MODULE 6│PHARMBIOSCI 5

MICROBIOLOGY
MICROBIOLOGY BACTERIAL ENVELOPE

• study of microorganisms which are large and diverse group • All concentric outer layers
of microscopic organisms that can occur as either single cell • Capsule
or in cluster arrangement including viruses which are • Outer Membrane
microscopic but acellular • Cell wall
• Cell Membrane
BACTERIOLOGY • Attachment protein
• Organ of locomotion
IINTRODUCTION TO BACTERIOLOGY
Capsule
MORPHOLOGY • Outermost layer, if present
• Encapsulated Bacteria:
Coccus • “Some Killers Have Pretty Nice Capsule”
• round/ circular • Streptococcus pneumoniae
• Klebsiella pneumoniae
• Haemophilus influenzae
• Pseudomonas aeruginosa
• Neisseria meningitidis
• Cryptococcus neoformans (fungi)
• Virulence factor (VF): K antigen → prevents phagocytosis
• Mucoid and slimy polysaccharide layer
• Identification: India ink stain

Outer membrane
• Major permeability barrier for Gram-negative bacteria
• Contains lipopolysaccharide (LPS) → endotoxin
Bacillus • Also present in Listeria spp. (Gram-positive) → not
• rod shaped converted to endotoxin (according to studies)
• Periplasmic Space: found between the outer membrane and
cell wall

Cell wall
• A.k.a. Peptidoglycan (PG) layer
• O antigen
• Present in all bacteria EXCEPT Mycoplasma spp.

Gram-Positive Gram-Negative
Gram reaction Blue/ violet Red/ pink
PG layer Thicker (7-8) Thinner (1-2)
Teichoic acid Present Absent
Spirochetes Periplasmic space Absent Present
• spiral shaped Toxin Produces Exotoxin Endotoxin

GRAM STAINING

• Most commonly used differential stain

Steps (VIAS) Gram (+) Gram (-)

Crystal Violet Primary Stain

Gram’s Iodine Mordant

Alcohol Decolorizer

Pleomorphic Safranin O Secondary stain/

• vary in shape Counter stain

Gram Staining: General Rules

All cocci are Gram-positive, EXCEPT NVM
• Neisseria
• Veillonella
• Moraxella

All bacilli are Gram-negative, EXCEPT BANCEL MP

• Bacillus
• Actinomyces
• Nocardia
• Streptomyces
• Corynebacterium, Clostridium
• Erysipelothrix
• Listeria, Lactobacillus
• Mycobacterium
• Propionibacterium
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 Bacteria that cannot be seen on Gram Staining Endospores
Thin or absent cell wall Thick mycotic acid layer • Main composition is calcium dipicolinate/ dipicolinic acid
MCLRT CLINM • Important for survival: resistance to heat, chemicals,
Mycoplasma (absent) Cryptosporidium (protozoan) dehydration
Chlamydia Legionella micdadei • Identification: Malachite Green Staining
Legionella pneumophila Isospora (protozoan) • Green: Spore
Rickettsia Nocardia (weakly acid fast) • Red: Vegetative cell
Treponema Mycobacterium (Gram-variable)

Acid Fact Staining

Carbol-Fucshin Fuchsia dye: Primary stain
Carbolic acid: Chemical mordant
Heat Physical Mordant
Acid alcohol Decolorizer
Methylene blue Secondary stain/ counterstain

• Ex. Bacillus, Clostridium

STAGES OF MICROBIAL GROWTH

Cell membrane
• Phospholipid bilayer embedded with protein
• Function: selective barrier for solutes, energy metabolism
(ATP production)
Attachment proteins
• Fimbriae – attachment to host cell
• Pili – attachment to another bacteria, conjugation (virulence Lag Phase
factor) • No replication, ↑ size, ↑ synthesis

Organ of locomotion Log Phase/ Maximum Exponential Phase

• Axial filament – corkscrew motion of spirochetes
• Flagella – forward locomotion of bacilli, H antigen
• Atrichous – no flagella
• Monotrichous – one flagellum on one end
• Lophotrichous – tufts of flagella on one end
• Amphitrichous – flagella on both ends
• Peritrichous – flagella all over the surface
• ↑ replication, ↑ antibiotic susceptibility
Stationary Phase
• Number of replications = Number of deaths
Death Phase/ Decline Phase
• Number of deaths > Number of replications

INTERNAL BACTERIA STRUCTURE Reasons for microbial death

• ↓ nutrients
• Nucleoid • ↑ toxins
• Plasmid
• Ribosomes Physical Requirement:
• Endospores
Temperature:
Nucleoid • Psychrophiles/ Cryophiles
• A.k.a. nuclear region/ nuclear body/ chromatin region/ • Cold temperature
chromatin body • Listeria monocytogenes
• Not a true nucleus due to lack of nuclear membrane • Mesophiles
(“primitive nucleus”) • Body temperature
• Circular double stranded (ds) DNA which contains essential • Medically important bacteria]
genetic formation • Thermophiles
• Hot temperature
Plasmid • Sporeformers (Bacillus, clostridium)
• Extrachromosomal circular dsDNA which contains non- pH
essential genetic formation: • Acidophiles
• Resistance (R plasmid) • Acidic pH
• Conjugation (F plasmid – Fertility) • Lactobacillus acidophilus, Lactobacillus casein (Yakult®)
• Toxin production • Neutrophiles
• Virulence • Neutral pH (7.2-7.6)
• Transposons (jumping genes) • Medically important bacteria
• Alkaliphiles/ Basophiles
Methods of Gene Transfer • Alkaline/ basi pH
• Vibrio cholera
• Transformation: free uptake of naked DNA in solution
• Transduction: bacteriophage-mediated (virus Osmotic Pressure
• Conjugation: via sex pili (F plasmid) • Halophiles
• Transposition: via transposons • ↑ salt content/ osmotic pressure
Ribosomes • Vibrio parahemolyticus (seafood/ oyster poisoning)
• Site of protein synthesis
• 70s = 30s + 50s → potential sites for antibacterial agents

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Nutritional Requirement Example For organisms that
Blood Agar Plate (BAP) Require high nucleic acid content
Energy source Milk agar Require high protein diet
• Phototrophs – light Chocolate Agar Plate (CAP) Require molybdenum from diet
(present in hemoglobin)
• Chemotrophs – redox potential (medically important)
Reducing Medium
Carbon Requirement
• For growth of obligate anaerobes
• Heterotrophs/ Organotrophs – organic carbon (medically
• Thioglycolate broth: the ONLY reducing medium
important)
• Simple Media using Candle Jar/ Gas Pak® → provides
• Autotrophs/ Lithotrophs – inorganic carbon
anaerobic environment
Selective Medium
Oxygen Requirement
Culture Media Selective For
Obligate aerobes MCA, EMB Enterobacteriaceae
• Require O2 for survival Colistin-Nalidixic Agarbor (CAN) Gram-positive organisms
PNBMC Thayer-Martin Neisseria spp.
• Pseudomonas Lowenstein-Jensen Mycobacterium tuberculosis
• Nocardia Loeffler’s Serum Medium, Tellurite Corynebacterium diphtheria
• Bacillus Medium
• Mycobacterium Campy BAP, Skirrow’s agar Campylobacter jejuni
• Corynebacterium Bordet-Gengou Medium Bordetella pertussis
Thiosulfate citrate bile salts Vibrio spp.
sucrose (TCBS)
Obligate anaerobes
• Grow only in the absence of O2
ABCEFP Differential Medium
• Actinomyces • Subdivided a big group of microorganisms into categories
• Bacteroides • Blood Agar Plate – for Streptococcus spp.
• Clostridium
Organisms Type of Hemolysis Zone of Hemolysis
• Eubacterium
α-hemolytic Partial hemolysis Green
• Prevotella
β-hemolytic Complete hemolysis Clear
γ-hemolytic Non-hemolytic Red
Microaerophiles
• Require ↓ O2, however ↑O2 concentration → toxic
• MacConkey agar (MCA) and Eosin Methylene Blue (EMB) –
• Campylobacter
for Enterobacteriaceae
• Helicobacter
Culture Lactose Fermenters Non-Lactose
Aerotolerant Medium Fermenters
• Tolerates O2 but cannot replicate in its presence MCA Pink colonies Colorless
LP EMB Purple black colonies Colorless
• Lactobacillus
• Propionibacterium E. coli: green metallic sheen

Facultative anaerobes GRAM POSITIVE COCCI

• Could thrive with or without O2
• THE REST Gram-Positive Cocci
CULTURE MEDIA
Catalase test
• Nutrient material for microbial growth in laboratory

Composition
Catalase (+) Catalase (-)
Chemically Defined Medium
• Exact composition is known
• For growth of photoautotrophs and chemoautotrophs
Staphylococcus Streptococcus
Complex/ Not Chemically Defined Medium
• Exact composition is not known
• For growth of most medically important bacteria
Staphylococcus
Tissue Culture Coagulase test
• For growth of viruses Mannitol Salt Agar (MSA)
Physical State

Liquid – no solidifying agents (agar) POSITIVE NEGATIVE

Staphylococcus aureus
Semi-solid – 0.5 to 1.0% agar
MSA: golden yellow colonies
Solid – 1.5-3.0% agar
Staphylococcus aureus
Function/ Use
• Pathogenic
• VF:
Simple Media • Lipase: causes boils, furuncle, carbuncle (clusters)
• Designed for unfastidious organisms • Exfloliatin: causes Staphylococcal scalded skin
• Nutrient agar/ broth syndrome (SSSS)
Enriched Media • Enterotoxin B: causes food poisoning, toxic shock
• Fortified with vitamins, nutrients, and other substances syndrome (SSSS + hypotension)
needed for the growth of fastidious organisms • β-lactamase/ penicillinase: antibiotic resistance

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 • Treatment:
• Anti-staphylococcal penicillin (Methicillin, Nafcillin, Streptococcus
Oxacillin)
• For MRSA: Vancomycin Blood Agar Plate
• For VRSA: Linezolid, streptogramins

NEGATIVE β-hemolytic

Bacitracin Sensitivity
Novobiocin Sensitivity

GABHS GBS

SENSITIVE: RESISTANT: SENSITIVE: RESISTANT:

Staphylococcus Staphylococcus Streptococcus Streptococcus
epidermidis saprophyticus pyogenes agalactiae

Staphylococcus epidermidis Streptococcus pyogenes

• MSA: Porcelain white colonies
• Normal flora of the skin Suppurative
• Presentation: bacterial endocarditis in patients with Respiratory Tract: pharyngitis (Strep throat)
Skin
prosthetic heart valves (observe post-op)
• Cellulitis
• Impetigo: honey crusted lesions
Staphylococcus saprophyticus • Erysipelas: painful red rash with orange peel
• MSA: colorless colonies
• Normal flora of the vagina Non-Suppurative
• Presentation Urinary tract infection in women Exotoxin A
• Treatment: Fluoroquinolones • Scarlet fever/ 2nd disease: sandpaper rash, strawberry tongue
• Toxic shock syndrome (less severe compared to
Staphylococcus)
Streptococcus M Protein (type III hypersensitivity):
• Rheumatic hear fever (RHF)
• Post-Streptococcal glomerulonephritis (PSGN)
Blood Agar Plate
Streptococcus agalactiae
• Normal flora of vagina
• Presentation: causes neonatal sepsis and meningitis
α-hemolytic • Treatment: Ampicillin + Gentamicin

Quellung Reaction
Optochin Sensitivity Streptococcus

SENSITIVE: RESISTANT:
Streptococcus Viridans
pneumoniae Streptococcus γ-hemolytic

Streptococcus pneumoniae 0.5% NaCl

• Pneumococcus
• Lancet-shaped diplococci
• VF: Capsule (Quellung reaction)
• Quellang Reaction POSITIVE: NEGATIVE:
• German word for “swelling” Enterococcus Streptococcus
• antibodies bind to bacterial capsule to make it spp. bovis
more opaque
• Prevention: PCV
Enterococcus
MOST COMMON CAUSE OF
• Normal flora of GIT
Community Acquired Pneumonia 2nd / 3rd generation cephalosporins
• Presentation: Nosocomial/ hospital-acquired infections:
(CAP) + extended macrolides meningitis, endocarditis
Meningitis in elderly 3rd generation cephalosporins • Treatment
Otitis media Penicillin • Vancomycin
• For VRE: Linezolid, streptogramins
Viridans Streptococcus
• S. mutans: normal flora of the mouth ESKAPE Pathogen: Associated with antimicrobial resistance
• Overgrowth may cause dental caries • Enterococcus faecium
• Presentation: Subacute bacterial endocarditis in patients • Staphylococcus aureus
with prosthetic heart valves • Klebsiella pneumoniae
• Acinetobacter baumanii
• Pseudomonas aeruginosa
• Enterobacter spp.

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 GRAM POSITIVE BACILLI MOT Presentation Prevention
Adult Ingestion of - Nausea, - Heat canned
Sporeformers botulism performed toxins vomiting, diarrhea, good at 100°C
• Bacillus from infected flaccid paralysis for 20 minutes
• Clostridium canned goods - COD: paralysis of - discard
respiratory defective/
muscles bulging goods
Bacillus Infant Ingestion of Flaccid paralysis Avoid honey
• Obligate aerobe botulism spores from → floppy baby during the 1st
• Bacillus anthracis infected honey syndrome year of life
• Bacillus cereus
• All are motile, EXCEPT B. anthracis Clostridium perfringens
• Some members could be sources of antibiotics • VF:
• Bacitracin: Bacillus subtilis • Enterotoxin: Clostridial food poisoning
• Polymixin B: Bacillus polymyxa • α toxin (lecithinase) ϴ toxin (hemolysin)
• necrotizing and hemolytic effects
Bacillus anthracis • produces target/ double hemolysis on BAP
• Manner of Transmission (MOT): entry of spores via • ϵ toxin: neurotoxic (animal studies) → bioterrorism
• Injured skin → cutaneous anthrax Presentation
• Mucous membranes → gastrointestinal anthrax Clostridial Myonecrosis
• Respiratory tract → inhalational anthrax • Severe muscular infection with gas gangrene
Presentation • Hemorrhage and red-black discoloration
Cutaneous anthrax Papule → vesicle → necrotic ulcer → • Usually seen in diabetic patients
eschar • Foul-smelling discharge: mixed infection
Gastrointestinal anthrax Causes bowel ulceration → sepsis • Complication: sepsis → death
Inhalational anthrax Wool sorter’s disease • Treatment
Pulmonary hemorrhage (fetal) • Penicillin
• Surgical debridement/ amputation
Bacillus cereus
• Presentation: food poisoning Clostridium difficile
• Self-limiting (fluid replacement) • Normal flora of the large intestines
Emetic form Diarrheal form • Associated with chronic antibiotic use:
Implicated food Fried rice Meat, vegetables • Clindamycin
Symptoms Vomiting, Diarrhea, • Amoxicillin, Ampicillin
abdominal cramps abdominal cramps Presentation
Pseudomembranous Colitis
• Overgrowth of C. difficile produces biofilm/ pseudo-membrane
Clostridium
→ diarrhea
• Obligate anaerobe
• Treatment
• All are motile, EXCEPT C. perfringens
• Most important for management: stop the above
• Subterminal spores: C. perfringens (club shaped)
antibiotics!
• Spherical and terminal spores: C. tetani (tennis racket/
• Treatment: Metronidazole (DOC), Vancomycin
drumstick appearance
• Clostridium tetani
Non-sporeformers
• Clostridium botulinum
• Actinomyces
• Clostridium perfringes
• Nocardia
• Clostridium difficile
• Streptomyces
• Corynebacterium
Clostridium tetani
• Erysipelothrix
• Spherical and terminal spore: tennis racket/ drumstick
• Listeria, Lactobacillus
appearance
• Mycobacterium
• MOT: skin penetration from soil contaminated objects
• Propionibacterium
(habitat)
• VF: Tetanospasmin
Actinomyces & Nocardia:
• MOA: inhibits release of inhibitory neurotransmitter agents
Actinomytes
(glycine, GABA → important to initiate muscle relaxation →
• Formerly classified under Kingdom Fungi
tetanic contraction → spastic paralysis
• Branching and Filamentous under microscope
Presentation
• Anaerobic
First sign: trismus/ lockjaw
Triad:
• Actinomyces israelii
• Spastic paralysis • Aerobic
• Opisthotonos (overarching of the back • Nocardia asteroides
• Sardonic smile (grin with raised eyebrow) • Actinomadura madurae
Tetanus neonatorum: from cutting the umbilical cord with unsterile
equipment (non-institutional/ home delivery) → spastic paralysis Actinomyces israelii
Cause of death (COD): paralysis of respiratory muscles • Anaerobic actinomycetes
• Treatment • Normal flora of the skin and oral cavity
• Metronidazole, Penicillin Presentation
• Tetanus toxoid ± Tetanus antitoxin Actinomycosis/ Lumpy jaw
• Spasmolytic agents (Diazepam) • Granulomatous abscess usually in the mandible
• Prevention: DPT • Treatment
• Penicillin
Clostridium botulinum
• VF: Botulinum toxin (Botox®) Nocardia asteroids
• MOA: inhibits release of acetylcholine from presynaptic • Aerobic actinomyces
neuron → flaccid paralysis • Weakly acid fast
• Destroyed by heating at 100°C for 20 minutes • Presentation: Nocardiosis (pneumonia)
• Clinical use: treatment of wrinkles • Treatment: TMP-SMZ
Actinomadura madurae
• Aerobic actinomyces
• Presentation: Mycetoma
• Bacteria: Actinomycetoma
• Fungi: Eumycetoma

