《传染病学 Infectious Disease》课程教学资源（MBBS）课程参考书籍教材：Infectious Diseases, A Clinical Short Course, Second Edition.pdf_大学文库

Preface THE END OF THE FEATURES OF THE SECOND ANTIBIOTIC ERA? EDITION Time and Newsweek magazines have heralded the This is the second edition of a textbook envisioned as End of the Antibiotic Era". Echoing the concerns of a 30-day tutorial designed to provide a solid ground many infectious disease and health policy experts, ing in the principles of clinical infectious diseases he Chicago Tribunes feature on"Unhealthy Hospi- The title has been changed from infectious Diseases in tals"warns that the"overuse of antibiotics are spawn- 30 Days to Infectious Diseases: A Clinical Short Course, ing drug-resistant germs that are spreading from hos- however the design and intention of our book has not pitals into the community at unprecedented rates. changed. As our title emphasizes we have created a Vancomycin resistant enterococcus(VRE), methicillin- concise overview of this important field that will resistant Staphylococcus aureus(MRSA) are now com- allow the busy physician, medical st nt, nurse only found in our hospitalized patients and a new practioner, and physician assistant to understand, hly virulent community-acquired methicillin diagnose and treat common infectious diseases resistant Stap/ ylococcus aureus(CMRSA) is infecting Mastering the field of infectious diseases seems high school and college athletes. Extensively drug. daunting, and many textbooks in the feld are over a resistant tuberculosis (XDR-TB) has resulted in near thousand pages in length. Our goal has been to make 100% mortality in an outbreak in South Africa. this task easier and more enjoyable. By indicating the "g ewly discovered infectious diseases such as SARS, number of days that should be allotted to the study vian Influenza, Ehrlichia, Lyme Disease, and West of each chapter, we have a created a schedule for com Nile Encephalitis are emerging as threats to our well- pletion of each lesson. By taking one small step at a being. Malaria remains a leading cause of death in time, a seemingly difficult task can be more readily many parts of the world. The 2001 bioterrorist attack achieved. The book has been shortened to make launched by mailing anthrax spores illustrates the completion within 30 days feasible. This has been critical need for all health providers to recognize the made possible by creating a wide array of tables that manifestations of this nearly forgotten pathogen and summarize the methods of clinical assessment, anti- others that can be used as weapons of mass destruc- infective agent doses, and drug toxicities; facts that tion. The AIDS epidemic continues to devastate sub- do not require memorization, but do need to be Saharan Africa, and is spreading at an alarming rate referred to when caring for patients in Asia and the former soviet Union, hiv strains Chapters are organized by organ system when pos resistant to antiretroviral therapy are incre sible, because this is how clinicians encounter infec throughout the United States and Europe. Diseases tious diseases. As in the last edition, guiding ques long believed to have non-infectious etiologies are tions begin each chapter to encourage the reader to now confirmed as having microbial origins. Infec- actively inquire as he or she reads the text. The poten tious diseases have re-emerged as one of the world s tial severity of each disease is assessed to give the inex- top healthcare priorities, and to meet the needs of the perienced clinician a sense of the speed with which 21st Century, health care providers must possess a care must be initiated. Key points are included in solid grounding in clinical infectious diseases shaded areas to emphasize the most important facts Copyright 2007 by The McGraw-Hill Companies, Inc. Click here for terms of use

Preface ■ THE END OF THE ANTIBIOTIC ERA? Time and Newsweek magazines have heralded the “End of the Antibiotic Era”. Echoing the concerns of many infectious disease and health policy experts, The Chicago Tribune’s feature on “Unhealthy Hospitals” warns that the “overuse of antibiotics are spawning drug-resistant germs that are spreading from hospitals into the community at unprecedented rates”. Vancomycin resistant enterococcus (VRE), methicillinresistant Staphylococcus aureus (MRSA) are now commonly found in our hospitalized patients and a new highly virulent community-acquired methicillin resistant Staphylococcus aureus (cMRSA) is infecting high school and college athletes. Extensively drugresistant tuberculosis (XDR-TB) has resulted in near 100% mortality in an outbreak in South Africa. Newly discovered infectious diseases such as SARS, Avian Influenza, Ehrlichia, Lyme Disease, and West Nile Encephalitis are emerging as threats to our wellbeing. Malaria remains a leading cause of death in many parts of the world. The 2001 bioterrorist attack launched by mailing anthrax spores