Bacteria

EXOTOXIC MODEL CORYNEBACTERIUM DIPHTERIAE • • •

I.

Received its name from the hide-like pseudomembrane that forms on the tonsils, palate, or pharynx Even though the exotoxin can cause fatty degeneration of heart muscle and nervous system, young children often die because their Airway is occluded. Exotoxins o Secreted proteins from microorganisms o Take form of A-B toxin where B interacts with a cell receptor as a ligand. A is then released, internalized and causes damage to the cell. GENUS CORYNEBACTERIUM A. CHARACTERISTICS  Club Shape Rods  Gram Positive  Non-spore forming  Non-acid fast  Aerobic or Facultative anaerobic  Catalase Positive  Non-motile B. CHEMOTAXONOMICALLY  Cell walls contain: • Meso-diaminopimelic acid • Arabino-galactan polymer • Short chain mycolic acids C. CORYNEBACTERIUM SPP.  World Wide D. CLOSELY RELATED GENERA  Rhodococcus, Nocardia, Mycobacterium

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II.

CORYNEBACTERIUM DIPHTERIAE A. PATHOGEN  Occurs naturally only in humans but we can infect farm animals  Produces Characteristic METACHROMATIC Granules that Stain Bluish Purple with Methylene blue.  Grows with Snapping division which results in Angular and Palisade arrangements that look like Chinese Letters. B. CYCLE OF INFECTION 1. Respiratory tract diphtheria is most common in temperate climate 2. Cutaneous diphtheria are seen in tropical areas a. Spread by Touch and Fomites b. Transmitted to cows by infected milker’s fingers c. Unpasteurized milk can then transmit the infection C. PATHOGENESIS 1. Classic AB exotoxic disease a. B domain binds to cell receptor and forms membrane channel for A b. A binds to Elongation Factor 2 (EF-2) and causes it to be ADP rebosylated and made inactive. Thus, the cell can no longer make proteins. 2. Toxin Production a. Low iron stimulates toxin production 3. Biological Toxin Effects a. Local pharyngeal membrane formation b. Heart, nerves, and kidney are most sensitive D. CLINICAL MANIFESTATIONS 1. Pharyngitis 2. Bullneck due to neck swelling which leads to difficult air passage 3. No lymphadenopathy 4. Open mouth and look for membrane, which is 1-3mm thick and is curling away from the tonsils, palate, uvula, or pharynx. 5. Foul breath associated with necrosis and the greenish or blackened membrane are hallmarks**** E. DIAGNOSIS 1. Elick Test and Schick Test F.

TREATMENT 1. Erythromycin or penicillin 2. Maintenance of open airway

G. PREVENTION 1. DPT in children 2. Td in adults (booster every 10 years)

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ENDOTOXIC MODEL NEISSERIA MENINGITIDIS •

ENDOTOXINS o Integral parts of microbial cell wall and are normally released only when the cell dies o Characteristic of Gram Negative Bacteria

I. NEISSERIA MENINGITIDIS A. CELLULAR MORPHOLOGY o Small Gram Negative Diplococcus o Bean Shaped o Non-motile B. PHYSIOLOGY o Aerobic or facultative o Oxidase Positive o Grow on Chocolate Agar o Sensitive to drying C. ANTIGENIC CHARACTERISTICS o Capsular Polysaccharide o Surface antigens include proteins for iron uptake from transferrin D. VIRULENCE FACTORS o Pili – Attach to cells of mucous membrane of pharynx or nasopharynx o Capsule – Anti-phagocytic o Endotoxin – Causes shock and necrosis o IgA protease E. CYCLE OF INFECTION o Enters through Upper Respiratory Tract o Invade and enter bloodstream to infect skin, eyes, joints, lungs, and meninges. F.

DISEASES o Causes mild to acute pharyngitis o Skin affected with Petechial Rash** along the nuchal rigidity are early signs of meningitis. o Spinal fluid is turbid. o Sequellae: Nerve Deafness  Skin Damage  CNS Damage  Death without treatment

G. LABORATORY IDENTIFICATION o Thayer Martin Agar (Chocolate agar plus vancomycin) H. MORBIDITY AND MORTALITY o Highest disease rate among children o Mortality is less than 10% with early diagnosis and treatment I.

TREATMENT o Before Lab diagnosis treat with Cephalosporin or Ampicillin o After lab diagnosis teat with Penicillin

J.

RELATED ORGANISMS

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o

Neisseria gonorrhoea, Moraxella, and Branhamella

PYOGENIC MODEL STAPYLOCOCCUS AUREUS I. CHARACTERISTICS OF STAPHYLOCOCCI A. CELLULAR MORPHOLOGY o Gram Positive Cocci o Grape like clusters B. PHYSIOLOGY o Non motile o Facultative anaerobes o Produce Catalase to breakdown hydrogen peroxide C. ECOLOGICAL NICHE o Normal flora of humans (Anterior nares, perineum, axillae) D. GENETIC ASPECTS o Antibiotic resistance is plasmid or transposon mediated. II. INFECTIOUS CYCLE • Mode of Transmission: Direct contact and Fomites • No vaccine to prevent disease. III. PATHOGENIC CHARACTERISTIC • Primary or opportunistic pathogens that can infect any organ or tissue • Excrete Coagulase*** • Toxic Shock Syndrome by Toxin-1 • Epidermolytic (exofoliative) toxin (scalded skin) IV. STAPHYLOCOCCAL DISEASES 1. Cause >80% of Suppurative diseases and are major cause of Nosocomial Infections*** 2. Toxic Shock Syndrome i. Associated with tampon use. S. aureus grows in vagina, producing exotoxins which cause symptoms of Fever, Hypotension, Diarrhea, Conjunctivitis, myalagia, and rash with desquamation. 3. Stapylococcal Food Poisoning i. Short term, Self limiting, Violent vomiting for 24-48 hours 4. Staphylococcus epidermidis infections i. Colonization of prostheses. Slimy capsule enhances adherence to tissue V. TREATMENT • Drain abscesses, remove foreign bodies (prostheses) • Penicillin or Erythromycin

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CAPSULAR MODEL STREPTOCOCCUS PNEUMONIAE • •

Most have Polysaccharide Capsule Cause Non-Invasive (Otitis media) and Invasive Infections (pneumonia, meningitis, sepsis)

I. CAPSULAR FUNCTION • Adhesins and invasions are essential during the contact of bacteria with their target cells and for invasion. • When the bacteria enter the circulation, capsules are required to counteract complement and phagocytic activity. II. BIOLOGICAL PROPERTIES A. CELLULAR MORPHOLOGY o Gram Positive Lancet-shaped Diplococci o Non-motile o Non-spore forming B. VIRULENT STRAINS PRODUCE A POLYSACCHARIDE CAPSULE o Encapsulated strains produce smooth colonies on agar C. PHYSIOLOGY o Facultative anaerobes o Require Choline o Catalase Negative** o Alpha Hemolysis on Sheep Blood Agar III. VIRULENCE FACTORS A. COLONIZATION AND MIGRATION FACTORS B. TISSUE DESTRUCTION C. PHAGOCYTIC SURVIVAL IV. INFECTIOUS CYCLE • Reservoir: Human Nasopharynx • Enter through respiratory tract • Causes Lobar Pneumonia, Meningitis, Bacteremia, and Otitis V. CLINICAL PRESENTATION • Accumulation of edema fluid (X-ray) • Sudden onset with Fever, Chills, and Sharp Pleural Pain and Rusty colored sputum due to Alveolar exudates containing erythrocytes*** VI. TREATMENT • Penicillin G or erythromycin