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 • Causes blockade of lymphatic GRAM NEGATIVE COCCI
Vessels → subcutaneous
Swelling → Madura foot Neisseria
• Treatment: General Characteristics:
• Ketoconazole (bacteria) • Kidney-shaped diplococci
• Amputation (fungi) • Catalase positive
• Oxidase positive
Streptomyces:
Source of Antibiotics Differentiation:
Carbohydrate utilization/ Fermentation test
Organism Antibiotic • N. gonorrhoeae – glucose only
Streptomyces erythreus Erythromycin • N. meningitidis – glucose and maltose
Streptomyces griseus Streptomycin
Streptomyces lincolnensis Lincomycin Isolation:
Streptomyces orientalis Vancomycin • For sterile specimen (ex. CSF): Chocolate agar plate (CAP)
Streptomyces roseosporus Daptomycin → black colonies
Streptomyces venezuelae Chloramphenicol • For non-sterile specimen (ex. genital discharge): Thayer-
Streptomyces orchidaceous Cycloserine
Matin = CAP + VCN
Streptomyces nodosus Amphotericin B
Streptomyces noursei Nystatin
• Vancomycin – Gram-positive
• Colistin – Gram-negative
• Nystatin – fungi
Corynebacterium:
• Modified Thayer Martin = CAP + VCN + Trimethoprim
Corynebacterium diphtheriae
(Proteus spp.)
• Non-moyile, club-shaped bacilli, Chinese character
arrangement/ palisades
Neisseria gonorrhoeae
• Identification (ID):
• Gonococcus
• Loeffler’s agar slant: for visualization metachromic
• VF:
Babes-Ernst granules
• Pili
• BAP: gray colonies
• β-lactamase: PPNG (penicillinase-producing N.
• Elek Test
gonorrhoeae)
• Diagnosis: Dacron swab
• Lipooligosaccharide: endotoxin
• VF: Diphtheria toxin
Presentation
• MOA: Fragment A → inhibits protein synthesis by
Genital Gonorrhea (tulo)
inhibiting elongation factor 2 → cell death • Males: penile discharge, dysuria, urethritis
Presentation • Females: asymptomatic → ascending infection
Cutaneous Diphtheria • Complication: Pelvic Inflammatory Disease → scarring →
• Necrotic skin lesion infertility
Pharyngeal Diphtheria
• Dirty gray pseudo-membrane Treatment:
• May extend to larynx/ trachea (bull neck appearance) → • Ceftriaxone IM single dose + Doxycycline BID for 7 days
obstruction • Doxycycline for contaminant Chlamydia infection
• Treatment: Erythromycin + Diphtheria antitoxin • Also treat the asymptomatic partner
• Prevention: DPT Ophthalmia Neonatorum
• Acquired via passage through infected vaginal canal
Erysipelothrix: • Prophylaxis: Silver nitrate, Erythromycin
Disseminated Gonococcal Infection
Erysipelothrix rhusopathiae
• Arthritis, dermatitis
• H2S producing (Triple Sugar Iron medium)
• H2S – Negative: no black precipitate formed
Neisseria meningitidis
• H2S – Positive: black precipitate formed
• Meningococcus
• Zoonotic infection
• VF:
• Greatest risk: fishermen, fish handlers, butchers (meat/ fish
• Capsule: A, C, Y, W – 135 (pathogenic subgroups)
vendor disease)
• Lipooligosaccharide (very potent)
Presentation
Presentation
Erysipeloid/ whale finger/ seal finger
Meningitis
• raised violaceous lesion on the finger without pus
• Most common cause in teenagers and young adults
• Treatment • Prevention: meningococcal vaccine (A, C, Y. W-135)
• Penicillin Meningococcemia
• Flu-like symptoms
Listeria: • Widespread thrombosis → Disseminated intravascular
Listeria monocytogenes coagulation (DIC) → bleeding
• Waterhouse-Friedrichsen syndrome: hemorrhage to the
adrenals
• ID:
• Shock (septic/ hypovolemic) → death
• Microscopy: tumbling motility • Treatment: Penicillin, Chloramphenicol, 3rd generation
• Motility medium: umbrella growth pattern cephalosporins
• Important food-borne pathogen: can survive • Prophylaxis: Rifampicin, Ciprofloxacin
• Refrigerator temperature
• Low pH GRAM NEGATIVE COCCOBACILLI
• ↑ salt content
Presentation • Haemophilus
Adult Human Listeriosis • Brucella
• Bacteremia (asymptomatic) • Francisella
Perinatal Human Listeriosis • Pasteurella
• Early onset syndrome:
• Stillbirth
• Bordetella
• Neonatal sepsis (granulomatosis infantseptica)
• Late onset syndrome: neonatal meningitis Haemophilus
Treatment: Ampicillin + Gentamicin • “Blood loving”
• Isolation: Chocolate agar plate
• Nutrients needed are inside the RBC
• Haemophilus influenzae
• Haemophilus aegypticus
• Haemophilus ducreyi

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Haemophilus influenzae GRAM NEGATIVE BACILLI
• Pfeiffer’s bacillus
• MOT: respiratory droplets Enterobacteriaceae
• VF: Capsule type b → most pathogenic • All are facultative anaerobes, oxidase negative
• Prevention: Hib vaccine • All are motile, EXCEPT
• Shigella
Presentation • Klebsiella
Community Acquired Pneumonia (CAP) 2nd or 3rd generation • Yersinia
cephalosporins + extended
macrolides H2S producing (SPaCEd)
Meningitis in infants and toddlers 3rd generation • H2S – Negative: no black precipitate formed
cephalosporins
• H2S – Positive: black precipitate formed
Most common cause of Meningitis
by Age group • Salmonella
Neonates GBS
• Proteus
E. coli • Citrobacter freundii
L. monocytogenes • Edwardsiella
Infants and H. influenzae
Toddlers Rapid Lactose fermenters (KrEE)
Teenagers N. meningitidis • Klebsiella
and young • Escherichia
adults
• Enterobacter
Elderly S. pneumoniae

Otitis media Amoxicillin Lactose fermenters

Acute bacterial epiglottitis 3rd generation • Citrobacter
cephalosporins (Ceftriaxone) • Serratia
• Salmonella arizonae
Haemophilus aegypticus • Shigella sonnei
• Koch-Week’s bacillus • Yersinia enterocolitica
• Presentation: Purulent conjunctivitis
• aegypticus = EYEgypticus Non-lactose fermenters
• Treatment: topical sulfonamide • Pathogenic pathogens
• Salmonella arizonae
Haemophilis ducreyi • Shigella (except) sonnei
• Presentation: Chancroid → soft painful chancre (genital • Yersinia enterolitica
ulcer) • Opportunistic pathogens
• vs. T. pallidum → hard, painless chancre • Proteus
• “You cry with ducreyi” • Providencia
• Treatment: • Morganella
• Azithromycin PO single dose • Edwardsiella
• Ceftriaxone IM single dose
Escherichia:
Brucella Escherichia coli
• Zoonotic infection • Colon bacillus
• Brucella abortus: (most common: “Bruce the cow”) • Most abundant aerobic flora of the colon
• Binds to fetal bovine protein erythritol → abortion • Most common flora of the colon: anaerobes
(not present in humans) (Bacteroides, Fusobacterium)
• Brucella melitensis: goat, sheep • Common indicator of fecal contamination of water (water
• Brucella suis: pigs potability)
• Brucella canins: dogs • EMB: green metallic
• MOT • Presentation: most common cause of UTI
• Ingestion of unpasteurized dairy products • Treatment: Nitrofurantoin, Fosfomycin, Fluroquinolones
• Direct contact (high risk butchers, veterinarians)
• Presentation: Brucellosis/ Bang’s disease/ Malta fever/ DIARRHEIC STRAINS
Undulant fever ETEC Enterotoxigenic Traveler’s diarrhea
• Treatment: Tetracycline + Gentamicin EPEC Enteropathogenic Infantile diarrhea
EIEC Enteroinvasive Produces Shigella-like dysentery
EAEC Enteroaggregative Persistent watery diarrhea
Francisella
EHEC Enterohemorrhagic VF: Shiga-like toxin (STEC)/ verotoxin
Francisella tularensis (VTEC)
• Zoonotic infection
• MOT: contact with rabbits (“Francis the rabbit”, bite of ticks O157:H7 strain → produces severe
• Presentation: Tularemia/ rabbit fever disease (Hamburger)
• Treatment: Streptomycin
Presentation:
Pasteurella • Dysentery
• Hemolytic-uremic
Pasteurella multocida syndrome (HUS): Renal
• Zoonotic infection failure, Anemia,
• MOT: dog or cat scratch Thrombocytopenia
• More common with cats, “Papa the cat”
• Presentation: Pasteurellosis/ Dog or cat scratch disease Treatment: Fluoroquinolones
• Treatment: Penicillin
Salmonella
Bordetella Salmonella typhi
Bordetella pertussis • Reservoir: poultry and dairy products
• VF: Pertussis toxin → lymphocytosis • Diagnosis: Widal test, Typhidot
• Isolation: Bordet-Gengou media (Potato-Blood-Glycerol Presentation
agar): pearl-like colonies Enterocolitis: most common manifestation (constipation/ diarrhea)
• Presentation: Whooping cough/ pertussis Enteric fever/ Typhoid fever
• Treatment: Macrolides • Prolonged high-grade fever
• Rose spots – rose-colored rash on the torso (rare)
• Prevention: DPT
• Chronic carrier state: gallblader

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 • Treatment: • Treatment:
• Ceftriaxone, Ciprofloxacin (Philippines) • Triple Therapy: OCA/ OCM
• Chloramphenicol (international literatures) • Omeprazole/ any PPI
• Clarithromycin
Shigella • Amoxicillin
• Medically important members: • Metronidazole
• Shigella dysenteriae: Group A – most common • Quadruple Therapy: TOMB
• Shigella flexneri: Group B – endemic in the Philippines • Tetracycline/ Amoxicillin
• Shigella boydii: Group C • Omeprazole/ any PPI
• Shigella sonnei: Group D – late lactose fermenter • Metronidazole
• Bismuth salicylate
VF: Shiga toxin
Neurotoxic Seizure Campylobacter:
Enterotoxic Dysentery Campylobacter jejuni
Cytotoxic Tenesmus/ Painful defecation • Oxidase positive
• Comma-, S-, or gull wing-shaped bacilli
• Treatment: self-limiting, if severe may give: • Culture: Skirrow/ Butzler medium
• Ciprofloxacin (adults) • Reservoir: dogs
• Azithromycin (children) Presentation
Similar to Shigellosis
Yersinia: • Crampy abdominal pain
Yersinia enterocolitica • Bloody diarrhea
• MOT: Fecal-oral route Complication: Guillan-Barré syndrome
• Presentation: enterocolitis
• Sometimes mistaken for appendicitis • Treatment: supportive
• Treatment: self-limiting, may give Doxycycline • May give fluoroquinolones

Yersinia pestis Pseudomonas:

• Zoonotic infection Pseudomonas aeruginosa
• MOT: bite of rat or flea (remember: “Yeye the rat”) • Colonies emit a fruity smell
• Inhibits soil, water, vegetation
Presentation • VF:
Bubonic plague Presence of enlarged suppurative lymph nodes • Capsule
in the groin and/ or axilla (buboes) • Exotoxin A: major VF, inhibits protein synthesis
Septicemic plague Hemorrhage, black gangrene (fingers, toes, • Pigments:
nose) → black death • Pyocyanin: blue pigment, stimulates inflammatory
Pneumonic plague Either from septic emboli or airborne response
• Pyoverdine: fluoresces in tissues
• Treatment: Aminoglycoside, Tetracycline • Pyorubin: dark red pigment
• Pyomelanin: black pigment
Other Gram-negative Bacilli • Presentation:
• Vibrio • Nosocomial infection: sepsis, meningitis
• Helicobacter • Hot tub folliculitis (jacuzzi)
• Campylobacter • Treatment:
• Pseudomonas • Antipseudomonal penicillin and cephalosporins
• Calymmatobacterium • Aminoglycosides
• Gardnerella
Calymmatobacterium:
Vibrio Calymmatobacterium granulomatis
General characteristics: • Formerly Klebsiella granulomatis
• Oxidase positive, motile • Presentation: Donovanosis/ Granuloma inguinale
• Comma-/ curve-shaped • Genital ulcer with beefy base
• Halophilic, EXCEPT V. cholerae • Pseudobuboes – nonsuppurative enlarged lymph nodes
• Treatment: Azithromycin
Organism TCBS Disease
Vibrio cholerae Yellow Cholera ! NOTE: Donovanosis is not caused by Leishmania
colonies donovani
Vibrio parahaemolyticus Green Seafood/ oyster
colonies poisoning ! Leishmania donovani: visceral leishmaniasis/
Vibrio vulnificus Blue-green Oyster poisoning kala-azar
colonies
Gardnerella:
Vibrio cholerae Gardnerella vaginalis
• VF: cholera toxin → ↑ cAMP → ↑ movement of water and • Normal flora of vagina
sodium into the intestinal lumen → rice watery diarrhea → • Presentation: Bacterial Vaginosis
dehydration • Foul smelling whitish vaginal discharge (fishy odor)
• Treatment: fluid replacement • Diagnosis: clue cells (vaginal cells embedded with bacteria)
• May give Tetracycline to shorten infection • Treatment: Metronidazole

Helicobacter: BACTERIA NOT SEEN ON GRAM STAINING

Helicobacter pylori
• Oxidase positive, motile • Mycoplasma
• Spiral shaped bacilli • Chlamydia
• VF: Urease → liberates ammonia → neutralizes gastric acid • Legionella pneomophila
• Diagnosis: Urea breath test • Rickettsia
• Presentation: • Treponema
• Halitosis • Mycobacterium (Gram-variable)
• Peptic ulcer disease (duodenal, gastric)
• Chronic gastritis
• Risk factor for gastric cancer

Module 6 – Microbiology Page 8 of 32 RJAV 2022

Mycoplasma: Disease Vector
Mycoplasma pneumoniae Spotted Fever
• No cell wall, pleomorphic Rickettsia rickettsi Rocky mountain Tick
• Smallest free-living organism (mollicutes) spotted fever
• Identification: Rickettsia akari Rickettsial pox Mite
• Microscopy: Diene’s stain → fried egg colonies Typhus
Rickettsia prowazekii Epidemic typhus Louse
• Presentation: Atypical pneumonia/ walking pneumonia
Rickettsia typhi Epidemic typhus Flea
• Mild symptoms only
Scrub Typhus
• Treatment: Macrolides Orientia tsutsugamushi Scrub typhus Chigger mite

Ureaplasma urealyticum Coxiella burnetti

• Non-gonococcal urethritis in males • Previously under Rickettsia
• Salpingitis and post-partum fever in females • Vector: ticks
• Associated with lung disease in premature infants of low birth • Presentation: Q fever
weight • Fever, rashes, headache (similar to Rickettsia)
• Treatment: Tetracycline, Ciprofloxacin
Chlamydia
• Obligate intracellular parasite Treponema
• Forms:
• Elementary body: Spirochetes: Treponema, Leptospira, Borrelia
• Extracellular
• Metabolically inert Treponema pallidum
• Infective form • Treponema: Greek for “coiled hair”
• Reticulate body
• Intracellular reproductive form Stages of Syphilis
• Chlamydia trachomatis Primary Syphilis
• Chlamydia pneumoniae • Hard, painless chancre
• Chlamydia psittaci • Self-limiting
Diagnosis: dark field microscopy
Chlamydia trachomatis Secondary Syphilis
• Condylomata lata: wart-like lesions on the genitals
Presentation
Diagnosis: serological testing
Eye Neonatal inclusion conjunctivitis: passage through
Non-treponemal tests: used for screening
infection infected birth canal
• VDRL: Venereal Disease Research Laboratory
Adult inclusion conjunctivitis: acute infection
• RPR: Rapid Plasma Reagin
Trachoma: chronic follicular conjunctivitis → blindness
Genital Males: penile discharge, dysuria, urethritis Treponemal tests: confirmatory test
infection Females: asymptomatic • FTAA: Fluorescent Treponemal Antibody Absorption
Lymphogranuloma venerum • MHA: Micro hemagglutination
• Self-limited genital ulcer
• Swelling of inguinal lymph nodes • Treatment: Penicillin (DOC), Erythromycin
• Jarisch-Herxheimer reaction: due to antigen released by dead
Treatment: Doxycycline T. pallidum → neutropenia, hypotension
Latent Syphilis
Chlamydia pneumoniae • Asymptomatic stage, last for around 10 years
• Formerly known as Taiwan acute respiratory (TWAR) agent Tertiary Syphilis
• Presentation: • Rare mainifestation after the advent of penicillin
• Atypical pneumonia • Gumma (Granulomatous lesions)
• Systemic manifestations: neurosyphilis, aortic aneurysm
• Risk factor for atherosclerosis 9recent studies)
• Treatment: Macrolides
Congenital Syphilis
Chlamydia psittaci Acquired during the 1st trimester of pregnancy
• MOT: inhalation from dried bird excrement Presentation:
• Presentation: • Intrauterine death
• Psittacosis: parrots (parrot fever) • Congenital abnormalities t birth:
• Ornithosis: other birds - Hutchinson’s triad: Hutchinson’s teeth, interstitial keratitis, CN VII
• Treatment: Macrolides deafness
- Saber shin
Legionella: - Scaphoid scapula
- Saddle nose
Legionella pneumophila • Silent infection: may not be apparent until 2 years old
• MOT: droplet transmission
• May spread through air-conditioning units that use Leptospira:
water cool air. Leptospira interrogans
Presentation
• MOT: through mucous membrane or breaks in the skin
Legionnaire’s Disease/ Legionellosis
coming in contact to water with infected urine (rodents, cats,
• Atypical pneumonia
• Treatment: Macrolides dogs, humans)
Pontiac fever Presentation
• Acute flu-like symptoms Leptospiremia, Leptospiruria
Anicteric Leptospirosis: mild, flu-like symptoms
Rickettsia Icteric Leptospirosis/ Weil’s disease: severe
• Meningitis, renal failure, liver failure
• Obligate intracellular parasite
• COD: Pulmonary hemorrhage
• Vector transmitted
• Prophylaxis: Doxycycline 200mg OD for 3-5days
• Diagnosis: Weil-Felix reaction
• Treatment:
• Presentation: triad of:
• Mild: Doxycycline
• Fever
• Moderate to Severe: Penicillin
• Rashes
• Headache
Borrelia:
• Treatment: Tetracycline, Chloramphenicol
Borrelia burgdorferi
• Vector: Ixodes tick
• Presentation: Lyme Disease

Module 6 – Microbiology Page 9 of 32 RJAV 2022

 • Bull’s eye rash/ erythema chronicum migrans: No. of Bacilli ↓ Paucibacillary ↑ Multibacillary
expanding rash Clinical presentation Hyposthetic Leonie facies, saddle
hypopigmented skin nose, nodular skin
lesions lesions
Borrelia recurrentis
Treatment Rifampicin + dapsone Rifampicin + Dapsone
• Presentation: relapsing fever (recurrent fever)
+ Clofazimine
• Endemic form: tick bite (rodent host)
• Epidemic form: body louse (human host)
PARASITOLOGY
Mycobacterium
PROTOZOA
• Mycobacterium tubercolosis
• Mycobacterium avium-intracellulare complex
Intestinal Protozoa
• Mycobacterium leprae

Mycobacterium tuberculosis • Giardia lamblia

• Koch’s bacillus • Entamoeba histolytica
• #8 leading cause of morbidity in the Philippines (as of 2010) • Cryptosporidium hominis
• VF: tuberculin and mycolic acid – stimulates type IV • Cyclospora cayetanensis
hypersensitivity/ cell-mediated immunity → immune system • Balantidium coli
causing damage to the body
• MOT: airborne transmission Giardia lamblia
• Also referred to as Giardia duodenales or Giardia intestinalis
Pathogenesis • MOT: ingestion of fecally contaminated water or food
Primary infection: initial infection usually during childhood → bacilli containing Giardia cysts or by direct-fecal contamination
walled by carinal lymph nodes • Presentation:
Secondary infection: • Acute or chronic diarrhea
• Reactivation: immunocompromised state usually in adulthood • Stools may be watery, semisolid, greasy, bulky and foul
• Pulmonary tuberculosis (PTB): classical apical infiltrates smelling
• Extrapulmonary (EPTB) • Diagnosis: stool exam (cysts, trophozoites)
- CNS: Tuberculous meningitis
• Treatment: Metronidazole or Nitazoxanide
- Vertebral column: Pott’s disease

