1. Involves the application of a series of dyes that leaves some bacteria purple and others pink. 
  2. CIAs: (Cristal Violet, Iodine, Acetone, Safranine)
  1. Stain purple à Gram-positive
  2. Stain red à Gram-negative.
  3. The specific stain reaction of a bacterium results from the structure of its cell wall 
  1. Gram Stain 
  1. “Murein gets the red out” [Allusion to an old eye-wash slogan]: 
  2. Peptidoglycan (aka murein) remains purple during Gram staining. The Gram negatives, devoid of murein, are red. Thus, murein prevents redness and are purple (positive). 
  1. Gram Negative cells 
  1. Gram Positive cells 
Gram positive cells
Gram negative cells
Cell wall: 
  • Inner cytoplasmic membrane
  • Outer peptidoglycan layer 
Cell membrane
Cell wall:
  • Thin peptidoglycan layer
  • Outer membrane with Lipopolysaccharide (LPS) 
Low lipid content 
High lipid content 
No endotoxin (excepcion: L. monocytogenes) 
Endotoxin (LPS) 
Sensible to lysozyme and penicillin attack 
Resistant to lysozyme and penicillin attack 
II. gRAM +
  1. Gram Positives Stain Purple (violet-blue) because of their thick Peptidoglycan layer 
  2. Gram+ has: +hick peptidoglycan layer. +eichoic acid in wall
  3. Comparisons 
  4. Pathogenesis Mechanism 
  5. Pathogenic: capable of produce disease.
  6. Virulence factor: a characteristic that increases the pathogenicity of bacteria.
  7. Entry to the host
      1. Polysaccharide capsule
  8. Adherence to host cells 
  1. Pili
  2. Fimbriae 
  1. Bacterial Toxins
  1. Exotoxins 
  2. Endotoxins 
  1. Consist of polysaccharides
  2. Function: evade phagocytosis by neutrophils and macrophages.
  3. E.g.: Strep pneumoniae, Neisseria meningitidis, Haemophilus type B.
  4. Spleen is the main site for destruction of capsulated bacteria.
  5. Quelling reaction: test the presence of encapsulated bacteria.
  6. Quellung reaction:
    1. Positive sign, Strep type confirmed “Quell-lung“: 
    2. Quell: Capsules swell [+ve test]. 
    3. Lung: S. pneumonia [type confirmed]. 
    4. You get pneumonia in your lung. 
  1. Exotoxins 
      1. 2 polypeptide components:
  1. One binds the protein to the host cell, 
  2. The other responsible for the toxic effect.
      1. Inactivated by moderate heating (60°C), 
      2. Formaldehyde-inactivated toxins, called toxoids, are useful in preparing vaccines . 
      3. Encoded by genes carried on plasmids or temperate bacteriophages. 
      4. Diphtheria toxin:
  1. Blocks protein synthesis. 
  2. Attachs an ADP-ribosyl group to human protein elongation factor EF-2, inactivating it. 
  3. Examples: Sthaphylococcus aureus, Bacillus cereus
  1. Endotoxin 
      1. Endotoxin features ENDOTOXIN:
      2. Endothelial cells/ Edema 
      3. Negative (gram- bacteria: LPS)
      4. DIC/ Death 
      5. Outer membrane 
      6. TNF 
      7. vii.O-antigen 
      8. viii.X-tremely heat stable 
      9. IL-1 
      10. Nitric oxide/ Neutrophil chemotaxis  
      11. The lipopolysaccharide contains: LIPID A (toxic portion)
      12. xii.Actions of Lipid A:
  1. Activate macrophages to secrete IL-1 (Fever) & IL-6
  2. Activate secretion of  TNF-alpha (tissue necrosis and shock)
  3. Induce secretion of NO from endothelial cells. 
Bacterial Genetics
  1. General information 
    1. Bacterial chromosome
      1. dsDNA double loop
      2. Haploid genome
      3. No nuclear membrane
    2. Diversity of genetic material
      1. Prokaryote genome replicates forming exact copy of itself
      2. Eukaryotes contribute ½ genome from each parent
      3. Prokaryotes must have mechanisms to account for the huge genetic diversity
        1. Mutations
        2. Transformation
        3. Transduction 
        4. Conjugation
        5. Transposon insertion 
  2. Mutations
    1. Change in genetic makeup 
      1. Increase diversity
      2. Produce new genes that might be favorable to survival 
  3. Transformation
    1. A way for bacteria to share genetic information and improve survivability
    2. Mechanism
      1. Bacterial cell lysis
      2. Release of naked DNA fragments from the lysed bacteria
      3. Naked DNA fragments are taken up by intact bacteria
      4. Incorporation of naked DNA into the genome of the recipient bacteria
        1. Bacteria must be closely related in order to internalize the naked DNA and incorporate it into their own genome
      5. Recipient bacteria is now transformed
    3. Example
      1. Frederick Griffith transformed smooth encapsulated pneumococci into rough encapsulated pneumococci using this technique  
  4. Transduction 
    1. Mechanism
      1. Bacteripophages are bacterial viruses
      2. They infect bacteria much like eukaruotes get infected by viruses
        1. Adsorption – binding of virus to specific receptors
        2. Penetration – deposit of bacteriophage DNA into bacteria
        3. Bacteriophage DNA takes over host RNA polymerase
        4. Bacteriophage DNA then makes more copies of itself
        5. Two types of bacteripphages
          1. Virulent – kill host
          2. Temperate –  its DNA becomes incorporated into bacteria DNA
          3. Prophage – the integrated bacteriophage DNA now found in the bacterial DNA
          4. Lysogenic bacteria – bacteria with a prophage in them.
          5. Lysogenic immunity – the ability of a prophage to suppress the ability of other similar prophage to infect the same bacteria
    2. Generalized Transduction
      1. After the bacteriophage DNA has taken over the bacteria’s replication mechanisms it makes capsid and enzymes
      2. This causes the bacterial DNA to be disintegrated over time since the bacteriophage DNA takes over
      3. Sometimes Bacterial DNA pieces are spared destruction
      4. If they are same size as the bacteriophage DNA they can be incorporated into the capsid 
      5. This bacterial DNA that is now in the bacteriophage can go on and be injected into another bacteria
      6. If this accidental bacteria DNA is similar to the host then it will be incorporated into its genome. If it codes for proteins that can give the new bacteria a survival edge (antibiotic resistance)
      7. vii.In this type of transduction the bacteriophage only carries bacterial DNA
      8. viii.Is more efficient than transformation because the genetic material is protected inside the bacteriophage
    3. Specialized Transduction
      1. Occurs with temperate phages
      2. The incorporated bacteriophage DNA becomes active and is spliced out of the bacterial genome
      3. It then starts making the bacteriophage parts
      4. If splicing is incorrect then pieces of bacterial DNA that lie next to it may be spliced, replicated and incorporated into the bacteriophage
      5. When it infects a new bacteria it can be incorporated back into the genome of the host and make proteins that can improve its survivability (antibiotic resistance)
  5. Conjugation 
    1. Direct transfer of bacterial DNA from cell to cell
    2. For it to occur one bacterium must have a self-transmissible plasmid (F-plasmid)
    3. Occurs between unrelated bacteria
    4. Plasmid is injected to another bacteria through a structure called sex pilus
    5. Bacteria that have F-plasmids are F+, those who don’t are F-
    6. After the bridge is formed between two bacteria one strand of the plasmid passes through and one remains in the F+ cell.  
    7. If the plasmid becomes integrated in the host cell DNA then it is referred to as a Hfr cell. 
    8. If this Hfr plasmid gets excised incorrectly it can take with it DNA from the host genome
      1. This plasmid that is formed is called an F’ plasmid (F prime plasmid)
    9. Many plasmids contain antibiotic resistance proteins
  6. Transposons
    1. Genetic material that can insert itself into a genome even if they are not homologous.  
    2. They are copied as part of the host DNA and make their products that way
    3. If they leave the DNA and are excised incorrectly they can carry new DNA with them to their next host
    4. Very important because they account for spread of antibiotic resistance to different bacterial genera. 
Bacterial Growth
  1. Binary Fission = Exponential Growth
  2. Four Phases of Growth
    1. Lag – Nr of cells stays the same
    2. Log – rapid exponential growth, generation time determined here
    3. Stationary – nutrients used up, Nr of new cells = Nr of dying cells
    4. Death Phase
  3. Important Normal Bacterial Flora
    1. Skin – Staphylococcus epidermidis 
    2. Nose – Staphylococcus aureus
    3. Mouth/throat – Viridans streptococci
    4. Colon – Bacteroides fragilis, Escherichia coli
    5. Vagina – Lactobacillus, E. coli, Group B streptococci
          1. Staphylococcus Aureus 
      1. Characteristics
  1. Cocci in grapelike clusters
  2. Coagulase (+) 
  3. Catalase (+)
  4. Colonies: golden/yellow and hemolytic
  5. Manitol positive
      1. Virulence factor
  6. Protein A:  component of the cell wall that binds to Fc component of  IgG, exerting as anti-opsonin
  7. Cytolytic exotoxins (hemolysins)
  8. Fibronectin: binding protein that promotes binding to mucosa
  9. Enterotoxin:  Superantigen  heat stable that  after ingestion cause food poisoning. 
  10. Toxic Shock Syndrome toxin: superantigen, cause TSS
  11. Exfoliatin : superantigen, causes Scalded skin syndrome and bullous impetigo
      1. Associated diseases- SOFT PAINS
  12. Skin infections (Impetigo, folliculitis, furuncles,  Carbuncles)
  13. Osteomyelitis
  14. Food poisoning 
  15. Toxic shock syndrome 
  16. Pneumonia
  17. Acute endocarditis (IV drug users)
  18. vii.Infective arthritis 
  19. viii.Necrotizing fasciitis 
  20. Sepsis 
      1. Treatment
  21. Penicillins:
        1. Oxacillin 
        2. Nafcillin 
  1. ii.Other:
