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223 Cards in this Set

  • Front
  • Back
3 Main Brain Infections
Meningitis
Encephalitis
Abcess
Diabetic Extremity Infection
DM caused by endocrine problem
Infection caused by neuropathy, vascular compromise, and immunologic impairment
Phenetic System
groups organsims based on phenotypic characteristics

genus and species
Phylogenetic system
groups organisms based on nucleic acid (more reliable)

RNA "typing" (genotyping)

strains
Eukaryotes
Animalia
Plantae
Protoctista
Fungi
Protozoa
Eukaryotes
unicellular or multicellular

no cell wall (petidoglycan)

cytoplasmic membrane: cytoskeleton (microfilaments, microtubules) and sterols present for support/protection, also use for communication

endocytosis and exocytosis

80s Ribosomes (60s+40s)

membrane bound nucleus with multiple chromosomes

extrachromasomal DNA within organelles

transcription (nucleus)
translation (cytoplasm)

genetic exchange: meiosis, zygote fusion
Prokaryotes (Bacteria)
unicellular

cell membrane: transport, motility, oxidative phosphorylation, DNA replication, communication

cell wall (peptidoglycan); Mycoplasma have no cell wall!

70s Ribosomes (50s+30s)

No nuclear membrane with a single chromosome

extrachromasomal DNA in plasmids

transcription/translation (cytoplasm)

genetic exchange: transformation, transduction, conjugation
Prokaryotes (Viruses)
Classified by Structure:

spikes (protein projections)

capsid: envelop (membrane) or naked

RNA or DNA without a nuclear membrane or proteins (no cell walls, organelles or ribosomes)

Shape: icosohedral and helical

Core: RNA or DNA virus, Single-stranded or DS genetic material; positive or negative/circular or linear structure
Prions
don't know what class to put in

just a protein
Cocci (spherical)
Staphylococcus aureus (clusters)

Streptococcus pyogenes (chains)

Streptococcus pneumonia (pairs)
Bacilli (rods)
Bacillus subtilis (clusters or pairs)

GNB
Coccobacilli (between cocci and bacilli)
Haemophilis influenzae
Pleiomorphic (polymorphic; comma-shaped bacilli)
Campylobacter jejuni
Spirochetes (spiral shaped)
Treponema palladium (Syphilis)
Gram positive organisms
thick peptidogylcan cell wall

no outer membrane

hold iodine/violet stain when decolorized with alcohol-acetone solution

cocci and bacilli
Gram negative organisms
thin peptidoglycan cell wall

outer membrane with porins

becomes clear when decolorized with alcohol-acetone solution

cocci and bacilli
Acid fast organisms
similar to Gram positive

have waxes and lipids in their cell wall (difficult to retain stain)

need different staining procedure to identify

MYCOBACTRIUM - virulence factors are mycolic acid, Wax D, sulfolipids, cord factor, and arabinogalactans)
Wall-less organisms
have no cell wall

does not stain

MYCOPLASMA
Gram positive cell structure
thick peptidoglycan cell wall (40+ layers of chain link mesh fence) - prevents complement lysis but still opsonized

teichoic and lipoteichoic acids
Gram negative cell structure
outer membrane with LPS containing:
Lipid A - endotoxin
Core oligosaccharide
O antigen

periplasmic space (cytoplasma) b/n inner and outer membrane

single layer of peptidoglycan
Staphylococcus aureus (CPS; Gram positive)
catalase +/coagulase +

facultative anaerobes

found primarily in the nares and on some people’s skin

causes impetigo, follicilitis, soft tissue infections, endocarditis, osteomyelitis, septic arthritis, pneumonia, wound and catheter associated infections, TOXIC SHOCK SYNDROME; can produce a localized or secondary infection;

produce EXOTOXIN that are proteases to digest nerve proteins and form pores in membranes as a virulence factor

MRSA – methicillin resistant strain acquired in community and nosocomially; resistant to beta-lactams due to production of beta-lactamases (penicillinases )
Staphylococcus epidermidis (CNS; Gram positive)
catalase +/coagulase –

facultative anaerobes

main microbe found on the skin; cause of many catheter-associated infections due to formation of biofilm; methicillin resistance exists nosocomially

have SLIME (increased adherence to plastic and metal surfaces) as a virulence factor

resistant to beta-lactams due to production of beta-lactamases (penicillinases )
Staphylococcus saprophyticus (CNS; Gram positive)
catalase +/coagulase –

facultative anaerobes

found in vagina; cause of UTIs
Streptococcus pyogenes (Gram positive)
catalase -/beta hemolysis

microaerophilic; found in oropharynx +/-

cause of pharyngitis, otitis, tonsillitis, impetigo, and cellulitis;

produces exotoxin; have PILLI (increased adherence to target tissue) as a virulence factor

bacitracin susceptible; NOT resistant to beta-lactams
Streptococcus agalactiae (Gram positive)
catalase -/beta hemolysis

found in gut and sometimes vagina +/-

cause of neonatal sepsis/meningitis; diabetic extremity infections

ACQUIRED IN BIRTH CANAL

bacitracin resistant
Streptococcus pneumoniae (Gram positive)
catalase -/alpha hemolysis; lysed by bile

microaerophilic; found in nasopharynx; cause of pneumonia (community acquired), otitis, and meningitis

has a CAPSULE to avoid phagocytosis as a virulence factor (vaccine can be made)

obtains resistance determinants by transformation – including beta-lactam resistance in community and nosocomially; resistant to beta-lactams due to altered PBPs

