Peface A well-developed knowledge of clinical microbiology is 4) Create a conceptual, organized approach to the or- critical for the practicing physician in any medical field. ganisms studied so the student relies less on memory Bacteria, viruses, and protozoans have no respect for and more on logical pathophysiology. the distinction between ophthalmology, pediatrics, The text has been updated to include current infor- trauma surgery, or geriatric medicine. As a physician mation on rapidly developing topics, such as HIV and you will be faced daily with the concepts of microbial AIDS (vaccine efforts and all the new anti-HIV medica- disease and antimicrobial therapy. Microbiology is one tions), Ebola virus, Hantavirus, E. coli outbreaks, Mad of the few courses where much of the "minutia" is regu- larly used by the practicing physician. Cow Disease, and brand-new antimicrobial antibiotics. This book attempts to facilitate the learning of mi- The mnemonics and cartoons in this book do not in- tend disrespect for any particular patient population or crobiology by presenting the information in a clear and entertaining manner brimming with memory aids. racial or ethnic group but are solely presented as mem- Our approach has been to: ory devices to assist in the learning of a complex and im- portant medical subject. 1) Write in a conversational style for rapid assimi- We welcome suggestions for future editions. lation. 2) Include numerous figures serving as "visual mem- MARK GLADWIN, MD ory tools" and summary charts at the end of each chap- BILL TRATTLER, MD ter. These can be used for "cram sessions" after the concepts have been studied in the text. 3) Concentrate more on clinical and infectious dis- ease issues that are both interesting and vital to the ac- tual practice of medicine. D CONTENTS Preface v PART 1 1 1 BACTERIAL TAXONOMY 1 2 CELL STRUCTURES, VIRULENCE FACTORS, and TOXINS 8 3 BACTERIAL SE( GENETICS 16 GRAM-POSITIVE BACTERIA 22 4 STREPTOCOCCUS 22 5 STAPHYLOCOCCUS 31 6 BACILLUS and CLOSTRIDIUM (SPORE-FORMING RODS) 38 7 CORYNEBACTERIUM and LISTERIA (NON-SPORE-FORMING RODS) 45 GRAM-NEGATNE BACTERIA 49 8 NEISSERIA 49 9 THE ENTERICS 54 10 HAEMOPHILUS, BORDETELLA, and LEGIONELLA 68 11 YERSINIA, FRANCISELLA, BRUCELLA, and PASTEURELLA 73 12 CHLAMYDIA, RICKETTSIA, and FRIENDS 78 13 SPIROCHETES 91 ACID-FAST BACTERIA 102 14 MYCOBACTERIUM 102 BACTERIA WITHOUT CELL WALLS 111 15 MYCOPLASMA 111 ANTI-BACTERIAL MEDICATIONS 114 16 PENICILLIN FAMILY ANTIBIOTICS 114 17 ANTI-RIBOSOMAL ANTIBIOTICS 125 18 ANTI-TB and ANTI-LEPROSY ANTIBIOTICS 133 19 MISCELLANEOUS ANTIBIOTICS 139 PART 2. FUNGI 144 20 THE FUNGI 144 21 ANTI-FUNGAL MEDICATIONS 155 PART 3 161 22 VIRAL REPLICATION and TAXONOMY 161 23 ORTHOMYXO and PARAMYXOVIRIDAE 172 24 HEPATITIS VIRIDAE 180 25 RETROVIRIDAE, HIV, and AIDS 190 26 HERPESVIRIDAE 204 27 REST OF THE DNA VIRUSES 209 28 REST OF THE RNA VIRUSES 214 29 ANTI-VIRAL MEDICATIONS 224 PART 4. PARASITES 231 30 PROTOZOANS 231 31 HELMINTHS 248 vi PART 5. VERY STRANGE CRITTERS 265 32 PRIONS (contributing author: Hans Henrik Larsen, M.D.) 265 PART 6. 