Entamoeba histolytica
Presentation
• MOT: main source of water food contamination is the
• Cough for ≥ 2 weeks: most • Night sweats
important clinical findings • Easy fatigability
asymptomatic carrier who passes cysts
• Hemoptysis • Dyspnea • Presentation
• Weight loss • Chest/ back pain • Asymptomatic infection
• Amebic colitis/ dysentery (mild severe, “flask-shaped”
Diagnosis ulcer)
Sputum Microscopy • Extraintestinal infection (amebic liver abscess*, amebic
• Gold standard for fiagnosis hepatitis)
• 2 sputum samples: at least 1 out of 2 must be positive • Diagnosis: Stool exam (cysts, trophozoites)
Tuberculin Skin Test (TST)/ Purified Protein Derivative (PPD)/ • Treatment:
Mantoux Test • Asymptomatic infection: luminal amebicide
• Positive result: wheal or erythema ≥10mm after 48-72hours
• Amebic colitis/ dysentery: tissue + luminal amebicide
• International literatures: ≥15mm is positive, but note that in
endemic countries (Philippines) the cutoff is ≥10mm • Extraintestinal infection: tissue + luminal amebicide
Culture: Lowenstein-Jensen medium
Free living amebae

Amebae MOT Disease

Naegleria fowwleri Invade the nasal Acute primary amebic
mucosa → extend into meningoencephalitis
the brain
Acanthamoeba spp Starts with eye and - Granulomatous
skin infection amebic encephalitis
(GAE)
- Acanthamebic
keratitis (contact lens
wearers)

Cryptosporidium hominis
• Infect the intestine in immunocompromised persons (e.g.,
those with AIDS)
Mycobacterium avium-intracellulare complex • MOT: acquired from infected animal or human feces or form
• 2 combined species fecally contaminated food or water
• Presentation: causes TB in AIDS patients (AIDS-defining • Presentation: water diarrhea, which is mild and self-limited
illness: usually seen in patients with advanced HIV infection/ 91 to 2 weeks) in normal persons (prolonged in
AIDS) immunocompromised or very young or old individuals)
• Treatment: Macrolides + RE • Diagnosis: Stool exam (cysts)
• Treatment: no broadly effective therapy
Mycobacterium leprae
• Hansen’s bacillus Cyclospora cayetanensis
• Obligate intracellular parasite with predisposition to cooler • MOT: waterborne and foodborne infections from various
parts of the body (ex: skin, nerves) types of fresh produce (raspberries, mesclun, and basil)
• Isolation: armadillo foot pad • Presentation: diarrhea, anorexia, fatigue, and weight loss
• MOT: nasal discharge from untreated lepromatous leprosy • Diagnosis: stool exam (oocysts, acid-fast positive)
patients • Treatment: Trimethoprim-sulfamethoxazole (TMP-SMZ)

Leprosy Tuberculoid Lepromatous Balantidium coli

Cell-mediated Strong Weak • Only member of the ciliate group that is pathogenic for
immunity humans
Lepromin skin test Positive Negative • MOT: outbreaks are associated with contamination of water
(Same principle as
supplies with pig feces
TST)
• Presentation:
Module 6 – Microbiology Page 10 of 32 RJAV 2022
 • Asymptomatic infection • Mucocutaneous leishmaniasis (Espundia) – primary
• Watery stools with blood and pus lesion → spread to the nasal and oral mucosa →
• Round-shaped ulcer producing severe and disfiguring facial mutilation
• Diagnosis: Stool exam (cysts, trophozoites) • Visceral leishmaniasis (Kala-azar) – of inoculation to
• Treatment: Tetracycline multiply → reticuloendothelial cells in spleen, liver,
lymph nodes and bone marrow
Sexually Transmitted Protozoa • Diagnosis: detecting either the amastigotes in clinical
specimens or the promastigotes in culture
Trichomonas vaginalis • Treatment: Na stibogluconate
• Most infections are asymptomatic or mild for both women
and men Plasmodium spp.
• Infection is normally limited to the vulva, vagina, and cervix: it • MOT: through the bite of an infective female Anopheles
does not usually extend to the uterus. mosquito (definitive host)
• Presentation: • Diagnosis: thick and thin films of blood
• Women: frothy yellow or cream-colored discharge, local • Thick film: used to detect the presence of organisms
tenderness, vulval pruritis, and burning • Thin film: establishing species identification
• Men: thin, white urethral discharge, GUT infection - Best time is midway between paroxysms of chills and fever
• Diagnosis: microscopic examination of vaginal or urethral (greatest number of intracellular organisms is present)
discharge • Treatment: (refer to drugs for malaria)
• Treatment: Metronidazole (both partners should be treated)
Plasmodium falciparum – most common, most virulent, most fatal
Blood and Tissue Protozoa • Malignant tertian malaria (36 to 48 hours)
• No selectivity in host erythrocytes; invades any RBC at any
• Trypanosoma spp. stage in its existence
• Shortest incubation period (7 to 10 days)
• Leishmania spp.
• Plasmodium spp. • Produces daily (quotidian) chills and fever
• Toxoplasma gondii • Mature gametocytes of P. falciparum are sausage-shape/
banana shape
• Babesia microti

Trypanosoma spp.: Plasmodium vivax – 2nd most common

• Benign tertian malaria (48 hours)
Trypanosoma brucei
• Trypanosoma brucei gambiense – West African • Invades only young, immature erythrocytes
trypanosomiasis • Capable of hypnozoite stage
• Trypanosoma brucei rhodesiense – East African
trypanosomiasis Plasmodium ovale – rarest spp.
• MOT: introduced through the bite of the tsetse fly (Glossina • Benign tertian malaria (48 hours)
• Selectivity for young, pliable erythrocytes
spp.) → multiply at the site on inoculation → induration and
swelling (the primary lesion) • Capable of hypnozoite stage
• Presentation: African Sleeping sickness syndrome
Plasmodium malariae
• Lassitude, inability to eat, tissue wasting,
unconsciousness, and death • Infect only mature erythrocytes
• Winterbottom sign – swelling of the posterior cervical • Longest incubation period (18 to 40 days)
• Quartan malaria (72 hours)
lymph nodes
• Diagnosis: thick and thin blood films, in concentrated
anticoagulated blood preparations from lymph nodes and Plasmodium knowlesi
• Malaria parasites of Old-World monkeys and pig-tailed
concentrated spinal fluid
• Treatment: macaques
• Non-CNS: Pentamidine, Suramin • Permissive in humans as well as in nonhuman primates
• No selectivity in host erythrocytes
• CNS: Eflornithine, Melasrsoprol
• Simian malaria or quotidian malaria (24 hours)
Trypanosoma cruzi
Toxoplasma gondii
• MOT: infective trypomastigote, which is present in the feces
of a reduviid bug (“kissing bug”) → enters the wound • MOT:
created by the biting → introduced when infected bug feces • Ingestion of improperly cooked meat (intermediate host)
• Ingestion of infective oocysts from contaminated cat
are rubbed into the conjunctiva, the bite site, or a break in
the skin. feces (definitive host)
• Presentation: American Sleeping disease (Chaga’s disease) • Transplacental transmission
• Presentation:
• Site of the bite: chagoma, Romana’s sign (unilateral
swelling of the eyelids) • Asymptomatic (most common)
• Acute Chaga’s disease: asymptomatic • Symptomatic
• Acute: chills, fever, headache, myalgia,
• Chronic Chaga’s disease: cardiomyopathy →
arrhythmia lymphadenitis, and fatigue
• Chronic: lymphadenitis, occasionally a rash,
• Brazilian Chaga’s disease: megaesophagus,
megacolon evidence of hepatitis, encephalomyelitis, and
• Diagnosis: thick and thin blood films or concentrated myocarditis
• Congenital infection: chorioretinitis (most common)
anticoagulated blood early in the acute stage
• Treatment: Nifurtimox; Benznidazole and other CNC disorder
• Diagnosis: serologic testing (detecting ABYs)
• Treatment: Pyrimethamine + Sulfadiazine (DOC);
Leishmania spp.
• Cutaneous leishmaniasis: L. tropica, L. Mexicana, L. major Pyrimethamine + Clindamycin (Alternative)
• Mucocutaneous leishmaniasis: L. brzilliensis
Babesia microti
• Visceral leishmaniasis: L. donovani, L. chagasi
• MOT: transmitted by adult female sandflies belonging to • MOT: human infection follows contact with an infected tick
genera Phlebotomus and Lutzomyia (Ixodes dammini)
• Presentation:
• Presentation:
• Cutaneous leishmaniasis (Oriental sore, Delhi boil) – • General malaise, fever without periodicity, headache,
red papule, appears at the site of the fly’s bite → chills, sweating, fatigue, and weakness
• Advance infection: hepatomegaly, splenomegaly,
enlarge and ulcerate
hemolytic anemia, renal failure
• Diagnosis: blood smear

Module 6 – Microbiology Page 11 of 32 RJAV 2022

 • Treatment: • Mechanical obstruction of the biliary and pancreatic
• Mild to moderate: Atovaquone + Azithromycin duct: epigastric pain and tenderness, vomiting, diarrhea
• Severe: Clindamycin + Quinine and exchange (occasionally bloody), and malabsorption
transfusion • Autoinfection: newly hatched larvae never exit the host
but, instead, undergo their molts within the intestine →
HELMINTHS chronic strongyloidiasis
• Diagnosis: Stool exam (presence of larval worms; eggs are
Intestinal Infections: Nematodes not visualized)
• Treatment: Ivermectin
• Enterobius vermicularis
• Trichuris trichiura Trichinella spiralis
• Ascaris lumbricoides • MOT: eating raw or improperly cooked meat infected with the
• Acylostoma duodenale larval stage of these nematodes
• Necator americanus • Presentation: caused by the larvae encysted in muscle
• Stongyloides stercoralis tissue
• Trichinella spiralis • Myalgia and weakness, and eosinophilia
• Capillaria philippinensis • Diagnosis: encysted larvae are detected in the implicated
meat or in a muscle biopsy specimen
Enterobius vermicularis • Treatment: symptomatic treatment (no effective treatment
• A.k.a. pinworm for the larvae)
• MOT: ingestion of embryonated eggs → larval worm is free • Adult worms in the intestine: Mebendazole
to develop in the intestinal mucosa • Severe infections: Steroids + Thiabendazole/
• Presentation: perianal pruritis (especially at night, caused Mebendazole
by presence of eggs that are laid around the perianal region)
• Diagnosis: Clinical manifestation → detection of the Capillaria philippinensis
characteristic eggs on the anal mucosa • MOT: ingestion of raw or undercooked fish (Hypselotris
• Treatment: Albendazole, mebendazole bipartite, “bagsit” in Ilocos Norte) results in infection of the
human host
Trichuris trichiuria • Presentation: abdominal/ gastrointestinal disease →
• A.k.a. whipworm protein-losing enteropathy
• MOT: eating food contaminated with infective eggs • Diagnosis: stool exam (presence of peanut-shape eggs,
• Presentation: larvae or adult worms)
• Asymptomatic • Treatment: Albendazole, Mebendazole
• Mild to moderate infection: lower abdominal pain,
distention and diarrhea Intestinal Infection: Trematode
• Severe infection: profuse bloody diarrhea, camps,
tenesmus, urgency, and rectal prolapse Fasciolopsis buski
• Migration of adult worm: appendicitis • A.k.a. giant intestinal fluke
• Diagnosis: stool exam (presence of “barrel-shape” eggs with • MOT: larval metacercarial stage Is ingested with uncooked
2 prominent plugs at the end) vegetation (water chestnuts or red caltrops) and then excyst
• Treatment: Albendazole, Mebendazole and mature in the intestine
• Presentation:
Ascaris lumbricoides • Attachment to the intestine: inflammation, ulceration,
• A.k.a. intestinal roundworm and hemorrhage
• MOT: eggs are ingested → larvae hatch in the duodenum → • Severe infection: abdominal discomfort (similar to
migrate in the circulatory system, lodge in lung capillaries → duodenal ulcer), as well as diarrhea
penetrate the alveoli, and migrate from the bronchioles → • Diagnosis: stool exam (large, golden, bile-stained eggs with
trachea and pharynx an operculum on the top)
• Presentation: • Treatment: Praziquantel
• Mechanical obstruction of the bowel
• Migration of adult worms and larvae Intestinal Infection: Cestodes
- Bowel: abdominal pain, bowel perforation and peritonitis
- Lungs: pneumonitis, Loeffler’s syndrome (cough, eosinophilia, • Taenia saginata
and pulmonary infiltrates) • Taenia solium
• Diagnosis: stool exam (presence of “decorticated” eggs) • Diphyllobothrium latum
• Treatment: Albendazole, Mebendazole • Hymenolepis nana
• Dipylidium caninum
Hookworms:
Ancylostoma duodenale – Old world hookworm Taenia saginata
Necator americanus – New world hookworm • A.k.a. beef tapeworm
• MOT: larvae penetrate host skin → end up in the small • MOT: cysticerci are ingested in insufficiently cooked beef →
intestine excystment, the larvae develop into adults in the small
• Presentation: intestine → egg production in maturing proglottids
• Skin penetration: allergic/ HS reaction • Presentation:
• Migration of the larvae → lungs: pneumonitis, • Asymptomatic
eosinophilia • Intestinal infection: vague abdominal pains, chronic
• Presence of the adult worms in the GIT: nausea, indigestion and hunger pains
vomiting and diarrhea • Diagnosis: Stool exam (presence proglottids, eggs, worm
• Feeding worms → blood loss: microcytic, hypochromic itself)
anemia • Treatment: Praziquantel; Niclosamide
• Diagnosis: (presence of eggs; larvae cannot visualize)
• Treatment: Albendazole, Mebendazole Taenia solium
• A.k.a. pork tapeworm
Strongyloides stercoralis • MOT: cysticerci are ingested in insufficiently cooked pork →
• A.k.a. threadworm excystment, the larvae develop into adults in the small
• MOT: like the hookworm, a skin penetrating larva enters the intestine → egg production in maturing proglottids
circulation and follows the pulmonary course • Presentation
• Presentation: • Asymptomatic
• Migrating larvae to the lungs: pneumonitis • Intestinal infection: abdominal discomfort. Chronic
indigestion, and diarrhea