VACCINE AVAILABLE!!!!
Streptococcus viridans (Gram positive)
catalase -/alpha hemolysis; not lysed by bile

microaerophilic; found in oropharynx and gut; cause of periodontal disease and endocarditis
Streptococcus bovis (Gram positive/ Lancefield group D)
catalase -/gamma hemolytic

microaerophilic; cause of endocarditis and intraabdominal infections
Enterococcus faecalis/faecium (Gram positive)
catalase -/gamma hemolysis

facultative anaerobes;

found in gut; cause of UTIs, intra-abdominal infections, and endocarditis

strain of vancomycin-resistant bacteria exists nosocomially (also resistant to ampicillin )
Peptostreptococcus/Peptococcus (Gram positive)
obligately anaerobic cocci

found in the oropharynx and gut; causes pleuropulmonary aspiration pneumonia and abscesses in the lung
Neisseria meningitidis (Gram negative cocci; nonmotile; diploccoci)
oxidase +/aerobe; grows on NYC media

found in nasopharynx +/-; cause of meningitis, has fimbriae which attach to host cells

has a CAPSULE to avoid phagocytosis as a virulence factor (vaccine can be made)

have PILLI (increased adherence to target tissue) as a virulence factor

INTRACELLULAR GROWTH in human/non-phagocytic cells to evade immune response as a virulence factor

have ENDOTOXIN/LPS that is released when lysed - resp. for ENDOTOXIN SHOCK (only occurs in Gram neg. bacteria)

VACCINE AVAILABLE!!! (young adults)
Neisseria gonorrhoeae (Gram negative cocci; nonmotile; diplococci)
oxidase +/aerobe; grows on NYC media

STD – not part of microflora; cause of gonorrhea, pelvic inflammatory disease and septic arthritis; can show up as a subclinical infection; has fimbriae which attach to host cells

have PILLI (increased adherence to target tissue) as a virulence factor

obtains resistance determinants by transformation –including cephalosporin and fluoroquinolones in community; produces broad-spectrum beta-lactamases
Moraxella catarrhalis (Gram negative cocci; Neisseria family; nonmotile; diplococci)
oxidase +/aerobe; no growth on NYC media

found in nasopharynx (especially children)

cause of otitis, conjunctivitis, and meningitis

produces broad-spectrum beta-lactamases
Acinetobacter (Gram negative cocci; Neisseria family; nonmotile; diplococci)
oxidase -/catalase +; aerobe

found in oropharynx and skin

cause of opportunistic infections of any organ

resistance to most broad-spectrum drugs exists nosocomially
Eikenella corrodens (Gram negative cocci; Neisseria family; nonmotile; diplococci)
aerobe

found in oropharynx (dental plaque) of 40-70% of people

cause of soft tissue ("clench fist") and human bite wound infections
Gemella (Gram negative cocci; nonmotile; diplococci)
oxidase -/catalase -; aerobe
Mycobacterium tuberculosis (Gram positive aerobic or facultative bacilli)
acid-fast positive rods; weakly gram positive

human is reservoir but not part of microflora; cause of tuberculosis; can produce a chronic or dormant infection; highly infectious organism but not very virulent


survives/replicates within phagocytes as virulence factor

Treatment: aminoglycosides, carbapenems, fluoroquinolones, and isoniazid

resistance to multiple drugs; exist in community
Nontypical Mycobacteria/NTM (Gram positive aerobic or facultative bacilli)
acid-fast positive; weakly gram positive

cause of opportunistic infections (tuberculosis-like disease in AIDS and other immunocompromised), soft tissue infections, and leprosy

treated using aminoglycosides, carbapenems, fluoroquinolones, and isoniazid
Nicardia asteroides (Gram positive aerobic or facultative bacilli)
acid fast rods; weakly gram positive

found in soil

causes opportunistic pulmonary infections
Bacillus anthracis/subilis/cereus (Gram positive aerobic or facultiative bacilli)
spore forming; facultative or aerobic

found in soil and contaminated food

cause wound infections and food poisoning; anthrax

produce EXOTOXIN that are proteases to digest nerve proteins as a virulence factor

VACCINE AVAILABLE!!!
Corynebacterium diptheriae (Gram positive aerobic or facultative bacilli)
catalase +; grow on tellurite agar and H2S Tinsdale agar; small, pleomorphic

found in the nasopharyngeal "carriers" in third-world countries

cause opportunistic infections; diphtheria

produces EXOTOXIN as virulence factor to inactivate G proteins
Corynebacaterium jekium (Gram positive aerobic or facultative bacilli)
catalase +; grow on tellurite agar and H2S Tinsdale agar; small, pleomorphic

non-sporeforming; microaerophilic/facultative

found in gut, skin, and vagina

cause of opportunistic infections
Listeria monocytogenes (Gram positive aerobic or facultative bacilli)
non-spore forming obligate aerobes

zoonosis

cause of opportunistic infections in pregnant women and neonates and elderly; can cause meningitis


survives/replicates within phagocytes as virulence factor
Clostridium botulinum (Gram positive anaerobic bacilli)
spore forming obligate anaerobes

found in contaminated food

cause of botulism and wound infections

produce EXOTOXIN that are proteases to digest nerve proteins as a virulence factor
Clostridium difficile (Gram positive anaerobic bacilli)
spore forming obligate anaerobes

not part of normal microflora but can reside in the gut (primarily in hospitalized patients)

cause of CDAD (an adverse reaction to antibiotic treatment – kills normal microflora so CD takes over ) - diarrhea is main symptom and it’s due to EXOTOXIN
Clostridum perfringens (Gram positive anaerobic bacilli)
spore forming obligate anaerobes

produce EXOTOXIN that are proteases to digest nerve proteins as a virulence factor

found in gut; cause of gas gangrene and intra-abdominal infections
Clostridium tetani (Gram positive anaerobic bacilli)
spore forming obligate anaerobes

found in soil; cause of tetanus

produce EXOTOXIN that are proteases to digest nerve proteins as a virulence factor