33 ANTIMICROBIAL RESISTANCE: ONE STEP TOWARD THE POST-ANTIBIOTIC ERA? (contributing author: Earnest Alexander, Pharm.D.) 269 BIOTERRORISM DEFENSE UPDATES: http://www.medmaster.netBioterrorismDefense.html Peface A well-developed knowledge of clinical microbiology is 4) Create a conceptual, organized approach to the or- critical for the practicing physician in any medical field. ganisms studied so the student relies less on memory Bacteria, viruses, and protozoans have no respect for and more on logical pathophysiology. the distinction between ophthalmology, pediatrics, The text has been updated to include current infor- trauma surgery, or geriatric medicine. As a physician mation on rapidly developing topics, such as HIV and you will be faced daily with the concepts of microbial AIDS (vaccine efforts and all the new anti-HIV medica- disease and antimicrobial therapy. Microbiology is one tions), Ebola virus, Hantavirus, E. coli outbreaks, Mad of the few courses where much of the "minutia" is regu- larly used by the practicing physician. Cow Disease, and brand-new antimicrobial antibiotics. This book attempts to facilitate the learning of mi- The mnemonics and cartoons in this book do not in- tend disrespect for any particular patient population or crobiology by presenting the information in a clear and entertaining manner brimming with memory aids. racial or ethnic group but are solely presented as mem- Our approach has been to: ory devices to assist in the learning of a complex and im- portant medical subject. 1) Write in a conversational style for rapid assimi- We welcome suggestions for future editions. lation. 2) Include numerous figures serving as "visual mem- MARK GLADWIN, MD ory tools" and summary charts at the end of each chap- BILL TRATTLER, MD ter. These can be used for "cram sessions" after the concepts have been studied in the text. 3) Concentrate more on clinical and infectious dis- ease issues that are both interesting and vital to the ac- tual practice of medicine. D CONTENTS Preface v PART 1 1 1 BACTERIAL TAXONOMY 1 2 CELL STRUCTURES, VIRULENCE FACTORS, and TOXINS 8 3 BACTERIAL SE( GENETICS 16 GRAM-POSITIVE BACTERIA 22 4 STREPTOCOCCUS 22 5 STAPHYLOCOCCUS 31 6 BACILLUS and CLOSTRIDIUM (SPORE-FORMING RODS) 38 7 CORYNEBACTERIUM and LISTERIA (NON-SPORE-FORMING RODS) 45 GRAM-NEGATNE BACTERIA 49 8 NEISSERIA 49 9 THE ENTERICS 54 10 HAEMOPHILUS, BORDETELLA, and LEGIONELLA 68 11 YERSINIA, FRANCISELLA, BRUCELLA, and PASTEURELLA 73 12 CHLAMYDIA, RICKETTSIA, and FRIENDS 78 13 SPIROCHETES 91 ACID-FAST BACTERIA 102 14 MYCOBACTERIUM 102 BACTERIA WITHOUT CELL WALLS 111 15 MYCOPLASMA 111 ANTI-BACTERIAL MEDICATIONS 114 16 PENICILLIN FAMILY ANTIBIOTICS 114 17 ANTI-RIBOSOMAL ANTIBIOTICS 125 18 ANTI-TB and ANTI-LEPROSY ANTIBIOTICS 133 19 MISCELLANEOUS ANTIBIOTICS 139 PART 2. FUNGI 144 20 THE FUNGI 144 21 ANTI-FUNGAL MEDICATIONS 155 PART 3 161 22 VIRAL REPLICATION and TAXONOMY 161 23 ORTHOMYXO and PARAMYXOVIRIDAE 172 24 HEPATITIS VIRIDAE 180 25 RETROVIRIDAE, HIV, and AIDS 190 26 HERPESVIRIDAE 204 27 REST OF THE DNA VIRUSES 209 28 REST OF THE RNA VIRUSES 214 29 ANTI-VIRAL MEDICATIONS 224 PART 4. PARASITES 231 30 PROTOZOANS 231 31 HELMINTHS 248 vi PART 5. VERY STRANGE CRITTERS 265 32 PRIONS (contributing author: Hans Henrik Larsen, M.D.) 265 PART 6. 