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OTHER STREPTOCOCCI I. CLASSIFICATION OF THE STREPTOCOCCI • C carbohydrate (Lancefield group serological designation) • Hemolytic Characteristics II. BETA HEMOLYTIC STREPTOCOCCI • Produce soluble hemolysins detectable on blood agar A. GROUP A: STREPTOCOCCUS PYOGENES o Bacitracin sensitive o Large zones of hemolysis B. GROUP B: STREPTOCOCCUS AGALACTIAE o Normal flora of human pharynx, GI and female genital tract o Small zones of hemolysis o Positive CAMP test C. GROUP C AND G o Found in pharynx o Cause sinusitis, bacteremia, endocarditis III. NON-BETA HEMOLYTIC STREPTOCOCCI • Alpha (Greening) or No hemolysis on Sheep Blood Agar Plate (BAP) A. GROUP D: ENTEROCOCCUS SPP. o Normal gut flora o Grow in presence of 40% bile or 6.5% NaCl o Inhibited but not killed by Penicillin. o Major Nosocomial Pathogens – Highly Resistant – Now also to Vancomycin*** B. STREPTOCOCCUS PENUMONIAE o Alpha hemolytic, Bile Soluble, Inhibited by Optochin** C. GROUPS H AND K: VIRIDANS STREPTOCOCCI o Alpha hemolytic, Not Bile Soluble, Not inhibited by optochin. o Cause Dental Caries

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MODEL RESPIRATORY TRACT INFECTIONS HAEMOPHILUS AND BORDETELLA HAEMOPHILUS INFLUENZA I. BIOLOGICAL CHARACTERISTICS A. MORPHOLOGY o Gram Negative Coccobacillus o Non-motile o Non-spore forming o Six Capsular Serotypes (A-F): Type B (polyriboylribitol phosphate, PRP or PRRP) causes most acute infections B. METABOLISM o Whole blood contains 2 factors Essential For Growth:  X Factor – Hemin, hematin, or protoporphyrin IX  V Factor – NAD o Aerobic, Facultative anaerobe C. RESISTANCE o Easily killed by

  

50°C for 30 minutes Desiccation Most antiseptics

II. VIRULENCE FACTORS 1. Capsule prevents phagocytosis 2. Endotoxin (LOS) III. INFECTIOUS CYCLE • Unimmunized children 2 months through 3 years are most susceptible • Non-life threatening by age 10 • Transmitted via droplet and fresh exudates IV. DISEASES CAUSED BY H. INFLUENZA • Begins as Nasopharyngitis • Coryza, Cellulitis around cheek, Otitis meda, epiglottis. • Infection to joints and meningitis. V. LABORATORY DIAGNOSIS • Positive Quellung Test establishes diagnosis • Bile Solubility Test: Bile soluble VI. TREATMENT • Ampicillin

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VII. PREVENTION • Type B Capsular (PRP) Antigen Vaccine for children OVER 18 Months (Ti Antigen) • Protein PRP Conjugate Vaccine for children UNDER 18 months (Td Antigen) VIII. OTHER RELATED SPECIES A. H. aegypticus  Koch Weeks Bacillus, Purulent Conjunctivitis B. H. parainfluenza  Subacute bacterial endocarditis C. H. suis  Acute swine influenza D. H. ducreyi  Venereal disease chancroid BORDETELLA PERTUSSIS (Whooping Cough) I. BIOLOGICAL CHARACTERISTICS A. MORPHOLOGY o Gram Negative Coccobacilli o Non-motile, Non-spore forming o Have Fibriae for attachment to cilia of respiratory epithelial cells B. PHYSIOLOGY o Aerobic o Inhibited by Fatty acids, sulfides, peroxides o Must be grown on media with charcoal, starch, blood, or ion exchange resins to bind inhibitors. C. GENETICS o bvg AS genes control virulence factors D. ANTIGENIC STRUCTURE o Fibriae, Filamentous hemaggultinin (FHA), Pertactin, LPS E. RESISTANCE o Killed by  Drying  50°C for 30 minutes  Most antiseptics and disinfectants II. INFECTIOUS CYCLE • Childhood disease with highest incidence in children under 7 • Highly communicable • Transmitted via aerosols III. DISEASES CAUSED • Colonization of ciliated epithelium o nasopharynx • Catarrhal Stage ( Most Contagious) lasts 10-14 days and is characterized by: o Rhinitis o Sneezing o Mild Cough • Paroxysmal Stage o Last 1-6 weeks o Severe coughing followed by “whoop” coughing • Convalescent Stage o Lasts weeks to months • Complications o Secondary infections are possible o Neurological complications o Pneumothorax o Hemorrhages

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IV. LAB DIAGNOSIS • Swat nasopharynx and plate onto Bordet Gengou Agar with and without penicillin V. TREATMENT • Erythromyocin, Tetracyclin, or Chloramphenicol • Resistant to sufonamides and Penicillin VII. PREVENTION • Whole Cell Vaccine (DTP) • New Acellular Vaccines (DtaP)

SYSTEMIC ZOONOTIC INFECTIONS I. BRUCELLOSIS A. DESCRIPTION o Zoonoses are diseases of vertebrate animals which are easily transmissible to man. o Not transmittable from man to man. o Systemic bacterial disease transmitted to humans by contact with unpasteurized milk o Characterized by continued, intermittent, or irregular fever and influenza like signs and symptoms of malaise, anorexia, fever, and profound muscular weakness. “UNDULANT FEVER” B. ETIOLOGIC AGENTS 1. B. melitensis (goats)** 2. B. abortus (cattle) 3. B. suis (swine) 4. B. canis (dog) C. BIOLOGICAL CHARACTERISTICS 1. Gram Negative Rod or Coccobacillus 2. Non-motile, Non-sporeforming 3. Facultative intracellular parasite 4. Strict aerobe D. PATHOTGENESIS o Lesions are granulomatous characterized by mononuclear cell proliferation, fibrin deposition, coagulation, necrosis, and fibrosis. E. TREATMENT 1. Timethorpim/Sulfamethozazole for 3 weeks + IM Gentamicin for 5 days – Children 8 or younger 2. Doxycycline for 3 weeks + IM Gentamicin for 5 days – Children over 8 3. Oral Doxycycline and Rifampin for 30 days – Adults II. PLAGUE A. DESCRIPTION o An infectious disease of rodents and rabbits transmitted to humans by the bite of an infected flea. o “Black Death” Disease B. ETIOLOGIC AGENT: YERSINIA PESTIS 1. Gram Negative Coccobacillus - Marked bipolar staining and safety pin appearance 2. Facultative anaerobes 3. Do Not Ferment Lactose 4. Oxidase Negative 5. Catalase Positive 6. Non-Hemolytic 7. 28°C is optimal growth temperature C. VIRULENCE FACTORS

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1. 2. 3. 4.

V-W antigens prevent phagocytosis Envelope (F-1) antigen prevents phagocytosis** Murine Toxin – produces shock Endotoxin – causes Febrile Response and Schwartzman reactions

1. 2. 3.

Buboes – Swollen lymph nodes Rapid rise in temperature, pneumonic signs, CNS abnormalities Pneumonic Plague – Pulmonary involvement from septic emboli

1. 2. 3.

Streptocycin Kanamycin Reporting to health authorities is Mandatory

D. DISEASES

E. TREATMENT

F.