illustrates the critical need for all health providers to recognize the manifestations of this nearly forgotten pathogen and others that can be used as weapons of mass destruction. The AIDS epidemic continues to devastate subSaharan Africa, and is spreading at an alarming rate in Asia and the former Soviet Union. HIV strains resistant to antiretroviral therapy are increasing throughout the United States and Europe. Diseases long believed to have non-infectious etiologies are now confirmed as having microbial origins. Infectious diseases have re-emerged as one of the world’s top healthcare priorities, and to meet the needs of the 21st Century, health care providers must possess a solid grounding in clinical infectious diseases. ■ FEATURES OF THE SECOND EDITION This is the second edition of a textbook envisioned as a 30-day tutorial designed to provide a solid grounding in the principles of clinical infectious diseases. The title has been changed from infectious Diseases in 30 Days to Infectious Diseases: A Clinical Short Course; however the design and intention of our book has not changed. As our title emphasizes we have created a concise overview of this important field that will allow the busy physician, medical student, nurse practioner, and physician assistant to understand, diagnose and treat common infectious diseases. Mastering the field of infectious diseases seems daunting, and many textbooks in the field are over a thousand pages in length. Our goal has been to make this task easier and more enjoyable. By indicating the number of days that should be allotted to the study of each chapter, we have a created a schedule for completion of each lesson. By taking one small step at a time, a seemingly difficult task can be more readily achieved. The book has been shortened to make completion within 30 days feasible. This has been made possible by creating a wide array of tables that summarize the methods of clinical assessment, antiinfective agent doses, and drug toxicities; facts that do not require memorization, but do need to be referred to when caring for patients. Chapters are organized by organ system when possible, because this is how clinicians encounter infectious diseases. As in the last edition, guiding questions begin each chapter to encourage the reader to actively inquire as he or she reads the text. The potential severity of each disease is assessed to give the inexperienced clinician a sense of the speed with which care must be initiated. Key points are included in shaded areas to emphasize the most important facts Copyright © 2007 by The McGraw-Hill Companies, Inc. Click here for terms of use

Anti-Infective Therapy Time Recommended to complete: 3 days Frederick Southwick. M.D GUIDING QUESTIONS Are we at the end of the antibiotic era? 6. Does one antibiotic cure all infections? 2. Why are"superbugs"suddenly appearing in ou 7. What are the strategies that underlie optimal 3. How do bacteria become resistant to antibiotics? 8. How is colonization distinguished from infection 4. How can the continued selection of highly resis and why is this distinction important? tant organisms be prevented? 5. Is antibiotic treatment always the wisest course of action? Despite dire warnings that we are approaching the end of They use one or two broad-spectrum antibiotics to treat antibiotic era, the incidence of antibiotic-resistant all p acteria continues to rise. The proportions of penicillin Many excellent broad-spectrum antibiotics can resistant Streptococcus pneumoniae, hospital-acquired effectively treat most bacterial infections without requir rancomycin-resistant Enterococcus(VRE)strains continue empiric broad-spectrum antibiotics has resulted in the to increase. Community-acquired MRSA(cMRSA)is selection of highly resistant pathogens. A simplistic now common throughout the world. Multiresistant approach to anti-infective therapy and establishment of Acinetobacter and Pseudomonas are everyday realities in a fixed series of simple rules concerning the use of these many of our hospitals. The press is now warning the lay agents is unwise and has proved harmful to patients public of the existence of "dirty hospitals. " As never Such an approach ignores the remarkable adaptability of fore, it is critical that health care providers understand bacteria, fungi, and viruses. It is no coincidence that the principles of proper anti-infective therapy and use these more primitive life forms have survived for nti-infective agents judiciously. These agents need to be millions of years, far longer than the human race. reserved for treatable infections-not used to calm the The rules for the use of anti-infective the atient or the patient's family. Too often, patients with dynamic and must take into account the ability of these viralieche physician's office expecting to be treated with the overuse of antibiotic, antifungal, and antiviral agents ions that do not warrant anti-infective therapy pathogens to adapt to the selective pressures exerted b antibiotics to fulfill those expectation ust end, or more and more patients will become Physicians unschooled in the principles of microbiol- infected with multiresistant organisms that cannot be ogy utilize anti-infective agents just as they would more treated. Only through the judicious use of anti-infective conventional medications, such as anti-infammatory therapy can we hope to slow the arrival of the end of the agents, anti-hypertensive medications, and cardiac drugs. antibiotic Copyright 2007 by The McGraw-Hill Companies, Inc. Click here for terms of use