    1. Vancomycin – for MRSA
    2. Linezolid 
    3. Daptomycin 
          1. Staphylococcus Epidermidis 
  1. Characteristics
  1. Catalase (+)
  2. Coagulase (-)
  3. In clusters
  4. Normal flora of the skin
  5. Colonies: gray 
  1. Associated diseases
  1. Common cause of infection of implants such as heart valves and catheters.
  1. Treatment
  1. Oxacillin
  2. Nafcillin 
          1. Staphylococcus Saprophyticus 
  1. Characteristics
  1. Catalase (+)
  2. Coagulase (-)
  3. Novobiocin resistant
  4. Associated with Cystitis in women. (“Honey moon cystitis”)
    1. Treatment
  1. Penicillin G
  2. Gram Positive Cocci 
      1. Classification by hemolytic ability 
  1. Gamma: Garbage (no hemolytic activity). 
  2. Alpha: Almost (almost lyse, but incomplete). 
  3. Beta: Best (complete lysis). 
      1. S. pneumoniae
  1. Characteristics
  1. Nonmotile encapsulated cocci 
  2. Lancet-shaped
  3. Usually in pairs or chains.
  4. Alpha hemolytic
  5. Optichin sensitive
  6. Bile sensitive 
  7. vii.Colonies: blood agar
  1. Virulence factor: 
  1. Polysaccharide capsule (antiphagocytic and antigenic)
  2. Pneumolysin 
  3. IgA protease (allows it to bind/colonize respiratory epithelium)
  4. Autolysin (hydrolase à produce cell lysis) 
  1. Associated Diseases
  1. Acute bacterial pneumonia
  2. Otitis media
  3. Sepsis
  4. Meningitis
  1. Treatment
  1. Amoxicilin/ Clavulanic Acid
  2. Ampicillin/ Sulbactam 
  3. Cephalosporins 
  4. Vancomycin 
      1. Viridians Streptococci 
  1. Facultative oral flora
  2. Alpha hemolytic
  3. Optichin resistant
  4. Streptococcus mutants 
  1. Associated with dental caries
  1. Streptococcus sanguis 
  1. Bacteremia and or endocarditis in patients with abnormal heart valves (remember a classic sign for endocarditis is microhemorrages in nails, they might show you a picture)
      1. Streptococcus pyogenes 
  1. Characteristics
    1. Cocci – Group A
        1. In chains
        2. Beta hemolytic
        3. Bacitracin sensitive
        4. Cell wall:  
        5. Fimbriae that contain M protein.
        6. Group A specific C-carbohydrate is composed of rhamnose and N-acetylglucosamine.
        7. Protein F (fibronectin-binding protein)
  1. Virulence factors
  1. Streptolysins 
  2. M protein (Most important antiphagocytic factor, blocks complement activation and it is associated with acute glomerulonephritis)
  3. Anti-C5a peptidase 
  4. Streptokinase – breaks down fibrin clot which allows it to invade tissues
  5. Hyaluronidase 
  6. Exotoxins A-C (superantigens – pyrogenic or erythrogenic exotoxins, cause scarlet fever)
  7. DNAses   
  1. AntibodySPAM: 
  1. Streptococcus Pyogenes: Antibody to M protein 
  2. Streptococcus pyogenes 
  1. Associated diseases caused NIPPLES 
  1. Necrotising fasciitis and myositis 
  2. Impetigo (no blisters, differentiates it from S. aureus, honey-crusted lesions)
  3. Pharyngitis 
  4. Pneumonia 
  5. Lymphangitis 
  6. Erysipelas and cellulitis 
  7. Scarlet fever/ Streptococcal TSS 
      1. Streptococcus agalactie 
  1. Catalase (-)
  2. Group B streptococci
  3. Found in vaginocervical tract of female carriers.
  4. Transmission to the infant at birth
  5. CAMP test Positive – CAMP factor compliments the sphingomyelinase of S. aureus to create e hemolytic pattern in form of arrowhead. None is hemolytic by itself but where they meet there’s enhanced hemolysis hence the arrowhead pattern.
  6. Associated Diseases:
    1. Meningitis in neonates
    2. Septicemia in neonates 
  7. Treatment: 
    1. Intrapartum profilaxins: Ampicilin during labor and delivery. 
      1. Enterococci 
  1. Previously known as group D
  2. Normal fecal floral
  3. Persist in fomites 
  4. Multiple antibiotic resistance
  5. Includes:
    1. E. Faecium 
    2. E. Faecalis 
  6. Associated Diseases (after instrumentantion of  Gastrointestinal system or genitourinary)
    1. UTI
    2. Sepsis
    3. Subacute endocarditis 
    4. Intra-abdominal abscesses.
  7. Skin infections
  1. Folliculitis
  2. Furuncles
  3. Carbuncles
  4. Impetigo
    1. Manifestations : tenderness, pruritic lesions, honey-colored crusts, erythematic base 
    2. Diagnosis: Clinical
    3. Treatment: Mupirocin 
  1. Osteomyelitis
  1. Pathophysiology
    1. Direct inoculation
    2. Hematogenous (most comon)
  2. Clinical manifestations
    1. Fever 
    2. Edema and Erythema
    3. Pain to palpation
    4. Reduction in the use of the extremity 
  3. Diagnosis
    1. X-Ray : bone remodeling (if normal MRI)
    2. MRI
    3. ESR  elevated + leucocitosis
  1. Infective Endocarditis
    1. Infection of the heart valves
    2. Etiology:
      1. Native (most common mitral valve)
      2. Streptococcus viridians, (50-60%)
      3. S. aureus (10 20%) Most common  in IV drug users (In IV users rigth side valves)
      4. HACEK group (haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella)
      5. Prostetic
      6. S. epidermidis
    3. Diagnosis 
      1. MAJOR Criteria:
        • 2 Blood cultures positive  (organisms involve in IE)
        • Echocardiographic valve vegetations or abscess
      2. Minor Criteria
        • Fever
        • Vascular lesions (Janeway lesions, petechias, splinter hemorrhages)
        • Osler nodes, Roth Spots
        • Heart condition o IV drug use
        • 1 blood culture or blood culture for organism not involve in IE
        • Echocardiogram not diagnostic (change in previous disease)
2 Major Criteria or 
1 major + 3 minor or
      1. minor
  1. Lab results: High Tech Lab Results Point At Endocarditis”: 
  1. Hematuria 
  2. Thrombocytopenia 
  3. Leukocytosis, -penia 
  4. Red blood cell casta 
  5. Proteinuria 
  6. Anemia 
  7. Elevated ESR 
  • Endocarditis
  1. Indications for surgery PUS RIVER: 
  1. Prosthetic valve endocarditis (most cases) 
  2. Uncontrolled infection 
  3. Supporative local complications with conduction abnormalities
  4. Resection of mycotic aneurysm 
  5. Ineffective antimicrobial therapy (eg Vs fungi) 
  6. Valvular damage (significant) 
  7. Embolization (repeated systemic) 
  8. Refractory congestive heart failure 
  1. Scalded skin syndrome
  1. Most common neonates and infants.
  2. After a Staphylococcus aureus infection.
  3. Staphylococcus  Exfoliative Exotoxin acts in desmoglein-1 producing detachment of the epidermis (granular cell layer)
  4. Clinical Manifestations:
  1. Fever
  2. Facial edema
  3. Rash 
  4. Dehydration
  5. Nikolsky sign
  1. Toxic shock syndrome
    1. Due to: TSS Toxin type-1 (TSST-1): Exotoxin Superantigen that binds MHCII (most common associated)
    2. Clinical Manifestations
  1. Fever Flu like symptoms (chills, myalgia, fatigue)
  2. Red maculo papular rash
  3. Hypotension
  4. Altered mental status
  5. Desquamation of the palms and soles
  6. Multiorganic failure
  1. Fermentation of N. gonorrhoeae vs. N. meningitidis 
  1. Gonorrhoeae: Glucose fermenter only. 
  2. MeninGitidis: Maltose and Glucose fermenter. 
  3. Maltose fermentation is a useful property to know, since it’s the classic test to distinguish the Neisseria types. 
          1. Neisseria Gonorrhoeae 
  1. Gram-negative diplococcus inside PMN
  2. Sexual transmitted
  3. Unencapsulated, nonmotile 
  4. Virulence factors:
    1. Pili: formed by pilin. Mediate attachment to mucosal surfaces and resistant to phagocytosis.
    2. Lypoligosaccharide (LOS)  O-antigen
  1. Associated Diseases:
    1. Urethritis 
    2. Cervicitis 
    3. Pharyngitis 
    4. Ophthalmia neonatorum 
  1. Diagnosis:
  1. Culture in Thayer-Martin medium.
  1. Treatment:
  1. Third generation Cephalosporin (Ceftriaxone)
  2. Due to high rates of coinfection with chlamydia give Azitromizin too. 
          1. Neisseria Meningitidis 
  1. Nonmotile Diplococcus 
  2. Kidney bean-shaped bacteria in pairs
  3. Large capsule
  4. Transmission: inhalation
  5. Virulence Factors:
    1. Pili 
    2. Capsule (polysaccharide with antiphagocytic activity)
  6. Associated Diseases: meningitis, deficiency of complement components C5-C8 predisposes to infection
  7. Diagnosis: CSF Fluid (Gram Stain – Culture)
  8. Meningitis 
    1. Headache
    2. Fever
    3. Hypotension à shock
    4. Generalized rash (due to intravascular coagulation)
    5. Photophobia
    6. Neck Stiffness
    7. Risk factors: Close contact (college dorms, military barracks..etc)
    8. Treatment: Ceftriaxone or cefotaxime 
    9. Prevention: rifampin or ciprofloxacin
        1. Corynebacterium diphtheriae 
    1. Characteristics 
  1. Small, pleomorphic, Tend to stain unevenly
  2. Colonizes throat and nasopharynx 
    1. Pathogenesis
  1. Exotoxin that inhibits eukaryotic protein synthesis (blocks ADP ribosylation of EF-2)
    1. Diagnosis
  1. Clinical, 
  2. Culture in Tinsdale’s agar
  3. Methylene blue stan: polychromatic granules or club-shaped rods arranged in V or L shapes.
  4. Disease: Diphtheria
    1. Fever
    2. Sore throat
    3. Cervical Lymphadenopathy 
    4. Cough
    5. Dyspnea 
    6. thick, gray, adherent pseudomembrane composed of cell debris from mucosa and inflammatory products
  5. Treatment: Erythromycin or penicillin.
        1. Listeria Monocytogenes 
    1. Short, gram positive rods. 
    2. Catalase positive 
    3. Tumbling motility
    4. Cold growth – motility at room temp is diagnostic, other bacteria motile at body temp.
    5. Diplobacilli or short chains
    6. Facultative Intracellular parasites
    7. Contaminate dairy products (ice cream, cheese, milk, yogurt)
    8. Most common is immunocompromised 
    9. Evades phagocytosis
    10. elaboratind listeriolysin O
    11. Crosses placenta: causes abortion of fetus in humans
    12. Associated disease: septicemia, meningitis
    13. Treatment: ampicillin and Trimethoprim/sulfamethoxazole 
    14. Listeria: motility 
  6. Istanbul sounds like Listambul = list + tumble. 
  7. Listeria has tumbling motility 
        1. Bacillus Anthracis 
    1. Blunt-ended bacilli that occurs in pairs or long chains
    2. Endospores (centraly located)
    3. Non-motile
    4. Virulence factors:
  1. Capsule (antiphagocytic)
  2. Exotoxins: edema factor (induce severe edema), lethal toxin (tissue necrosis)
    1. Transmission by  contact with contaminated dust or animal product. (spores) 
    2. Cutaneous Anthrax: papule à painless, black pustule à crust
    3. Pulmonary anthrax: due to inhalation of spores.  Wide mediastinum due to  hemorrhagic lymphadenitis.
      Clinical manifestations: Fever, fatigue, malaise, muscle aches, respiratory distress
      à sepsis
    4. Treatment: 
  3. Doxycycline 
  4. Erythromycin
  5. Ciprofloxacin + rfampin + vancomycin (pulmonary) 
        1. Bacillus cereus 
  1. Causes Food poisoning by enterotoxins
  2. Associated with reheated fried rice 
        1. Clostridium difficile 
  1. Anaerobic gram-positive rods
  2. Normal flora of GI tract
  3. Enterotoxins:
      1. Toxin A: fluid secretion, stimulates inflammatory response.
      2. Toxin B: cytotoxin that interfieres with protein synthesis.
  4. Diagnosis: 
      1. Culture
      2. Elisa
  5. After a course of antibiotic therapy (specially clindamycin, ampicillin or other cepahlosporins) Clostridium proliferates and produce diarrhea.