VACCINE AVAILABLE!!!
Propionibacterium acnes (Gram positive anaerobic bacilli)
non-spore forming

found on skin; cause of acne and folliculitis
Escherichia coli (Gram negative aerobic or facultative bacilli)
5 major strains that present differently due to pilli (attach at different sites) and LPS

Non-fermenter(MacConkey) - rapid agar growth; facultative anaerobes

found primarily in the gut (also colonize in the URT in hospitalized individuals) but also can be zoonotic

causes UTIs, gastroenteritis, diabetic extremity infections, and abdominal infections; has fimbriae which attach to host cells

produce SIDEROPHORES to scavenge iron for metabolism as a virulence factor

have PILLI (increased adherence to target tissue) as a virulence factor


produces EXOTOXIN as virulence factor to inactivate G proteins

INTRACELLULAR GROWTH in human/non-phagocytic cells to evade immune response as a virulence factor


ESBL producer
Klebsiella pneumoniae (Gram negative aerobic or facultative bacilli)
Non-fermenter (MacConkey) - rapid agar growth; facultative anaerobes

found in the gut

cause of UTIs, abdominal infections, folliculitis, and pneumonia (especially in alcoholics );

has a CAPSULE to avoid phagocytosis as a virulence factor (vaccine can be made)

resistance to 3rd generation cephalosporins exists nosocomially; produces broad spectrum beta-lactamases (ESBL producer )
Enterobacter cloacae (Gram negative aerobic or facultative bacilli)
Non-fermenter (MacConkey) - rapid agar growth; facultative anaerobes

found in the gut

cause of UTIs, abdominal infections, and diabetic extremity infections

resistance to 3rd generation cephalosporins exists nosocomially; has inducible (AmpC) cephalosporinases; one bug that seems to be able to develop resistance during therapy
Citrobacter freundii (Gram negative aerobic or facultative bacilli)
Non-fermenter (MacConkey) - rapid agar growth; facultative anaerobes

found in the gut

cause of UTIs, abdominal infections, and diabetic extremity infections

has inducible (AmpC)cephalosporinases
Morganella morganii (Gram negative aerobic or facultaive bacilli)
Non-fermenter (MacConkey) - rapid agar growth; facultative anaerobes

found in the gut

cause of UTIs, abdominal infections, and diabetic extremity infections
Proteus mirabilis/vulgari (Gram negative aerobic or facultative bacilli)
Non-fermenter (MacConkey) - rapid agar growth; facultative anaerobes

found in the gut

cause of UTIs, abdominal infections, folliculitis, and diabetic extremity infections
Providencia stuartii (Gram negative aerobic or facultative bacilli)
Non-fermenter (MacConkey) - rapid agar growth; facultative anaerobes

found in the gut

cause of UTIs, abdominal infections, and diabetic extremity infections
Serratia marcescens (gram negative aerobic or facultative bacilli)
Non-fermenter (MacConkey) - rapid agar growth; facultative anaerobes

found in the gut

cause of UTIs, abdominal infections, and diabetic extremity infections

has inducible (AmpC) cephalosporinases
Salmonella enterica (Gram negative aerobic or facultative bacilli)
Non-fermenter (MacConkey) - rapid agar growth; facultative anaerobes

zoonosis and contaminated food are sources; fecal/oral contact

cause of typhoid fever, gastroenteritis, and septicemia; has fimbriae which attach to host cells

produce SIDEROPHORES to scavenge iron for metabolism as a virulence factor

has a CAPSULE to avoid phagocytosis as a virulence factor (vaccine can be made)

have PILLI (increased adherence to target tissue) as a virulence factor

INTRACELLULAR GROWTH in human/non-phagocytic cells to evade immune response as a virulence factor

VACCINE AVAILABLE!!!
Shigella flexneri (Gram negative aerobic or facultative bacilli)
Non-fermenter (MacConkey) - rapid agar growth; facultative anaerobes

found in contaminated food

cause of dysentery and gastroenteritis

INTRACELLULAR GROWTH in human/non-phagocytic cells to evade immune response as a virulence factor

inherently ACID-RESISTANT in stomach
Yesinia enterocolitica (Gram negative aerobic or facultative bacilli)
Non-fermenter (MacConkey) - rapid agar growth; facultative anaerobes

zoonosis; freshwater streams

cause of gastroenteritis
Yesinia pestis (Gram negative aerobic or facultative bacilli)
Non-fermenter (MacConkey) - rapid agar growth; facultative anaerobes

zoonosis

cause of "plague"
Pseudomonas aeruginosa (Gram negative aerobic or facultative bacilli)
Non-fermenter (MacConkey) - rapid agar growth; obligate aerobes (oxidze glucose); polar lagella

found in water, soil, and food (colonize in gut and URT in hospitalized)

cause of nosocomial pneumonia, UTIs, respiratory infections in cystic fibrosis patients, and wound infections in burn patients

resistance exists to many drugs nosocomially; exhibits beta-lactam resistance by reducing outer membrane permeability; has inducible (AmpC) cephalosporinases; treated using a beta-lactam drug along with an aminoglycoside
Burkholderia cepacia (Gram negative aerobic or facultative bacilli; Pseudomonas family)
Non-fermenter (MacConkey) - rapid agar growth; facultative anaerobe