Module 6 – Microbiology Page 12 of 32 RJAV 2022

 • Cysticercosis: infection with the larval stage of T.
solium, the cysticercus, which normally infects pigs;
lodge in vital areas such as the brain and eyes
- Eye infection: loss of VA
- Brain infection: hydrocephalus, meningitis, CN damage,
seizures, hyperactive reflexes, and visual defect
• Diagnosis:
• Intestinal infection: stool exam (presence of proglottids,
eggs, worm itself)
• Cysticercosis: appearance of calcified cysticerci in soft-
tissue roentgenograms, surgical removal of
subcutaneous nodules, and visualization od cysts in the
eye/brain
• Treatment:
• Intestinal infection: Niclosamide
• Cysticercosis: Praziquantel; Albendazole
Diphyllobothrium latum
• A.k.a. fish tapeworm
• MOT: ingestion of sparganum (ribbon-like larval worm) in raw
or insufficiently cooked fish (which also ingested copepods
which ingested the coracidium)
• Presentation:
• Asymptomatic infection
• Intestinal infection: epigastric pain, abdominal
cramping, nausea, vomiting and weight loss
• Vit. B12 deficiency: megaloblastic anemia and
neurologic manifestations
• Diagnosis: stool exam (presence of bile-stained operculated
egg with its knob at the bottom of the shell)
• Treatment: Niclosamide
Hymenolepis nana
• A.k.a. dwarf tapeworm
• MOT: embryonated eggs (coming from His mice and beetle)
are ingested and develop in the intestinal villi into a larval
cysticercoid stage
• Presentation: Asymptomatic infection
• Diagnosis: stool exam (presence of embryonated eggs with
six-hooked embryo and polar filaments)
• Treatment: Praziquantel
Dipylidium caninum
• A.k.a. dog tapeworm; pumpkin seed tapeworm
• MOT: development of larval worms in dog and cat fleas →
crushed by the teeth of the infected pet → carried on the
tongue to the child’s mouth when the child kisses the pet or
the pet licks the child
• Presentation:
• Asymptomatic infection
• Intestinal infection: abdominal discomfort, anal pruritus and
diarrhea
• Diagnosis: stool exam (reveals the colorless egg packets,
proglottids)
• Treatment: Praziquantel
Blood and Tissue Infection: Nematodes
• Wuchereria bancrofti
• Brugia malayi
• Loa loa
• Onchocerca volvulus
• Dracunculus medinensis
• Larva migrans
Lymphatic filariasis:
Wuchereria bancrofti
Brugia malayi
• MOT: introduction of infective larvae, present in the saliva of
biting a mosquito, into a bite wound
• Species of mosquitoes: Anopheles, Aedes and Culex
mosquitos
• Presentation:
• Acute infection: fever, lymphangitis and lymphadenitis
with chills, and recurrent febrile attacks
• Obstruction of lymph nodes: enlargement of extremities,
scrotum and testes (filarial elephantiasis)
Module 6 – Microbiology
• Diagnosis: demonstration of microfilariae in the blood
(Giemsa-stained blood films)
• Treatment: Diethylcarbamazine (DEC)
Loa loa
• A.k.a. African eye worm
• MOT: vector is a biting fly called Chrysops (mangofly)
• Presentation: Chronic infection
• Migration to extremities: fugitive or Calabar swellings
• Migration to the eyes: irritation, painful congestion,
edema of the eyelids and impaired vision
• Diagnosis: demonstration of microfilariae in the blood
• Treatment: Diethylcarbamazine (DEC); Surgical removal of
worms (immobilizing the worm with instillation of 10%
cocaine)
Onchocerca volvulus
• MOT: introduction of larvae through the skin during the biting
and feeding of the Similium (blackfly)
• Characterized by infection involving the skin, subcutaneous
tissue, lymph nodes and eyes
• Presentation:
• Acute infection: fever, eosinophilia and urticaria
• Migration to tissue and to the eyes: SQ nodules; River
blindness (near the streams where the blackflies breed);
hanging groin (nodules are present in the genitalia)
• Diagnosis: demonstration of microfilariae in skin nip
preparations from the intrascapular or gluteal; region
• Treatment: Ivermectin; surgical removal of the encapsulated
nodule
Dracunculus medinensis
• A.k.a. Guinea worm
• MOT: ingestion of water from so-called step walls; the gravid
female worm discharges larvae from lesions on the arms,
les, feet, and ankles → infect Cyclops spp. In the water
• Presentation: gravid female creates the vesicle and the
ulcer in the skin
• Diagnosis: observing the typical ulcer (presence of the larval
worms)
• Treatment:
• Slowly wrapping the worm on a twig/ surgical removal
Larva migrans
• Occurs when humans (dead end hosts) are infected with
nematodes that normally parasitize animal hosts
• Eosinophilia is a common feature
Forms:
Cutaneous larva migrans (CLM)
• A.k.a. creeping eruptions
• Causative agent: Ancylostoma caninum (dog hookworm)
• MOT: bare skin (often the hands and feet) contacts the
soilborne larvae
Visceral larva migrans (VLM)
• Causative agent: Anisakis (heringworm)
• Hosts: marine mammals (seals, dolphins, whales)
• MOT: ingestion of the Intermediate hosts (cod, herring,
salmon, rockfish)
• Presentation: abdominal pain that mimics appendicitis or
SBO
Ocular/ Neural larva migrans (OLM, NLM)
• Causative agent: Toxocara canis (dog roundworm);
Toxocara cati (cat roundworm); Baylisascaris procyonis
(racoon roundworm)
• MOT: larvae hatch out of the eggs in the intestines and
migrate throughout the circulation
Blood and Tissue Infection: Trematodes
• Fasciola hepatica
• Clonorchis sinensis
• Paragonimus westermani
• Schistosoma spp.
Page 13 of 32 RJAV 2022
Fasciola hepatica • Diagnosis: imaging and ultrasonography (determines the
• A.k.a. sheep liver fluke presence/ location of the cyst)
• MOT: ingestion of watercress that harbors the encysted • Treatment: surgical reaction of the cyst (treatment of
metacercariae choice); Albendazole, Mebendazole, or Praziquantel (if
• Presentation: inoperable)
• Liver infection: hepatomegaly, hepatitis
• Bile duct infection: biliary obstruction MYCOLOGY
• Diagnosis: stool exam (presence of operculated eggs
indistinguishable from the eggs of F. buski) FUNGI
• Treatment: Bithionol, Triclabendazole
• Eukaryotic
Clonorchis sinensis • Saprophytic: derive nutrients and energy from decaying
• A.k.a. Chinese liver fluke/ Oriental liver fluke matter
• MOT: requires 2 intermediate hosts • Important for decomposition of organic matter
• Snail: eggs are eaten by the snail, and then • Culture: Saboraud’s dextrose agar
reproduction begins in the soft tissues of the snail → • Inhabits the environment, EXCEPT Candida albicans
cercariae (normal flora)
• Freshwater fish (ingested by humans): cercariae encyst • Most are plant pathogens
and develop into infective metacercariae
• Presentation: Fungal Components
• Asymptomatic infection (most common)
• Biliary obstruction: adenocarcinoma of the bile ducts Cell Wall
• Gallbladder infection: cholecystitis, cholelithiasis • Chitin – major structural protein
• Diagnosis: Stool exam (presence of operculated eggs with • β-Glucan – site of antifungal actions
prominent shoulders and a tiny knob at the posterior pole)
• Treatment: Praziquantel Cell Membrane
• Phospholipid bilayer embedded with proteins
Paragonimus westermani • Contains Ergosterol → site of antifungal action
• A.k.a. lung fluke
• MOT: requires 2 Intermediate hosts Spores
• Snail: eggs are eaten by the snail, and then • Important for fungal reproduction
reproduction begins in the soft tissues of the snail → • Vs. bacterial spores: important for survival
cercariae • Has both sexual and asexual spores
• Freshwater crabs/ crayfish (ingested by humans):
cercariae encyst and develop into infective Hyphae
metacercaria • Basic morphologic element of multicellular, filamentous fungi/
• Presentation: molds
• Larval migration to tissues: chills, and high eosinophilia • Branching cylindrical tubes that could be:
• Adult worm migration to the lungs (mimics PTB): fever, • Septated: presence of internal cross-walls
cough and increased sputum (blood tinged and dark • Aseptated/ Coenocytic
with eggs → rusty sputum)
• Cerebral paragonimiasis: brain and spinal cord infection Mycelium – group of intertwined hyphae that accumulates during
• Diagnosis: sputum and stool exam (presence of golden growth
brown, operculated eggs) • Vegetative mycelium – found underneath the substrate for
• Treatment: Triclabendazole absorption of nutrients
• Aerial/ reproductive mycelium – forms spores
Schistosomes
• A.k.a. blood fluke Phylum Sexual Asexual Hyphae Examples
• MOT: contact water infested with the infectious cercariae spores spores
Ascomycota Ascospores Conidia Septated Yeast: Candida
(coming from the Intermediate host snails) → burrow into saccharomyces
exposed skin → schistosomes Molds:
• Schistosoma japonicum – found in superior mesenteric veins dermatophytes,
systemic mycoses*
• Schistosoma mansoni – found in inferior mesenteric veins Zygomycota Zygospores/ Sporangio- Sparsely Bread molds:
• Schistosoma haematobium – found in vesicular and pelvic Oospores spore septated Rhizopus,
plexus Rhizomucor,
Mucor, Absidia,
• Presentation: Cunninghamella
• Penetration of the cercariae: dermatitis Basidiomycota Basidiospores Conidia Complex Mushrooms,
• Katayama syndrome: fever, chills, cough, urticaria, Cryptococcus
arthralgias, lymphadenopathy, splenomegaly, and *Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis,
Paracoccidioides brasiliensis
abdominal pain
• Liver infection: fibrosis → hepatomegaly → portal
MORPHOLOGY
hypertension → ascites
• Bladder obstruction and fibrosis (S. haematobium)
Molds
• Diagnosis: stool exam (presence of eggs with different
• Multicellular filamentous fungi
morphology)
• Made up of hyphae
• Treatment: Praziquantel
• Example: Dermatophytes (ringworm infections)
Blood and Tissue Infection: Cestode
Yeast
• Unicellular round-to oval-shaped fungi
Echinococcus granulosus • Reproduce via budding
• Accidental human infection, with humans serving as dead- • Colonies on culture media resemble bacterial colonies
end intermediate hosts • Examples: Cryptococcus neoformans, Candida albicans
• MOT: eggs are ingested by humans → larval stage called an
oncosphere hatches → enters the circulation → liver (most Thermal Dimorphic Fungi
common), lungs, CNS • Exist as
• Found in nature: • Molds in room temperature
• Adult worm: intestines of canines • Yeast in body temperature
• Larval cyst: sheep, cattle, swine, deer, moose, elk • Examples: Malassezia furfur, Sporothrix schenkii, Penicillium
• Presentation: formation of the unilocular cyst (slow-growing marneffei, systemic mycoses
tumor-like and space-occupying structure

Module 6 – Microbiology Page 14 of 32 RJAV 2022

 CLINICAL MANIFESTATION OF FUNGAL DIESEASE Cutaneous mycoses

TOXICOSIS • Infections that extend deeper into the epidermis, also include
invasive hair and nail disease
Mycotoxicosis • Invoke inflammatory response: pain, welling, itching
• Poisonous toxins produced by fungi during normal metabolic • Causative agent: Dermatophytes
activity • Trichophyton spp.: affects skin, hair, nails
• Examples: • Microsporum spp.: affects skin, hair
• Aflatoxin • Epidermophyton spp.: affects skin, nails
• Produced by Aspergillus flavus Presentation: Dermatophytes/ Tinea/ Ringworm Infection
• Acquired via ingestion of improperly stored nuts/ Tinea capitis Scalp
grains Tinea barbae Beard
• Ergot Alkaloids Tinea corporis Trunk
• Produced by Claviceps purpurea Tinea imbricata Trunk/ limbs in concentric pattern
Tinea manuum Hand
Mycetismus Tinea unguium Nail
• Ingestion of poisonous mushroom Tinea cruris Groin “Jock itch”
• Example: Amanita phalloides → produces amatoxin which is Tinea pedis Foot “Athletes’ foot”
hepatotoxic
Subcutaneous mycoses
HYPERSENSITIVITY • Infections initially involving the dermis, subcutaneous tissue,
muscle, fascia
• Type I hypersensitivity • Superficial lesions extending along the lymphatics develop
• Fungal spores are allergenic later
• Presents as eczema (skin asthma), asthma, hay fever • MOT: skin penetration
• Sporotrichosis
MYCOSIS • Chromoblastomycosis
• Phaeohypomycosis
• Fungal infection • Mycetoma
• Superficial mycosis
• Cutaneous mycosis Sporothrix schenkii
• Subcutaneous mycosis • Thermal dimorphic fungi
• Systemic mycosis • Presentation: Sporotrichosis/ rose gardener’s disease
• Opportunistic mycosis • Nodular skin lesions → ulcer
• Diagnosis:
Superficial mycoses • KOH mount: conidia arranged in rosette-like clusters
• Treatment:
• KISS (potassium iodide saturated solution)
• Infections limited to the outermost layer of skin (stratum
• Amphotericin B: systemic infections
corneum of epidermis) and hair
• Oral itraconazole
• Do not invoke inflammatory response
• No pain
Chromoblastomycosis
• No swelling/ elevated skin lesions
• May be caused by one of the following dematiaceous fungi:
• No itching
• Phialophora verrucose
• Malassezia furfur
• Cladosporium carionii
• Exophiala werneckii
• Rhinocladiella aquaspera
• Trichosporon beigelii
• Fonsacea pedrosoi
• Piedraia hortai
• Fonsacea compacta
• Presentation: wart-like lesions with black dots extending
Malassezia furfur
along the lymphatics
• Thermal dimorphic fungi
• Treatment:
• Presentation: Tinea Versicolor/ Pityriasis Versicolor (an an)
• Itraconazole + Flucytosine
• Irregular patches of discrete, serpentine,
• Surgical excision
hypopigmented macules
• Diagnosis:
Phaeohypomycosis
• KOH mount: spaghetti and meatballs appearance
• May be caused by one of the following dematiaceous fungi:
• Wood’s UV lamp: pale greenish to yellow fluorescence
• Exophiala jeanselmei
over the lesion
• Philaphora richradsiae
• Treatment: Topical imidazole
• Bipolaris specifera
• Wangiella dermatitidis
Exophiala werneckii
• Cladophialophora bantiana
• Dematiaceous fungi – produces black pigment
• Presentation:
• Presentation: Tinea Nigra
• Solitary encapsulated cyst in the subcutaneous tissue
• Black macules usually seen at the palm
• Sinusitis
• Treatment: Topical Imidazole, Whitfield’s ointment®
• Brain abscess (C. bantiana)
(Salicylic acid + Benzoic acid)
• Treatment: Itraconazole/ Amphotericin B + Flucytosine
Piedraia hortai
Mycetoma
• Dematiaceous fungi
• Causative agents:
• Presentation: Black Piedra
• Bacteria: Actinomycetoma (Actinomadura madurae)
• Hard, black nodules on hair shart (scalp)
• Fungi: Eumycetoma
• Treatment:
• Pseudoallescheria boydii
• Shaving of affected hair
• Exophiala jeanselmei
• Topical salicylic acid
• Madurella mycetomatis
• Madurella gresia
Trichosporon beigelii
• Acromnium falciforme
• Presentation: soft, grayish white/ beige nodules on hair shaft
• Presentation: causes blockade of lymphatic vessels →
(scalp or axilla)
subcutaneous swelling → Madura foot
• Treatment:
• Treatment:
• Shaving of affected hair
• Ketoconazole (bacteria)
• Topical Imidazole: prevents infection
• Amputation (fungi)
Module 6 – Microbiology Page 15 of 32 RJAV 2022
Systemic mycoses Mucormycosis/ Zygomycosis
• Causative agent: bread molds (Glomerulomycta/
• Members are thermal dimorphic fungi Zygomycota)
• MOT: inhalational spores • Rhizopus spp.
• Presentation: asymptomatic to flu-like illness • Rhizomucor spp.
• Mainly differentiated by geographical location and risk factors • Cunninghamella spp.
Blastomycosis • Mucor spp.
North American Blastomycosis South American Blastomycosis / • Absidia spp.
Paracoccidioidomycosis • Presentation:
Blastomyces dermatitidis Paracoccidioides brasiliensis • Rhinocerebral mucormycosis: sinusitis
Presentation: Presentation: • Thoracic mucormycosis: pulmonary symptoms (cough),
• Pulmonary infiltrate: • Respiratory granuloma chest pain, SOB)
most common • Painful sores • Cutaneous mucormycosis: black eschar (invasive)
• Lesions of the bones, • Ulcers in the
• Treatment:
genitalia, CNS pharyngeal mucosa
Treatment: Itraconazole, Treatment: Itraconazole • Amphotericin B
Amphotericin B (severe) • Surgical debridement

Opportunistic mycoses Penicilliosis

Penicillium marneffei
• Thermal dimorphic fungi
Seen in patients with:
• Reservoir: bamboo rats
• Alteration in normal flora
• Presentation: Penicilliosis
• Immunocompromised state: DM, AIDS, immunosuppressive
• High mortality rate if untreated
therapy, etc.
• Treatment: amphotericin B, Itraconazole
• Candidiasis
• Cryptococcosis
VIROLOGY
• Aspergillosis
• PCP
DNA VIRUSES
• Mucormycosis
• Penicilliosis Adenovirus
Parvovirus
Candidiasis: Poxvirus
Candida albicans Herpesviruses
• Normal flora of oral cavity and vagina Papillomaviruses
• Most common opportunistic mycosis
Polyomaviruses
Presentation: Superficial Candidiasis
Intertriginous infections: occurs in moist, warm parts of the body Hepatitis viruses
Thrush – whitish pseudomembrane with curd-like appearance ADENOVIRUS
• Vaginal: alteration of normal flora
• Oral: inhaled corticosteroid use, AIDS
• Treatment: Nystatin
• MOT: aerosols, direct conact, fecal-oral contaminated
Onychomycosis: nail infection swimming pools
• Treatment: Allylamines • Morphology: nonenveloped (naked) icosadeltahedral capsid
• Patho:
Presentation • Infects mucoepithelial cells in the repiratory tract,
Systemic candidiasis gastrointestinal tract, and conjunctiva or cornea
• Candidemia, Endocarditis:Due to intravenous drug abuse, • Persists in lymphoid tissue
damage to skin of GI tract • Presentation
• Esophagitis: AIDS-defining illness • Pharyngitis/ pharyngoconjunctival fever
• UTI: due to indwelling catheters • Gastroenteritis
Treatment: amphotericin B + flucytosine/ fluconazole/caspofungin
• ARI
Chronic Mucutaneous Candidiasis
• Rare disease of childhood
• Conjunctivitis/ Keratoconjunctivitis (pink eye)
• Associated with immunodeficiencies • Diagnosis: virus isolation from the site or secretion →
relevant to the disease → immunoassays/ genome assays
• Prevention: handwashing and chlorination of swimming
Cryptococcosis pools
Cryptococcus neoformans
• VF: capsule PARVOVIRUS
• MOT: inhalation of dried pigeon excrement with dry,
minimally encapsulated yeast cells • Smallest DNA virus
• Presentation: cryptococcosis → meningitis • Members: B19 and bocavirus (only infectious to humans)
• Treatment: Amphotericin B + Flucytosine • MOT: spreads by respiratory and oral secretions (droplet
transmission)
Aspergillosis • Morphology:
Aspergillus fumigatus • Naked icosahedral capsid
• Presentation: • Single-stranded (+ or – sense) DNA genome
• Allergic bronchopulmonary aspergillosis • Patho:
• Fungal ball/ Aspergilloma: asymptomatic • B19 targets and is cytolytic for erythroid precursor cells;
• Invasive aspergillosis can cross the placenta
• Treatment: • Bocavirus also initiates infection in the human
• Amphotericin B respiratory tract, replicates in the respiratory epithelium
• Voriconazole: DOC for invasive aspergillosis B19 Bocavirus
• Erythema infectiosum • mild or severe acute
(5th disease) respiratory disease
PCP
- Children: slapped-cheek - 2 years old: bronchiolitis
Pneumocystis jiroveci appearance
• Formerly classified as a protozoan • Polyarthritis (adults)
• Formerly known as Pneumocystis carinii • Aplastic crisis (in
• Presentation: pneumonia in immunocompromised host/ PCP persons with chronic
(Pneumocystis carinii pneumonia) anemia)
• Treatment: TMP-smz • Hydrops fetalis
• Diagnosis: clinical presentation; immunoassays, genomic
assays
Module 6 – Microbiology Page 16 of 32 RJAV 2022
 • Treatment/ Prevention: no specific antiviral treatment or HERPESVIRUSES
means of control is available
• MOT: contact, bodily fluids, aerosols (VZV)
POXVIRUSES • Considered as ubiquitous viruses
• Can cause lytic, persistent, latent and (for EBV)
• Largest, most complex virus immortalizing infections
• DNA virus that replicates in the cytoplasm • Morphology: large, enveloped, icosadeltahedral capsids
• Morphology: complex, oval to brick-shaped containing double-stranded DNA genomes
• MOT:
• Aerosols and contact: smallpox Classification of Human Herpesviruses
• Direct contact: the rest of poxviruses
Biologic Properties Examples
Sub- Growth cycle & Latent Genus Official Common
Poxviruses Causing Disease in Humans family Cytopathology infections Name Name
Genes Virus Primary Host Disease α Shirt, cytolytic Neurons Simplex 1 Herpes
Small pox (now simplex
Variola Humans virus type 1
eliminated)
Localized lesion; 2 Herpes
simplex
used for virus type 1
Vaccinia Humans
smallpox Varicella 3 Varicella-
vaccination zoster virus
Human β Long, cytomegalic Glands, Cytomegalo 5 Cytomegalo-
Buffalopox Waterbuffalo infections rare; Kidneys virus
Orthopoxvirus localized lesions Long, Lymphoid Roseola 6 Human
lymphoproliferative tissue herpesvirus
Human
6
Rodents, infections rare; 7 Human
Monkeypox
Monkeys generalized herpesvirus
disease 7
Human γ Variable, Lymphoid Lympho- 4 Epstein-Barr
infections rare; lymphoproliferative tissue crypto virus
Cowpox Cows Rhadino 8 Kaposi
localized
sarcoma-
ulcerating lesion
associated
Orf Sheep herpesvirus
Pseudo
Cows Human
cowpox Herpesvirus Properties/ Diseases
Parapoxvirus infections rare;
Bovine
localized lesion Herpes simplex virus (HSV)-1 - Involves skin above the waist
popular Cows
(direct contact) - Presentation: gingivostomatis;
stomatitis
pharyngotonsillitis;
Molluscum Many benign
Molluscipoxvirus Humans keratoconjunctivitis; cold sores;
contagiosum skin nodules
keratitis; herpetic encephalitis;
Human eczema herpeticum; herpetic
Tanapox Monkeys infections rare; whitlow
localized lesion
Herpes simplex virus (HSV)-2 - Involves skin above waist
Human (sexual transmission) - Presentation: neonatal infection;
Yatapoxvirus infections very herpetic whitlow; genital herpes;
rare and herpetic meningitis
Yabapox Monkeys
accidental;
Varicella-Zoster virus (VZV) Varicella
localized skin
- CM: chickenpox
lesions
- Maculopapular lesion forms a thin-
walled vesicle on an erythematous
Disease Associated with Poxvirus base (“dewdrop on a rose petal”
Virus Disease Source Location - More prevalent on the trunk and
Variola Small pox (now Humans Extinct head
extinct)
Vaccinia Used for smallpox Laboratory product ---- Zoster
vaccination - Recurrence of a latent varicella
Orf Localized lesion Zoonosis: sheep, Worldwide infection
goat - Presentation: herpes zoster
Cowpox Localized lesion Zoonosis: rodents, Europe - Severe pain in the area innervated
cats, cows by the nerve (dermatomes)
Pseodocowpox Milker’s nodule Zoonosis: dairy Worldwide Cytomegalovirus (CMV) - Most common viral cause of
cows congenital defects
Monkeypox Generalized Zoonosis: Africa - MOT: acquired from blood, tissue
disease monkeys, squirrels and most body secretions
- Presentation: congenital infection;
Bovine popular Localized lesion Zoonosis: calves, Worldwide
perinatal infection
stomatitis virus beef cattle
Human herpes virus (HHV) 6 - Presentation: Roseola (infantem
Tanapox Localized lesion Rare zoonosis: Africa
monkeys &7 subitem, 6th disease)
- Rapid onset of high fever of a few
Yabapox Localized lesion Rare zoonosis: Africa
days’ duration, which is followed by
monkeys, baboons
a rash
Molluscum Many skin lesions Humans Worldwide
Epstein-Barr virus (EBV) - Saliva initiates infection of oral
contagiosum
epithelia and tonsillar B cells
- Presentation: Infectious
Clinically Important Poxviruses mononucleosis (kissing disease);
Poxvirus Disease/ Properties Nasopharyngeal carcinoma; Burkitt
Orf virus - Poxvirus of sheep and goat lymphoma; Hodgkin’s disease
- Presentation: contagious pustular Human Herpes virus (HHV) 8 - Associated with HIV/AIDS
dermatitis or sore mouth infection infections
Cowpox - Similar to vaccine/ variola - Presentation: Kaposi sarcoma
immunologically and in host range
- Presentation: deep red hemorrhagic • Diagnosis: tzanck smear (HSV); culture, immunologic tests
lesions
(EBV serology), PCR genome analysis
Molluscum contagiosum - Small, pink, wart-like tumors on the
face, arms, back, and buttocks • Treatment:
- Pearl-like umbilicate nodules • Acyclovir: most common herpesviruses
Variola - Eradicated, 1980 • Ganciclovir: CMV
- Presentation: smallpox • None: EBV
• Prevention: vaccine (VZV)