  6. Associated disease:
      1. Diarrhea with pseudomembranous exudate, composed of mucus, fibrin, inflammatory cells over an ulcerated epithelium.
  7. Difficult to be in a Closet with someone having explosive foul smelling diarrhea, because it would smell and there would be no air in there. 
      1. Clostridium Difficile causes explosive foul smelling diarrhea and is an anaeorbe (no air)
  8. Treatment: discontinue antibiotic. Administer metronidazol or vancomycin. 
        1. Clostridium botulinum
    1. Characteristics 
  1. Spores present in soil and sediments.
  2. Neurotoxin à blocks acetylcholine release at the neuromuscular junction à inhibits contraction and cause flaccid paralysis.
    1. Associated diseases
  1. Classic Botulism:  
    1. Symptoms initiate 12 – 36 hours after ingestion of contaminated food.
    2. Dyplopia, dysphagia, progressive paralysis that can produce respiratory paralysis.
  2. Wound botulism: a wound become contaminated with the organism.
  3. Infant botulism: 
    1. Also Known as “floppy baby syndrome” 
    2. C. botulinum spores are present in honey or other formula supplements, after ingestion à C. botulinum colonizes large bowel of infants
    3. Lethargy,  hypotonia, feeding problems.
    1. Diagnosis
  1. Culture
  2. Toxin is identifiable in serum, stool and food.
    1. Treatment
  1. Antitoxin binds the unbound toxin.
  2. Supportive measures (Mechanical ventilation)
  3. Penicillin in the wound infection 
        1. Clostridium perfringens 
  1. Characteristics 
  1. Nonmotile 
  2. Encapsulated
  3. Normal flora of vagina and GI tract.
  4. Exotoxins:
    1. α Toxin:  a lecithinase, causes lysis of endothelial cells.
    2. At least 11 more toxins.
  1. Enterotoxin:  binds to receptors  interfering with ion transport and leading to loss of fluid 
  1. Associated Diseases:
  1. Gas Gangrene: spores are introduced into tissue. Toxins produce cell necrosis and fermentation of tissue (gas). 
    1. Clinical manifestations:
  • After deep surgery or severe trauma
  • Muscle swelling
  • Pain
  • Crepitants 
  • Fever, altered mental status, hypotension (systemic toxicity) 
  1. Anaerobic cellulitis:
    1. Affects only fascia, does not involve muscle tissue.
  1. Food poisoning:
    1. Nausea, abdominal cramps, diarrhea.
    2. 8 – 18 hours after consumption of contaminated food (usually undercooked)
    3. Duration 24 -48 hours.
    4. Autolimited 
  1. Diagnosis
  1. Gram stain, 
  2. Nagler reaction (very specific for C. perfringens) 
  3. anaerobe culture.
  1. Treatment
  1. debridement, Hyperbaric oxygen chamber, penicillin high dose.
        1. Clostridium tetani 
    1. Characteristics 
  1. Long, slender rod and round terminal spore (racquet-shaped bacillus)
  2. Growth on anaerobic blood agar.
  3. Spores are present in soil.
  4. Wounds became contaminated and tetanus spores germinate and grow.
    1. Tetanus toxin:
    1. Transported by retrograde neuronal flow or blood
    2. 2 fragments, B fragemnt binds to neurons, A fragment blocks neurotransmiter release at inhibitory synapses.
    3. Effect:  muscle spasm. 
    1. Treatment:  SAD RAT: 
    2. Sedation 
    3. Antitoxin 
    4. Debridement 
    5. Relaxant 
    6. Antibiotic 
    7. Tracheostomy 
    8. Prevention: Active immunization with tetanus toxoid (fromalin-inactivated toxin). Boost given every 10 years.
  1. If immediate passive immunity is required: tetanus immunoglobulin.
Enteric gram- rods
        1. Campylobacter Jejuni 
  1. Curved, spiral
  2. Single, polar flagellum
  3. Darting motion
  4. Microaerophillic 
  5. Do not ferment carbohydrates
  6. Transmission: fecal/oral, direct contact, exposure to contaminated meat or water supplies.
  7. Grows well at 42°C
  8. Most common cause of dysenteric diarrhea in US
  9. Campylobacter Jejuni 
  10. Associated Diseases:
      1. Enteritis:
    1. 2- 7 days of incubation
    2. Fever
    3. Heeadache 
    4. Myalgia 
    5. Abdominal cramping
    6. Diarrhea (Can be disenteric)
    7. Psudoappendicitis 
    8. Complications: Reactive arthritis and Guillain-Barre Syndrome
        1. Proteus  
    1. Disease: 
  1. Firstly, “PROTeus hates PROTons”: 
  2. So what does it do to fight the protons? It has a urease that raises the pH. Urea is in urine, so Proteus causes UTIs. The resulting alkaline environment promotes the precipitation of struvite stones containing insoluble phosphates of magnesium and phosphate.