PREVENTION

1. Chemoprophylaxis with tetracycline recommend for those with a family history 2. Formalin killed vaccine for those with occupational exposure risk III. TULAREMIA (FRANCISELLA TULARENSIS) A. DESCRIPTION o Infectious disease of wild animals especially rabbits that is transmitted to humans by direct contact, arthropod vector transmission, and ingestion of contaminated meat. B. BIOLOGICAL CHARACTERISTICS 1. Gram Negative Coccobacillus with Bipolar Staining 2. Obligate Aerobe 3. 35°C is optimal growth temperature 4. Requires Cysteine and other growth factors C. VIRULANCE FACTORS 1. Jellison Type A – More virulent tick borne rabbit tularemia 2. Jellison Type B – Waterborne rodent or sheep carried D. DISEASES o Resemble those of plague with Primary Ulcer at site of entry and Lymphadenopathy. o 10% develop Painless, Non-Pruritic Rash E. PATHOGENESIS AND HOST RESPONSE 1. Ulceroglandular Form – Ulcer at site of infection 2. Oculoglandular Disease – Site of infection is Conjunctival Sac with Papule Formation 3. Typhoidal Type – Due to uncooked meat 4. Pulmonary Disease 5. Agglutinating IgM and IgG antibodies. F.

TREATMENT 1. Streptomycin or Gentamicin 2. Tetracycline and Chloramphenicol

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IV. ANIMAL BITE INFECTIONS A. PASTEURELLA MULTOCIDA 1. DESCRIPTION  Normal flora of nasopharynx of dogs and cats. 2. ETIOLOGIC AGENT i. Gram Negative Rod Shaped with bipolar staining ii. Non-hemolytic on blood agar iii. 37°C optimal temperature 3. PATHOGENESIS AND HOST RESPONSE i. Local infection at site of bite followed by regional lymphadenitis ii. Cat bite progress to pyarthroses, necrotizing synovitis, and osteomyelitis 4. EPIDEMIOLOGY i. 1 to 2 million animal bites per year in the U.S. 5. TREATMENT i. Wound Irrigation ii. Debridement iii. Suturing iv. Antibiotic prophylaxis and therapy for bite. Penicillin, Amoxicillin, Dicloxacillin. B. DF-2 (CAPNOCYTOPHAGIA CANIMORSUS) 1. DESCRIPTION  Gram Negative Opportunistic pathogen that can cause multiple organ disease in humans.  Mostly due to dog bites 2. DIAGNOSIS  Supported when severe sepsis develops after a bite in an immunodeficient patient  Blood smears reveal Gram Negative Bacilli within Neutrophils 3. TREATMENT  Penicillin G C. STREPTOBACILLUS MONILIFORMIS 1. DESCRIPTION  Found in pharynx of wild and lab rats  Rat Bite Fever in laboratory workers after a bite  Haverhill Fever in those with ingestion of contaminated milk  Gram Negative, Non-encapsulated, Occurs in chains and filaments  Most Distinguishing characteristic is Spontaneous Development of L-Phase Variants*** 2. PATHOGENESIS AND HOST RESPONSE

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3.

 Maculopapular Rash develops in 48 hours*** along with acute arthritis TREATMENT  Pencillin G

V. CAT SCRATCH DISEASE (CSD) - BARTONELLA A. INTRODUCTION o Characterized by development of a Primary Inoculation Lesion at the site of Cat Scratch, followed by Subacute Regional Lymphadenitis. *** o 50% only have Regional Lymphadenopathy o 10% have Perinaud’s Oculoglandular Syndrome (due to rubbing the eye after holding a cat) o Benign and Self limiting o Most common cause of chronic regional lymphadenitis in children B. DESCRIPTION o Motile** o Aerobic o Gram Negative o Warthin Starry Silver Imprgnations Stain and Brown Hopps Tissue Gram Stain o BARTONELLA SPP.**** C. DIAGNOSIS o Supported when following are met:  Exposure to cat  Regional Lymphadenitis**  Positive IFA test for B. henselae with titer greater than 1:64 in acute phase serum**  Other causes of lymphadenopathy have been excluded. D. EPIDEMIOLOGY o Primarily a disease of children with 60% of the patients being less than 12 years old** E. TREATMENT o No specific treatment – Recover completely within months o Treatment of cat with Doxycycline or Linicomycinseveral

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ENTERIC BACTERIA • •

Include Gram Negative Bacilli and Vibrios found normally in the Intestinal Tract. Gram Negative Bacilli - Coliforms o Oxidase Negative** o Grow on MacConkey Agar o Characteristics used to differentiate rely on biochemical tests. o Antigens of the Cell Wall are used in diagnosis:  Somatic or “O” Antigens  Flagella or “H” Antigens  Capsule or “K” Antigens

•

Vibrios o Oxidase Positive** o Cause Cholera o Associated with vertebrate or invertebrate species in fresh and brackish waters

•

Campylobacters o Microaerophillic o Oxidase positive** o Motile o Curved to Spiral rods

I. COLIFORMS • Oxidase Negative** • Lactose fermenters • Normally found in large intestine A. ESCHERICHIA COLI 1. Indicator of fecal pollution of water, food, and dairy products. 2. Diarrheal Disease and Meningitis in neonates due to K1 capsular antigen 3. Enterotoxigenic E. coli (ETEC) i. Acquired through ingestion of contaminated foods ii. Causes “Travelers diarrhea”

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4. 5.

6. 7.

iii. Heat Labile Toxin (LT) – Increase cAMP iv. Heat Stable Toxin (ST) – Increase guanylyl cyclase Enteropathogenic E. coli (EPEC) i. Gastroenteritis in infants of developing countries. Enterohemorrhagic E. coli (EHEC) i. Blood in diarrhea ii. No Fecal leukocytes iii. Sorbitol Negative (SMAC agar) iv. Undercooked ground beef is main cause** v. Hemolytic Uremic Syndrome (HUS) develops in 10% characterized by: 1. Microangiopathic Hemolytic Anemia 2. Thrombocytopenia 3. Thrombosis of Glomerular Capillaries Enteroinvasive E. coli (EIEC) i. Dysentery – Fever, blood, small volume, pus ii. Epithelial Invasion Enteroaggregative E. coli (EAEC) i. Causes watery diarrhea

B. KLEBSIELLA 1. K. pneumonia or K. oxytoca 2. Non-motile, Ferments every sugar** 3. Lobar pneumonia, urinary tract infection, wound infections C. ENTEROBACTER 1. E. cloacae and E. aerogenes 2. Motile D. SERRATIA 1. S. marcescens 2. Orange to Red pigment at room temperature 3. Nosocomial infections A. CITROBACTER 4. C. freundii and C. koseri 5. No intestinal infection E. PROTEUS 1. Swarms plate and Stinks**8 2. Lactose negative 3. Urease positive II. PRIMARY PATHOGENS A. SHIGELLA 1. Acute Bacillary Dysentery (Bowel movements, bloody stool, mucus, abdominal cramps, and tenesmus) 2. Related to E. coli and cannot be differentiated with DNA hybridization 3. Transmitted by fecal-oral route 4. Antigen A  S. dysenteriae 5. Antigen B  S. flexneri 6. Antigen C  S. boydii 7. Antigen D  S. sonnei – Often associated with Day Care Centers**

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8. Lactose Negative, Non-motile, Anaerogenic 9. Smooth appearance forming colonies are Pathogenic B. SALMONELLA 1. Gram Negative, Aerobic 2. Food borne infection is a major problem 3. Gastroenteritis – Loose stools of moderate volume without blood for several weeks 4. Bacteremia 5. Enteric Fever – Typhoid Fever 6. Treatment includes Ampicillin, Streptomycin, and Tetracycline III. OTHER ZOONOTIC GRAM NEGATIVE AGENTS - YERSINIOSIS A. YERSINIA ENTEROCOLITICA AND YERSINIA PSEUDOTUBERCULOSIS B. Ingestion of contaminated food  Acute Enteritis and Appendicitis C. Virulence Factors – AIL, YOP, and Invasin D. Neonates to 5 years  Acute Gastroenteritis with watery diarrhea without blood E. 5 – 15 years  Acute mesenteric adenitis F. All ages  Food poisoning