Module 6 – Microbiology Page 17 of 32 RJAV 2022

 PAPILLOMAVIRUSES POLYOMAVIRUSES

• MOT: direct contact, sexual contact (sexually transmitted • MOT: inhalation or contact with contaminated water or saliva
disease), fomites, passage through infected birth canal • Formerly part of the Papovaviridae family (which no longer
• Formerly part of Papovaviridae family (which no longer exists)
exists) • Commonly associated with IC state (HIV/ AIDS)
• Morphology: small, naked capsid, DNA genome • Infections are ubiquitous
• Patho: infects the epithelial cells of the skin or mucous • Morphology: small naked capsid, DNA genome
membranes
• Presentation: different type of warts and cancer Polyomaviruses Diseases
JC Virus Progressive multifocal leukoencephalopathy
Skin Warts Common Less Common BK Virus Hemorrhagic cystitis in bone marrow
Cutaneous Syndromes transplant recipients
Skin Warts Ki and Wu virus Found in nasopharyngeal aspirates from
Plantar wart 1 2, 4 children with respiratory infections
Common wart 2, 4 1, 7, 26, 29 Merkel cell polyomavirus Merkel cell carcinomas
Flat wart 3, 10 27, 28, 41 SV40 Virus Progressive multifocal leukoencephalopathy
Epidermodysplasia 5, 8, 17, 20, 36 9, 12, 14, 15, 19, 21-25, 38,
verruciforms 46 • Diagnosis: confirmed by the presence of PCR amplified viral
Mucosal Syndromes DNA in cerebrospinal fluid and MRI or CT evidence of
Benign Head and Neck Tumors lesions
Laryngeal papilloma 6, 11 --- • Treatment: Cidofovir
Oral papilloma 6, 11 2, 16
Conjunctival 11 --- HEPATITIS VIRUSES
papilloma
Anogenital Warts
Condyloma 6, 11 1,2, 10, 16, 30, 44, 45
• MOT:
acuminatum • HAV, HEV: fecal-oral transmission
Cervical intraepithelial 16, 18 31, 33, 35, 39, 45, 51, 52, 56, • HBV, HCV, HDV: spread in blood, tissue and semen;
neoplasia, cancer 58, 59, 66, 68, 69, 73, 82 STDs (blood borne hepatitis)
(high-risk types) • Patho: liver disease defines symptoms
• Diagnosis: RT-PCR, ELISA
Association of Viruses with Human Cancers’ • Treatment: Antiviral drugs (refer to antiviral agents)
• Prevention: Vaccination, Hygiene
Virus Family Virus Human Cancer
Papillomaviridae Human Genital tumors Comparative Features of Hepatitis Viruses
papillomavirus Squamous cell carcinoma
Oropharyngeal carcinoma Feature Hepatitis A Hepatitis B Hepatitis Hepatitis D Hepatitis
Herpesviridae Epstein-Barr virus Nasopharyngeal carcinoma C E
Burkitt lymphoma Common “infectious” “serum” “Non-A, “Delta “Enteric
name Non-B agent” Non-A,
Hodgkin’s disease post- Non-B”
B-cell lymphoma transfusion
”
Human Kaposi sarcoma Virus Picornavirus Hepadnavirus Flavivirus; Viroid-like; Calicivirus
structure ; capsid, (+) ; envelope, envelope, envelope, -like;
Herpesvirus B Primary effusion lymphoma RNA DNA (+) RNA circular capsid, (+)
Hepadnaviridae Hepatitis B virus Hepatocellular carcinoma RNA RNA
Polyomaviridae Merkel cell virus Merkel cell carcinoma Trans- Fecal-oral Parenteral, Parenteral, Parenteral, Fecal-oral
mission sexual sexual sexual
Retroviridae Human T- Adult T-cell leukemia Onset Abrupt Insidious Insidious Abrupt Abrupt
lymphotropic virus Incubation 15-50 45-160 14-180+ 15-64 15-50
period
Human AIDS related malignancies (days)
immunodeficiency Severity Mild Occasionally Usually Co-infection Normal
severe subclinical; with HBV patients,
virus 70% occasionall mild;
Flaviridae Hepatitis C virus Hepatocellular carcinoma chronicity y severe; pregnant
super- women,
infection severe
• Diagnosis: PCR genome analysis of cervical swabs and with HBV
tissue specimens often
severe
• Treatment: Vaccines for HPV types Mortality <0.5% 1%-2% =4% High to very Normal
high patients,
1-2%;
Bivalent (Cervarix) Quadrivalent (Gardasil) Nine-Valent Vaccine
pregnant
(Gardasil-9) women,
• HPV types 16 and • HPV types 6, 11, • In 2014, the FDA 20%
18 16 and 18 approved a new Chronicity No Yes Yes Yes No
• Administered by • Administered nine-valent L1 VLP / carrier
intramuscular intramuscularly at vaccine that targets state
injection at months months 0, 2 and 6 HPV types 6, 11, Other None Primary Primary Cirrhosis, None
0, 1 and 6 • Approved for the ff: 16 and 18 (the disease hepatocellular hepato- fulminant
• The vaccine is - Vaccination of girls and types also targeted associa- carcinoma, cellular hepatitis
approved for women ages 9-26 years by the quadrivalent tion cirrhosis carcinoma,
cirrhosis
females 9-25 years of age to prevent genital HPV vaccine) as
Lab Symptoms Symptoms Symptoms Anti-HDV ---
of age warts and cervical cancer well as five
diagnosis and anti- and serum and anti- ELISA
caused by HPV types 6, additional HAV IgM levels of HCV
11, 16 and 18 oncogenic HPV HBsAg, ELISA,
- Vaccination of the same types (31, 33, 45, HBeAg, and genome
population to prevent 53 and 58) anti-HBc IgM testing
precancerous or • Administered
dysplastic lesions, intramuscularly at
including cervical AIS, months 0,2 and 6
CIN 2/3, VIN 2/3, VaIN • Approved for the
2/3 and CIN 1 same indications
- Vaccination of boys and as with the
men 9-26 years of age to quadrivalent
prevent genital warts (Gardasil) vaccine
caused by HPV types 6
and 11
- Vaccination of people 9-
26 years of age to prevent
anal cancer and
associated precancerous
Interpretation of Serologic Markers of Hepatitis B Virus
lesions due to HPV types Infection
6, 11, 16 and 18

Module 6 – Microbiology Page 18 of 32 RJAV 2022

 Serologic Disease State Healthy State TOGAVIRUSES
Reactivity
Early (Pre Early Acute Chronic Late Reso - Vaccin -
• Arboviruses (arthropod-borne viruses, except rubella)
-symptomatic) acute acute lved ated • Humans are usually “dead-end” hosts
Anti-HBc - - + + +/- + - • Broad host range (vertebrate, invertebrates)
Anti-HBe - - - - +/- +/- - • Major genera: Alphavirus, Rubivirus (rubella), and Arterivirus
Anti-HBs - - - - - + + (non-pathogenic)
HBeAg - + + + - - - • Diagnosis: RT-PCR
HBsAG + + + + + - -
• Treatment: No treatment exists for arbovirus disease and
Infectious virus + + + + + - -
rubella, other than supportive
• Prevention:
RNA VIRUSES: POSITIVE SENSE • Elimination of its vector and breeding grounds
(arboviruses)
Picornaviruses • Vaccination (MMR vaccine)
Coronaviruses Virus Vector Host Distribution Disease
Alphaviruses
Togaviruses
Sindbis Aedes & Birds Africa, Subclinical
Calciviruses (Noroviruses) other Australia,
mosquitos India
Flaviviruses Semliki Aedes & Birds East & West Subclinical
Retroviruses forest other Africa
mosquitos
Reoviruses Venezuelan Aedes, Rodents, North, South Mild
Equine Culex horses & Central systemic;
encephalitis America severe
PICORNAVIRUSES
encephalitis
Easter Aedes, Birds North & Mild
• Small (pico) RNA viruses, naked capsid structure equine Culiseta South systemic,
• Members: encephalitis America, encephalitis
• Enteroviruses (major group, fecal-oral route) Caribbean
• Rhinovirus (major group, aerosol/ direct contact) Western Culex, Birds North & Mild
• Cardioviruses equine Culiseta South systemic,
• Aphthoviruses encephalitis America encephalitis
Chikungunya Aedes Human, Africa, Asia Fever,
• Hepatoviruses (Hepatitis A)
monkeys Arthralgia,
• Treatment: no antiviral drugs are effective arthritis
• Prevention: handwashing and disinfection
Prominent Clinical Findings in Congenital Rubella Syndrome
Picornaviruses Group Diseases/ Properties
Polioviruses Enterovirus - Presentation: Paralytic polio
- Asymmetric flaccid paralysis with • Cataracts and other ocular defects
no sensory loss • Heart defects
- Prevention: vaccine (2) • Intrauterine growth retardation
1. Inactivated polio vaccine • Failure to thrive
(IPV)/ Salk vaccine • Mortality w/in the 1st year
2. Live attenuated oral polio • Microcephaly
vaccine (OPV)/ Sabin
vaccine
• Mental retardation
Coxsackie A Enterovirus Vesicular lesions NOROVIRUSES
- Herpangina
- HFMD (a16) • Norwalk virus
- Hemorrhagic conjunctivitis (A24) • MOT: fecal-oral route (contaminated food and water)
Coxsackie Enterovirus - Myocarditis • Resistant to environmental pressure: detergents, drying and
- Pleurodynia (Bornholm disease) acid
Rhinovirus Rhinovirus Most important cause of the common • Presentation: outbreaks of gastroenteritis (resolves after 48
cold and upper respiratory tract
infections
hours, without serious consequences)
• Diagnosis: RT-PCR
• Treatment: No specific treatment
CORONAVIRUSES
FLAVIVIRUSES
• MOT: droplet transmission, aerosols, direct contact
• Solar/ club/ petal shaped/ corona-like appearance
• Arboviruses (arthropod-borne viruses, except Hepa C)
• Patho:
• Humans are usually “dead-end” hosts
• Infects epithelial cells of upper respiratory tract
• Broad host range (vertebrate, invertebrates)
• Reinfection occurs in the presence of serum antibodies
• Diagnosis: RT-PCR
• Glycoprotein “corona” helps this enveloped virus
• Treatment: No treatments exist for arbovirus diseases and
survive the GIT
rubella, other than supportive
• Severe ARI is exacerbated by inflammatory responses
• Prevention:
• Human coronaviruses:
• Elimination of its vector and breeding grounds
1. 229E (alpha coronavirus)
(arboviruses)
2. NL63 (alpha coronavirus)
• Vaccines (Japanese encephalitis virus, yellow fever
3. OC43 (beta coronavirus)
virus, dengue virus)
4. MERS-CoV (beta coronavirus, causing MERS)
5. SARS-CoV (beta coronavirus, causing SARS)
Virus Vector Host Distribution Disease
6. SARS-CoV-2 (beta coronavirus, causing COVID-19)
Flaviviruses
• Presentation:
Dengue Aedes Human, Worldwide, Mild
• Common colds monkeys esp. tropics systemic;
• Gastroenteritis breakbone
• Respiratory infections: SARS, MERS, COVID-19 fever,
• Diagnosis: RT-PCR (respiratory and stool samples) dengue
• Treatment: No vaccine or specific antiviral therapy is hemorrhagic
available fever, &
dengue
shock
syndrome

Module 6 – Microbiology Page 19 of 32 RJAV 2022

 Yellow Aedes Human, Africa, Hepatitis, HTLV-5), Rous
fever monkeys South hemorrhagic Sarcoma Virus
America fever (chickens)
Japanese Culex Pigs, Asia Encephalitis D Have nucleocapsid core w/ Mason-Pfizer
encephalitis birds cylindrical form monkey virus
West Nile Culex Birds Africa, Fever, Lentivirinae Have onset of disease, cause Human immune
encephalitis Europe, encephalitis, neurologic disorders & deficiency virus* (HIV-
Central hepatitis immunosuppression, are 1, HIV-2), visna virus
Asia, North viruses w/ D-type cylindrical (sheep), caprine
America nucleocapsid core arthritis/ encephalitis
St. Louis Culex Birds North America Encephalitis virus (goats)
encephalitis Spumavirinae Cause no known clinical Human foamy virus
Russian Ixodes & Birds Russia Encephalitis disease but cause
Spring- Derma characteristic vacuolated
summer centor *foamy* cytopathology
encephalitis ticks Human Retrovirus sequences that are Human placental virus
Endogenous integrated into human genome
Powassan xodes Small North Encephalitis Retroviruses
encephalitis ticks mammals America (HERVs)
Dengue warning signs
REOVIRUSES
• Abdominal pain or tenderness
• Persistent vomiting • Double: double virus
• Clinical fluid accumulation • MOT:
• Mucosal bleed • Fecal-oral (rotavirus, orthoreovirus)
• Lethargy, restlessness • Vector borne (coltivirus, orbivirus)
• Liver enlargement > 2cm • Morphology:
• Laboratory: increase in HCT concurrent w/ rapid decrease in • Double-layered capsid virion
platelet count • Icosahedral symmetry
• Double-stranded genomic segments
Clinical Stages of Dengue • Resistant to environmental and GI conditions
• Diagnosis: ELISA (stool); RT-PCR
• Treatment: No approved antiviral agent
• Prevention: Vaccine (rotavirus)

Virus Disease
Orthreovirus Mild upper respiratory tract illness, GIT illness,
biliary atresia
Orbivirus/ Coltivirus Febrile illness with headache & myalgia
(zoonosis)
Rotavirus Gastrointestinal tract illness, respiratory tract
illness (?)
*Reovirus is the most common name of the family Reoviridae & for the
specific genus Orthoreovirus

RNA VIRUSES: NEGATIVE SENSE

Paramyxoviruses
Filoviruses
Zika Virus
• Cause microcephaly Arenaviruses
Bunyaviruses
Types of mosquitos:
• Culex mosquito Orthomyxoviruses
• A. aegypti Rhabdoviruses
• A. albopictus (Asian Tiger mosquito)

RETROVIRUSES PARAMYXOVIRUSES

• Subfamilies: • MOT: droplet transmission

• Oncovirinae (HTLV-1, HTLV-2, HTVL-5) • Genera: Morbillivirus, Paramyxovirus, and Pneumovirus
• Lentivirinae (HIV-1, HIV-2) • Patho: induce cell-to-cell fusion, causing multinucleated
• Spumavirinae (nonpathogenic) giant cells (syncytia)
• MOT: blood and semen (sexual contact) • Diagnosis: symptomatology, RT-PCR genome analysis of
• Morphology: respiratory secretions
• RNA-dependent DNA polymerase (reverse • Treatment: symptomatic treatment (majority of
transcriptase), 2 copies of tRNA, protease, and paramyxovirus); aerosolized ribavirin (RSV)
integrase enzymes • Prevention: vaccines (MMR)
• Replicates in nucleus
• Patho: AIDS; leukemia Paramyxoviridae
• Diagnosis: RT-PCR, ELISA (screening), western blot
(confirmatory) Genus Human Pathogen
• Treatment: ARV agents Morbillivirus Measles virus
Paramyxovirus Parainfluenza viruses 1 to 4
Subfamily Characteristics Examples: Mumps virus
Oncovirinae Are associated w/ ---- Pneumovirus Respiratory syncytial virus
cancer and neurologic Metapneumovirus
disorders
B Have eccentric Mouse mammary Paramyxoviruses: Measles Virus
nucleocapsids core in mature tumor virus
virion
C Have centrally located Human T-cell • A.k.a. Rubeola
nucleocapsid core in mature lymphotropic virus • One of the 5 classic childhood exanthems, along w/ rubella,
virion (HTLV-1, HTLV-2, roseola, 5th disease and chicken pox