        1. Escherichia coli  
  1. Normal flora of the colon
  1. Virulence depend of the strain
  2. Fimbriae or pili that  improve the adherence to mucosal surfaces.
  3. Facultative anaerobe
  4. Ferment lactose.
  5. Transmission: fecal/oral route 
  6. Types of intestinal infections:
    1. Enterotoxigenic (ETEC) 
      1. Traveler diarrhea
    2. Enteropathogenic (EPEC)
      1. Watery diarrhea of long furation
      2. Mostly in infants 
      3. Often in developing countries 
    3. Enterohemorrhagic (EHEC)
      1. Bloody diarrhea
      2. Hemorrhagic colitis 
      3. Hemolytic uremic syndrome
    4. Enteroinvasive (EIEC)
      1. Bloody diarrhea 
    5. Enteroadherent  (EAEC)
      1. Persistent watery diarrhea in children and patients infected with HIV 
        1. Enterotoxigenic E Coli (ETEC) 
  7. Cause of traveler’s diarrhea
  8. Watery diarrhea
  9. Colonize the small intestine
  10. Enterotoxins: 
    1. Heat-stable: ñcGMP levels
    2. Heat-labile: ñcAMP levels 
    3. Secretion of chloride ions and water by the intestinal mucosa
    4. Inhibition of reabsorption of sodium
        1. Escherichia Coli – Enteropathogenic (EPEC) 
  11. Cause of diarrhea in infants
  12. The E. coli attach to mucosal cells in the small intestine, causing destruction of microvilli.
  13. Watery diarrhea that can become chronic
        1. Escherichia Coli – Enterohemorrhagic (EHEC) 
  14. Bind to cells in the large intestine
  15. Most common strain: O157:H7
    1. Hemolytic Uremic Syndrome (HUS):
      1. Fever
      2. Acute Renal Failure, 
      3. Microangiopathic hemolytic anemia (Schistocites)
      4. Thrombocytopenia
  16. Production of Exotoxin (Shiga-like toxin)
        1. E. Coli – Other diseases 
  17. Urinary Tract infections:
    1. E. coli is the most common cause
    2. Caused by uropathogenic strains (contains P fimbriae, hemolysin, colicin V)
    3. Treatment: Ciprofloxacin, TMP/SMX
  18. Neonatal meningitis:
    1. Most common cause in neonates
    2. Treatment: Cefotaxime 
  19. Nosocomial infections (Sepsis/bacteremia, endotoxic shock, pneumonia)
    1. Treatment: ampicillin, cefotaxime, Ciproflocacin, TMP/SMX 
        1. Helicobacter pylori
  20. Curved or spiral organism
  21. Corkscrew motility
  22. Urease productor (neutralize stomach acid)
  23. Microaerophilic 
  24. Pathogenesis: colonizes gastric mucosal cells in the stomach.
  25. Chronic inflammation of the mucosa.
  26. Associated Disease:
  1. Acute gastritis
    1. Dyspepsia
    2. Heartburn
    3. Diarrhea
  2. Duodenal and gastric ulcers.
    1. High association with duodenal ulcers.
    2. Risk factor for gastric carcinoma and gastric B-cell lymphoma
  3. Treatment: Amoxicillin + Clarithromycin + Proton pump inhibitor. 
        1. Klebsiella 
  1. Large
  2. Nonmotile bacilli
  3. Associated Diseases: You tell the patient: “Get UPS you fat alcoholic“: 
    1. UTI 
    2. Pneumonia 
    3. Sepsis 
    4. Fat capsule 
    5. Get up=nonmotile since no flagella. 
    6. Alcoholic=commonly seen in alcoholic and nosocomial patients. 
        1. Salmonella 
  4. Flagellated rods
  5. Catalase-positive
  6. Oxidase-negative
  7. Facultative anaerobes
  8. Ferment glucose (no lactose)
  9. Fecal/oral transmission
  10. Chronic carriers
  11. Association with pet turtles
  12. Salmonella invade epithelial cells. 
  13. Salmonella 
  14. Associated diseases:
  1. Gastroenteritis
    1. By Salmonella enteriditis or typhimurium 
    2. Nausea, vomiting, 
    3. Nonbloody diarrhea
    4. Fever
    5. Abdominal cramp
    6. Self-limited
  2. Osteomyelitis 
    1. In patients with Sickle cells. 
  3. Enteric (typhoid) fever:
    1. Due to Salmonella typhi 
    2. Fever, chills, 
    3. Headache
    4. Anorexia, 
    5. Diarrhea or constipations
    6. Maculo papular rash
    7. Complication: intestinal hemorrhage
    8. Treatment: Ceftriaxone, Ciprofloxacin 
        1. Shigella 
  1. Nonmotile, Nonencapsulated 
  2. Ferment glucose
  3. Transmission: from person to person, with contaminated food or water
  4. Pathogenesis: 
    1. Invasion and destruction of the large intestine mucosa.
    2. Exotoxin (shiga toxin)
  5. Diagnosis: culture of stool
  6. Clinical manifestations: 
    1. Bloody Diarrhea
    2. Dehydration
    3. Abdominal cramps
  7. Treatment: ciprofloxacin or azithromycin 
        1. Yersinia Enterocolitica 
  8. Motile
  9. No capsule
  10. Found in contaminated water supplies, unpasteurized milk, 
  11. Fever, abdominal pain, diarrhea.
  12. Ulcerative lesions in the terminal ileum.
  13. Necrotic lesions in Peyer patches
  14. Treatment: Ciprofloxacin, TMP/SMX
        1. Vibrio 
  15. Short, curved, rod-shaped
  16. Rapidly motile  (Motility:  Vibrio Vibrates“)
  17. Facultative anaerobes
  18. Pathogenic:
    1. Vibrio Cholerae 
    2. Vibrio parahemolyticus 
    3. Vibrio vulnificus 
        1. Vibrio cholera 
  19. Transmitted by contaminated water and undercooked seafood from contaminated waters
  20. Not common in US
  21. Disease is caused by an enterotoxin:
    1. A subunit
      1. A1 ADP-ribosyl transferase that acts on Gs protein à ñcAMP 
      2. A2 facilitates penetration of the cell membrane
    2. B subunit: bind to GM1 ganglioside receptor
  22. Clinical manifestations:
    1. Watery diarrhea (massive)
    2. Rice-water stools
    3. Dehydration
  23. Diagnosis: Culture on blood agar
  24. Treatment: Liquids and doxycycline. 
        1. Vibrio Parahemolyticus 
  25. Ingestion of contaminated and inadequately cooked seafood, usually oysters
  26. Watery Diarrhea
  27. Nauseas, 
  28. Vomiting
  29. Abdominal cramps
  30. Self-limiting (around 72 hours) 
        1. Vibrio vulnificus 
  31. Consumption or contact with contaminated seafood (oysters)
  32. Affect only immunocompromised patients (especially liver disease)
  33. Clinical manifestations:
    1. Vomiting, 
    2. Diarrhea
    3. Abdominal pain
    4. Blistering dermatitis
    5. Pemphigus 
  34. Treatment:  ceftriaxone, doxycycline 
Non-enteric Gram Negative Bacteria 
  1. Bordetella pertussis 
  1. Disease associated: whooping cough (pertussis)
  2. Aerobic
  3. Encapsulated coccobacilli 
  4. Grows single or in pairs
  5. Transmission: droplets spread by coughing
  6. Diagnosis: culture, Direct fluorescent antibody (DFA) test, serologic test.
  7. Treatment: Erythromycin 
  1. Francisella tularensis 
  1. Pleomorphic coccobacilli 
  2. Facultative intracellular parasites
  3. Host: RABBITS, birds, 
  4. Infection: contact with infected animal tissues.
  5. Occupational risk: veterinarians, hunters, trappers. 
  6. Associated disease: tularemia
    1. Papule à ulcer within few days.
    2. Spread to lymph nodes à various organs, tissues
    3. Treatment: Gentamicin or streptomycin 
  1. Haemophilus influenzae 
  1. Pleomorphic 
  2. May or may not be capsulated
  3. Virulence factor. 
    1. Capsule(Hib)
    2. IgA protease
  4. Normal flora of the upper respiratory tract
  5. Transmission: respiratory droplets
  6. Associated diseases
    1. Otitis
    2. Epiglotitis
    3. Sinusitis
    4. Pneumonia
    5. Meningitis.
  7. Diagnosis: 
    1. Culture
    2. Gram stain of Steril sites
  8. Treatment: 
    1. Third generation cephalosporin (ceftriaxone ot cefotaxime)
    2. TMP/SMX
    3. Amoxicillin/ Clavulanate 
    4. Legionella pneumophila 
  1. Legionella pneumophila 
  1. Facultative intracellular parasites
  2. Unencapsulated 
  3. Coccobacilli 
  4. Normal habitat is soil and water 
  5. Transmission
    1. Inhalation of aerosolized organism
  6. Pathology 
    1. Macrophages phagocytose L. pneumophila à inside the macrophage the organism multiply until the cell ruptures, releasing a new crop of bacteria.
  7. Legionnaires’ disease: 
    1. Atypical pneumonia
    2. Usually in patients with pulmonary disease or immunocompromise.
    3. Fever, malaise, myalgia, anorexia, headache, cough + Diarrhea (watery)
    4. Treatment: Azyrhromycin, Levofloxacin.
  1. Psedomonas aeruginosa 
  1. Gram-negative
  2. Encapsulated, motile rod
  3. Oxidase positive
  4. Obligate aerobe
  5. Produce diffusible green and blue pigments
  6. Nosocomial infections
  7. Associated diseases:
    1. Localized infections: keratitis, otitis extena, UTI, pneumonia.
    2. Systemic infections: bacteremia 
  8. Treatment: antipseudomonal B-lactams, ceftazidime, tobramycin, cyprofloxacin 
  9. Pseudomona features AERUGINOSA: 
  1. Aerobic 
  2. Exotoxin A 
  3. Rod/ Resistance 
  4. UTIs, burns, injuries 
  5. Green-blue dressings 
  6. Iron-containing lesions 
  7. vii.Negative gram 
  8. viii.Odor of grapes 
  9. Slime capsule sometimes (in CF pt) 
  10. Adherin pili 
          1. Mycoplasma Pneumoniae 
  1. Prokaryotic organism
  2. No peptidoglycan cell walls – membrane composed of a lipid bilayer 
  3. Pleomorphic 
  4. Transmitted by respiratory droplets
  5. Associated diseases: 
    1. Atypical pneumonia: “walking pneumonia”, chills, malaise, fevers, dry cough, 
    2. Treatment: self-limited, azythromycin 
  6. Mycoplasma Pneumoniae 
  7. Complications:
    1. CNS disturbances, a
    2. erythema multiform
    3. Hemolytic anemia (cold agglutinins is an IgM antibody)
  8. Treatment: doxycycline or azithromycin.
          1. Mycobacterium tuberculosis
  9. Pulmonary disease (82%)
  10. Extrapulmonary disease (18%)
  11. Mycobacterium tuberculosis: culture identification 
  12. Rough, Tough, Buff”: 
    1. Rough: colony isn’t smooth but rough like breadcrumbs. 
    2. Tough: colony stuck to plate well, and tough to remove. 
    3. Buff: buff is a color, a cream/coffee shade
  13. ENT Manifestations of TB
    1. Scrofula
      1. matted lymphadenopathy: posterior triangle
    2. Laryngeal TB
      1. edema, ulcers, polypoid changes: arytenoids
    3. Oral TB
      1. painless ulcers: tongue
    4. Aural TB
      1. thickened TM–>hyperemia–>multiple perfs
      2. thin, watery otorrhea–>thick, cheesy d/c
          1. Actinomyces
  1. Part of normal oral cavity flora
  1. 50% of infections occur in face & neck
  2. forms abscesses with sulfur granules
  3. draining sinus tracts
          1. Rickettsia 
  1. Obligate intracellular organisms
  1. Coccobacillary shaped
  2. Double-layered, gram negative cell wall.
  3. Transmission: arthropods (fleas, mites, ticks, lice)
  4. Classic triad —Headache, fever, rash (vasculitis)
  5. Associated diseases:
    1. Rocky mountain spotted fever
  6. Treatment: Doxycycline, chloramphenicol 
          1. Ehrlichia 
  1. Parasitize leukocytes and grow in cytoplasmic vacuoles
  1. Inclusions called morulae 
  2. Associated diseases: 
    1. Erlichiosis (E. chaffensis)
      1. Fever, myalgia, moderate to severe leucopenia and thrombocytipenia.
      2. Diagnosis: Antibody assays and Polymerase chain reaction method.
      3. Treatment: doxycycline 
          1. Chlamydia 
  3. Obligatory intracellular bacteria
  4. Infect columnar epithelial cells
  5. Survive by replication that results in the death of the cell
  6. Takes on two forms in its life cycle:
    1. Elementary body (EB)
    2. Reticulate body (RB)
  7. Risk Factors 
    1. Adolescence
    2. New or multiple sex partners
    3. History of STD infection
    4. Presence of another STD
    5. Oral contraceptive user
    6. Lack of barrier contraception 
  8. Transmission
    1. Sexual or vertical
    2. Highly transmissible
    3. Incubation period 7-21 days
    4. Significant asymptomatic reservoir exists in the population
    5. Re-infection is common
    6. Perinatal transmission results in neonatal conjunctivitis in 30%-50% of exposed babies
  9. Chlamydiaceae Family
    (species that cause disease in humans)

    1. Clinical Syndromes Caused by C. trachomatis
    2. C. trachomatis Infection in Men
      1. Urethritis–One cause of non-gonococcal urethritis (NGU)
        • Majority (>50%) asymptomatic
        • Symptoms/signs if present: mucoid or clear urethral discharge, dysuria
        • Incubation period unknown (probably 5-10 days in symptomatic infection)
    3. C. trachomatis Complications in Men
      1. Epididymitis
      2. Reiter’s Syndrome 
        • Rarely occurs in women
    4. C. trachomatis Infections in Women
      1. Cervicitis
        • Majority (70%-80%) are asymptomatic
        • signs of infection, when present, include: 
          1. Mucopurulent endocervical discharge
          2. Edematous cervical ectopy with erythema and friability
      2. Urethritis
        • Usually asymptomatic
        • Signs/symptoms, when present, include dysuria, frequency, pyuria
      3. Pelvic Inflammatory Disease (PID)
        • Salpingitis
        • Endometritis
      4. Perihepatitis (Fitz-Hugh-Curtis Syndrome)
      5. Reiter’s Syndrome
    5. C. trachomatis Syndromes Seen in Men or Women
      1. Non-LGV serovars
        • Conjunctivitis
        • Proctitis
        • Reiter’s Syndrome
      2. LGV serovars
        • Lymphogranuloma venereum
    6. C. trachomatis Infections in Infants
      1. Perinatal clinical manifestations:
        • Inclusion conjunctivitis
        • Pneumonia
    7. C. trachomatis Infections in Children
      1. Pre-adolescent males and females:
        • Urogenital infections
          1. Usually asymptomatic
          2. Vertical transmission
          3. Sexual abuse
  1. Testing Technologies – Diagnosis 
    1. Non-culture tests
      1. Nucleic Acid Amplification Tests (NAATs)
      2. Non-Nucleic Acid Amplification Tests (Non-NAATs)
      3. Serology
    2. Culture 
      1. Historically the “gold standard”
      2. Variable sensitivity (50%-80%)
      3. High specificity
      4. Use in legal investigations
      5. Not suitable for widespread screening 
    3. Serology
      1. Rarely used for uncomplicated infections (results difficult to interpret)
      2. Criteria used in LGV diagnosis
        • Complement fixation titers >1:64 suggestive
        • Complement fixation titers > 1:256 diagnostic
        • Complement fixation titers <  1:32 rule out
  1. Partner Management
    1. Sex partners should be evaluated, tested, and treated if they had sexual contact with the patient during the 60 days preceding the onset of symptoms or diagnosis of chlamydia.
    2. The most recent sex partner should be evaluated and treated even if the time of the last sexual contact was >60 days before symptom onset or diagnosis.