IV. VIBRIONACEAE A. GENERAL CHARACTERISTICS 1. Gram Negative Rods 2. Motile with single Polar Flagellum 3. Oxidase Positive 4. Grow on MacConkey Agar B. VIBRIO 1. VIBRIO CHOLERA  Low tolerance for acid  3 Serologic Subgroups (AB-Ogawa, AC-Inaba, ABC-Hikojima)  Spread primarily in contaminated water  Vomiting, watery diarrhea with Mucus Flecks (rice water stool)*** 2. NON-CHOLERA VIBRIOS  Caused by consumption of Raw Shellfish 3. VIBRIO PARAHEMOLYTICUS  Gastroenteritis**  Raw Seafood and Sashimi or contamination after cooking 4. VIRBIO VULNIFICUS  ONPG positive  Raw Oysters  Gastroenteritis 16 hours after ingestion C. CAMPYLOBACTER 1. CAMPLYOBACTER JEJUNI  Sensitive to environmental stresses  Found in Retail Chicken***, Raw milk, and Non-chlorinated water  Infects mucosal surfaces of jejunum, ileum, and colon  May cause Guillain-Barre Syndrome** 3. CAMPYLOBACTER FETUS  Gastroenteritis and invasion of blood stream are more common

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D. HELICOBACTER PYLORI o Urease producer, Ammonia to neutralize stomach acid o Causes Gastritis, Gastric and Duodenal Ulcers o Precursor of gastric adenocarcinoma o Treatment: Proton Pump Inhibitor (Omeprazole), Bismuth Compounds E. PLEISOMONAS SHIGELLOIDES o Non-Lactose fermenter o Genetically is more like E. coli than vibrios o Self limiting gastroenteritis F.

AEROMONAS HYDROPHILA o Gastroenteritis in healthy people, Septicemia in immunocompromised patients

OPPORTUNISTIC ENVIRONMENTAL AND MISCELLANEOUS ORGANISMS I. LEGIONELLA PNEUMOPHILA A. BIOLOGICAL CHARACTERISTICS 1. Gram Negative Bacilli 2. Aerobic 3. Catalase and Oxidase Positive 4. Fastidious – High Cysteine and Low Sodium levels to grow 5. Survive in tap water at room temperature for over a year B. VIRULENCE FACTORS o Beta Lactamase Producer C. INFECTIOUS CYCLE o Reservoir: Non-marine aquatic environments such as lakes and ponds o Transmission: Aerosal to lungs o Upper respiratory tract o Not communicable from human to human D. PATHOGENESIS o Inhaled  Alveolar Macrophage  Lyse macrophage after replication causing lung damage E. DISEASES o Legionnair’s Disease - Patients present with Anorexia, Malaise, Headach, and a Rapid Fever to 39-40°C. o Pontiac Fever – similar to Legionnair’s disease but more milder. F.

TREATMENT o Erythromycin

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G. PREVENTION o Hyperchlorination of water

II. PSUEDOMONADS A. CHARACTERISTICS 1.Grow on MacConkey agar 2. Strict Aerobes 3. Oxidase Positive 4. Gram Negative, Motile with Polar flagellum B. PSUEDOMONAS AERUGINOSA 1. Blue Green Pigment 2. 42°C optimal temperature 3. Fruity odor 4. Pellicle (membranous surface film) in broth culture 5. Lactose Negative 6. Contaminates water – humidifiers and contact lens solutions

III. BURKHOLDERIA A. BURKHOLDERIA PSEUDOMALLEIL o Gram Negative o Aerobic o Grow in water o Acquired by direct inhalation or inoculation o Meliodosis – acute pneumonia** o Glanders – Disease in horses with acute pulmonary lesions** B. BURKHOLDERIA CEPACIA o Gram Negative, Aerobic, Grow in water o Causes Pulmonary Infection in cystic fibrosis IV. STENOTROPHOMONAS MATOPHILIA

• •

Gram Negative, Aerobic, Grow in water, solutions, ice machines, etc Causes Bacteriemia, Pneumonia, Meningitis, Wound infections, Urinary tract infections

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MYCOBACTERIA I. GENUS MYCOBACTERIUM A. CHARACTERISTICS OF GENUS MYCOBACTERIUM 1.Stain as Acid Fast (Gram Neutral/Positive) slim Rods 2. Obligate Aerobes 3. Non-Motile, Non-Spore Forming 4. Very Slow Growing 5. Unique Cell Wall Structure: a. 2 backbones: Peptidoglycan and Arabinogalactan b. 60% lipid content, Very hydrophobic c. Development of mycolic acids d. Outer envelope varies with species 6. Resistance to physical stress due to hydrophobic wall B. ACID FAST STAIN 1. Distinguishes Mycobacteria from other genera 2. Once stained, cells resist Decolorization 3. Classic Ziehl Neelsen Stain – Stain Red, other genera decolorize and counterstain blue II. MYCOBACTERIAL DISEASE A. PATHOGENESIS o By-Stander disease o Granulomas result from CMI processes. Bacilli multiply in macrophages. o Host damage results from Hypersensitivity to Mycoproteins o M. ulcerans is the Only Mycobacterium known to produce and Exotoxin**

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B. DEFENSE o Cell mediated but incomplete (Macrophages kill intracellular mycobacteria) o Mycobacteria are Inhibited and Dormant, Not Killed. Must be actively contained for life C. CLINICAL SYNDROMES 1. Primary Infection  Handled well by host. Most lesions heal by fibrosis and organisms slowly die. Some remain for decades as opportunists 2. Reactivation Disease  Reactivated due to immunosuppression, malnutrition, alcoholism, and diabetes 3.Granuloma  Asymptomatic, rounded lesions  Single or multiple  Fibrous encapsulation of caseous lesion D. DIAGNOSTIC TOOLS o Purified Protein Derivative (PPD) skin test for Delayed Hypersensitivity o Acid Fast Smearw

III. MAJOR PATHOGENIC MYCOBACTERIA A. MYCOBACTERIUM TUBERCULOSIS 1. INTRODUCTION o Causes Tuberculosis 2. ETIOLOGIC AGENT o Acid-Alcohol Fast o Wax D, cell wall oligomer is very strong immunoadjuvant** o Aerobic at 37°C optimal** o Virulent strains show “Cording” on oleic acid albumin agar 3. HOST FACTORS o Multifactorial causation (genetic and environment influences) 4. CYCLE OF INFECTION o Transmission from person to person via the aerosol route. o Respiratory tract to alveolus 5. PATHOGENESIS o Tubercles result from Hypersensitivity to tuberculoproteins and depend on the concentration of antigen at a location and the degree of tissue hypersensitivity. 6. CLINICAL SYMPTOMS o 80% is pulmonary tuberculosis o 90% it is asymptomatic or mild influenza like disease. o Chronic fever, weight loss, night sweats, and productive coughing with hemoptysis characterize the disease*** o Tuberculoma – Local lesions like Prosecutor’s Wart 7. DIAGNOSTIC STUDIES o Positive Niacin test confirms M. tuberculosis**