Despite dire warnings that we are approaching the end of the antibiotic era, the incidence of antibiotic-resistant bacteria continues to rise. The proportions of penicillinresistant Streptococcus pneumoniae, hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) strains continue to increase. Community-acquired MRSA (cMRSA) is now common throughout the world. Multiresistant Acinetobacter and Pseudomonas are everyday realities in many of our hospitals. The press is now warning the lay public of the existence of “dirty hospitals.” As never before, it is critical that health care providers understand the principles of proper anti-infective therapy and use anti-infective agents judiciously. These agents need to be reserved for treatable infections—not used to calm the patient or the patient’s family. Too often, patients with viral infections that do not warrant anti-infective therapy arrive at the physician’s office expecting to be treated with an antibiotic. And health care workers too often prescribe antibiotics to fulfill those expectations. Physicians unschooled in the principles of microbiology utilize anti-infective agents just as they would more conventional medications, such as anti-inflammatory agents, anti-hypertensive medications, and cardiac drugs. They use one or two broad-spectrum antibiotics to treat all patients with suspected infections. Many excellent broad-spectrum antibiotics can effectively treat most bacterial infections without requiring a specific causative diagnosis. However, overuse of empiric broad-spectrum antibiotics has resulted in the selection of highly resistant pathogens. A simplistic approach to anti-infective therapy and establishment of a fixed series of simple rules concerning the use of these agents is unwise and has proved harmful to patients. Such an approach ignores the remarkable adaptability of bacteria, fungi, and viruses. It is no coincidence that these more primitive life forms have survived for millions of years, far longer than the human race. The rules for the use of anti-infective therapy are dynamic and must take into account the ability of these pathogens to adapt to the selective pressures exerted by the overuse of antibiotic, antifungal, and antiviral agents. The days of the “shotgun” approach to infectious diseases must end, or more and more patients will become infected with multiresistant organisms that cannot be treated. Only through the judicious use of anti-infective therapy can we hope to slow the arrival of the end of the antibiotic era. 1 Time Recommended to complete: 3 days Frederick Southwick, M.D. GUIDING QUESTIONS Anti-Infective Therapy 1 1. Are we at the end of the antibiotic era? 2. Why are “superbugs” suddenly appearing in our hospitals? 3. How do bacteria become resistant to antibiotics? 4. How can the continued selection of highly resistant organisms be prevented? 5. Is antibiotic treatment always the wisest course of action? 6. Does one antibiotic cure all infections? 7. What are the strategies that underlie optimal antibiotic usage? 8. How is colonization distinguished from infection, and why is this distinction important? Copyright © 2007 by The McGraw-Hill Companies, Inc. Click here for terms of use

2/ CHAPTER 1 KEY POINTS About Anti-Infective Therapy 1. Too often, antibiotics are prescribed to fulfill the atients expectations, rather than to treat a true acterial infection 2. A single antibiotic cannot meet all infectious disease needs Transduction 3. Physicians ignore the remarkable adaptability of bacteria, fungi, ses at thei 4. Anti-infective therapy is dynamic and requires a basic understanding of microbiology. 