          1. Treponema pallidum 
  1. Non-culturable spirochete
  2. Virulence factors: 
    1. adhesion factors, 
    2. hyaluronidase, 
    3. capsule/glycocalyx 
  3. Syphilis 
    1. Symptoms & Diagnosis 1º syphilis:
      1. Incubation period: 10 days – 3 months 
      2. Clinical Manifestations: Painless ulcer 
      3. Diagnostic:
        Dark-Field microscopy 
    2. Treatment: Penicillin IM Doxicicline x 14 days 
    3. Symptoms & Diagnosis 2º syphilis:
      1. Time period: 1 – 2 months after the ulcer 
      2. Clinical M.:  maculopapular rash on the soles and palms, malaise, lymphadenopathy 
      3. Diagnostic:
        VDRL, RPR, FTA-ABS
      4. Treatment: Penicillin IM, Doxicicline x 14 days 
    4. Symptoms & Diagnosis 3º syphilis:
      1. Time Period: > 1year 
      2. Clinical Manifestations: Neuro manifestations (tabes dorsalis, Argyll Robertson pupil)
        Cardiovascular: aortic aneurysm 
      3. Diagnostic:
        VDRL, RPR, FTA-ABS
      4. Treatment: Penicillin IM 
          1. Borrelia Burgdorferi 
  4. Transmitted by the tick Ixodes (also vector for Babesia).
  5. Lyme Disease
    1. Cutaneous lesions
      1. erythema chronicum migrans
    2. Nonspecific symptoms
      1. malaise, fatigue, headache, fevers, chills, myalgias, arthralgias, lymphadenopathy
    3. Late manifestations
      1. neurologic
      2. cardiac
  • Components 
    • Genome (DNA or RNA)
    • A protein-containing structure (capsid)
    • Envelop (present only in certain viruses) 
  • Classification – DNA 
Morphology rule of thumbDNA:
  1. Double-stranded Nuclear replication ‘Anhedral symmetry 
  2. Rule breakers: pox (cytoplasmic), parvo (single-stranded). 
  1. Adenovirus – non encapsulated ds DNA virus 
  1. Structure
    1. Medium sized (36 kb) dsDNA genome, naked capsid
  2. Pathogenesis
    1. respiratory or fecal oral transmission
    2. replication in nucleus; moderately host dependent
    3. local spread; viremia
    4. cellular and humoral immunity important; virus encodes countermeasures against MHC I expression and apoptosis
    5. direct cell damage from replication; respiratory illness, conjunctivitis, gastroenteritis, cystitis
  3. Diagnosis
    1. culture, viral antigen detection
  4. Treatment/prevention
    1. live military vaccine 
  1. Parvovirus – non encapsulated single stranded DNA virus
  1. Structure
    1. Small (5 kb) linear ssDNA genome, naked capsid
  2. Eg. Parvovirus B19
  3. Pathogenesis
    1. respiratory transmission
    2. replication in nucleus, very host dependent, needs S phase cells or helper virus
    3. viremia
    4. antibody important in immunity
    5. targets erythroid lineage cells; fifth disease (symptoms immunological); transient aplastic crisis; hydrops fetalis
  4. Diagnosis
    1. serology, viral nucleic acid
  5. Treatment/prevention
    1. none 
  1. Polyomavirus – non encapsulated double stranded DNA virus
  1. Structure
    1. Small (5 kb) circular dsDNA genome, naked capsid
  2. Pathogenesis
    1. respiratory transmission
    2. replication in nucleus; very host dependent
    3. viremia
    4. persistence in kidneys; reactivation with immune compromise
    5. inapparent infection; hemorrhagic cystitis; PML
  3. Diagnosis
    1. viral nucleic acid
  4. Treatment/prevention
    1. cidofovir ? 
  1. Human Papillomavirus (HPV) – non encapsulated double stranded DNA virus
  1. Small DNA virus
  2. More than 100 types identified based on the genetic sequence of the outer capsid protein L1
  3. 40 types infect the mucosal epithelium
  4. HPV virus biology
  5. Greater than 100 subtypes
    1. About 15-20 cancer related types (type 16 and 18 associated with 67% of cervical cancer)
    2. All of these 15-20 subtypes associated with 99.7% of cervical cancer
  6. Persistent HPV infection is a necessary condition for the development of cervical cancer
  7. Over 80 non-cancer causing subtypes
    1. Types 6 and 11 are responsible for causing over 90% of all anogenital warts
  8. No available antiviral treatment for any HPV subtypes
  9. Modes of Transmission
  10. Skin-skin contact
    1. Genital-genital
    2. Manual-genital
    3. Oral-genital
  11. Does not require penile vaginal sexual intercourse
  12. Condoms of uncertain effectiveness
    1. As opposed to discharge diseases like HIV, gonorrhea, syphilis
  13. Anogenital Warts
    1. Prevalence
      1. 1% of sexually active adults
    2. Treatment
      1. 40% or more resolve spontaneously
      2. Recurrence is fairly common
      3. Various agents including Aldara, cryosurgery (freezing), podophylin, cautery
  14. Cervical Cancer Risk Factors
    1. Risk factors for persistent HPV infection
      1. Lifetime number of sexual partners
      2. Age at first intercourse
      3. Smoking
      4. Oral contraceptive use
      5. Male partner sexual behavior
    2. Additional risk factors
      1. Age
      2. Genetics
      3. Low socioeconomic class
      4. Nutrition
      5. Immune suppression
Herpes viruses
  1. Herpes simplex Virus -1 (HSV-1) and Herpes Simplex Virus -2 (HSV-2)- ds stranded linear DNA enveloped virus
  1. Transmission
    1. Direct contact through mucous membranes
    2. The virus is considered shedding when there is obvious open sores.  This is the most common case.   The virus can also shed when there is no obvious sore.  
    3. Sexually transmitted 
    4. The reservoir for HSV-1  and HSV-2 is usually in sensory neuron ganglia.  Here it replicates and returns along the neuron to cause recurrent skin lesions.
  1. Clinical pathologies
  1. Gingivostomatitis  ( cold sores)
      1. Painful sores in lip and mouth area
      2. Heals spontaneously without scaring
      3. Can be accompanied by viral symptoms (fever, sweat, malaise, etc..)
      4. Vesicle in appearance
      5. May be pruritic at first
      6. The first outbreak is usually the worst one
      7. Can reoccur in stressful situations or in immunocompromised patients
  1. Herpetic keratitis of eye
  1. Herpes inflammation of the eye
  2. Reoccurs commonly  
  3. Most common cause of corneal blindness in US
  1. Encephalitis 
  1. Most common cause of viral encephalitis
  2. Usually reactivation of latent infection in immunocompromised individuals
  3. Temporal abscesses in patient with fever, headache and CNS symptoms
  1. Genital herpes
  1. Painful group of vesicles on external genetalia of men or women
  2. Can occur inside the vagina and cervix in women
  3. Does not cause scars
  1. Neonatal herpes infection
  1. Part of TORCHES organisms
  2. Infection occurs as the baby moves through birth canal 
  3. Risk of transmission increases with active herpes outbreak during delivery
  4. These children can have disseminated herpes infection, CNS involvement, skin, eye, and any other organ.
  1. VII.Diagnosis
  1. Tzanck smear
  1. Multinucleated giant cells
  1. Viral cultures
  1. PCR
  2. Serology
  3. Direct fluorescence antibody testing 
  1. Varicella-zoster virus – ds stranded enveloped DNA virus
  1. Transmission 
    1. Varicell
      1. Highly contagious
      2. Respiratory droplets
      3. Direct contact with ruptured vesicles
    2. Zoster 
      1. Reactivation
      2. Virus comes from dorsal root ganglia
  2. Clinical pathologies
    1. Varicella
      1. Chicken pox
      2. Rash vesicles look like fluid filled vesicles on top of a red base
      3. Rash first develops on the trunk and face, spreads to involve entire body
      4. Vesicles rupture and form scab in crops, disease will continue until all vesicles form scabs
      5. Scabs can cause scarring
      6. Has a 2 week incubation period
      7. Fever and headache symptoms
      8. Immunocompromised patients can have pneumonia or encephalitis due to varicella  
    2. Zoster
      1. Painful eruption of vesicles in a single dermatome along back and side of trunk
      2. Vesicles scab over like varicella
      3. Go away in 3 weeks
      4. Pain can be present for 1-2 months in elderly patients 
  3. Diagnosis 
    1. Tzanck smear
      1. Multinucleated giant cells
  4. Treatment 
    1. Acyclovir 
    2. Valacyclovir
    3. Chicken pox vaccine
    4. Zoster immune globulin
  1. Cytomegalovirus – ds stranded enveloped linear DNA virus
  1. Transmission
    1. Virus is found in saliva, milk, urine and tears
    2. Higher chance of transmission in the setting of prolonged exposure such as in household or day care
    3. Can be sexually transmitted 
  2. Clinical pathologies
    1. Asymptomatic
    2. Part of TORCHES organisms
    3. CMV mononucleosis
    4. Reactivation in immunocompromised patients
      1. Pneumonia
      2. Retinitis
      3. Esophagitis
      4. Disseminated disease 
  3. Diagnosis
    1. CMV serology
    2. Histology
      1. + intranuclear and cytoplasmic inclusion bodies
    3. CMV antigen testing
    4. PCR testing for CMV DNA
  4. Treatment
    1. Ganciclovir
    2. Foscarnet
  1. Epstein-Barr virus (EBV) – ds stranded enveloped linear DNA virus 
  1. Transmission
    1. Intimate contact by asymptomatic shedders of RBV
    2. Infects B-cells and transforms them
  2. Clinical pathologies
    1. Infectious mononucleosis
      1. Fever
      2. Sore throat
      3. Severe lethargy
      4. Enlarged lymph nodes
      5. Enlarged spleen – can rapture easily
    2. Associated with Burkitt’s B-cell lymphoma 
  3. Diagnosis
    1. Elevated Heterophile antibody 
    2. Elevated atypical lymphocytes 
    3. Serology 
      1. IgM antibodies against viral capsid antigens
  1. Human Herpes Virus 6 (HHV-6) – ds stranded enveloped linear Dna virus
  1. Transmission
    1. Saliva
  2. Clinical Pathologies
    1. Roseola
      1. High fever that lasts 3-5
      2. Followed by rash of the trunk which lasts 1-2 days
  1. Human Herpes Virus 8 (HHV-8) – ds stranded enveloped linear Dna virus
  1. Transmission
    1. Sexually transmitted
    2. High incidence among male homosexual population
  2. Clinical pathologies
    1. Kaposi Sarcoma
Pico Called Flavio To Return Renzo’s Corona“: 
  • Picornavirus 
  • Calicivirus 
  • Flavivirus 
  • Togavirus 
  • Retrovirus
  • Reovirus 
  • Coronavirus 
  1. Human Immunodeficiency Virus (HIV): is a lentivirus (a member of the retrovirus family) that causes acquired immunodeficiency syndrome (AIDS). AIDS is characterized by the infection and destruction of helper (CD4) T-lymphocytes, which results in a loss of cell-mediated immunity.
  1. Characteristics of the virus:
  1. Icosahedral (20 sided), enveloped virus of the lentivirus subfamily of retroviruses (retroviruses transcribe RNA to DNA)
  2. Viral envelop contains specific viral glycoproteins embedded that are synthesized by the env gene:
    1. gp120: mediates attachment to the CD4 protein. The gene that codes for the CD4 protein mutates rapidly resulting in antigenic variants that make it difficult to create an effective vaccine.
    2. gp41: mediates fusion with the host cell.
  1. The icosahedral nucleocapsid surrounds the internal nucleic acids and is composed of the following proteins:
    1. p24 (core antigen): synthesized by the gag gene and is used as a marker of infection
    2. p15
  1. Two viral strands of RNA found in the core are surrounded by an outer protein coat.
  2. Genome of the virus:
    1. Retroviral genes: gag, pol and env
    2. Regulatory genes: 
      • Required for replication: tat and rev
      • Not required for replication: nef, vif, vpr, and vpu
  1. Viral Replication
  1. HIV attaches to a susceptible host cell by attaching the gp120 envelope protein to the CD4 protein on the cell. Simultaneously, gp120 also attaches to chemokine receptors (CXCR4 and CCR5). Mutations in the genes involved in the production of the chemokine receptors are associated with a resistance to HIV infection.