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9. TREATMENT o Report the case to Public Health authorities o Triple Chemotherapy o Isoniazid (INH) – inhibits synthesis of mycolic acids and mycobacterial DNA o Pyrazinamide (PZA) – Bactericidal, active against dormant mycobacteria at acid pH o Rifampin – blocks initiation of RNA transcription o Ethambutol – blocks syntheis of arabinogalactan o Streptomycin – inhibits protein synthesis o Must use drugs in combinations or it is not useful. B. MYCOBACTERIUM BOVIS 1. ETIOLOGIC AGENT o Produces tuberculosis in animals** 2. CYCLE OF INFECTION o Source: Infected cattle and their products, milk, cheese, meat. o Transmission: Ingestion or airborne o Primary site of colonization: Cervical and Mesenteric Lymph Nodes** 3. CLINCICAL SYNDROME o Extrapulmonary lesions especially of cervical and mesenteric lympn nodes. 4. LABORATORY DIAGNOSIS o DNA of M. bovis and M. tuberculosis have 100% homology with only a few different genetic markers. o M. bovis is Niacin Negative** 7. TREATMENT o Same as M. tuberculosis

C. BACILLE OF CALMETTE AND GUERIN (BCG) 1. VACCINE STRAIN o Mutant of M. bovis isolated on a Glycerol-Potato-Bile Medium** o BCG vaccination is successful. Administration is Intradermal 2. BCG AS IMMUNOADJUVANT o Used as immunoadjuvant for superficial bladder cancer** 3. LABORATORY IDENTIFICATION o Niacin Negative** 4. TREATMENT o With usual Antitubercular drugs D. MYCOBACTERIUM LEPRAE 1. ETIOLOGICAL AGENT o Obligate Intracellular Parasite o Slow multiplication within phagocytes, skin histiocytes, and Schwann cells. o Seen in armadillos and hedgehogs** 2. INFECTIOUS CYCLE o Much injury is due to denervation. 3. TREATMENT o Triple Therapy: Dapsone, Rifampin, Clofazimine o Treat until skin smears are free of bacilli E. MYCOBACTERIUM ULCERANS 1. CHARACTERISTICS

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o Grows at 30°C, NOT 37°C** 2. EPIDEMIOLOGY o Usually in the Tropics o Reservoir: Plants of warm temperate rain forest o Source: Silt of shallow water o Transmission: Aerosol o Ulcerating Necrosis** 3. CLINICAL SYNDROME o Begins as PainLess “Oil” or lump under skin. In a few weeks a shallow Ulcer with necrotic base develops at the site of lump. **** 4.TREATMENT o Surgical excision and grafting o Antimicrobial treatment is often unsuccessful

ACTINOMYCETES • • • • • •

Filamentous bacteria related to corynebacteria and mycobacteria and superficially resembling fungi. Grow as Gram Positive Some are Acid Fast Most are free living (soil). Anaerobic species are normally in the Mouth Some Aerobic species found in soil cause disease in humans and animals

I. ACTINOMYCOSIS • Chronic Suppurative disease forming draining sinus tracts A. MORPHOLOGY AND IDENTIFICATION o Typical finding is a Sulfur Granule in pus*** o Gram positive colony surrounded by Eosinophillic “clubs” o A. israilii does not hydrolyze starch but A. bovis does.** o Catalase Negative B. PATHOGENESIS AND PATHOLOGY o Found on teeth and tonsillar crypts C. CLINICAL FINDINGS o Characteristic appearance is a Hard, Red, Non-tender Swelling that usually develops slowly. Eventually drains forming a Chronic sinus extract with little tendency to heal****

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Cervicofacial Disease – Swollen erythematous in the jaw area, producing draining fistulas Throacic actinomycosis – Resembles subacute Pulmonary infection (mild fever, cough, purulent sputum). Eventually lung tissue is destroyed, sinus tracts may erupt to chest wall, invasion of ribs. o Abdominal Actinomycosis – Follows a ruptured appendix or an ulcer o Genital Actinomycosis – From intrauterine device most common in females. D. DIAGNOSTIC LABORATORY TESTS o Sulfur granules under microscope o Molar tooth shaped yellow colonies “looking like bread crumbs” on BHIA (brain heart infusion blood agar). ***** o o

II. NOCARDIOSIS • Aerobic organisms that occur in soil • Cauls Nocardiosis (human pulmonary disease that may spread to other parts of the body) A. MORPHOLOGY AND IDENTIFICATION o Gram Positive o Colonies are waxy or chalky winkled with pigmentation varying from yellow to red. o Urease Positive B. PATHOGENESIS AND CLINICAL FINDINGS o Pulmonary Nocardiosis – begins as chronic lobar pneumonia and then spreads to rest of body. o Primary Cutaneous – Resulting Mycetoma is characterized by local subcutaneous swelling o Ocular – Infections from contaminated lenses or solution III. ACTINOMYCOTIC MYCETOMA • Localized granulomatous lesion with hypertrophy and draining sinus tracts.

ANAEROBES ANAEROBES: FUNCTIONAL DEFINITION • Fail to grow in air or 10% CO2 • No superoxide dismutase or catalase • Laminar flow ANAEROBIC BACTERIA • Part of normal flora, especially GI tract • Outnumber aerobes 1000:1 • Most infections are ENDOGENOUS and of Mixed aerobic/anaerobic etiology. Mixed Infections. MIXED INFECTIONS • Proximity to a mucosal site • Pyogenic, very Foul Smelling • Often due to predisposing conditions: surgery, injuries, contaminated wounds • Clinical Clue: Profusion of mixed organisms on Gram Stain which fail to grow on routine culture**

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COMMON MIXED INFECTIONS • Head and neck • Acute Necrotizing Ulcerative Gingivitis (ANUG) • Abscesses • Peritonitis • Bites • Aspiration pneumonia (Mendelson’s Syndrome) • Gangrene INFECTIONS WHICH SELDOM INVOLVE ANAEROBES • Spontaneous peritonitis • Urinary tract infection • Meningitis • Pharyngitis • Bronchitis • Pneumonia (except aspiration pneumonia) • GI infections (except C. difficile) ANAEROBIC BACTERIOLOGY • Non-Spore Formers are Endogenous of Lower Virulence and tend to be opportunistic • Spore Formers are Exogenous of Higher virulence due to Exotoxins • ID cultured organisms by Gas Liquid Chromatography CLINICAL APPROACH • Never order anaerobic cultures from any site which has normal flora • Prefer aspirates or biopsies to swabs • Use anaerobic transport medium

ANAEROBIC GRAM POSITIVE COCCI: PEPTOSTREPTOCOCCUS • Normal flora of GI, GU, and Skin • Occasionally cause infections contiguous with mucosal sites • Require 5-7 days to grow in culture • Sensitive to most antibiotics ANAEROBIC GRAM POSITIVE NON-SPORE FORMING RODS 1. ACTINOMYCES 2. PROPIONIBACTERIUM 3. MOBILUNCUS 4. LACTOBACILLUS 5. EUBACTERIUM AND BIFIDOBACTERIUM ACTINOMYCOSES • Ray Fungus • Non-acid fast, Fastidious, and Slow growing

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• • • • • • • • • •

Normal flora of Upper Respiratory tract, GI tract, and Female genital tract. Not Skin! Chronic granulomatous infections with wood induration, multiple sinus tract formation, and sulfur granules Associated with disruption of normal mucosal barriers Endogenous 6 month therapy Cervicofacial – Lumpy Jaw Throacic – Secondary aspiration Abdominal – Metastatic Pelvic – From abdomen or associated with IUD CNS – Brain or epidural abscess