found in plants, soil, and water

cause respiratory infections in cystic fibrosis patients
Stenotrophomas maltophilia (Gram negative aerobic or facultative bacilli; Pseudomonas family)
Non-fermenter (MacConkey) - rapid agar growth; facultative anaerobe

found in hospital enviroment

opportunistic patohogen; causes UTI, wound infections, catheter-associated infections

carbapenem resistance exists nosocomially; produces carbapenemases
Alcaligenes xyloxidans (Gram negative aerobic or facultative bacilli)

fastidious (need special culture technique - more time to grow; longer time to diagnose) falcultative anaerobe

found in soil and water

opportunistic pathogen; causes RTI
Campylobacter jejuni (Gram negative aerobic or facultative bacilli)
fastidious (need special culture technique - more time to grow; longer time to diagnose) falcultative anaerobe

microaerophilic; spiral/curved morphology

zoonosis

causes gastroenteritis
Helicobacter pylori (Gram negative aerobic or facultative bacilli)
fastidious (need special culture technique - more time to grow; longer time to diagnose) falcultative anaerobe

microaerophilic; spiral/curved morphology

human reservoir

cause of peptic ulcer disease
Gardnerella vaginalis (Gram negative aerobic or facultative bacilli)
found in vagina

causes bacterial vaginosis
Haemophilus influenzae (Gram negative aerobic or facultative bacilli)
fastidious (need special culture technique - more time to grow; longer time to diagnose) falcultative anaerobe

found in nasopharynx

causes otitis, epiglottis, meningitis in children, bronchitis, pneumonia in adults (especially smokers)

has a CAPSULE to avoid phagocytosis as a virulence factor (vaccine can be made)

obtains resistance determinants by transformation

produces broad-spectrum beta-lactamases

VACCINE AVAILABLE!!!
Haemophilus ducreyi (Gram negative aerobic or facultative bacilli)
fastidious (need special culture technique - more time to grow; longer time to diagnose) falcultative anaerobe

STD - human reservoir

causes chancroid
Brucella melitensis (Gram negative aerobic or facultative bacilli)
zoonosis

causes brucellosis
Bordetella pertussis (Gram negative aerobic or facultative bacilli)
human is reservoir

causes whooping cough in infants; older individuals has less severe disease

INTRACELLULAR GROWTH in human/non-phagocytic cells to evade immune response as a virulence factor

produces EXOTOXIN as virulence factor to inactivate G-proteins

VACCINE AVAILABLE!!!
Francisella tularensis (Gram negative aerobic or facultative bacilli)
zoonosis: found in rabbits and rodents

causes tularemia (BIOTERRORISM)
Pasteurella multocida (Gram negative aerobic or facultative bacilli)
found in dogs: animal oropharynx

causes bite wound infections

readily treatible
Legionella pneumophilia (Gram negative aerobic or facultative bacilli)
found in contaminated water (air conditioner collecting pans)

causes Legionnaire's disease


survives/replicates within phagocytes as virulence factor
Vibrio cholerae/parahemolyticus (Gram negative aerobic or facultative bacilli)
Fermenter (rapid agar growth)

produces EXOTOXIN as virulence factor to inactivate G proteins

found in sewage-contaminated water, shellfish (raw)

causes Cholera, gastroenteritis

VACCINE AVAILABLE!!!
Bacteroides fragillis (Gram negative obligate anaerobe bacilli)
difficult to treat

found in gut: main organism in ileum and colon

causes abdominal infections and absesses

only bacteria susceptible to metronidazole; produces broad-spectrum beta-lactamases
Prevotella bivia/distens(Gram negative obligate anaerobe bacilli)
found in vagina

causes PID
Prevotella melaninogenica/denticola/
distens/intermedia/oralis/oris (Gram negative obligate anaerobe bacilli)
found in oropharynx

causes pluropulmonary aspiration pneumonia and absesses
Fusobacterium nucleatum (Gram negative obligate anaerobe bacilli)
found in the oropharynx and gut

causes gingivitis and sepsis
Actinomyces israelii (other bacteria)
found in oropharynx

causes periodontal disease and actinomycosis
Chlamydia pneumoniae (other bacteria)
found in the oropharynx?

causes pneumonia in elderly

OBLIGATE INTRACELLULAR GROWTH in human/non-phagocytic cells to evade immune response as a virulence factor


treated using tetracyclines, macrolides, and fluoroquinolones
Chlamydia trachomatis (other bacteria)
STD - greatest cause of blindness worldwide (not US)

causes nongonococcal urethrits and PID; also trachoma

treated using tetracyclines, macrolides, and fluoroquinolones
Mycoplasma pneumoniae (other bacteria)
lack cell wall; highly pleiomorphic

found in oropharynx and gut

causes pneumonia and RTIs

treated using tetracyclines, macrolides, and fluoroquinolones
Ureaplasma urealyticum (other bacteria)
lack cell wall; highly pleiomorphic

found in vagina

causes UTI
Rickettsia rickettsii (other bacteria)
OBLIGATE INTRACELLULAR GROWTH in human/non-phagocytic cells to evade immune response as a virulence factor

transferred by TICKS (arthropod normal flora)!!!

causes Rocky Mountain Spotted Fever

treated using tetracyclines, macrolides, and fluoroquinolones
Bartonella henselae (other bacteria)
obligate intracellular parasite in eukaryotic cells; fastidious

zoonosis (trauma)

causes Cat Scratch Fever, bacillary angiomatosis in immunocompromised
Coxiella burnetti (other bacteria)
obligate intracellular parasite in eukaryotic cells

zoonosis (inhalation)

causes Q fever
Ehrlichia chaffeensis (other bacteria)
obligate intracellular parasite in eukaryotic cells

transferred by TICKS!!!
causes Ehrlichosis
Borrelia burgdorferi (other bacteria)
spirochete (coiled morphology) with motility via axial filament

transferred by TICKS!!!