  2. Gp41 proteins mediate the fusion of the viral envelope with the cell membrane allowing the entrance of the core (nucleocapsid and genome) into the cell.
  3. The viral RNA and core are released into the cytoplasm where reverse transcriptase transcribes the RNA genome into double-stranded DNA.
  4. The double-stranded viral DNA moves into the cell nucleus where it integrates into the host cell DNA due to the action of a viral enzyme called integrase.
  5. Viral RNA is synthesized by the cellular enzyme RNA polymerase II using integrated viral DNA as a template.  
  6. Full-length genomic RNAs are transported to the cytoplasm where they are assembled in a process that results in the formation and release of mature infectious virions.
  1. Methods of transmission:
  1. Sexual transmission
  2. Exposure to infected blood, blood products; Transplantation of infected tissues or organs
  3. Sharing contaminated needles (IV drug users)
  4. Perinatal transmission
Clinical manifestations: 
Figure 2: Evolution of the HIV infection
d. Infection phase: 
  1. 2-4 weeks after infection
  2. Influenza-like symptoms: fatigue, fever, sore throat, lymphadenopathy
  3. HIV antibody test is often negative but becomes positive within 3 to 6 weeks; this process is known as seroconversion. Note: if the antibody test is negative but HIV is still suspected, then a PCR assay should be conducted.
  4. Slight decrease in CD4 count, self-limited
  5. p24 antigen present
  1. Clinical latency period:
  1. HIV continues to reproduce, CD4 count gradually declines from its normal value of 500-1200 because of virus budding from cells, fusion of uninfected cells with virally infected cells and apoptosis
  2. B cells have a decreased response to antigens, possibly because of a blockage of T cell/B cell interactions by viral proteins binding to the CD4 site
  3. CD8 cells initially increase and may remain elevated
  4. Immunologic changes: 
    1. Antibodies produced to all major antigens
    2. First antibodies detected are produced against the gag proteins p24 and p55
    3. Followed by antibodies to p51, p120 and gp41
    4. As disease progresses, antibody levels decrease
  5. Once CD4 counts drop below 500, an HIV infected person is at risk for opportunistic infections
  1. Immunodeficiency – AIDS:
  1. CD4 count drops below 400 and there is an increase in the incidence and severity of opportunistic infections: 
    1. Persistent Herpes-zoster infection (shingles)
    2. Pneumocystis carinii pneumonia (PCP) 
    3. Tuberculosis (TB)
    4. Oral candidiasis (thrush)
    5. Oral hairy leukoplakia
    6. Cryptosporidiosis
    7. Isosporiasis 
    8. Cytomegalovirus
    9. Toxoplasmosis
    10. Cryptococcosis
    11. Non-Hodgkin’s lymphoma
    12. Kaposi’s sarcoma (KS): is a rare neoplasm of the blood vessels. It manifests as bluish-red, oval-shaped patches that may eventually become thickened. Lesions may appear singly or in clusters. 
  1. Diagnosis:
  1. ELISA Testing
    1. Highly sensitive and specific
    2. Antibodies detected in ELISA include those directed against: p24, gp120, gp160 and gp41
    3. ELISAs are for screening only; false positives do occur and may be due to alcoholism, syphilis, and immunoproliferative diseases
  2. Other Screening Tests
    1. Agglutination tests using latex particles, gelatin particles or microbeads coated with HIV antigen; Agglutination occurs in the presence of antibody
    2. Dot-Blot Testing utilizes paper or nitrocellulose impregnated with antigen; Patient serum is filtered through and anti-antibody is added with an enzyme label; Color change indicates a positive test.
  3. Western Blot
    1. ‘Gold Standard’ for confirmation
    2. Utilizes a lysate prepared from the HIV virus. The lysate is subjected to electrophoresis to separate the HIV proteins (antigens)
    3. Specific bands form where antibody has reacted with different antigens
    4. The following antigens must be present: p17, p24, p31, gp41, p51, p55, p66, gp120 and gp160
    5. Interpretation of results:
      • Negative: no bands
      • Positive: minimum of 3 bands directed against the following antigens: p24, p31, gp41 or gp120/160
      • CDC criteria requires 2 bands of the following: p24, gp41 or gp120/160
  1. Indirect immunofluorescence
    1. Can be used to detect both virus and antibody to the virus
    2. Antibody is detected by testing patient sera against an antigen applied to a slide; The patients sera is incubated, washed and a fluorescent antibody is added to visualize patient’s antibodies 
    3. Virus is detected by fixing patient cells to a slide and incubating the slide with antibody
  1. Detection of p24 HIV antigen
    1. The p24-antigen screening assay is an enzyme immunoassay (EIA) performed on serum or plasma.
    2. Test is not recommended for routine screening as appearance and rate of increase are unpredictable
    3. Sensitivity lower than ELISA
    4. Most useful for the following:
      • Early infection suspected in seronegative patient
      • Newborns
      • Monitoring disease progression
  1. Polymerase Chain Reaction (PCR)
    1. Looks for HIV DNA in the WBCs of a person
    2. PCR amplifies tiny quantities of the HIV DNA present, each cycle of PCR results in doubling of the DNA sequences present
    3. The DNA is detected using radioactive or biotinylated probes
    4. Once the DNA is amplified, it is placed on nitrocellulose paper and allowed to react with a radiolabeled probe, a single-stranded DNA fragment unique to HIV, which will hybridize with the patient’s HIV DNA if present
    5. Radioactivity is determined
  1. Virus isolation
    1. Virus isolation can be used to definitively diagnose HIV
    2. The best sample is peripheral blood; cell growth in culture is stimulated to amplify the number of cells releasing virus
    3. Infection is confirmed by detecting reverse transcriptase or p24 antigen in the supernatant
  2. Viral Load Tests
    1. Measures the amount of HIV RNA in one mL of blood
    2. Take 2 measurements 2-3 weeks apart to determine baseline
    3. Repeat every 3-6 months in conjunction with CD4 counts to monitor viral load and T cell counts or 4-6 weeks after starting or changing antiretroviral therapy to determine its effect on viral load
  3. Testing of Neonates
    1. Difficult due to the presence of maternal IgG antibodies
    2. Measurement of p24 antigen by PCR 
  1. Treatment: 
  1. Antiretroviral therapy:
    1. Two nucleoside reverse transcriptase inhibitors
    2. One protease inhibitor
  2. Preventative medications must be started if
CD4 < 200
CD4 < 50
  • Pneumocystis carinii pneumonia (PCP)
  • Cryptococcal meningitis
  • Toxoplasmosis
    1. Mycobacterium avium
    2. Cytomegalovirus infections
Orthodox Rhabbi’s Party Around Fine Bunnies”
  • Orthomyxovirus 
  • Rhabdovirus 
  • Paramyxovirus 
  • Arenavirus 
  • Filovirus 
  • Bunyavirus 
  1. Hepatitis A Virus 
      1. Naked RNA virus
      2. Transmission: fecal/oral
        1. Close personal contact
          (e.g., household contact, sex contact, child day care centers)
        2. Contaminated food, water
          (e.g., infected food handlers, raw shellfish)
        3. Blood exposure (rare)
          (e.g., injecting drug use, transfusion)
      1. Related to enteroviruses, formerly known as enterovirus 72, now put in its own family: heptovirus 
      2. Difficult to grow in cell culture: primary marmoset cell culture and also in vivo in chimpanzees and marmosets 
      3. Incubation period:
        1. Average 30 days
        2. Range 15-50 days
      4. Jaundice by
        1. <6 yrs,  <10%
      5. age group:
        1. 6-14 yrs, 40%-50%
        2. >14 yrs, 70%-80% 
      6. Complications
        1. Fulminant hepatitis
        2. Cholestatic hepatitis
        3. Relapsing hepatitis
      7. Chronic sequelae: None 
      8. Laboratory Diagnosis 
        1. Acute infection:  HAV-IgM in serum by EIA.
        2. Past Infection: HAV-IgG by EIA.
        3. Cell culture – difficult and take up to 4 weeks, not routinely performed
        4. Direct Detection – EM, RT-PCR of faeces. Can detect illness earlier than serology but rarely performed. 
        5. Hepatitis A Prevention – Immune Globulin 
      9. Pre-exposure
        1. travelers to intermediate and high
          HAV-endemic regions
      10. Post-exposure (within 14 days)
        1. Routine
        2. household and other intimate contacts
        3. Selected situations
        4. institutions (e.g., day care centers)
        5. common source exposure (e.g., food prepared by infected food handler) 
  1. Hepatitis B Virus
      1. Double stranded DNA virus,the + strand not complete
      2. Replication involves a reverse transcriptase.
      3. Hepatitis B virus (HBV) has been classified into 8 genotypes (A-H).
      4. It has not yet been possible to propagate the virus in cell culture. 
      5. Hepatitis B – Clinical Features 
        1. Incubation period: Average 60-90 days, Range 45-180 days
      6. Clinical illness (jaundice):
        1. <5 yrs, <10%
        2. 5 yrs, 30%-50%
      7. Acute case-fatality  rate:
        1. 0.5%-1%
      8. Chronic infection:
        1. <5 yrs, 30%-90%
        2. 5 yrs, 2%-10% 
      9. Premature mortality from chronic liver disease:  
        1. 15%-25%  
      10. Chronic Hepatitis B Diseases 
    1. Chronic Persistent Hepatitis – asymptomatic
    2. Chronic Active Hepatitis – symptomatic exacerbations of hepatitis
    3. Cirrhosis of Liver
    4. Hepatocellular Carcinoma 
      1. Modes of Transmission 
        1. Sexual – sex workers and homosexuals are particular at risk.
        2. Parenteral – IVDA, Health Workers are at increased risk.
        3. Perinatal – Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal
transmission is the main means of transmission in high prevalence populations.
      1. Diagnosis – serology 
    1. HBsAg – used as a general marker of infection.
    2. HBsAb – used to document recovery and/or immunity to HBV infection. 
    3. anti-HBc IgM – marker of acute infection.
    4. anti-HBcIgG – past or chronic infection.
    5. HBeAg – indicates active replication of virus and therefore infectiveness.
    6. Anti-Hbe – virus no longer replicating. However, the patient can still be positive for HBsAg which is made by integrated HBV.
    7. HBV-DNA – indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy. 
  1. Treatment 
    1. Interferon – for HBeAg +ve carriers with chronic active hepatitis. 
    2. Lamivudine – a nucleoside analogue reverse transcriptase inhibitor. Well tolerated, most patients will respond favorably. However, tendency to relapse on cessation of treatment. Another problem is the rapid emergence of drug resistance.
    3. Adefovir – less likely to develop resistance than Lamivudine and may be used to treat Lamivudine resistance HBV. However more expensive and toxic
    4. Entecavir – most powerful antiviral known, similar to Adefovir 
    5. Successful response to treatment will result in the disappearance of HBsAg, HBV-DNA, and seroconversion to HBeAg.
III.  Hepatitis C Virus
    1. Chronic Hepatitis C Infection 
    2. The spectrum of chronic hepatitis C infection is essentially the same as chronic hepatitis B infection.
    3. All the manifestations of chronic hepatitis B infection may be seen, albeit with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma. 