PROPIONIBACTERIUM • Propionic acid is main fermentation product • Normal flora of skin, conjunctiva, oropharynx and female genital trace • Most common is P. acnes MOBILUNCUS • Rods with Pointed Ends • Normally present in low numbers in female genital tract, Increase in bacterial vaginosis • No LPS • Sensitive to Vancomycin medication LACTOBACILLUS • Lactic acid is major fermentation product • Normal flora of GI and GU tract • Vancomycin resistant

ANAEROBIC GRAM NEGATIVE COCCI: VEILLONELLA • Predominant anaerobe in oropharynx ANAEROBIC GRAM NEGATIVE RODS 1.BACTEROIDS – Clinically important 2. PORPHYROMONAS – Assaccarolytic, Pigmented 3. PREVOTELLA – Small, saccarolytic and bile sensitive 4. FUSOBACTERIUM - Fusiform VIRULENCE FACTORS • Adhesion promotoes (capsules, pili) • Antiphagocytic Factors (Capsules, Ig protease, LPS, succinic acid) • Tissue Destroying Enzymes (Phospholipase C) • Catalase and Superoxide Dismutase

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BACTEROIDS FRAGILIS • Gram Negative Rod • Relatively O2 tolerant even though it is an anaerobe • Opportunistic • B-lactamase producer • Penicillin resistant FUSOBACTERIUM NECROPHORUM AND NUCLEATUM • Fusiform Gram Negative Rods • Normal flora of mouth, GI, and Vagina • Cause pneumonia • With oral spirochaetes, cause ANUG VINCENT’S ANGINA • ANUG • Associated with stress and breakdown in oral hygiene • Trench Mouth of WWI • Mouth pain and Extreme Halitosis • Treatment: Hydrogen peroxide with mouth rinses

SPORE FORMING BACTERIA CLOSTRIDIUM AND BACILLUS CLOSTRIDIUM • Gram Positive, Anaerobic, Spore Forming • Highly Virulent due to exotoxins and enzyme production 1. CLOSTRIDIUM PERFRINGENS (C. WELCHII) • 20% of clostridial isolates • Most common member (80%) of the “Histoxic Clostridia” which cause Gas Gangrene • A cause of Food poisoning • Can be contaminant of blood cultures

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•

5 toxin types (A-E)

• •

Defined on the basis of production of 4 main lethal toxins: α, β, e, t α-toxin (phospholipase C) plays a major role in myonecrosis

GAS GANGRENE AKA CLOSTRIDIAL MYONECROSIS • Toxin mediated breakdown of muscle tissue associated with bacterial growth • Liquefaction of muscle, gas production, toxemia • Rapidly progressive and life threatening** • Requires Surgical debridement CLOSTRIDIUM PERFRINGENS FOOD POISONING • Type A strains are very common • Improperly cooked meat or gravy • Initial cooking activates spores. Ingested bacteria ensporulate in alkaline environment of small intestine, releasing enterotoxin when they lyse • Self limiting ENTERITIS NECROTICANS: PIG-BEL OR DARMBRAND • Severe necrosis of the small bowel due to β-toxin of C. perfringens type C • Affects mainly children at meat feasts • Due to overeating particular meat in combination with semicooked yams (tyrpsin inhibitors) in the malnourished (decrease pancreatic trypsin) • Trypsin destroys β-toxin 2. CLOSTRIDIUM SEPTICUM • Very motile • Aggressive bacteremia with metastatic myonecrosis. • 80% of patients with bacteremia have an underlying malignancy • Leukemia, lymphoma, cancer of large bowel 3. CLOSTRIDIUM TETANI • Found in soil and intestinal contents of animals • Elaborates neurotoxin tetanospasmin, which produces spastic paralysis. • A disease of unvaccinated. Often associated with minor puncture wounds • Risus sardonicus, Trismus (Lockjaw) first, Then Opisthotonus (extended body, flexed arms)**** • Treatment: Tetanus Antitoxin, Muscle Relaxants, Surgical Wound Care. Admit

4. CLOSTRIDIUM BOTULINUM • Worldwide distributed in soil and aquatic habitats • Can produce botulinum neurotoxin (BoNT), the most lethal poison known • Acute Flaccid Paralysis • 7 antigenic types of toxins (A-G) • A, B, E, F cause most human botulism BOTULISM • BoNT acts at presynaptic junction and prevents release of Ach

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•

4 Types: o Food Borne – Ingestion of preformed toxin o Wound – Wound infection o Infant – Ingestion of spores o Intestinal – Older children and adults

FOOD BORNE BOTULISM • Usually home canned food, smoked fish • BoNT is heat labile • No taste or production of gas • One case is an outbreak • Treatment: Trivalent (ABE) botulinal antitoxin STAT! • Intensive Ventilatory Care WOUND BOTULISM - Treatment • ABE antitoxin for adult cases • Penicillin • Respiratory support as required INFANT BOTULISM • Constipation is FIRST Sign • Lethargy, weakness • Floppy infant • Occasional cause of SIDS • Children <1 year should not be fed honey! BOTOX • Revolution in plastic surgery • Small doses of BoNT injected directly into muscle for spasm (blepharospasm or strabismus) or for cosmetic reasons • Ever wonder why faces of Hollywood actors are not as expressive as they used to be? Bo Tox! 5. CLOSTRIDIUM DIFFICILE • Major cause of Antibiotic Associated Diarrhea (AAD) and Pseudomembranous Colitis (PMC)**** • Most common cause of hospital acquired diarrhea • Asymptomatic in 50% for infants <1year, decreases to 3% by age 3 • Hospitalized patients become colonized, sometimes develop diarrhea, often after antibiotic therapy • Toxin A, Toxin B. Substance that inhibits Bowel motility. • EIA test available to detect toxins A and B. Most sensitive and specific test is toxigenic culture. • Treatment: Discontinue antibiotic. Give Metronidazole. PO bacitracin is next step. Fecal transplant is last resort. Avoid Vancomycin.

BACILLUS • Large Gram Positive Rods, Spore forming, Aerobic**** • Common in soil and water 1. BACILLUS CEREUS • Soil organism • Spores often contaminate rice.

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• • •

Bacteria are Motile Eye Infections – Usually secondary to foreign body** Food Poisoning – Emetic and diarrheal types**

FOOD POISONING • Spores are activated by cooing and germinate if termpearture permits. Enterotoxin is produced during growth phase. • Emetic form associated with rice • Diarrhoeal form associated with meat dishes and sauces • Self limiting 2. BACILLUS ANTHRACIS • Non-Motile** • Nonhemolytic • Medusa Head Colonies** • Primarily pathogenic to herbivores • Virulence factor genes (Capsule and toxin) are coded on plasmids • The first bacterium shown to be causative of an infectious disease • The first vaccine produced was attenuated B. antracis to protect sheep, BUT not the first vaccination. BACILLUS ANTHRACIS TOXINS • Toxin composed of 3 proteins: o PA – protective antigen o EF – edema factor (adenylate cyclase) o LF – lethal factor • PA binds to specific cell receptors and forms channels to allow EF and LF into the cell • Edema Toxin = PA + EF • Lethal Toxin = PA + LF ANTHRAX • Cutaneous – Incubation forms Malignant Pustule*** • Pulmonary (Woolsorters Disease) – Inhaled spores transported to macrophages to mediastinal lymph nodes where they germinate and result in sepsis. Very rapid progression. Mortality 97% untreated, 75% with treatment. • Gastrointestinal – Very rare, contaminated meat ANTHRAX BIOTERRORISM • Occurs in the US today with Mails DIAGNOSIS AND TREATMENT OF ANTHRAX • Cutaneous: Swab pustule for Gram and M’Fadyean stains and culture. • Possible aerosol exposure: Treatment and nasal swab • Pulmonary: Blood culture, paired blood for serology. Notify authorities • Treatment – Ciprofloxacin or Doxycycline recommended, 60d course SEXUALLY TRANSMITTED DISEASES 1. NEISSERIA GONORRHOEAE • Gram Negative Diplococci, Usually intracellular • Fastidious