causes Lyme disease
Treponema palladum (other bacteria)
spirochete (coiled morphology) with motility via axial filament

STD - human reservoir

causes syphilis

CROSS PLACENTAL BARRIER
RNA Viral Replication
(determines therapy - easy to treat)
Steps:
1. Attach receptors
2. Enter cell (endocytosis)
3. Uncoat (loses envelope/capsule)
4. Replicates (RNA-->mRNA-->Protein)
5. Assemble
6. Egress (leave and kill cell)
Retro-RNA Viral Replication
(determines therapy - never eradicate)
Steps:
1. Attach receptors
2. Enter cell (endocytosis)
3. Uncoat (loses envelope/capsule)
4. Replicates (RNA-->mRNA-->Protein) and incorporates genome inside human cell forever!
5. Assemble
6. Egress (leave and kill cell)
General Overview of Viral Replication
DNA Virus:
unwind/copied-->+mRNA-->protein

ssRNA Virus: -RNA-->+mRNA-->protein

dsRNA Virus: unwind-->+mRNA-->protein

Retro-RNA Virus:
copied/inserted into DNA-->-RNA-->+mRNA
-->protein

**polarity exists in ssRNA viruses (+ strands can directly synthesize proteins while (-) strands must first have their complimentary strand made ); all genomes are linear
Enterovirus (+ssRNA Virus)
cause poliovirus

VACCINE AVAILABLE!!!
Rhinovirus (+ssRNA virus)
causes common cold
Hepatovirus (RNA virus)
causes Hepatitis A virus

VACCINE AVAILABLE!!!
Astrovirus (+ssRNA Virus)
cause gastroenteritis and diarrhea
Calcivirus (+ssRNA virus)
causes Norwalk virus; gastroenteritis
Flaviviridae (+ssRNA virus)
causes Dengue and Yellow fever virus

located in liver

VACCINE AVAILABLE!!!
Hepatitis C virus (+ssRNA virus)
causes Chronic Hepatitis C
Alphavirus (+ssRNA virus)
causes Eastern Equine Encephalitis virus

VACCINE AVAILABLE!!!
Rubivirus (+ssRNA virus)
causes Rubella virus

affects on skin and mucous membranes

CROSS PLACENTAL BARRIER

VACCINE AVAILABLE!!!
HTLV Retroviruses (Retro-RNA virus)
causes Human T-lymphocyte viruses

affects brain, lymphoid
Lentivirinae (Retro-RNA virus)
causes HIV-1 and HIV-2 (AIDS)

affects brain, lymphoid

CROSS PLACENTAL BARRIER
Rotavirus (dsRNA virus)
causes Rotavirus

affects GI; diarrhea

VACCINE AVAILABLE!!!
Hantavirus (-ssRNA virus)
causes Hantaan virus
Influenzavirus A,B (-ssRNA virus)
causes Influenza

affects upper/lower respiratory tract

VACCINE AVAILABLE!!!
Arenavirus (-ssRNA virus)
causes Lymphocytic Choriomeningitis virus and Lassa Fever virus
Filovirus (-ssRNA virus)
causes Ebola virus and Marburg virus

affects systemically (fever, diarrhea, muscle aches, etc.)
Vesiculovirus (RNA virus)
causes Vesicular Stomatitis virus (VSV)
Lyssavirus (-ssRNA virus)
causes Rabies virus

affects brain

VACCINE AVAILABLE!!! Works Post-Infection
Paramyxovirus (-ssRNA virus)
causes Newcastle disease virus
Morbillivirus (-ssRNA virus)
causes Measle virus

VACCINE AVAILABLE!!!
Rubulavirus (-ssRNA virus)
causes Mumps virus

VACCINE AVAILABLE!!!
Pneumovirus/Respiratory syncytial virus/RSV (-ssRNA virus)
causes respiratory illness in infants
Orthohepadnavirus (Retro? DNA virus)
causes Chronic Hepatitis B

VACCINE AVAILABLE!!!
Papillomavirus (dsDNA virus)
causes Human Papillomavirus and Condyloma acuminatum (genital warts)
Mastadenovirus (dsDNA virus)
causes Adenovirus

affects GIT, nose
Alphaherpesvirinae Herpes Simplex viruses types 1 and 2 (HSV-1 and HSV-2) - (dsDNA) - Herpes family
causes genital/mucocutaneous herpes in normal host and can spread systemically: encephalitis, mucoutaneous disease in the immunocompromised host, neonatal systemic infections and keratoconjuctivitis

CROSS PLACENTAL BARRIER
Betaherpesvirinae/Cytomegalovirus (dsDNA) - Herpes family
causes CMV retinitis in transplanted ocular tissue patients and HIV patients, esophagitis in immunocompromised

affects liver, lymphoid

CROSS PLACENTAL BARRIER
Gammaherpesvirinae (dsDNA) - Herpes family
causes Epstein-Barr virus (EBV)/mononucleosis

affects throat, liver, lymphoid
Roseolovirus (dsDNA) - Herpes family
causes Human herpes virus 6 (HHV-6)

affects skin and mucous membranes
Varicellovirus/Varicella-zoster virus/VSV (dsDNA) - Herpes family
causes Varicella (chickenpox) and Herpes zoster in normal or immunocompromised

VACCINE AVAILABLE!!!
Orthopoxvirus (dsDNA)
causes Variola (smallpox)

