microbial growth in the large would want to keep the concentration of the drug in the blood intestine, diarrhea. Most antibiotic-associated diarrhea is be- above the MIC at all times. nign and resolves with cessation of the drug, but suppression of the anaerobic bacteria of the colon predisposes to infection Table 26-1. Major Cellular Sites of Action by Antimicrobial Classes with Clostridium difficile. The current C. difficile epidemic Site of Mechanism of Action Antimicrobial strain can cause life-threatening colitis, especially if due to the BI/NAP1/027 strain. Other forms of superinfection resulting Cell wall -lactam (penicillin) Vancomycin from the suppression of normal microbial flora include vaginal Echinocandin candidiasis and oral thrush. Other types of toxicities and their Cell membrane Cyclic lipopeptide (daptomycin) most common manifestations include hepatotoxicity, mani- Triazole (fluconazole) fested as elevation of liver enzymes (which is often asymptom- Ribosome Macrolide atic); myelosuppression, manifested as leukopenia or throm- Aminoglycoside bocytopenia; renal toxicity, manifested as progressive decline Linezolid Tetracycline in renal function or electrolyte abnormalities; auditory toxicity, manifested as high-frequency hearing loss; vestibular toxicity, Nucleic acid synthesis Fluoroquinolones Antiviral (acyclovir) manifested as dizziness or vertigo; and central nervous system 5-Flucytosine toxicity, manifested as change in mental status or seizure. Be- Metabolic pathway Trimethoprim-sulfamethoxazole cause they often go unrecognized, drug-drug interactions may Ethambutol be particularly prone to cause serious toxicity. 26-2 APIC Text of Infection Control and Epidemiology Figure 26-1. Optimal dosing of antimicrobial drugs possessing concentration-dependent killing action. CLASSIFICATION AND REVIEW OF COM- carbapenems. All β-lactam drugs possess bactericidal activity by inhibiting cell wall synthesis. The original penicillin, penicillin MONLY USED DRUGS G, is a natural product synthesized by the mold Penicillium, The major classification of antimicrobials is based on the broad which possesses important activity against spirochetes (such as category of microorganisms against which the drugs possess ac- that which causes syphilis). Natural penicillins also have activity tivity; these include antibacterials (Table 26-2), antivirals (Table against enterococci, most streptococcal species, and anaerobic 26-3), antifungals (Table 26-4), and antiparasitics. bacteria found in the human mouth. Natural penicillin remains the drug of choice for the treatment of group A streptococcal pharyngitis and other infections caused by this pathogen, despite more than 50 years of use. Antibacterials Penicillins As a result of penicillin G’s lack of activity against Gram-neg- The first major antibacterials of the antibiotic era were the ative bacteria, the aminopenicillins, including ampicillin and natural penicillins, which came into widespread use in the amoxicillin, were developed. These drugs possess activity 1940s. All penicillins contain a β-lactam ring, which comprises against Gram-negative organisms such as Escherichia coli and the core structure of not only the natural and semisynthetic Haemophilus influenzae, while retaining all of the Gram-pos- penicillins, but also all cephalosporins, monobactams, and itive and anaerobic activity of the natural penicillins. In re- Figure 26-2. Optimal dosing of antimicrobial drugs possessing time-dependent killing action. Antimicrobials and Resistance 26-3 Table 26-2. Classification of Antibacterials and Representative Table 26-4. Classification of Antifungals and Representative Drugs Drugs Class Subclass Representative Drug(s) Class Subclass Representative Drug Polyenes Nonlipid formulation Amphotericin B Penicillins Natural penicillins Penicillin G Lipid formulations Amphotec, Abelcet, and Cephalosporins First generation Cefazolin Ambisome Second generation Cefuroxime Azoles Triazole Fluconazole and voriconazole Third generation Ceftriaxone Other Echinocandin