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• • •

Does not tolerate desiccation or cold Cytochrome oxidase positive Oxidizes glucose, but not maltose nor lactose

N. GONORRHOEAE VIRULENCE FACTORS • Por A protein (porin protein) type A bearing strains resist serum killing • Opa proteins (opacity proteins) mediate adherence • RMP proteins (reduction modifiable proteins) stimulate Ab that block serum killing • LOS (lip-oligosaccharide) has lipid A and CO • Pilin protein (pili) mediates initial attachment N. GONORRHOEAE INFECTION SYNDROMES • Urethritis/Cervicitis (occasionally pharyngitis and proctitis) • Arthritis-dermatitis syndrome • Monoarthritis (classically) • Prepubescent females: Vaginitis GONORRHOEA- “THE CLAP” • Le Clapatier is a Paris Neighborhood • Sexually acquired urethritis/cerrvicitis • Incubation period 2-5 days • Incidence has dropped dramatically in developed countries • Profuse, inflammatory urethral discharge in males** • Females often asymptomatic, but at risk for PID, DGI COMPLICATIONS OF GONORRHOEA • Disseminated Infection: Sepsis, skin, joints • Fitz-Hugh-Curtis Syndrome (perihepatitis) • Opthalmia neonatorum • Pelvic inflammatory disease (chronic pelvic pain and sterility) • Profuse Purulent Discharge** DIAGNOSIS OF GONORRHOEA • Urethral, Cervical, Throat, Rectal swabs • Typical Gram Stain of Genital specimens • Inoculation of Selective medium (Thayer-Martin) at bedside • Gene probe commercially available, but gives no information on antibiotic resistance TREATMENT • Cefixime or Ciprofloxacin • Ceftriaxone 2. NEISSERIA MENINGITIDIS • Not an STD • Oxidizes Glucose and Maltose** • Causes acute meningococcemia, meningitis and chronic meningococcemia • Endemic in a belt across sub-Saharan Africa • Rest of the world has sporadic cases and epidemic outbreaks 3. HAEMOPHILUS DUCREYI • CHANCROID (Sof Chancre) – Painful Genital Ulcers + lymphadenopathy

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• • • •

More common in tropics Gram Negative Short Rods, often in “school of fish” arrangement Can culture for confirmation Treatment same as gonorrhoea

4. KLEBSIELLA GRANULOMATIS • Graunloma Inguinate – Chronic and progressively destructive infection of the skin and mucous membranes of the external genitalia • Similar to K. rhinoscleromatis (Slavic leprosy) and K. ozoaenae (chronic atrophic rhinitis) • Diagnosis: Donovan Bodies (intracytoplasmic rods which stain with Giemsa Wright’s stain) • Late Destructive lesions if untreated 5. SYPHILIS A. PRIMARY SYPHILIS – Chancres B. SECONDARY SYPHILIS – Palms and soles, Condylomata lata, C. TERTIARY SYPHILIS – Gummata, Charcot’s Joint D. CONGENITAL SYPHILIS – Hutchinson’s Teeth DIAGNOSIS OF SYPHILIS • Primary: Dark field of DFA microscopy of chancre fluid • Seondary/Tertiary: Serology o Nontreponemal (reaginic) –VDRL o Treponemal –TPI, MHA-TP, FTA-Abs TREATMENT FOR SYPHILIS • Benzathine penicillin G IM x 1-2 weekly doses • IV penicillin G for congenital and late syphilis • IV pen G is the only treatment for Neurosphyilis and for syphilis in pregnancy. Desensitize if allegoric • Jerisch Herxheimer reaction

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SPIROCHAETES 1. TREPONEMA PALLIDUM • Spirochaetes, Gram Negative Corkscrew rods with Axial flagella and an outer sheath • Cannot be cultured on artificial media • Primary, secondary, and tertiary stages • Most chronic infectious disease: 1/3 rule • Primary – Chancre at site of initial inoculation after 3 weeks, goes away! • Secondary – Maculpapular eruption including palms and soles, condylmoata lata (6 months)

•

Tertiary – Endarteritis obliterans  Gummata (years)

2. TREPONEMA CARATEUM • PINTA- Acute and chronic nonvenereal skin infection • Skin discoloration leads eventually to depigmentation • Found only in isolated rural populations living under crowded, unhygienic conditions in the American tropics 3. BORRELIA • Highly Motile spirochaetes • Flagella beneath outer membrane • Linear chromosomes • Maintained in nature by cycling through wild animals and the ticks that feed upon them (except 2 species – B. recurrentis and B. duttonii) BORRELIA RECURRENTIS • Louse-Borne (epidemic) Relapsing Fever** • Now mainly in Africa (Ethiopian Highlands) • Periods of fever lasting 2-9 days alternate with afebrile periods of 2-4 days • Up to 10 relapses typical • Diagnosis by finding spirochaetes on direct exam of peripheral blood during febrile periods • Treatment: Tetracycline and Treat lice! BORRELIA DUTTONII • TICK BORNE (ENDEMIC) RELAPSING FEVER • Similar to Louse Borne type but Sporadic • Illness tends to last longer • Most patients unaware of tick bite BORRELIA BURGDORFERI: LYME DISEASE • Ixodes Scapulatris – The Deer Tick

• • •

1st Stage – 3rd to 4 weeks, Flu like symptoms 2nd Stage – weeks to months, Arthralgia, arthritis, meningitis, Bell’s Palsy, painful radiculopathy, cardiac conduction defects, myocarditis 3rd Stage – months to years, chronic arthritis and progressive CNS disease

DIAGNOSIS OF LYME DISEASE • Erythema migrans** • Visit to risk area • Lack of known tick bites irrelevant • ELISA, Western Blot, PCS

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MANAGEMENT OF LYME DISEASE • Tuck pants into socks. Inspect for ticks. • Early – Penicillin or Doxycycline. Late – IM or IV Ceftriaxone 4. LEPTOSPIRA • Worldwide either free living or associated with animal hosts • Infection usually results from direct or indirect (water or soil) exposure to animal urine

• • • •

1st Phase (1 to 2 weeks) – Fever, malaise. Decreases or disappears after 1 week 2nd Phase – Aseptic meningitis, hepatitis, nephritis, conjunctivitis, IgM titre increases Diagnoses – Seriology + urine and blood culture Treatment – Penicillin or Doxycycline effective if given early

5. SPIRLILLUM MINUS • Common form of sporadic Rat-Bite Fever in Asia (Japan) • Spirillary Fever or Soduku • Distinctive Reddish Purple Skin Plaques • Incubation period 1-3 weeks • Previously healed bite wound reactivates when symptoms appear • 10% untreated mortality