VACCINE AVAILABLE!!!
Trichophyton tonsurans,
Microsporum canis (Dermatologic fungal infection)
causes Tinea captitis (scalp ringworm)

found in animals and humans
Microsporum gypseum/canis,
Trichophyton rubrum (Dermatologic fungal infection)
causes Tinea corporis (scalp ringworm)

found in soil and humans
Epidermiphyton floccosum, Trichophyton rubrum (Dermatologic fungal infection)
causes Tinea cruris (jock itch)

found in humans
Trichophyton mentagrophytes, T. rubrum (Dermatologic fungal infection)
causes Tinea pedis (athlete's foot)

found in humans
Trichophyton rubrum (Dermatologic fungal infection)
causes Onychomycosis (nail infection)

found in humans

most difficult to treat b/c under nailbed
Blastomyces dermatidies (Systemic yeast infection)
causes Blastomycosis (lung fungal infection)

found in decaying plant material
Coccidoides immitis (Systemic yeast infection)
causes Coccidiodidomycosis (lung fungal infection)

found in soil
Histoplasma capsulatum (Systemic yeast infection)
causes Histoplasmosis (Ohio and Mississippi River valleys)

found in soil and bird poop
Aspergillus flavus, A. fumigatus (Systemic mold infection)
only occurs in immunocompromised (leading cause of death in cancer patients is fungal)

Lung fungal infection

found in decaying plant material and soil
Candida albicans (Systemic yeast infection)
only occurs in immunocompromised (leading cause of death in cancer patients is fungal)

Mouth fungal infection

found in human gut and oral cavity
Cryptococcus neoformans (Systemic yeast infection)
only occurs in immunocompromised (leading cause of death in cancer patients is fungal)

Brain fungal infection

found in fruit, pigeon droppings, and plants
Cryptosporidium parvum (Apicomplexa Protozoa- apical microtubule complex; reproductive cycle may incude sexual stage)
causes diarrhea in immunocompromised

found in domestic and wild animals

all stages develop in epithelial cells of stomach or intestine

Treatment: TMP/SMX (anti-folates)
Isospora bella (Apicomplexa Protozoa- apical microtubule complex)
causes diarrhea in immunocompromised

found in contaminated food or water with ooCYSTS

complex reproductive cycle with obligatory intracellular asexual reproduction in epithelium of small intestine and sexual stage

Treatment: TMP/SMX (anti-folates)
Plasmodium flaciparum/ovale/malriae/vivax (Apicomplexa Protozoa- apical microtubule complex)
causes Malaria

transmitted by arthropods

develops in hepatocytes in humans from erythrocytes; gametocytes taken up by mosquitoes during feeding with sexual stage in mosquitoes

DDT used in US but still found at Airports

Treatment: Quinolone Antimalarials
Toxoplasma gondii (Apicomplexa Protozoa- apical microtubule complex)
causes Toxoplasmosis (CNS infection) in immunocompromised (AIDS) and pregnant women - CROSS PLACENTAL BARRIER

transmission may be congenital, contaminative or via food chain

oocytes produced by felines and passed through feces

beef, pork, mutton contain CYSTS!!!

can infect pets, pests, and food

Direct Infection: eat pigs, beef
Indirect Infection: cat litter box disease from CYSTS)


survives/replicates within phagocytes as virulence factor

Treatment: Pyrimethamine with either Sulfonamides or Clindamycine (anti-folates)
Giardia intestinalis(Sarcomastigophora Protozoa - flagella, asexual)
causes diarrhea

found in extracellular lumen of small intestine

transmission by CYSTS!!!

Treatment: Metronidazole
Leishmania (Sarcomastigophora Protozoa - flagella, asexual)
causes cutaneous and visceral infection

intracellular (develops in macrophages)

transmission by arthropods

lacks flagella in vertebrate hosts
Trichomonas vaginalis (Sarcomastigophora Protozoa - flagella, asexual)
causes vaginitis

transmitted venereally

extracellular in vagina and urethra of both sexes

no cyst stage

Treatment: Metronidazole
Trypanosoma (Sacomastigophora Protozoa - flagella, asexual)
causes sleeping sickness

extracellular or intracellular
Entamoeba (Sarcomastigophora/Sarcodina Protozoa - pseudopods; asexual)
causes diarrhea (amebiasis) and liver abscess

extracellular and invasive

originally located in large intestine by may move into liver through portal system

trasmission via CYSTS

Treatment: Metronidazole
Babesia (Sarcomastiophora/Sarcodina - pseudopods; asexual)
causes Babesia

transmitted through TICKS and blood transfusions
Pneumocystis (unclassified Protozoa)
causes Pneumonia (PCP) in AIDS patients
TORCHS
Bugs that can cross placental barrier:

Toxoplasma
Rubella
Cytomegalovirus (CMV)
HSV
HIV
Syphilis
What is the only bug that can be acquired in the birth canal?
Streptococci
Rank Infectious Diseases by most mortalities in 2002
Lower respiratory infections
HIV/AIDS
Diarrhea
Tuberculosis
Malaria
Measles
Pertussis
Tetanus
Mengitis
Syphilis
Hepatitis B
Tropical Disease
Pertussus
normal microbial flora
microorganisms (mostly bacteria) commonly found on or in the bodies of healthy individuals.

Some are present extended periods of time and others are only briefly.

Most are commensal - bacteria benefit from symbiotic rlnship.
colonization
the growth of microorganism on/in body WITHOUT deleterious effects to the host due to the organism or immune response.

transcient colonization: organism eliminated rapidly

stable conlonization: organism remain long-term

colonization resistance: keeps human alive through protection (keeping pathogens away) and constant immune stimulation (low level).