Caspofungin Fourth generation Cefepime Nucleoside analogue Flucytosine Fifth generation Ceftobiprole Other ß–lactams ß-lactam/ß-lactamase Piperacillin/tazobactam inhibitor 1960s and 1970s, penicillins with antipseudomonal activity Monobactams Aztreonam were developed, including piperacillin. Then, β-lactamase Carbapenems Imipenem inhibitors were added to existing penicillins to inhibit bacterial Fluoroquinolones Antipseudomonal Ciprofloxacin enzymes from lysing the β-lactam chemical ring structure to Antistreptococcal Moxifloxacin broaden the activity of the base penicillin for three groups of pathogens: anaerobic bacteria, methicillin-susceptible but peni- Miscellaneous Macrolides Azithromycin cillin-resistant Staphylococcus aureus (MSSA), and Gram-neg- Lincosamines Clindamycin ative bacteria. Currently used β-lactam/β-lactamase inhibitor Aminoglycosides Gentamicin combinations include amoxicillin-clavulanate, ampicillin-sulbac- Sulfa drugs Trimethoprim/ tam, and piperacillin-tazobactam. sulfamethoxazole Glycopeptides Vancomycin Cephalosporins Nitroimidazoles Metronidazole Several generations of cephalosporins are available. The first- Oxazolidinone Linezolid generation cephalosporins include cefazolin and cephalexin Cyclic lipopeptide Daptomycin with activity primarily against Gram-positive bacteria, most Polymyxin Colistin sulfate E. coli, more than half of all Klebsiella pneumoniae at most institutions, and most strains of Proteus mirabilis. Second- generation drugs include cephalosporins with enhanced activity against H. influenzae (e.g., cefotaxime, cefuroxime) sponse to the rapid spread of penicillin-resistant staphylococci and cephalosporins with enhanced antianaerobic activity throughout the United States in the 1950s, penicillinase-resis- (e.g., cefoxitin). Both categories of second-generation tant penicillins were developed. The first of these, methicillin, cephalosporins possess increased activity against enteric was released in 1962 and now has been largely replaced by Gram-negative bacilli and Neisseria spp. other penicillinase-resistant penicillins with less toxicity, such as nafcillin and oxacillin (IV) and dicloxacillin (oral). To combat Third-generation cephalosporins (e.g., cefotaxime and the rising incidence of Pseudomonas infections in the late ceftriaxone) have enhanced activity against Gram-negative bacilli. They achieve high blood concentrations and penetrate into relatively sequestered body sites, such as the central Table 26-3. Classification of Antivirals and Representative Drugs nervous system. Third-generation cephalosporins are important in the treatment of community-associated meningitis. However, Class Subclass Representative Drug(s) penicillin and cephalosporin resistance among Streptococcus Drugs for Herpesviridae For herpes simplex Acyclovir pneumoniae is increasing and may limit the usefulness of these For cytomegalovirus Ganciclovir drugs as empirical therapy. Although the antipseudomonal Drugs for influenza For influenza A and B Oseltamivir and zanamivir third-generation drug ceftazidime is important in the treatment Miscellaneous For respiratory syncytial Ribavirin of nosocomial meningitis due to Gram-negative bacilli, its virus use is discouraged because of its association with extended- Antiretrovirals (drugs Nucleoside reverse Emtricitabine spectrum β-lactamases.2 Cefditoren is an oral agent with for HIV) transcriptase inhibitors increased potency against S. pneumoniae, including strains Nonnucleoside reverse Efavirenz that have only intermediate susceptibility to penicillin. Cefdinir transcriptase inhibitors has the benefits of being taken only once daily, having an oral Protease inhibitor Atazanavir suspension, and a similar spectrum of activity compared to Fusion inhibitor Enfuvirtide other agents in the same class. Entry inhibitor Maraviroc Cefepime, a fourth-generation cephalosporin, has broad-spec- Integrase inhibitor Raltegravir trum activity against Gram-negative bacteria, including Pseudo- 26-4 APIC Text of Infection Control and Epidemiology