    4. Risk Factors Associated with Transmission of HCV 
  1. Transfusion or transplant from infected donor
  2. Injecting drug use
  3. Hemodialysis (yrs on treatment)
  4. Accidental injuries with needles/sharps
  5. Sexual/household exposure to anti-HCV-positive contact
  6. Multiple sex partners
  7. Birth to HCV-infected mother
    1. Laboratory Diagnosis 
  1. HCV antibody –. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears.
  2. HCV-RNA – various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy.
  3. HCV-antigen – an EIA for HCV antigen is available. It is used in the same capacity as HCV-RNA tests but is much easier to carry out. 
    1. Treatment 
  1. Interferon – may be considered for patients with chronic active hepatitis. 
  1. Ribavirin – there is less experience with ribavirin than interferon. However, recent studies suggest that a combination of interferon and ribavirin is more effective than interferon alone. 
  1. Hepatitis D Virus 
  1. The delta agent is a defective virus which shows similarities with the viroids in plants. 
  2. The agent consists of a particle 35 nm in diameter consisting of the delta antigen surrounded by an outer coat of HBsAg. 
  1. The genome of the virus is very small and consists of a single-stranded RNA
  1. Hepatitis D – Clinical Features 
  1. Coinfection 
    1. severe acute disease.
    2. low risk of chronic infection.
  2. Superinfection 
    1. usually develop chronic HDV infection.
    2. high risk of severe chronic liver disease.
    3. may present as an acute hepatitis.
  1. Hepatitis D Virus Modes of Transmission 
  1. Percutanous exposures
    1. injecting drug use
  2. Permucosal exposures
    1. sex contact
  1. Hepatitis E Virus
    1. Calicivirus-like viruses
      1. unenveloped RNA virus, 
      2. Positive stranded RNA genome 
      3. very labile and sensitive 
    2. Hepatitis E – Clinical Features 
      1. Most outbreaks associated with faecally contaminated drinking water.
      2. In the United States and other nonendemic areas, where outbreaks of hepatitis E have not been documented to occur, a low prevalence of anti-HEV (<2%) 
      3. Minimal person-to-person transmission.
  1. Influenza Virus 
    1. Clinical manifestations
Having Flu Symptoms Can Make Moaning Children A Nightmare”
  1. Headache 
  2. Fever 
  3. Sore throat
  4. Chills 
  5. Myalgias 
  6. Malaise 
  7. vii.Cough 
  8. viii.Anorexia 
  9. Nasal congestion 
  • Systemic Infections by True Pathogens 
    • Histoplasma capsulatum
    • Coccidioides immitis
    • Blastomyces dermatitidis
    • Paracoccidioides brasiliensis 
        1. Histoplasmosis: Ohio Valley Fever
  1. Histoplasma capsulatum – most common true pathogen; causes histoplasmosis
    1. Typically dimorphic
    2. Distributed worldwide, most prevalent in eastern and central regions of US
    3. Grows in moist soil high in nitrogen content
    4. Inhaled conidia produce primary pulmonary infection that may progress to systemic involvement of a variety of organs and chronic lung disease.
    5. Treatment – Amphotericin B, ketoconazole
  1. Coccidiomycosis: Valley Fever 
    1. Coccidioides immitis – causes coccidioidomycosis
    2. Distinctive morphology – blocklike arthroconidia in the free-living stage and spherules containing endospores in the lungs
    3. Lives in alkaline soils in semiarid, hot climates and is endemic to southwestern U.S.
    4. Arthrospores inhaled from dust, creates spherules and nodules in the lungs
    5. Amphotericin B treatment 
  1. Blastomyces dermatitidis: North American Blastomycosis 
    1. Blastomyces dermatitidis- causes blastomycosis
    2. Dimorphic
    3. Free-living species distributed in soil of a large section of the midwestern and southeastern U.S.
    4. Inhaled 10-100 conidia convert to yeasts and multiply in lungs
    5. Symptoms include cough and fever.
    6. Chronic cutaneous, bone, and nervous system complications
    7. Treatment – Amphotericin B 
  1. Paracoccidioidomycosis 
    1. Paracoccidioides brasiliensis
    2. Distributed in Central and South America 
    3. Lung infection occurs through inhalation  or inoculation of spores.
    4. Systemic disease is not common.
    5. Treatment -Ketoconazole, amphotericin B, sulfa drugs 
  2. Subcutaneous Mycoses 
    1. Lymphocutaneous sporotrichosis
    2. Chromoblastomycosis
    3. Mycetoma
  3. Sporothrix schenckii 
    1. Sporotrichosis (rose-gardener’s disease)
    2. Very common saprobic fungus that decomposes plant matter in soil 
    3. Infects appendages and lungs
    4. Lymphocutaneous variety occurs when contaminated plant matter penetrates the skin and the pathogen forms a nodule, then spreads to nearby lymph nodes.
  4. Chromoblastomycosis 
    1. A progressive subcutaneous mycosis characterized by highly visible verrucous lesions
    2. Etiologic agents are soil saprobes with dark-pigmented mycelia and spores
    3. Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporium carrionii
    4. Produce very large, thick, yeastlike bodies, sclerotic cells 
  5. Mycetoma 
    1. When soil microbes are accidentally implanted into the skin
    2. Progressive, tumorlike disease of the hand or foot due to chronic fungal infection; may lead to loss of body part
    3. Caused by Pseudallescheria or Madurella 
  6. Cutaneous Mycoses 
    1. Infections strictly confined to keratinized epidermis (skin, hair, nails) are called dermatophytoses- ringworm and tinea
    2. 39 species in the genera Trichophyton, Microsporum, Epidermophyton
    3. Closely related and morphologically similar 
    4. Causative agent of ring worm varies case to case 
    5. Natural reservoirs- humans, animals, and soil
    6. Infection facilitated by moist, chafed skin
    7. Long infection period followed by localized inflammation and allergic reactions to fungal proteins
    8. Ringworm of scalp (tinea capitis) affects scalp and hair-bearing regions of head; hair may be lost.
    9. Ringworm of beard (tinea barbae) affects the chin and beard of adult males; contracted mainly from animals.
    10. Ringworm of body (tinea corporis) occurs as inflamed, red ring lesions anywhere on smooth skin.
    11. Ringworm of groin (tinea cruris) “jock itch” affects groin and scrotal regions. 
    12. Ringworm of foot and hand (tinea pedis and tinea manuum) is spread by exposure to public surfaces; occurs between digits and on soles.
    13. Ringworm of nails (tinea unguium) is a persistent colonization of the nails of the hands and feet that distorts the nail bed.
    14. Treatment of dermatophytes includes topical antifungal agents 
      1. Tolnaftate miconazole applied for several weeks.
      2. Lamisil or griseofulvin 1-2 years
  7. Superficial Mycoses 
    1. Tinea versicolor – caused by Malassezia furfur; elicits mild, chronic scaling, mottling of skin; also implicated in folliculitis, psoriasis, and seborrheic dermatitis
    2. White piedra – caused by Trichosporon beigelii; whitish or colored masses develop scalp, pubic, or axillary hair
    3. Black piedra – caused by Piedraia hortae; dark-brown to black gritty nodules, mainly on scalp hairs 
  8. Opportunistic Mycoses 
    1. Most important fungal pathogens:
      1. Aspergillus
      2. Candida 
      3. Cryptococcus
      4. Pneumocystis
      5. Rhizopus
      6. Mucor
      7. vii.Absidia 
  9. Infections by Candida: Candidiasis 
    1. Candida albicans
      1. Widespread yeast
      2. Infections can be short-lived, superficial skin irritations to overwhelming, fatal systemic diseases.
      3. Budding cells of varying size that may form both elongate pseudohyphae and true hyphae
      4. Forms off-white, pasty colony with a yeasty odor 
      5. Normal flora of oral cavity, genitalia, large intestine or skin of 20% of humans
      6. Account for 80% of nosocomial fungal infections
      7. vii.Account for 30% of deaths from nosocomial infections
      8. viii.Thrush – occurs as a thick, white, adherent growth on the mucous membranes of mouth and throat
      9. Vulvovaginal yeast infection – painful inflammatory condition of the female genital region that causes ulceration and whitish discharge
      10. Cutaneous candidiasis – occurs in chronically moist areas of skin and in burn patients 
      11. Diagnosis and Treatment 
        1. Presumptive diagnosis made if budding yeast cells and pseudohyphae are found; germ tube
        2. Growth on selective, differential media differentiates Candida species
        3. Topical antifungals for superficial infections, amphotericin B and fluconazole for systemics 
  10. Cryptococcosis and Cryptococcus neoformans 
    1. Cryptococcus neoformans causes cryptococcosis.
    2. A widespread encapsulated yeast that inhabits soil around pigeon roosts 
    3. Common infection of AIDS, cancer or diabetes patients
    4. Infection of lungs leads to cough, fever, and lung nodules
    5. Dissemination to meninges and brain can cause severe neurological disturbance and death. 
    6. Diagnosis and Treatment 
      1. Negative stain demonstrating encapsulated budding yeast
      2. Biochemical tests, serological testing
      3. Systemic infection requires amphotericin B and fluconazole. 
  11. Pneumocystis (carinii) jiroveci and Pneumocystis Pneumonia 
    1. A small, unicellular fungus that causes pneumonia (PCP), the most prominent opportunistic infection in AIDS patients
    2. This pneumonia forms secretions in the lungs that block breathing and can be rapidly fatal if not controlled with medication.
    3. Pentamidine and cotrimoxazole 
  12. Aspergillosis: Diseases of the Genus Aspergillus 
    1. Very common airborne soil fungus
    2. 600 species, 8 involved in human disease; A. fumigatus  most commonly
    3. Serious opportunistic threat to AIDS, leukemia, and transplant patients
    4. Infection usually occurs in lungs – spores germinate in lungs and form fungal balls; can colonize sinuses, ear canals, eyelids, and conjunctiva
    5. Invasive aspergillosis can produce necrotic pneumonia, and infection of brain, heart, and other organs.
    6. Amphotericin B and nystatin 
  13. Zygomycosis 
    1. Zygomycota are extremely abundant saprobic fungi found in soil, water, organic debris, and food.
    2. Genera most often involved are Rhizopus, Absidia, and Mucor.
    3. Usually harmless air contaminants invade the membranes of the nose, eyes, heart, and brain of people with diabetes and malnutrition, with severe consequences. 