**There are many more non-human cells in the body than human cells. (exterior-skin; interior-mucous membrane, GI, RT, and vaginal)
infection
invasion of cells, tissues or organs by pathogenic microorganisms which cause the body injury followed by an immune response that leads to further damage

it is usually accompanied by disease (signs and symptoms)
Which microbes make up our normal flora on our skin?
Skin:
Staph. epidermidis
Staph. aureus
Propionibacterium acnes
Corynebacterium

Which microbes make up our normal flora on our face?
Mouth and Tongue:
Strep. Vieridans
Lacotobacilli
Neisseria
Candida albicans (transcient)


Gums and Tonsils: (obligate gram neg. anaerobes)
Fusobacterium
Veillonella
Prevotella

Nose:
Staph. auerus
Strep. pneumoniae
Strep. pyogenes
Haemophalus influenzae
Neisseria meningitidis
Which microbes make up our normal flora in our GIT?
Ileum:
Bacteroidis fragilis
E. coli
Enterococcus faecalis
Enterococcus faecium

Colon:
Bacteroides fragilis (anaerobic gram neg.)
Prevotella (anaerobic gram neg.)
Fusobacterium (anaerobic gram neg.)
Clostrisdium (anaerobic gram pos.)
Peptostreptococcus (gram pos. anaerobe)
E. coli (gram neg. facultative)
Klebsiella (gram neg. facultative)
Proteus (gram neg. facultative)
Enterobacter (gram neg. facult.)
Streptococci viridans (gram pos.)
Lactobacilli (gram pos.)
Entercocci (gram pos.)
Which microbes are located in the vagina?
Doderlein's bacilli
Lactobacilli (gram pos)
Peptostreptococcus (gram pos anaerobe)
Clostridium (anaerobic gram pos)
Corynebacterium (gram pos)
Prevotella (gram neg. facultative)
Gardnerella vaginalis (gram neg. aerobe)
Streptococcus agalactia (gram pos. aerobe)
What purpose does skin serve as a non-immune defense?
physical barrier

normal microflora

dryness

sloughing of cells to remove bacteria

acidic environment from secretions that inhibit microbe growth
What purpose does mucous membranes in the GI, RT, and UT serve as a non-immune defense?
barrier

goblet cells

cilia

GALT and MALT produce IgA
What purpose does respiratory tract serve as a non-immune defense?
trapping system from air turbulence and nose with ciliated cells

saliva has lysozymes, lactoerrin and IgA

macrophages in alveolar cells
What purpose does GIT serve as a non-immune defense?
gastric acid kill bacteria but not spores (Clostridia have spores and H.pylori and Shigella are acid resistant)

pancreatic enzymes

cell turnover (shedding) and peristalsis

microflora

**Note: PPIs cause increased aspirations of microbes and lead to more infections.
What purpose does genitourinary tract serve as a non-immune defense?
flushing

acidity and solutes in urine (ammonia)

kidney hypertonicity prevents upward spread of bacteria

males have 4x's longer urethra so lower UTI incidences
What are factors that govern the initiation of an infection?
size of microbe (more bugs, increase infection)

virulence

immune competence

presence of underlying disease (DM)

compromised blood low

anatomical obstruction

indwelling foreign body (devices)

age/immunosenescence
What are the stages of infection?
1. Encounter: food, water, air body fluids (sex, blood, etc.), insects, animals, fomites, etc.

2. Entry (skin, mucous memb., inoculation -injection, trauma, bite, surgery)

3. Local infection (primary lesion): colonization/virulence; adhere (fimbrae)

4. Multiplicaton

5. Contiguous spread: cellular invasion (macrophages and PMN by phagocytosis and endocytosis) and tissue invasion (between cells)

6. Evasion of host defenses

7. Systemic spread (blood and lymph)

8. Distal lesions (secondary)

9. Damage: altered host cell functon, endo/extoxins, immune response

10. Outcome: trasmission to a new host; recovery or not

**Immune system attacks at steps 3,4,5,6.
What are the types of infections?
acute infection: rapid onset (hour-days) and brief duration (days-weeks)

chronic infection: organism persits for months-years

dormant infecton: cyclical periods of infection

carrier state: host sheds bacteria or spores to others (never fully recovered from infection)

secondary infection: microbial infectiom followng a different infection (ex. otitis media following viral infection)

mixed (polymicrobial) infection: two or more bacteria infecting the same tissue
What are opportunistic infections?

What are the risk factors?
caused by opportunistic pathogens incapableof infecting individuals with normal host defenses

Risk factors:
-neutropenia (chemotherapy)
-impaired cell-mediated immunity (chemotherapy, immunosupp. therapy)
-impaired humoral immunity (chemotherapy, steroids)
-loss of skin (catheter, devices)
-loss of mucous membranes (chemotherapy, prior infection)
-surgery (organ transplant)
-alteration of normal microbial flora (chemotherapy, hospital environment)
-blood products, donor organs (bone marrow, solid organ transplant)
Which microbes cause skin-soft tissue infections (SSTIs)?
Impetigo, Lymphangitis, Cellulitis:
Staph. aureus, Strep. pyogenes (crusty)

Folliculitis:
Staph. aureus, Kliebsella pneumonia, Enterobactor, Pseudomonas, Propionbacterim acnes, and Corynebacterium

Human bite wounds:
Eikenella, Staph. aureus, Strep

Animal bite wounds:
Pasteurella, Staph aureus, Strep
Necrosis: Corynebacterium, Bacteriodes, Strep. pyogenes