5. The"shotgun"approach to infectious diseases Donor Recipient must end, or we may truly experience the end of Bacteria the antibiotic era Transformation ANTIBIOTIC RESISTANCE GENETIC MODIFICATIONS LEADING TO Figure 1-1 Mechanisms by which bacteria transfer ANTIMICROBIAL RESISTANCE antibiotic resistance genes. To understand why antibiotics must be used judi ciously, the physician needs to understand how bacte- ria are able to adapt to their environment. point second bacterium and serves as bridge for the mutations can develop in the dna of bacteria as they transfer of the plasmid DNA from the donor to replicate. These mutations occur in the natural envi- the recipient bacterium. Using this mechanism,a ronment, but are of no survival advantage unless the single resistant bacterium can transfer resistance bacteria are placed under selective pressures. In the to other bacteria case of a mutation that renders a bacterium resistant to 2. Transduction. Bacteriophages are protein-coated a specific antibiotic, exposure to the specific antibiotic allows the bacterial clone that possesses the antibiotic DNA segments that attach to the bacterial wall and resistance mutation to grow, while bacteria without the ject DNA in a process called"transduction. These infective particles can readily transfer resis- mutation die and no longer compete for nutrients. tance genes to multiple bacteria. Thus the resistant strain becomes the dominant bacte- 3. Transformation. Donor bacteria can also release rial flora. In addition to point mutations bacteria can also use three major mechanisms to transfer genetic linear segments of chromosomal DNA, which material among themselves hen taken up by recipient bacteria and incor ated into the recipient's genome. This process 1.Conjugation. Bacteria often contain circular called "transformation, "and the naked DNA double-stranded DNA structures called plasmids capable of incorporating into the genome of recip These circular dna structures lie outside the bac. nt bacteria is called a transposon(Figure 1.1) terial genome( Figure 1.1). Plasmids often carry Natural transformation most commonly occurs in resistance(“R”) genes. Through a mechanism Streptococcus, Haemophilus, and Neisseria species called "conjugation, plasmids can be transferred Transposons can transfer multiple antibiotic resis- from one bacterium to another. The plasmid ance genes in a single event and have been shown encodes for the formation of a pilus on the donor to be responsible for high-level vanco n resIs- bacterias outer surface. The pilus attaches to tance in enterococci

■ ANTIBIOTIC RESISTANCE GENETIC MODIFICATIONS LEADING TO ANTIMICROBIAL RESISTANCE To understand why antibiotics must be used judiciously, the physician needs to understand how bacteria are able to adapt to their environment. Point mutations can develop in the DNA of bacteria as they replicate. These mutations occur in the natural environment, but are of no survival advantage unless the bacteria are placed under selective pressures. In the case of a mutation that renders a bacterium resistant to a specific antibiotic, exposure to the specific antibiotic allows the bacterial clone that possesses the antibiotic resistance mutation to grow, while bacteria without the mutation die and no longer compete for nutrients. Thus the resistant strain becomes the dominant bacterial flora. In addition to point mutations bacteria can also use three major mechanisms to transfer genetic material among themselves: 1. Conjugation. Bacteria often contain circular, double-stranded DNA structures called plasmids. These circular DNA structures lie outside the bacterial genome (Figure 1.1). Plasmids often carry resistance (“R”) genes. Through a mechanism called “conjugation,” plasmids can be transferred from one bacterium to another. The plasmid encodes for the formation of a pilus on the donor bacteria’s outer surface. The pilus attaches to a second bacterium and serves as bridge for the transfer of the plasmid DNA from the donor to the recipient bacterium. Using this mechanism, a single resistant bacterium can transfer resistance to other bacteria. 2. Transduction. Bacteriophages are protein-coated DNA segments that attach to the bacterial wall and inject DNA in a process called “transduction.” These infective particles can readily transfer resistance genes to multiple bacteria. 3. Transformation. Donor bacteria can also release linear segments of chromosomal DNA, which is then taken up by recipient bacteria and incorporated into the recipient’s genome. This process is called “transformation,” and the naked DNA capable of incorporating into the genome of recipient bacteria is called a transposon (Figure 1.1). Natural transformation most commonly occurs in Streptococcus, Haemophilus, and Neisseria species. Transposons can transfer multiple antibiotic resistance genes in a single event and have been shown to be responsible for high-level vancomycin resistance in enterococci. 2 / CHAPTER 1 1. Too often, antibiotics are prescribed to fulfill the patient’s expectations, rather than to treat a true bacterial infection. 2. A single antibiotic cannot meet all infectious disease needs. 3. Physicians ignore the remarkable adaptability of bacteria, fungi, and viruses at their patient’s peril. 4. Anti-infective therapy is dynamic and requires a basic understanding of microbiology. 5. The “shotgun” approach to infectious diseases must end, or we may truly experience the end of the antibiotic era. KEY POINTS About Anti-Infective Therapy Figure 1–1. Mechanisms by which bacteria transfer antibiotic resistance genes