33 ANTIMICROBIAL RESISTANCE: ONE STEP TOWARD THE POST-ANTIBIOTIC ERA? (contributing author: Earnest Alexander, Pharm.D.) 269 BIOTERRORISM DEFENSE UPDATES: http://www.medmaster.netBioterrorismDefense.html PART 1. BACTERIA CHAPTER 1. BACTERIAL TAXONOMY All organisms have a name consisting of two parts: the genus followed by the species (i.e., Homo sapiens). Bac- DISACCHARIDE teria have been grouped and named primarily on their morphological and biochemical/metabolic differences. However, bacteria are now also being classified accord- ing to their immunologic and genetic characteristics. This chapter focuses on the Gram stain, bacterial mor- phology, and metabolic characteristics, all of which en- able the clinician to rapidly determine the organism causing a patient's infection. GRAM STAIN Because bacteria are colorless and usually invisible to light microscopy, colorful stains have been developed to visualize them. The most useful is the Gram stain, which separates organisms into 2 groups: gram-positive bugs and gram-negative bugs. This stain also allows the clinician to determine whether the organism is round or rod-shaped. For any stain you must first smear the substance to be stained (sputum, pus, etc.) onto a slide and then heat AMINO ACIDS it to fix the bacteria on the slide. There are 4 steps to the Gram stain: 1) Pour on crystal violet stain (a blue dye) and wait 60 seconds. Fige 1-1 2) Wash off with water and flood with iodine solu- tion. Wait 60 seconds. Both gram-positive and gram-negative organisms 3) Wash off with water and then "decolorize" with have more than 1 layer protecting their cytoplasm and 95% alcohol. nucleus from the extracellular environment, unlike an- 4) Finally, counter-stain with safranin (a red dye). imal cells, which have only a single cytoplasmic mem- Wait 30 seconds and wash off with water. brane composed of a phospholipid bilayer. The layer just outside the bacterial cytoplasmic membrane is the pep- When the slide is studied microscopically, cells that tidoglycan layer or cell wall. It is present in both absorb the crystal violet and hold onto it will appear gram-positive and gram-negative organisms. blue. These are called gram-positive organisms. How- ever, if the crystal violet is washed off by the alcohol, Fig. 1-1. The peptidoglycan layer or cell wall is these cells will absorb the safranin and appear red. composed of repeating disaccharides with 4 amino acids These are called gram-negative organisms. in a side chain extending from each disaccharide. Gram-positive = BLUE Fig. 1-2. The amino-acid chains of the peptidoglycan I'm positively BLUE over you!! covalently bind to other amino acids from neighboring chains. This results in a stable cross-linked structure. Gram-negative = RED The enzyme that catalyzes the formation of this linkage No (negative) RED commies!! is called transpeptidase and is located in the inner cy- toplasmic membrane. The antibiotic penicillin binds to The different stains are the result of differences in the and inhibits this enzyme. For this reason the enzyme is cell walls of gram-positive and gram-negative bacteria. also called penicillin binding protein (see page 114). 1 CHAPTER 1. BACTERIAL TAXONOMY Figure 1-2 ( ) - . A - . I , - - . Figure 1-3 Fig. 1-5. T - S , . L - Fig. 1-3. T - , 1) - - 2) . 3) I , - . I , - . - . T ( - ) - Fig. 1-4. T - . G- - cell - - , , , . . T T - - . T . T . T - , Figure 1-4 2 CHAPTER 1. BACTERIAL TAXONOMY GRAM-NEGATIVE CELL ENVELOPE OUTER MEMBRANE MUREIN LIPOPROTEIN PEPTIDOGLYCAN LAYER (CELL WALL) PERIPLASMIC SPACE CYTOPLASMIC MEMBRANE EMBEDDED PROTEINS Figure 1-5 lipoprotein called murein lipoprotein.