Module 6 – Microbiology Page 20 of 32 RJAV 2022

 • MOT: droplet transmission (highly contagious) ARENAVIRUSES
• Prodrome: high fever and CCC and P – cough, coryza,
conjunctivitis, and photophobia • Sandy appearance (arenosa, meaning “sandy”) because of
• Presentation: the ribosomes in the virion
• Maculopapular rashes (starts below the ears and • Infect specific rodents and are endemic to the rodents’
spreads over the body) habitat
• Kolpik spots (grains of salt surrounded by a red halo; • MOT: inhalation of aerosols, consumption of contaminated
establish the certainty of measles) food, or contact with fomites
• Diagnosis: symptomatology • Diagnosis: RT-PCR
• Treatment: symptomatic management • Treatment: Ribavirin (Lassa fever); supportive therapy (other
• Prevention: arenaviruses)
• MMR vaccine
• Measles vaccine can be given as early as 6 months of Arenaviruses
age (especially if there is an outbreak) Lassa virus
• Complications: South American Hemorrhagic Fever viruses
• Viral pneumonia – accounts for 60% of the death • Junin Virus (Argentina HF)
caused by measles • Machupo virus (Bolivian HF)
• Guanarito virus (Venezuelan HF)
• Otitis media • Sabia virus (Brazilian HF)
• Subacute sclerosing panencephalitis (SSPE) – • Chapare virus (Chapare HF)
extremely serious, very late neurologic squeal of • Lujo virus (Lujo HF)
measles LCM virus (lymphocutic choriomeningitis)

Paramyxoviruses: Mumps BUNYAVIRUSES

• MOT: direct person – to – person contact and respiratory • “supergroup” of at least 200 enveloped, segmented,
droplets negative-strand RNA viruses
• Only one serotype is known • Genus: Bunyavirus, Phlebovirus, Nairovirus, and Hantavirus
• Patho: infection of parotid gland, testes and CNS • Most are arboviruses (mosquito, ticks, or flies), except
• Presentation: Hantaviruses (rodents)
• Swelling of parotid gland (infectious parotitis) • Most are arboviruses except hantavirus (rodents)
• Swelling of other glands (epididymoorchitis, oophoritis, • Presentation: encephalitis; others cause hepatic necrosis or
mastitis, pancreatitis, and thyroiditis) hemorrhagic disease
• Meningoencephalitis • Diagnosis: RT-PCR
• Orchitis (testes) may result to sterility, but rare • Treatment: No specific therapy for infections
• Diagnosis: RT-PCR, immunoassays
• Treatment: symptomatic management Notable Bunyaviridae Genera
• Prevention: vaccine (MMR)

Paramyxoviruses: Parainfluenza Virus Bunyavirus Bunyamwera virus, Mosquito Febrile illness, Rodents,
California encephalitis, small
encephalitis rash mammals,
• MOT: person to person contact and respiratory droplets virus, La Crosse primates,
• Examples: Parainfluenza 1, 2, 3 and 4 virus, Oropouche marsupials,
virus; 150 birds
• Presentation: members
• Parainfluenza 1, 2, 3: laryngotracheobronchitis (croup) Phlebovirus Rift Valley fever Fly, Tick Sandfly fever, Sheep,
• Subglottal swelling virus, sandfly fever hemorrhagic cattle,
• “Seal bark” cough virus, Heartland fever, domestic
virus; 38 members encephalitis, animals
• Parainfluenza 4: mild URTI conjunctivitis,
• Diagnosis: RT-PCR myositis
• Treatment: Nairovirus Crimean –Congo Tick Hemorrhagic Hares,
hemorrhagic fever fever cattle, goats,
• Nebulized cold virus; 6 members seabirds
• Hot steam Uukuvirus Uukuniemi virus; 7 Tick --- Birds
members
Hantavirus Hantaan virus None Hemorrhagic Rodents
Paramyxoviruses: Respiratory Syncytial Virus (RSV) fever with renal
syndrome,
• Prevalent in young children/infants (≤2 years of age) adult
respiratory
• MOT: aerosols; direct contact distress
• Presentation: syndrome
• Bronchiolitis – infants Sin nombre None Hantavirus Deer mouse
pulmonary
• URTI with rhinorrhea – older children and adults syndrome,
• Diagnosis: RT-PCR shock,
• Treatment: pulmonary
edema
• Ribavirin – approved for treatment of infants
• Supportive (administered of O2, IV fluids, and nebulized
cold steam) ORTHOMYXOVIRUSES

FILOVIRUSES • MOT: inhalation of small aerosol droplets

• Members
• Members: Marburg and Ebola viruses • Influenza A (pathogenic zoonotic)
• Endemic in bats or wild monkeys • Influenza B (pathogenic)
• MOT: contact with the animal reservoir or direct contact with • Influenza C (mild disease)
infected blood or secretions • Morphology:
• Morphology: filamentous, enveloped, negative-strand RNA • Enveloped, segmented negative – sense RNA genome
viruses • 2 glycoproteins, hemagglutinin (HA) and neuraminidase
• Presentation: severe or fatal hemorrhagic fevers (endemic (NA)
in Africa) • Membranes (M2) protein and is internally lined by the
• Diagnosis: RT-PCR matrix (M1) protein
• Treatment: No antiviral meds have proved effective • Segmented genome promotes genetic diversity caused by
• Prevention: rVSV – ZEBOV vaccine (vaccine for Ebola mutation and reassortment
virus) • Antigenic drift
• Minor antigenic changes
• Accumulation of point mutations in the gene
Module 6 – Microbiology Page 21 of 32 RJAV 2022
 • Antigenic shift • Symptoms: nervousness, apprehension,
• Major antigenic changes hallucinations, and bizarre behavior
• Result in the appearance of a new subtype • Increase SNS activity: lacrimation, pupillary
• Most likely to result in an epidemic dilatation, and increase salivation and perspiration
• Genetic reassortment between human, swine, and • Other neuro symptoms: Hydrophobia (fear of
avian influenza viruses water), Aerophobia (fear when feeling a breeze),
• Influenzas B and C viruses do not exhibit antigenic Painful spasm of the throat muscle
shift • Coma
• Seizures/ convulsions
Diseases Associated with Influenza Virus infection • Major cause of death: cardiorespiratory arrest
• Diagnosis:
Disorder Symptoms • RT-PCR (preferred method)
Acute influenza infection Rapid onset of fever, malaise, myalgia, sore • Intracytoplasmic inclusions consisting of aggregates of
in adults throat, and nonproductive cough viral nucleocapsids (Negri bodies)
Acute influenza infection Acute disease similar to that in adults but with • Animal observation: changes in behavior for 10 days
in children higher fever, GI tract symptoms (abdominal • Treatment:
pain, vomiting), otitis media, myositis, & more
frequent croup
• No proven antiviral agent
Complications of Primary viral pneumonia • Postexposure prophylaxis is the only hope for
influenza virus infection Secondary bacterial pneumonia preventing overt clinical illness in the affected person
Myositis and cardiac involvement 1. Local treatment of the wound-washed immediately with
Neurologic syndromes: soap and water
• Guillain – Barre syndrome 2. Immunization/ vaccination
• Encephalopathy a. Rabies vaccine (within 2 weeks)
• Encephalitis
b. Passive immunization (HRIG)
• Reye syndrome
• Prevention: effective control of rabies in domestic and wild
animals through vaccination
Laboratory Diagnosis of Influenza Virus Infection

Test
Cell culture in 1° monkey kidney or
Madin – Darby canine kidney cells
Hemadsorption to infected cells
Hemagglutination
Hemagglutination inhibition
Antibody inhibition of
Hemadsorption
Immunofluorescence, ELISA
Serology:
Hemagglutination inhibition,
hemadsorption inhibition, ELISA,
immunofluorescence, complement
fixation
Genomics: RT-PCR
Detects
Presence of virus; limited
cytopathologic effects
Presence of hemagglutinin protein
on cell surface
Presence of virus in secretions
Type and strain of influenza virus
or specificity of antibody
Identification of influenza type and
strain
Influenza virus & antigens in
respiratory secretion or tissue
culture
Seroepidemiology
Identification of influenza type and
strain

• Treatment:
• Neuraminidase inhibitors (influenza A and B):
• Oseltamivir,
• Zanamivir
• Viral uncoating inhibitors (influenza A):
• Amantadine,
• Rimantadine

RHABDOVIRUSES

• Genus
• Vesiculovirus
• Lyssavirus (rabies and rabies–like viruses)
• Plant rhabdovirus group (unnamed)
• Other ungrouped rhabdoviruses of mammals, birds, IMMUNOLOGY
fish, and arthropods
• Most important pathogen: rabies virus IMMUNE RESPONSE
• MOT: transmitted in saliva and acquired from the bite of a
rabid animal • Response generated against a potential pathogen is called
• Morphology: Bullet-shaped, enveloped, negative-sense, an immune response
single-stranded RNA
• Patho: 1. Innate immunity
• Replicates in the muscle at the site of the bite • 1st line of defense
• Length of the Incubation Period is determined by the • Nonspecific to the invading pathogen
infection site to the CNS • Rapidly mobilized at the initial site of injection
• Incubation Period: 1-3 months (may be as short as 1 (immediate response)
week or more than a year) • Lacks immunologic memory (does not confer long
• Presentation: lasting protective immunity)
• Short prodromal phase
• 2-10 days 2. Adaptive immunity
• Symptoms: malaise, anorexia, headache, • 2nd defense system
photophobia, N&V, sore throat and fever • Specific for the pathogen
• Acute neurologic phase • Confers protective immunity to reinfection
• 2-7 days • Produces specific antibodies
Module 6 – Microbiology Page 22 of 32 RJAV 2022
 • Branches: - Memory cells –
a. Humoral Immunity – mediated by B cells immunologic memory
(matures to become memory cells and plasma T lymphocytes (T cells):
cells) • CD4 + T cells (Helper T cells) Stimulation if the differentiation
and proliferation of B cells and
Function:
cytotoxic T cells
• Memory cells – immunologic memory • CD8 + T cells (Cytotoxic T Direct-attack cells that is
• Plasma cells – antibody production cells) capable of killing
b. Cellular-mediated immunity – mediated by T microorganisms and at times,
cells (helper T cells [CD4 + cells]; cytotoxic T cells even some of the body’s own
[CD8 + cells]) cells
• Suppressor T cells Capable of suppressing the
Innate Immunity Adaptive Immunity functions of both cytotoxic & T-
helper cells
- skin (epithelium) & mucous - Lymphoid cells (T cells & B
• Natural Killer cells Contribute to innate immunity by
membranes cells)
providing protection against
- phagocytic cells
viruses and Other intracellular
- NK cells
pathogens; play a critical role in
- Toll-like receptors
antibody-dependent cellular
- Cytokines
cytotoxic (ADCC)
- Complement system

Major Features: Innate Vs Adaptive Immune Response IMMUNOGLOBULINS: Antibodies

Innate Adaptive •A protein that is produced in response to a particular

Characteristics
Rapid, immediate response
Antigen nonspecific
No memory, not long-lasting
protection
Immunologic components
Natural barriers to infection: skin,
mucous membranes
Cells: phagocytes, NK cells, innate
lymphoid cells
Mediators: complement defensins,
cytokines sensors (TLR, NOD-like
receptors, RAG-1)
FORMS OF IMMUNITY
Slow response
Highly antigen specific
Induces memory, responds rapidly
& vigorously to second antigen
exposure
T lymphocytes-cell mediated,
B lymphocytes-antibody mediated,
APCs
Secreted molecules (cytokines,
chemokines, complement)
pathogen is called the antibody
• Make up about 20% of the plasma proteins
• Substance that induces the production of antibodies is called
the antigen
Factors that determined immunogenicity:
• Recognition of foreignness
• Size (large, complex proteins)
• <10, 000 MW are weak immunogens
• Very small molecules are nonimmunogenic
• Haptens: small molecules when combined with a carrier
protein/polysaccharide becomes immunogenic (e.g.,
lipids and amino acids)
• Chemical and Structural complexity
• Genetic constitution of the host
• Dosage, route and timing of antigen administration

1. Active immunity
• Contact with a foreign antigen (infectious agent)
• Individual actively produces antibodies (long lasting)
• Examples:
• Clinical or subclinical infection
• Immunization with live or killed organism
• Exposure to microbial products (toxins and
toxoids)
• Transplantation of foreign tissue

2. Passive immunity
• Administration of preformed antibodies
• Receives a large concentration of antibody immediately
(not long lasting)
• Useful when the px has no time to
• produce an antibody response
• Needle-prick injuries (without prior vaccination)
• Immunodeficiencies
• Post-exposure prophylaxis (e.g., Rabies)

CELLULAR RESPONSE AGAINST INFECTION

Concentration of the different White Blood Cells in the blood IgG IgA IgM IgD IgE
Polymorphonuclear neutrophils 62.0% Heavy chain γ α µ δ ε
Polymorphonuclear eosinophils 2.3% symbol
Monocytes 0.4% Valence 2 4 5 2 2
Lymphocytes 30.0% MW 143,000 159,000 900,000 177,000 188,000
(Daltons) – – – –
Cells Functions 160,000 447,000 185,000 200,000
Serum conc 8-16 1.4 – 4.0 0.4 – 2.0 0.03 Trace
Neutrophils Phagocytosis; elevated during
(mg/mL) amounts
bacterial infection & acute
(adult)
inflammatory reactions
Serum t½ 21 7 7 2 2
Basophils Release of histamine
Percentage 80 15 5 0.2 0.002
Eosinophils Release of histamine; elevated
of total IG in
during parasitic infestation
serum
Monocytes Phagocytosis (mobile, periphery)
Complement Yes (+) No Yes (++) No No
Macrophages Phagocytosis (fixed, tissues);
fixing
antigen presentation
capacity
B lymphocytes Antigen presentation; matures
Placental + - - - -
(B cells) into:
transfer to
- Plasma cells – antibody
fetus
production

Module 6 – Microbiology Page 23 of 32 RJAV 2022

 class switching, or inability to produce specific
subclasses of antibody
Name Properties Structure • Very susceptible to bacterial infection
IgA Found in mucous, saliva, tears, and Severe combined immunodeficiency (SCID)
breast milk. • Defects in both B and T cell function
Protects against pathogens • Susceptible to infection by virtually any microbe
IgD Part of the B cell receptor.
Activates basophils and mast cells
2. Secondary immunodeficiency
IgE Protects against parasitic worms. • Ex: infections (HIV/AIDS), malignancies, drugs
Responsible for allergic reactions (immunosuppressants)

IgG Secreted by plasma cells in the blood. Condition T cell T cell B cell Serum Incidence
Able to cross the placenta into the fetus # function # antibodies
XLA, Bruton ✓ ✓ ↓↓ ↓ Rare
IgM May be attached to the surface of a B
syndrome
cell or secreted into the blood.
Responsible for early stages of immunity RAG1 or ↓↓ ↓↓ ↓↓ None Rare
RAG2 def
HYPERSENSITIVITY REACTIONS X-SCID ↓↓ ↓ ✓ ↓ Rare
XLP, Duncan ✓ ↓ ✓ ✓ or ↓ Rare
• Condition in which an exaggerated or augmented immune syndrome
response occurs that is harmful to the host X-hyper IgM ✓ ↓ ✓ IgM ↑↑ Rare
(CD40 or No IgG,
• Requires a presensitized stated (occur after the 2nd
CD40L IgE or IgA
encounter w/ that specific antigen)
mutation)
• Types:
Wiskott – ✓ ↓ ✓ ↓ Rare
• Antibody-mediated (type I, II, III)
Aldrich
• Cellular-mediated (type IV) syndrome
SCID: ADA ↓↓ ↓↓ ↓ ↓ Very rare
IMMUNODEFICIENCY DISEASES or PNP def
HLA def ↓ ↓ ✓ Poor Ag Very rare
1. Primary immunodeficiency response
• Defect is intrinsic to the cells of the immune system Ataxia ↓ ↓ ✓ IgE↓, IgA↓, Uncommon
• Genetically determined and inherited as a single gene defect telangiectasia IgG2↓
• Examples: DiGeorge ↓↓ ↓ ✓ IgG↓, IgE↓, Very rare
a. Phagocyte’s deficiency syndrome IgA↓
Chronic granulomatous disease (CGD) IgA ✓ ✓ ✓ IgA↓ common
• phagocytic cells do not kill microbes due to genetic deficiency
defect in cytochrome b-558
• defect in the ability of phagocytic cell to produce DRUGS/ AGENTS
peroxide and superoxide
ANTIBACTERIAL AGENTS
Chédiak-Higashi syndrome
• neutrophil granules fuse when the cells are I. Mechanisms of Antibacterial action
immature in the bone marrow → can phagocytose
bacteria but have greatly diminished ability to kill • Inhibition of cell wall synthesis
them • Inhibition of protein synthesis
• Inhibition of cell metabolism
Asplenic individuals • Inhibition of nucleic acid transcription and replication
• lack the filtration mechanism of spleen • Interactions with plasma membrane
macrophages (great risk factor for encapsulated
microorganisms) Inhibition of cell wall synthesis
b. Complement deficiencies A. BETA-LACTAM ANTIBIOTICS
Deficiencies of C1q, C1r, C1s, C4 and C2:
• susceptibility to pyogenic (pus-producing), PENICILLINS
staphylococcal and streptococcal infections
a. History
Deficiency of C3: • Discovered by Alexander Fleming
• higher incidence of pyogenic infections • Old: Penicillium notatum
• New: Penicillium chrysogenum
Defects of the properdin factors: • Isolated by Florey & Chain by freeze drying/ lyophilization
• also results in an increased susceptibility to
pyogenic infection infections b. Properties
• Contains an unstable bicyclic system
Deficiencies of C5 through C9: • Beta-lactam & Thiazolidine ring
• defective cell killing, which raises the susceptibility • Nucleus: 6-Aminopenicillanic acid (6-APA)
to disseminated infections by Neisser spp. • Precursors: Cysteine & Valine
• Shape: half open book
c. Lymphocyte Deficiencies
Deficiency in T cell infection c. Structure-activity relationship (SAR)
• Susceptible to opportunistic infections by: • Addition of electron withdrawing group – acid stability
1) Viruses, especially enveloped and non- • Addition of bulky groups – penicillin’s resistant
cytolytic viruses and recurrences of viruses • Addition of amino group – increase spectrum activity
that establish latent infections,
2) Intracellular bacteria d. Mechanism of action (MOA)
3) Fungi • Irreversibly inhibits transpeptidase by covalently binding to
4) Some parasites the serine residue of the active site thus inhibiting cell wall
synthesis
Deficiency in B cell function
• Complete lack of antibody production e. Classification of Penicillin
(hypogammaglobulinemia), inability to undergo

Module 6 – Microbiology Page 24 of 32 RJAV 2022

e.1. Narrow spectrum penicillins / Natural penicillins • Cefpodoxime
1. Penicillin G • Cefprozil
• aka Benzyl penicillin • Cefotetan
• given IV • Loracarbacef
• depot forms: Benzathine penicillin & Procaine penicillin • 3rd Gen
• DOC: Syphilis • Cefoperazone
• Ceftriaxone
2. Penicillin V • Ceftibuten
• aka Phenoxymethyl penicillin • Cefdinir
• given PO • Cefixime
• Cefotaxime
e.2. Penicillinase-resistant penicillins / Antistaphylococcal • Moxalactam
penicillins • Ceftidoxime
1. Methicillin • Cefditoren
• Prototype • 4th Gen
• s/e: Interstitial nephritis • Cefepime
• emergence of MRSA • Cefpirome