  1. Trypanosoma brucei 
    1. Associated disease: 
      1. “I went on a TRYP to AFRICA“: 
      2. TRYPanosoma brucei causes AFRICAn sleeping sickness 
  2. Trichomoniasis 
    1. Pathogen – Trichomonas vaginalis 
      1. Flagellated protozoan
      2. Reproduces at pH 5 – pH 6
    2. Symptoms
  1. Men: often asymptomatic
  2. Women: foul-smelling, yellow-green discharge; irritation
    1. Diagnosis 
      1. Saline wet mount: oval shaped  or fusiform-shaped protozoan.
      2. KOH preparation: Whiff test + 
    2. Epidemiology
      1. Usually through sexual intercourse
      2. Transmission to newborns during birth
    3. Prevention and treatment
      1. Metronidazole 
      2. No long-term immunity
    4. 5 F’s: 
  3. Flagella 
  4. Frothy discharge 
  5. Fishy odor (sometimes) 
  6. Fornication (STD) 
  7. Flagyl (metronidazole) Rx 
  1. Toxoplasma gondii 
    1. Clinical manifestations:
      1. My Cat Eats Mice”:
  1. Mononucleosis-like illness 
  2. Chorioretinits/ Congenital infection 
  3. Encephalitis 
  4. Myocarditis 
    1. Teratogens 
        1. Toxoplasma 
        2. Rubella 
        3. CMV 
        4. Herpes simplex, Herpes zoster (varicella), Hepatitis B,C,E 
        5. Syphilis 
  • Classification of Antibiotics
    1. Bacteriostatic
    2. Bactericidal
  • Inhibitors of Cell Wall Synthesis
    1. Beta Lactam Antibiotics
    2. Penicillins
    3. Cephalosporins
    4. Carbapenems
    5. Monobactams
        1. Penicllins 
  1. Derived from the fungus Penicillium 
  2. Therapeutic concentration in most tissues
  3. Poor CSF penetration
  4. Renal excretion
  5. Side effects: hypersensitivity, nephritis, neruotoxicity, platelet dysfunction
  6. Natural Penicillins
      1. Penicillin G, Penicillin V
  1. Antistaphylococcal Penicillins
  1. Methicillin
  2. Nafcillin
  3. Oxacillin
  4. Dicloxacillin
  1. Aminopenicillins
  1. Amoxicillin +/- clavulanate
  2. Ampicillin +/- sulbactam
  1. Antipseudomonal Penicillins
  1. Carbenicillin
  1. Ticarcillin +/- clavulanate
  2. Piperacillin +/- tazobactam
        1. Cephalosporins 
  1. Structurally similar to penicillins 
  2. Therapeutic concentration in many tissues 
  3. 3rd and 4th generation into CSF
  4. Renal Excretion
  5. Side Effects
      1. 1.allergy
      2. 2.disulfiram-like effect
      3. 3.anti-Vitamin K
  1. Generations of Cephalosporins
  1. 1st generation
          1. Cephalothin – Oral 
          2. Cephalexin – IV 
          3. Cephapirin –IV
          4. Gram positive coverage
          5. Skin infections
  1. 2nd generation
  1. Cefuroxime
  2. Cefoxitin
  3. Cefaclor
  4. Cefotetan
  5. More gram negative coverage than 1st generation
  6. Anaerobic coverage
          • Cefotetan
          • Cefoxitin
          • Cefmetazole
  1. 3rd generation
  1. Ceftriaxone
  2. Cefotaxime
  3. Ceftazidime
  4. Antipseudomonal activity
          • Ceftazidime, cefotetan, and cefoxitin
  1. Cerebrospinal fluid penetration and therefore meningitis Rx
          • Ceftriaxone 
  1. 4th generation
  1. Cefepime – IV
  2. Hospital use
  3. CNS activity
  4. Resistant to most beta lactams 
        1. Monobactams
      1. Aztreonam
  1. single beta lactam ring
  2. narrow spectrum: gram-negative aerobes
  1. Enterobacteriacea
  2. Pseudomonas
  1. given IV/IM
  1. renal excretion
  2. little cross-reactivity with other beta lactams
  3. side effects: phlebitis, rash, elevated LFT’s
  1. Carbapenems
          1. Meropenem/Imipenem
  1. broad spectrum
  2. active against MRSA
  3. given IV
  4. penetrates CSF
  5. renal metabolism and excretion
  6. addition of cilastin
  7. vii.side effects: GI upset, eosinophilia, neutropenia, lowering of seizure threshold 
  1. Vancomycin
  1. Tricyclic glycopeptide
  2. Inhibits synthesis of phospholipids and cross-linking of peptidoglycans
  3. Activity against gram-positive organisms
  4. Useful for beta lactam resistant infections
  5. Widely distributed, penetrates CSF
  6. Renal elimination, follows creatinine cl.
  7. Side effects
  1. Phlebitis
  2. Red man syndrome
  3. Ototoxicity
  4. Nephrotoxicity
  1. Protein Synthesis Inhibitors
  1. Human Ribosome
  1. 80S
  2. 40S
  3. 60S
  1. Bacterial Ribosome
  1. 70S
  2. 30S
  3. 50S
  1. Tetracyclines
  1. Isolated from Streptomyces aureofaciens
  2. Reversibly bind 30S ribosomal subunit
  3. Penetrate sinus mucosa, saliva and tears
  4. Metabolized in liver–>excreted in bile–> reabsorbed–>eliminated in urine
  5. Side effects: GI upset, hepatotoxicity, photosensitivity, bony deposition
  6. Contraindicated in pregnant or breast feeding women, children under 8 y/o
  1. Aminoglycosides
  1. Derived from Streptomyces and Micormonospora
  2. Irreversible binding to 30S subunit
  3. Actively transported into bacterial cells
  4. Variable tissue penetration, unreliable CSF levels
  5. Concentrate within perilymph
  6. Renal elimination
  7. Nephrotoxicity, ototoxicity, neurotoxicity
  1. Macrolides
  1. Macrocyclic lactone structure
  2. Irreversible binding to 50S subunit
  3. Therapeutic concentrations in oropharyngeal and respiratory secretions
  4. No CSF penetration
  5. Metabolized in liver, excreted in feces and urine
  6. Side effects: GI upset, ototoxicity, hepatotoxicity
  1. Chloramphenicol
  1. Isolated from Streptomyces
  2. Reversible binding to 50S subunit
  3. Broad spectrum of activity
  4. Indicated for severe anaerobic infections or unresponsive life-threatening infections
  5. Widely distributed, enters CSF
  6. Metabolized in liver (inhibits P-450), eliminated in urine
  7. Toxicities: reversible anemia, hemolytic anemia, aplastic anemia, gray baby syndrome
  1. Clindamycin
  1. Semisynthetic derivative of Lincomycin
  2. Irreversible binding to 50S subunit
  3. Covers anaerobes and gram + aerobes
  4. Widely useful for head and neck infections
  5. Penetrates saliva, sputum, pleural fluid, and bone, but not CSF
  6. Metabolized in liver–>reabsorbed–>eliminated in urine
  7. Side effects: rash, neutropenia/thrombocytopenia, pseudomembranous colitis
Inhibitors of Metabolism
  1. Sulfonamides
  1. Derived from Prontosil
  2. Competitive antagonist of PABA
  3. Wide distribution, penetrate CSF, cross placenta
  4. Metabolized in liver, eliminated in urine
  5. Side effects: rash, angioedema, Stevens-Johnson syndrome, kernicterus
  6. Avoid in pregnancy and infants
  1. Trimethoprim
  1. Interfere with the production of folic acid coenzymes that are required for purine and pyrimidine synthesis
  1. Inhibits dihydrofolate reductase
  1. 1000x higher affinity for bacterial enzyme than human enzyme
  2. Similar spectrum and pharmacokinetic profile as sulfas
  3. Side effects: folate deficiency anemia, leukopenia, granulocytopenia
  1. Co-Trimoxazole (TMP/SMX)
  1. Combination gives synergistic antibacterial action
  2. Inhibitors of Nucleic Acid Function/Synthesis
  1. Fluoroquinolones
  1. Bind bacteria DNA gyrase (topoisomerase II)
  2. Concentrate in sinus and middle ear mucosa, penetrate cartilage and bone
  3. Partially metabolized in liver–>GI or renal excretion
  4. Side effects: nausea, dizziness, phototoxicity, nephrotoxicity
  5. Avoid in pregnant or nursing women
  6. Use in children–possible effect on articular cartilage
  1. Antimycobacterial Therapy
  1. Must address two distinct populations of tubercle bacilli
  1. First-line treatment:  regimens of 3-4 drugs for 6 months to 2 years
  2. Second-line therapy:  reserved for multi-drug resistant organisms or unresponsive infection
  3. First-Line Agents
  1. Isoniazide
  2. Rifampin
  3. Pyrazinamide
  4. Ethambutol
  5. Streptomycin
  1. Isoniazide
  1. most potent drug
  2. inhibits formation of outer mycolic acid
  3. widely distributes and penetrates CSF
  4. metabolized in liver, excreted in urine, saliva, and sputum
  5. side effects: hypersensitivity, neruopathy, hepatotoxicity
  1. Rifampin
  1. from Streptomyces
  2. antibacterial and anti-tubercule
  3. interferes with RNA transcription
  4. wide distribution, penetrates CSF
  5. metabolized in liver
  6. gives orange-red color to stool, urine and tears
  7. side effects: rash, GI upset, hepatotoxicity 
  1. Pyrazinamide
  1. hydrolyzed to pyrazinoic acid
  2. unclear mechanism
  3. widely distributed, including CSF
  4. side effects:  GI upset, hepatotoxicity, hyperuricemia
  1. Ethambutol
  1. inhibits cell wall synthesis and maintenance
  2. widely distributed, penetrates CSF
  3. partially metabolized, excreted in urine
  4. potential for optic neuritis
  1. Streptomycin
  1. aminoglycoside
  2. binds 30S subunit
  3. penetrates synovial, pleural, pericardial, and ascitic fluids but not CSF
  4. renal excretion
  5. side effects: hypersensitivity, paraesthesias, auditory or vestibular dysfunction, nephrotoxicity
Antimycobacterials for Leprosy
  1. Dapsone
  1. structurally related to sulfonamides
  2. PABA antagonist
  3. activity against M. leprae
  4. also effective for pneumocystis and brown recluse spider bites
  5. wide distribution
  6. acetylated in liver, eliminated in urine
  7. side effects: erythema nodosum leprosum, peripheral neuropathy, methemoglobinemia 
  1. Clofazimine
  1. synthetic phenazine dye
  2. binds DNA and inhibits replication and transcription
  3. activity against M. leprai and MAI
  4. wide distribution, does not penetrate CSF
  5. partially metabolized, excreted in bile
  6. side effects:  GI upset, red/purple discoloration of skin and body fluids
  7. Prophylactic Antibiotics
  1. Cover bacterial flora involved in the surgical field
  1. Administer within 2 hours before or 3 hours after surgery has begun
  2. Maintain therapeutic blood level during lengthy procedures
  3. Continue prophylaxis for the 24 hour period surrounding surgery
  4. Effective Prophylactic Regimens
  1. Cefazolin +/- metronidazole
  2. Cefoperozone
  3. Clindamycin +/- gentamycin or amikacin
  4. Amoxicillin/clavulanate
  5. Ampicillin/sulbactam
  6. Ticarcillin/clavulanate
  1. Topical Antibiotic Prophylaxis
  1. Clindamycin or Peridex oral rinses
  2. significantly reduce bacterial counts in the oral cavity
  3. both immediate effect and prolonged effect for approximately 4 hours
  4. reduce post-op wound infections alone and in combination with parenteral antibiotic therapy