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CHLAMYDIA CHLAMYDIA • Small Obligate Intracellular Bacteria • Unable to synthesize ATP – Energy Parasites • Structurally similar to small Gram Negative bacteria Except Cell Wall contain No Peptidoglycan** • Reproductive cycle different from other bacteria UNIQUE REPRODUCTIVE CYCLE • Intracellular form is the reticulate body • RB divides repeatedly by Binary Fission until a large cytoplasmic inclusion is formed over 48 hours • RB’s condense to form elementary bodies which are released into the environment by lysis of the host cell • EB’s are phagocytosed by susceptible host cells • The EB reorganizes into the larger RB CHLAMYDIA SPECIES 1. C. TRACHOMATIS 2. C. PSITTACI 3. C. PNEUMONIAE 1. CHLAMYDIA TRACHOMATIS • Inclusion bodies stain with iodine • 2 groups of serovars that cause different syndromes: o A to K  Trachoma Biovar (D to K cause genital tract infections) o L1, L2, L2a, and L3  Lymphogranuloma Venereum Biovar TRACHOMA • Servoars A, B, Ba, and C most common • Chronic infection leads to scarring and trichiasis • Leading cause of blindness in developing countries • Easily prevented with intermittent medication NON-GONOCOCCAL URETHRITIS/CERVICITIS • Serotypes D-K usually • Most common cause, especially in college students

• •

Females often asymptomatic, but at risk for PID  Infertility, Chronic Pelvic Pain Neonates born to infected mothers at risk for inclusion conjunctivitis, occasionally infant pneumonia

LYMPHOGRANULMOA VENEREUM • Uncommon in North America and Europe • Transient papules on external genitalia followed in 1-2 months with PAINFUL inguinal and perirectical Lymphadenopathy • Groove Sign** DIAGNOSIS • Direct: Iodine staining • ELISA, NA probes, NA amplification, Urine, Tissue culture

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TREATMENT • LGV – Tetracycline or Macrolide for 21 days • Urethritis or Ocular Infections – 7 days • Neonatal Conjunctivits or Pneumonia – Macrolide for 10 days 2. CHLAMYDIA PSITTACI • Psittacosis (ornithosis) • Transmitted by inhalation of dust contaminated with feces or respiratory secretions of infected birds (History) • Pneumonia often associated with headache and splenomegaly • Diagnosis: 4x rise is CF Ab or IIF TREATMENT FOR ORNITHOSIS • Macrolide or Tetracycline for 7 to 10 days 3. CHLAMYDIA PNEUMONIAE • Community acquired pneumonia, bronchitis, sinusitis • Person to person transmission • Common, but seldom diagnosed due to poor availability of reagents • Tentalizing associations of high antibody titres with coronary atherosclerosis and asthma – trial underway.

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LISTERIA LISTERIA MONOCYTOGENES • First isolated 1926 by EGD Murray • Gram Positive • B-hemolytic Rod • Oxidase Negative with Characteristic Tumbling • End-over-End Motility at 22 degrees but Not at 37 degrees • Primary habitats are soil and decaying vegetable matter • Has been isolated from mammals, birds, crustaceans, fish, and insects • Common contaminant of foods especially unpasteurized cheese (Mexican soft cheese) • Tolerant of salt, Drying and refrigeration PATHOGENESIS • Primarily food borne • Entry into enterocytes or M cells in Peyer’s patches mediated by internain proteins via surface glycoproteins • Phagolysosome acid activates exotoxins listeriolysin O and 2 kinds of phospholipase C • Phagolysosome lyses, bacterium escapes into cytosol, and replicates • ActA protein at one end of bacterium coordinates assembly of actin, which pushes bacterium through cell membrane and into adjacent cell! INFECTIONS • Adults – Meningitis, encephalitis, sepsis, often with monocytosis • Immunocompromised increased risk • Tropism for CNS • Pregnant – Influenza like illness, if untreated --> amnioitis, fetal infection • Abortion, still birth, premature birth DIAGNOSIS • Meningitis very aggressive: 20-50% mortality, Neurologic sequelae common • Lab often misidentified as Enterococcus • Have high index of suspicion in meningitis or when Hx of suspect food ingestion • Blood and CSF cultures TREATMENT • Resistant to Cephalosporins • Treat with Ampicillin + Gentamicin • Co-Trimoxazole for Penicillin Allergic patients FOOD POISONING • Listeriosis is an example of true food borne infection • Primary infection syndromes of Listeria are NOT Gastroenteritis, unlike most forms of food poisoning • Food poisoning originally thought (in error) to be due to Ptomaines (putresine and cadaverine)

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FOOD POISONING SYNDROMES • Heavy Metal Poisoning • Toadstools (Amanita) • Cereals infected with Claviceps purpura (ergot) • Botulism • Fish toxin poisoning (histamine, scromboid, ciguatera, fugu, paralytic shellfish)

MYCOPLASMATACEAE MYCOPLASMA AND UREAPLASMA CHARACTERISTICS • Smallest free living organisms known • Gram Negative in structure but not in staining • No Cell Walls, Resistant to cell wall attacking antibiotics (penicillin) • Cell membrane contains sterols, which must be in growth medium • Slow growing • Ubiquitous • Frequently contaminate tissue cultures • Pass through filters designed to trap bacteria • Related to Clostridia • Are anaerobes, but most not strict MYCOPLASMA • 100 species • 11 primarily colonize and infect human UREAPLASMA • 6 species • Primarily colonizes/infects humans DISEASE ASSOCIATIONS • Pneumonia – M. pneumoniae • NGU – M. genitalium • Postpartrum Fever – M. hominis and U. urealyticum • Arthritis in immunosuppressed and hypogammaglobulinemic – M. hominis and U. urealyticum 1. MYCOPLASMA PNEUMONIAE • 2nd most common cause of community acquired pneumnia • 20% cases overall, 50% of pediatric cases • Only 3% of infected develop pneumonia overall. • Summer outbreaks every 3 to 4 years • PATHOGENESIS: o P1 protein adheres to neuraminic acid receptor on respiratory epithelium o Organism remains extracellular o Mucosal damage occurs via H2O2 o Cilia are paralyzed o Inflammatory infiltrate is lymphocytic, and contributes to pathology • CLINICAL FEATURES:

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o CXR – Looks worse than would expect o Anorexia, nausea, vomiting, diarrhea, musculoskeletal myalgia and arthralgia o Erythema mutiforme and other skin eruptions o Transient hemolytic anemia o Meningoencephalitis (70% hospitalized) o Relapses, persistent cough • DIAGNOSIS o Culture: Slow, requires special media, Not widely used o Serology: Complement Fixation Test, look for 4x rise in titres. Since symptoms develop slowly, initial specimen may have high titre o Cold agglutinin Test • TREATMENT o B-lactam and sulfonamide drugs ineffective. Use Macrolides, Tetracycline and Fluoroquin. 2. MYCOPLASMA GENITALIUM • Sexually transmitted • The most important cause of NGU after Chlamydia trachomatis • Also found in high proportion of asymptomatic adults • Treatment: Tetracycline or Macrolide for 7 days 3. MYCOPLASMA HOMINIS • A genital commensal, sexually transmitted • Postpartum sepsis – 10% of cases • Sepsis in immunocompromised • Arthritis in hypogammaglobulinemic • Usually isolated from blood cultures • TREATMENT o Resistant to Macrolides o Infections in immunocompromised patients very hard to cure with antibiotics alone o Immunocompromised – One of the last indications for antiserum prepared in animals AIDS –ASSOCIATED MYCOPLASMAS? • Isolated from AIDS patients • Contribute to cell death with HIV in vitro • Many informed investigators believe mycoplasmas are involved in AIDS 4. UREAPLASMA UREALYTICUM • A genital commensal, Sexually Transmitted • Very small colonies; splits urea • Established roles in postpartum fever and arthritis in immunosupressed and hypogammaglobulinemic patients • Moderate evidence for causality: NGU, Infection stones, pneumonia/chronic lung disease in very low birth weight infants

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