2. Nafcillin e. Clinical Uses

• Can be given to px with renal problems • Cefalexin – used for UTI in pregnant
• Cefazolin – pre-surgical prophylaxis
3. Oxacillin, Cloxacillin, Dicloxacillin • Ceftriaxone – New DOC: Typhoid fever
• Isoxazolyl penicillins – Contains 3-phenyl & 5-methyl • Antipseudomonal cephalosporins (Cefoperazone,
• Dicloxacillin – best absorbed Cefotaxime, Ceftazidime, Ceftriaxone, Moxalactam) – have
useful antipseudomonal activity
e.3. Broad spectrum penicillins / Aminopenicillins
1. Ampicillin f. Side effects / Adverse effects
• given IV • Hypersensitivity
• Prodrugs: Bacampicillin, Hetacillin, Ciclacillin • Disulfiram-like reaction & Hypoprothrombinemia
• + Sulbactam = Unasyn • N-Methyl-5-thiotetrazole (MTT) containing cephalosporins:
• DOC: Listeria monocytogenes • Cefamandole, Cefotetan, Moxalactam, Cefoperazone

2. Amoxicillin given PO CARBAPENEMS

• + clavulanic acid = Co-Amoxiclav
• commonly used in respiratory infections a. Properties
• Differ from penicillin in that the sulfur atom has been
e.4. Extended spectrum penicillin/ Antipseudomonal penicillin replaced by carbon atom
1. Carbenicillin, Ticarcillin • Broad spectrum of activity, including P. aeruginosa
• Carboxypenicillin
• Carboxyl at the α-position b. Drugs

2. Piperacillin, Azlocillin, Mezlocillin 1. Thienamycin

• Ureidopenicillin • isolated from Streptomyces cattleya
• Urea at the α-position • inactivated by Renal dehydropeptidase-I
• Piperacillin – most potent
2. Imipenem
CEPHALOSPORINS • N-formimidoylthienamycin
• + Cilastin (renal dehydropeptidase inhibitor) = Tienam
a. History
• Cephalosporin C – the first cephalosporin 3. Meropenem
• Old: Cephalosporium acremonium • 2nd generation carbapenem
• New: Acremonium chrysogenum • Resistant to dehydropeptidases & B-lactamases

b. Properties 4. Ertapenem
• Contains an unstable bicyclic system • Benzoic acid contributes to high protein binding and prolongs
• Beta-lactam & Dihydrothiazine the half-life of the drug
• Nucleus: 7-Aminocephalosporanic acid (7-ACA)
• Precursors: Cysteine & Valein MONOBACTAM
• Better acid stability & resistance to B-lactamase
a. Properties
c. Mechanism of action (MOA) • Monocyclic B-lactams
• Irreversibly inhibits transpeptidase by covalently binding to • Inactive against gram positive. Moderate activity against a
the serine residue of the active site thus inhibiting cell wall narrow group of gram-negative bacteria, including P.
synthesis aeruginosa.

d. Generation of Cephalosporin b. Drugs

• Based on their bacterial spectrum of activity and B-
lactamase resistance 1. Aztreonam
• 1st Gen • isolated from Chromobacterium violaceum
• Cefalexin
• Cefadroxil B. CYCLOSERINE
• Cefazolin
• Cephalotin • Sources: Streptomyces garyphalus, S. orchidaceus, S.
• Cephradine lavendulus
• 2nd Gen • MOA: Prevent the formation of D-ala-D-ala (inhibits L-alanine
• Cefaclor racemase & D-ala, D-ala ligase)
• Cefoxitin • Use: Second-line drug for tuberculosis
• Cefuroxime
• Cefonicid
• Cefamandole

Module 6 – Microbiology Page 25 of 32 RJAV 2022

 C. BACITRACIN c. Drugs

• A polypeptide from Bacillus subtilis, isolated from a fracture 1. Gentamicin

fragment from Margaret Tracy • source: Micromonospora purpurea
• MOA: Binds to the lipid carrier 2. Tobramycin
• Use: + Polymyxin B for the topical treatment of skin • source: Streptomyces tenebravius
infections.
• s/e: nephrotoxic & hematotoxic 3. Amikacin
• Action is enhanced by zinc • semi synthetically derived from Kanamycin
• first prepared in Japan
D. VANCOMYCIN
4. Neomycin
• A glycopeptide from Streptomyces orientalis • source: Streptomyces fradiae
• MOA: Inhibits transglycosidation, inhibits synthesis of 5. Kanamycin
mucopeptide polymer • source: Streptomyces kanamyceticus
• DOC: MRSA (IV), C. difficile induced Pseudomembranous
colitis (PO) 6. Streptomycin
• s/e: red-man syndrome (remedy: slow infusion) • source: Streptomyces griseus
• 1st aminoglycoside discovered
E. TEICOPLANIN • 1st effective agent used against tuberculosis

• A glycopeptide from Actinoplanes teichomyceticus d. Side effects

• MOA: long alkyl chain anchors the antibiotic to the outer • Allergic reactions
surface of the cell membrane • Ototoxicity
• Use: treatment of gram-positive infections • most ototoxic: KAN
• most vestibulotoxic: SG
F. FOSFOMYCIN • Nephrotoxicity
• most nephrotoxic: NTG
• Synthetic derivative of Phosphoric acid • Neuromuscular paralysis
• MOA: inhibits UDP-N-acetyl glucosamine enolpyruvyl
transferase B. TETRACYCLINES
• Use: UTI cause by E. coli
a. Properties
Interactions with Plasma Membrane • Consists for 4 fused rings with a system of conjugated
double bonds.
A. POLYMYXINS • Broadest spectrum of the antibiotics
• Have activity against gram positive & negative, spirochetes &
• Cation polypeptides atypical bacteria
• MOA: bind to phospholipids on the cell membrane of gram- • *Chlortetracycline – Streptomyces aureofaciens
negative bacteria • DOC: Lime disease, rickettsia
• s/e: Nephrotoxic and neurotoxic
b. Mechanism of action (MOA)
1. Polymyxin B • Binds to the 30s subunit of ribosomes which prevents
• source: Bacillus polymyxa aminoacyl-tRNA from binding to the mRNA ribosome
• + Bacitracin for skin infections complex
• + Dexamethasone & Neomycin for eye infections
c. Classes of tetracyclines
2. Colistin • Short Acting
• aka Polymyxin E • Tetracycline
• source: Aerobacillus colistinus • Oxytetracycline
• For refractory urinary tract infections & gram-negative • Intermediate Acting
infections • Metacycline
• Demeclocycline
B. GRAMICIDIN A • Long Acting
• Doxycycline
• Source: Bacillus brevis • Minocycline
• MOA: acts as ionophore allowing the loss of K+ ions • Very long acting
• Tigecycline
C. DAPTOMYCIN d. Interactions
• Products containing metals
• Cyclic lipopeptide from Streptomyces roseosporus • Dairy products and drugs containing divalent and trivalent
• Use: reserve agent for SSTIs metals
• Decreased absorption of tetracycline due to chelation
Inhibition of Protein Synthesis • Penicillin – antagonism

e. Side effects / Adverse reactions

A. AMINOGLYCOSIDES
• Photosensitivity
a. Properties • Fanconi-like syndrome
• taking expired tetracycline
• Amino sugars joined by a glycosidic linkage
• derived from Streptomyces spp (mycin) or Micromonospora • Tooth discoloration & stunting of growth
spp. (micin) • Contraindicated to pregnant women & young children
• given IV (except: neomycin)
• + penicillins = synergism C. MACROLIDES
• for the treatment of serious infections caused by gram-
a. Properties
negative bacilli
• Common chemical characteristics:
b. Mechanism of action (MOA) • 14-membrane lactone ring
• Ketone group
• Bind to 30s ribosomal subunit to prevent the reading of the
mRNA • Glycosidically linked amino sugar

Module 6 – Microbiology Page 26 of 32 RJAV 2022

b. Mechanism of action (MOA) G. LINEZOLID
• Binds to the 50s ribosomal subunit, inhibiting translocation.
• classified under oxazolidinones, synthetic antibiotics
c. Drugs • MOA: Binds to 50s preventing the formation of the 70s
complex
1. Erythromycin (Ilotycin) • DOC: VRSA
• source: Streptomyces erythraeus, from Iloilo
• Ester salts Inhibition of DNA Replication
• Estolate – lipid soluble, acid stable prodrug with better
oral absorption; s/e: Cholestatic jaundice A. QUINOLONES
• Ethyl succinate – prodrug with more lipophilicity –
longer duration of action • patterned after Nalidixic acid (NegGram)
• Gluceptate – water soluble salt of glucoheptanoic acid • synthetic antibacterial agent
for parenteral use
• Lactobionate – also used for parenteral means a. Mechanism of action (MOA)
• Substitute for penicillin in allergic patients • inhibits DNA Gyrase Topoisomerase
• Motilin agonist
• DOC: Legionnaire’s disease b. Generations of Quinolones
2. Clarithromycin Generation Drugs Activity
• Methylated erythromycin
• More stable in gastric acid and has improved oral absorption st
1 gen Nalidixic acid, Moderate gram (-) act
• Use: treatment of ulcers causes by H. pylori Cinoxacin
2nd gen Ciprofloxacin, Improved act against gram (-),
3. Azithromycin Lomefloxacin, has act against G (+) &
• Contains a 15-membered macrocycle with N-methyl group Ofloxacin, Atypical microorganism
• Extensive tissue distribution Norfloxacin,
• Food decreases absorption Enofloxacin
• Hydrate forms: 3rd gen Gatifloxacin, Retained gram (-) act,
• Dehydrate - Zithromax Gemifloxacin, improved gram (+) & atypical
• Monohydrate – Azytha Sparfloxacin, act
Moxifloxacin,
4. Roxithromycin Levofloxacin
• Semisynthetic macrolide derived from erythromycin (+N- 4th gen Trovafloxacin Retained gram (-), gram (+),
oxime side chain) atypical microorganism, also
for anaerobic microorganism
D. LINCOSAMIDES
c. Structure Activity Relationship (SAR)
a. Properties • Nucleus: 1,4 dihydro-4-oxo-3 pyridine carboxylic acid
• Sulfur containing antibiotics • At 2, addition of groups greatly reduces or abolishes activity
• At 5,6,7,8, may be substituted with good effects
b. Mechanism of action (MOA) • At 6, + F increases antibacterial activity
• Binds to 50s ribosomal subunit (same with macrolides) • Fluoroquinolones – broad spectrum (+, -)
• At 7, + Piperazine provides activity against Pseudomonas
c. Drugs aeruginosa
• At 1, small alkyl substitution provides greater potency
1. Lincomycin • At 8, + Halogen, side effect is photosensitivity
• source: Streptomyces lincolnensis • Highest – Lomefloxacin
• Lowest – Sparfloxacin
2. Clindamycin
d. Interactions
• 7-chloro-7-deoxy derivative of lincomycin • Enzyme inhibitor
• potent drug for anaerobic bacteria • Products containing divalent and trivalent metals
• a/e: Clostridium difficile induced pseudomembranous colitis
• DOC: Vancomycin, Metronidazole B. NITROFURANS
E. CHLORAMPHENICOL • Nitro heterocyclic compounds
• Derivatives of 5-nitro-2-furaldehyde
• Source: Streptomyces venezuelae
• MOA: Binds to 50s subunit, inhibiting peptidyl transferase a. Mechanism of action (MOA)
• DOC: Typhoid fever (new: Ceftriaxone) • Inhibit Nucleic acid synthesis
• + palmitic acid = chloramphenicol palmitate (reduced
bitterness) b. Structure Activity Relationship (SAR)
• a/e: Aplastic anemia, Gray baby syndrome • Nitro at 5th position – antibacterial activity
• Toxicophore: Nitro group
c. Drugs
F. STREPTOGRAMINS
1. Nitrofurantoin
• MOA: Binds to different regions of the 50s subunit and form • used in UTI
a complex with it
2. Nitrofurazone
1. Pritinamycin • used topically in Burns
• source: Streptomyces pristinaespiralis
• Quinupristin & Daflopristin 3. Furazolidone
• used in bacterial or protozoal Diarrhea
2. Quinupristin
• inhibits peptide chain elongation 4. Metronidazole
• Effective against trichomonas, amoeba, giardia, anaerobic
3. Daflopristin bacteria
• interferes with the transfer of the peptide chain from one • DOC: C. difficile induced Pseudomembranous colitis
tRNA to the next

Module 6 – Microbiology Page 27 of 32 RJAV 2022

Inhibition of Cell Metabolism ANTIMYCOBACTERIAL DRUGS

A. SULFONAMIDES TUBERCULOSIS

a. History FIRST LINE DRUGS

• Discovered by Gerard Domagk
• Studied a bright red dye, Prontosil, which was metabolized in 1. Rifampicin (Rifampin, R)
vivo to sulfanilamide
• Source: S. meditirranei
b. Mechanism of action (MOA) • MOA: inhibits RNA polymerase
• Inhibits dihydropteroate synthetase, thus preventing folic acid • most active agent in clinical use for TB patients
synthesis • S/E / Interactions: red-orange secretions, hepatoxicity,
• Active form: Ionized enzyme inducer

c. Structure Activity Relationship (SAR) 2. Isoniazid (H)

• para-amino group is essential for activity and must be
unsubstituted • aka Isonicotinic acid hydrazine, INH
• The aromatic ring and the sulfonamide functional groups are • MOA: inhibit synthesis of mycolic acid
both required • S/E: peripheral neuropathy, hepatoxicity
• Both the sulfonamide and amino group must be directly • AD: Give pyridoxine/ vitamin B6
attached to the aromatic ring
• The aromatic ring must be para-substituted only 3. Pyrazinamide (Z)
• The sulfonamide nitrogen must be primary or secondary
• aka Pyrazinecarboxamine, PZA
d. Side effects / Adverse effects • MOA: unclear
• Crystalluria, Hypersensitivity (rash SJS), Hemolytic anemia • first line drug for short term treatment
in G6PD, Nausea, Kernicterus • prodrug of pyrazinoic acid
• S/E: hyperuricemia, hepatotoxicity
e. Other antimetabolites (PYRIMIDINES)
4. Ethambutol (E)
1. Trimethoprim
• MOA: Bacterial dihydrofolate reductase inhibitor • MOA: inhibits arabinosyl transferase inhibiting the formation
of mycobacterial cell wall
2. Pyrimethamine • S/E: optic neuritis (blue-green vision)
• MOA: Protozoal dihydrofolate reductase inhibitor
5. Streptomycin
f. Drugs / Drug combinations
• first and oldest antibiotic effective in the Tx of TB
1. Sulfalazine
• Prodrug of 5-aminosalicylic acid SECOND LINE DRUGS
• Used in ulcerative colitis
1. Capreomycin
2. Co-trimoxazole • Source: S.capreolus
• Sulfamethoxazole + Trimethoprim (synergistic combination) • s/e: ototoxicity, nephrotoxicity
• Uses: 1st attack of UTI, P. carinii pneumonia (DOC)
2. 4-Aminosalicylic acid
3. Co-trimazine • aka para-aminosalicylic acid, PAS
• Sulfadiazine + Trimethoprim • MOA: inhibits dihydropteroate synthetase
• One of the very first drugs used for tuberculosis
4. Sulfadiazine + Pyrimethamine
• Used in Toxoplasmosis 3. Ethionamide
• Analog of isoniazid
5. Sulfadoxine + Pyrimethamine • s/e: hepatotoxicity
• Used in Malaria
4. Cycloserine
6. Silver sulfadiazine + Mafenide 5. Respiratory fluoroquinolones
• Used in Burns
LEPROSY
B. SULFONES
Drugs:
• MOA: inhibit dihydropteroate synthetase
1. Clofazimine (Lamprene)
1. Dapsone • A phenazine red dye
• Used in leprosy Contraindicated in G6PD deficiency, may • MOA: bind to nucleic acids
cause hemolytic anemia • Used in Dapsone resistant lepromatous leprosy
• s/e: brownish-black skin discoloration
MISCELLANEOUS AGENTS
2. Dapsone
1. Methenamine (Urothropin)
3. Rifampicin
• Urinary antiseptic used in UTI **For tuberculoid leprosy (mild), dapsone + rifampicin is given. However, for
• Formaldehyde release in low pH is required for antibacterial lepromatous leprosy (severe), clofazimine is added to the regimen.
effect
• Given with acidifying agents (NH4Cl) to optimize the ANTIPROTOZOAL AGENTS
effect
• Certain bacteria produce urease, causing resistance • protozoal infections: malaria, amoebiasis, giardiasis,
• Give acetohydroxamic acid (Lithostat) – urease inhibitor trichomoniasis, toxoplasmosis, P carinii pneumonia

Module 6 – Microbiology Page 28 of 32 RJAV 2022

Amoebiasis (8 DIME) Leishmaniasis

Amebicides that are effective against both intestinal & 1. Sodium Stibogluconate
extraintestinal forms of the disease: • MOA: inhibit phosphofructokinase
• aka Sodium antimony gluconate
1. Emetine and Dehydroemetine • Tx of Leishmaniasis
• alkaloids from Ipecac
• MOA: inhibit protein synthesis by preventing protein ANTHELMINTICS
elongation (protoplasmic poison)
• Also used for balatidial dysentery, fascioliasis, • are drugs that are capable of eliminating parasitic worms or
paragonimiasis helminths
• Limited use due toxic effects (GI, cardiovascular, • helminths: Cestodes (tapeworms), Trematodes (flukes),
neuromascular) Nematodes (roundworms

2. Metronidazole (Flagyl, Protostat) Nematodes

• MOA: covalent binding of reactive intermediate from the
reduction of 5-nitro group to the DNA → lethal effect 1. Piperazine
• Tx of amoeba, giardiasis, trichomonas, anaerobic bacterial • MOA: block response of ascaris muscle to Ach → leading to
infections placid paralysis
• a/e: disulfiram like effect (if taken with alcohol) • Tx of pinworm roundworm

3.Tinidazole 2. Pyrantel Pamoate

• MOA: depolarizing Nm blocking agent → spastic paralysis
Amebicides that are effective only against intestinal form: • should not be used with piperazine (opposite effects)
• Tx of pinworm, roundworm (ascaris)
1. 8-hydroxyquinoline
• MOA: chelation of metal ions 3. Thiabendazole
• MOA: inhibit fumarate reductase / antimitotic /
2. Iodoquinol antimicrotubule
• a derivative of 8-hydroxyquinoline • broad spectrum anthelminthic
• for acute and chronic intestinal amebiasis • In veterinary practice as anthelmintic in livestock
3. Diloxanide
• Tx of asymptomatic carriers of E. histolytica 4. Mebendazole
• from discovery of α-dichloroacetamides • MOA: irreversibly blocks glucose uptake → depleted
glucose/ antimitotic/ antimicrotubule
Pneumocystis carinii pneumonia (CAP) • broad spectrum (whip, pin, round, hook)

1. Cotrimoxazole 5. Albendazole
• Sulfamethoxazole + Trimethoprim • MOA: antimitotic/ antimicrotubule
• DOC for PCP • broad spectrum

2. Pentamidine Isethionate 6. Ivermectin

• prophylaxis for African trypanosomiasis (rapidly distributed to • from Streptomyces avermitilis
tissues where it is stored) • MOA: stimulating gaba → blocked interneuron-motor neuron
transmission
3. Atovaquone • Tx of onchocerciasis (river blindness) – Oncocerca volvulus
• analog of Ubiquinone a component of mitochondrial electron
transport chain 7. Diethylcarbamazine (DEC)
• MOA: Interfere with the electron transport chain as it is • MOA: unknown
antimetabolite for ubiquinone • Tx of Filiariasis

Trypanosomiasis (BS MEN) Trematodes

1. Eflornithine 1. Praziquantel
• MOA: irreversible inactivation of Ornithine decarboxylase • MOA: increase Ca2+ membrane permeability → loss of Ca
• Tx of African sleeping sickness → contraction → paralysis → phagocytosis (DEATH)
• myelosuppressive (→ anemia, leukopenia, • Broad spectrum
thrombocytopenia) • Agent of choice for blood flukes (schistosomes)

2. Nifurtimox 2. Niridazole
• Tx of South American trypanosomiasis (T. cruzi) • for schistosomiasis

3. Benznidazole 3. Oxamniquine
• Tx of Chagas disease • MOA: inhibit DNA, RNA, Protein synthesis
• Tx of Schistosoma mansoni
4. Melarsoprol
• DOC for later stages of both forms of African 4. Bithionol
trypanosomiasis • Agent of choice for liver fluke (Fasciola hepatica) and lung
fluke (Paragonimus westermani)
5. Suramin
• Bisurea derivative containing six sulfonic acid groups Cestodes
• used as a long-term prophylactic agent for trypanosomiasis
(due to high protein binding, effect can last up to 3 months) 1. Niclosamide
• MOA: inhibit Oxidative phosphorylation
Toxoplasmosis

1. Sulfadiazine + Pyrimethamine
• most effective therapy

Module 6 – Microbiology Page 29 of 32 RJAV 2022

 ANTIFUNGAL DRUGS C. ALLYLAMINES

A. POLYENES • MOA: inhibit squalene epoxidase

• Structure: contains conjugated double bonds in macrocyclic 1. Naftifine (Naftin)

lactone rings 2. Terbinafine (Lamisil)
• MOA: forms “pores” channel on the cell membrane 3. Tolnaftate (Tinactin)

Drugs: D. OTHER ANTIFUNGALS

1. Amphotericin B 1. Flucytosine
• source: Streptomyces nodosus • Nucleoside antifungal (Pyrimidine antimetabolite)
• Prodrug of 5-flurouracil
2. Nystatin • Used in combination with Amphotericin B in Cryptococcal
• source: Streptomyces noursei meningitis
• DOC for candida infections • MOA: inhibits DNA & RNA synthesis

3. Natamycin 2. Griseofulvin
• source: Streptomyces natalensis • Source: Penicillum griseofulvum
• MOA: “mitotic spindle/microtubule poison” – inhibiting mitosis
• DOC for refractory ringworm infections of the body nails,
hair, feet
• Long duration of treatment (3-6 mos)
• Poor bioavailability
• Solutions:
• Micronized
• Taken with fatty food to increase abs

E. ECHINOCANDINS

• MOA: inhibits synthesis of β (1,3)-D-glucan, thus inhibiting

fungal cell wall synthesis
• Potent against Aspergillus & most Candida species
B. AZOLES • s/e: flushing (rapid infusion)
• Drugs: Anidulafungin, Caspofungin, Micafungin
• MOA: inhibits C-14 α-demethylase to block demethylation of
lanosterol to ergosterol. F. TOPICAL AGENTS FOR DERMATOPHYTOSES
• SAR:
a. Imidazole or 1,2,4-triazole ring bonded by a N-C linkage Fatty Acids
b. 2 or 3 aromatic rings increases potency
c. Addition of halogen increases potency 1. Propionic acid
• Groups of azoles (based on structure):
• Triazole – Ketoconazole, Itraconazole, Fluconazole 2. Sodium Caprylate
Posaconazole, Voriconazole • from caprylic acid, component of coconut & palm oils
• Imidazole – Clotrimazole, Miconazole, Econazole
For systemic fungal infections: 3. Undecylenic acid
• from destructive distillation of castor oil
1. Ketoconazole (Nizoral)
• Used in systemic fungal infections (before), topical (now) 4. Salicylic acid (SA) & Benzoic acid (BA)
• needs acidic pH to be absorbed Whitfield’s ointment
• s/e, interactions: hepatoxicity, antiandrogenic effects,
enzyme inhibitor ANTIVIRAL AGENTS
• reduced production of testosterone, impotence, loss of libido,
gynecomastia, dec. sperm count A. NON-RETROVIRAL AGENTS
2. Itraconazole (Sporanox) ANTIHERPES AGENTS
• Alternative to Ketoconazole
• Not hepatotoxic, no adrenal suppression 1. Acyclovir
• Needs acidic pH to increase absorption • Chemistry: guanosine derivative
• Spectrum: HSV-1, HSV-2, VZV (10x more potent for HSV
3. Fluconazole (Diflucan) than VZV)
• Lipophilic (crosses BBB) • Requires phosphorylation (viral kinases)
• DOC & Prophylaxis for Cryptococcal meningitis • MOA:
• Competition with deoxy GTP for the viral DNA
4. Posaconazole polymerase
• Broad acting synthetic antifungal • Chain termination following incorporation
• Structurally similar to Itraconazole • Route: P.O., I.V.
• a/e: gastrointestinal disturbances (n/v, diarrhea), headaches • Clinical use: DOC for the ff:
• HSV encephalitis
5. Voriconazole • Neonatal HSV infection
• Broad acting synthetic antifungal • Serious HSV/VZV infection
• Structurally similar to Fluconazole • ADR: Reversible renal toxicity (crystalline nephropathy
• DOC for invasive aspergillosis interstitial nephritis)
• a/e: virtual & auditory hallucinations, hepatotoxicity
For superficial fungal infections: 2. Valacyclovir
• Chemistry: L-valyl ester of acyclovir
6. Clotrimazole (Canesten) • Rapidly converted to acyclovir after oral admin. Via 1st pass
7. Miconazole (Daktarin) enzymatic hydrolysis in the liver intestine
8. Econazole • ADR: at high doses, confusion, hallucinations, and seizures
9. Tioconazole

Module 6 – Microbiology Page 30 of 32 RJAV 2022

3. Famciclovir • MOA: block the M2 proton ion channel of the virus particle →
• Chemistry: diacetyl ester prodrug of 6-deoxypenciclovir inhibit uncoating of the viral RNA
• PK: rapidly deacetylated and oxidized by 1st pass • PK:
metabolism to penciclovir • Amantadine is excreted unchanged in the urine
• Spectrum: active in vitro against HSV-1, HSV-2, VZV, EBV, • Rimantadine undergoes extensive metabolism
and HBV • Clinical use:
• Requires phosphorylation (viral kinases) • Prevention of clinical illness when initiated before
• Unlike acyclovir, however, penciclovir does not cause chain exposure
termination • Limit the duration of clinical illness by 1-2 days when
administered as treatment
4. Docosanol • ADRs:
• Chemistry: saturated 22 carbon aliphatic alcohol • GIT (nausea, anorexia)
• MOA: inhibits fusion between the host cell plasma • CNS nervousness, light headedness, difficulty in
membrane and viral envelope concentrating, insomnia)
• Dosage: 10% cream • Livedo reticularis (amantadine–induced)

5. Trifuridine ANTIHEPATITIS AGENTS

• Chemistry: trifluoro thymidine
• MOA: intracellularly by host cell enzymes, and then 1. Interferon alfa
competes with thymidine triphosphate • Examples:
• Interferon alfa-2b: chronic HBV & HCV infection
6. Ganciclovir • Interferon alfa-2a; alfacon–1: chronic HCV infection
• Chemistry: acyclic guanosine analogue • CI:
• Requires triphosphorylation • Hepatic decompensation
• MOA: competitively inhibits viral DNA polymerase and • Autoimmune diseases
causes termination of viral DNA elongation • Cardiac arrhythmias
• Spectrum: CMV • DI:
• PK: Poor oral BA • Didanosine: hepatic failure
• Route: IV only • Zidovudine: cytopenia
• Clinical Use: CMV retinitis in immunocompromised patients • ADR:
• ADR: myelosuppression (most common) Agent Uses / Properties

7. Valganciclovir Adefovir dipivoxil Slower to suppress HBV DNA levels; least

• Chemistry: L-valyl ester prodrug of ganciclovir likely to induce HBeAg seroconversion
• PK: Should be taken with food Entecavir Completely inhibits all (3) functions of HBV
• Clinical use: CMV retinitis DNA polymerase transcription of the negative
strand
8. Foscarnet
Lamivudine Inhibits HBV DNA polymerase & HIV reverse
• Chemistry: phosphonoformic acid; inorganic pyrophosphate
transcriptase
analog
• MOA: inhibits herpesvirus DNA polymerase, RNA Telbivudine Induced greater rates of virologic response
polymerase, and HIV reverse transcriptase than either lamivudine or adefovir in
• Not requiring activation by phosphorylation comparative trials
• Route: IV only (poor oral BA) Tenofovir disoproxil Antiretroviral agent, has a potent activity
• Clinical use: against HBV; activity against lamivudine - &
• End-organ CMV entecavir-resistant hepatitis virus isolates
• Ganciclovir/ Acyclovir resistant CMV
• Flu-like syndrome (6 hrs after admin)
• ADRs:
• Transient elevation of hepatic enzymes (8-12 weeks of
• Renal impairment
therapy)
• Hypo/ hypercalcemia
• Hypo/ hyperphosphatemia
Treatment for Hepatitis B
• Hypokalemia
• Hypomagnesemia
Treatment for Hepatitis C
• DI:
• Pentamidine →hypocalcemia
Agent Classification Uses / Properties
• Zidovudine → anemia Combination with sofosbuvir for treatment
Daclatasvir NS5A inhibitor
of HCV genotypes 1, 2, and 3
9. Cidofovir Elbasvir NS5A inhibitor In vitro activity against most major HCV
• Chemistry: cytosine nucleotide analogue genotypes
Ledipasvir NS5A inhibitor Fixed-dose combination with sofosbuvir;
• Phosphorylation is independent of viral enzymes not recommended for treatment of HCV
• MOA: acts both as a potent inhibitor of and as an alternative genotype 2 infection or genotype 3
substrate for viral DNA polymerase Ombitasvir NS5A inhibitor Fixed-dose combination with paritaprevir
and ritonavir for the treatment of HCV
• Clinical use: genotype 4
• CMV retinitis Velpatasvir NS5A inhibitor 1st once-daily single-tablet
• Route: I.V regimen with pangenotypic activity
Fixed-dose combination with ombitasvir,
• CI: px w/ renal insufficiency Dasabuvir NS5B
paritaprevir, and ritonavir for treatment of
• ADR: dose dependent proximal tubular nephrotoxicity, polymerase
HCV genotype 1
inhibitor
• Mx: prehydration using normal saline Sofosbuvir NS5B Administered in combi w/ several other
polymerase anti-HCV medications
ANTI-INFLUENZA AGENTS inhibitor
Grazoprevir NS3/ 4A protease Combination with elbasvir for treatment of
1. Neuraminidase Inhibitors inhibitor HCV genotypes 1 & 4
• Oseltamivir (PO); Zanamivir (inhalational); Peramivir (IV) Paritaprevir NS3/ 4A protease Fixed-dose combination with ombitasvir &
ritonavir for treatment of HCV genotype 4
• Spectrum: Influenza A and B inhibitor
Simeprevir NS3/ 4A protease 2nd generation protease inhibitor
• Chemistry: sialic acid
inhibitor
• MOA: interfere w/ release of progeny influenza A and B virus Spectrum: influenza A & B,
Ribavirin Guanosine
from infected host cells, thus halting the spread of infected analog parainfluenza, RSV, paramyxoviruses,
host cells. HCV, HIV-1
2. Adamantanes
• Amantadine, Rimantadine

Module 6 – Microbiology Page 31 of 32 RJAV 2022

 RETROVIRAL AGENTS
NRTIs
• MOA: competitive inhibition of HIV-1 reverse transcriptase
• Results to: premature chain termination due to inhibition of
• binding w/ the incoming nucleotide
• Intracytoplasmic activation via phosphorylation by cellular
enzymes to the triphosphate form
• ADRs: mitochondrial toxicity
• Peripheral neuropathy
• Lipoatrophy
• Hepatic steatosis
• Pancreatitis
Agent Uses/ Properties
Abacavir Recommended for use of pregnancy;
screening for HLA-B*5701 before initiation of
abacavir therapy is important
Didanosine (ddl) Associated with peripheral distal sensory
neuropathy and dose- dependent pancreatitis
Emtricitabine (FTC) Recommended for use of pregnancy; tenofovir
and emtricitabine is recommended as pre-
exposure prophylaxis; active against HBV and
HIV
Lamivudine (3TC) Active against HBV and HIV; recommended for
use of pregnancy
Stavudine (d4T) Major toxicities: peripheral neuropathy, lactic
acidosis with hepatic steatosis, lipodystrophy
Tenofovir disoproxil Activity against HIV and HBV; recommended
fumarate for use of pregnancy; serum creatinine should
be monitored
Tenofovir alafenamide Activity against HIV and HBV; appears to have
less renal & bone toxicity than tenofovir
disoproxil fumarate
Zidovudine (AZT) 1st antiretroviral agent to be approved and has
been well studied; recommended for use of
pregnancy; most common AE is macrocytic
anemia & neutropenia; other AE includes
lipoatrophy, myopathy
NNRTIs
• MOA: bind directly to HIV-1 reverse transcriptase → resulting
in allosteric inhibition of RNA & DNA-dependent polymerase
• PK: All NNRTI agents are substrates for CYP3A4 & can act
as:
• Inducers (Nevirapine)
• Inhibitors (Delavirdine)
• Mixed inducers & inhibitors (Efavirenz, Etravirine)
• AE: GIT disturbances & skin rashes (SJS)
Agent Uses/ Properties
1st
Generation:
Delavirdine Known teratogen; skin rashes occur during 1-3
weeks of therapy
Efavirenz Long t ½ (40-55 hours); toxicity occurs when
taken w/ high fat meal (taken NPO); principal
toxicity involves the CNS; recommended for
use in pregnancy (initiated after 8 weeks AOG)
2nd Generation:
Etravirine Designed to be effective against strains of HIV
that had developed resistance to 1st gen
NNRTIs
Nevirapine Excellent oral BA (>90%); single dose of
nevirapine (200 mg) can prevent transmission
from mother to newborn when administered at
the onset of labor, then 2-mg/kg dose to the
neonate within 3 days of delivery
Rilpivirine Must be administered w/ a meal (preferably
high fat or >400 kcal); dependent on gastric
acid environment for absorption; recommended
for use in pregnancy
PROTEASE INHIBITORS (PI)
• MOA: preventing post-translational cleavage of the Gag-Pol
polyprotein →prevent the processing of viral proteins into
functional conformations →production of immature,
noninfectious viral particles
• Pls do not need intracellular activation
• PK: All of the PIs are extensively metabolized by
• CYP3A4 (ritonavir having the most pronounced inhibitory
effect and saquinavir the least)
Module 6 – Microbiology
Agent Uses/ Properties
Atazanavir Recommended for use in pregnancy; requires
acidic medium for absorption and exhibits pH-
dependent aqueous solubility
Darunavir Recommended for use in pregnancy; co-
administered with ritonavir or cobicistat;
contains sulfa moiety
Fosamprenavir Prodrug of amprenavir; contains sulfa moiety
Indinavir Requires acidic medium for absorption; most
common AE unconjugated hyperbilirubinemia
and nephrolithiasis; insulin resistance is noted
Lopinavir Available only in combi with low-dose ritonavir
as a pharmacologic “booster”; recommended
for use in pregnancy
Nelfinavir Most common AEs associated are diarrhea
and flatulence
Ritonavir Pharmacologic “booster”; Di w/ saquinavir →
QT prolongation, PR interval prolongation
Saquinavir Should be taken within 2 hours after a fatty
meal for enhanced absorption
Tipranavir Use for treatment-experienced patients who
harbor strains resistant to other PI agents; DI
with ritonavir →IC hemorrhage
FUSION INHIBITORS
1. Enfuvirtide
• HIV attachment: binding of the viral envelope glycoprotein
complex gp160 (consisting of gp120 & gp41) to CD4 + cells
→ conformational changes in gp120 that enable access to
the chemokine receptors CCR5 or CXCR4 → conformational
changes in gp120, allowing exposure to gp41 and leading to
fusion of the viral envelope with the host cell membrane
• MOA: binds to the gp41 subunit of the viral envelope
glycoprotein →preventing fusion of the viral and cell
membrane
• Route: SQ (the only parenteral ARV)
• AE:
• Injection site reaction
• Eosinophilia
ENTRY INHIBITORS
1. Maraviroc
• MOA: binds to the host protein CCR5, one of two chemokine
receptors necessary for entrance of HIV into CD4+ cells
• Clinical use: approved for use in combination w/ other ARV
in adult px infected only with CCR5-tropic HIV-1
INTEGREASE INHIBITORS
• MOA: integrase, a viral enzyme essential to the replication of
both HIV-1 and HIV-2
• Dolutegravir, Elvitegravir, Raltegravir
• ADRs: headache & GIT effects
Agent Uses/ Properties
Dolutegavir Should be taken 2 hours before or 6 hours after
cation-containing antacids or laxatives,
sucralfate, oral iron supplements, oral calcium
supplements or buffered medications; inhibits
the renal organic cation transporter OCT, →
increase serum concentration of dofetilide &
metformin
Elvitegravir Requires boosting wiyh an additional drug,
such as well as certain intestinal transport
proteins or ritonavir
Raltegravir Recommended for use in pregnancy; does not
interact w/ CYP450 system; metabolized by
glucuronidation the CYP450 system but is
metabolized by glucuronidation, particularly
UGT1A1
OTHER ANTIVIRAL AGENTS
Agent Uses/ Properties
Palivizumab Prevention of RSV infection in high-risk infants
and children
Imiquimod Topical treatment of external genital and
perianal; effective for molluscum contagiosum
Page 32 of 32 RJAV 2022