Treatment: drug that covers Staph, Strep, simple gram neg., Pseudomonas, and anaerobes
Which microbes cause onychomycosis (nail fungus)?
Trichophyton, Epidermophyton, and Microsporum

**Diagnose with KOH test
What microbes cause bone and joint infections?
Post trauma osteomyelitis:
Staph. aureus, Strep, gram neg. bacilli

Osteomyelitis:
Staph. aureus, gram neg. bacilli

Implanted devices:
Staph. epidermidis, Staph aureus, Strep, Enterococci, Enterobacter, Pseudomonas

Bite wounds:
Eikenella (human), Pateurella (animal)

IV drugs:
Pseudomonas, Staph

Osteomyelitis Tuberculosis:
Mycobacterium

Osteomyelitis in Immuno.:
Aspergillosis, Candida

Osteomyelitis in Sickle Cell:
Salmonella

Sepsis Arthritis:
Neisseria gonorrhoeae, Staph. aureas, Strep., gram neg. anaerobes
What microbes cause URTIs?
Otitis media (Risk factors): Viral, Strep. pneumonia, Haemophilis influenzae, Moraxella catarhalis, Strep. pyogenes, Staph. aureus, E.coli, Pseudomonas, Mycoplasma

Pharyngitis (Complications): Viral, Strep. pyogense, Haemop. influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, Corny diphtheriae (EMERGENCY)

Laryngitis (Croup): Parainfluenzae, RSV

Epiglottis (EMERGENCY): Haemop. influenzae

Sinusitis: Strep. pneumoniae, Haemop. influenze, Moraxella catarrhalis, Viruses, Strep. pyognes, Staph. aureus, Anaerobes
What microbes cause LRTIs?
Acute bronchitis: Mycoplasma, Chlamydia

Chronic Bronchitis: H. influnzae, Strep. pneum. Moraxella catarrhalis, Neisseria, Kleibella pneumonia, Psuedomonas, Serratia marcescens

Bronchiolitis (infants): RSV (55%), Parainfluenza

CA-Pneumonia: Strep, Haemophilis, Moraxella, Mycoplasma, Chlamydia, MSSA/MRSA, Anaerobes, Legionellla, Enterobact. Psuedomonas

HA-Pneumonia: Enterobact, Pseudomonas, Staph, Legionella, Anaerobes, Acinetobacter

Aspriation Pneumonia: Anaerobes and gram pos.

Fungal Pneumonia/Immuno.: Fungi - Aspergillus, Cryptococcus, Candida, and parasites

Tuberculosis: Mycobacterium tuberculosis
What microbes cause meningitis and CNS infections?
Meningitis (bacteria, virus, fungi): Strep. pneumoniae, Staph (MS/MRSA), Neisseria, Haemop. influenze, Listeria monocytogenes (opportunisitic), Enterobacteriaceae, Pseudomonas, and Viral (low mortality)

Encephalitis (usually caused by viruses): Herpes, Fungi, Listeria - high mortality

Brain Absess (usually bacterial): Staph (MS/MRSA), Strep, Haemo. influenzae, Enterobacteriaceae, Psuedomonas, Bacteroides fragillis, Anaerobes

Shunt Infections: Staph or Strep

Venous Sinus Thrombosis: Staph or Strep
What is bacteremia?
invasion of blood by pathogenic bacteria

Primary bacteremia: nosocomial infection from catheter or inoculation

Secondary: invasion of microbes from another site of infection into the blood

Infective endocardistis (IE): infection of the endocardial surface of heart, usually valves

Acute bacterial endocarditis (ABE): infection caused by Staph. aureus and is characterized by high fevers and has a rel. short toxic course of few days-weeks.

Subacute bactrial endocarditis (SBE): less severe infection caused by less virulent bacteria characterized by lower fevers, anorexia, weight loss, and night sweats lasting for several weeks
What microbes cause endocarditis?
Native Valve (Streptococcal): Strep. viridans and Strep. bovis

Staphylococcal IV drug user: MSSA/MRSA

Staphylococcal Prostetic Valves: MRSE, MSSA/MRSA, GNB

Enterocococcal: Enterococcus faecalis

HACEK (rare): oral bugs (slow) Haemop., Actinobacillus, Cardiobacteria, Eikenella, Kiegella

GNB (rare): Enterobacteria, Psuedomonas

Fungal: Candida, Aspergillus
What microbes cause Diarrhea?
Enterotoxigenic Diarrhea (Cholera), Enterohemorrhagic Diarrhea (E. coli), Traveler's Diarrhea (Shigella), Salmonella, Campylobacteriosis, Cryptosporidiosis, Staph, Clostridium/CDAD, Yersiniosis, Invasive Entamoeba (Dysentery), Giardia, Viral Gastroenteritis
What microbes cause GI infections?
Peritonitis (alcholism, chronic liver disease) - mostly gram neg. enterics and anaerobes: E. coli, K. pneumonia, Strep.

Biliary Tract/Cholangitis - mostly gram neg. enterics, anaerobes: E. coli, B. fragilis, Psuedomonas...some gram pos.: Strep. viridans/aureus post surgery

Fungal Peritonitis (CAPD): Candida

Cholecytitis (gall bladder): E. coli, Entrics, Enterococcus, Anaerobes (rare)

Peptic Ulcer Disease: Helicobacter pylori
What microbes cause UTIs?
Acute Cystitis: E. coli (90%), Staph. saprophyticus

CA-Pyelonephritis: E. coli, Protus

HA-Pyelonephritis: GNB: E. coli, Pseudomonas, Enterococcus

Catheter-Associated UTI: MRS, MSSA/MRSA, Enterococcus
**Vancomycin covers all

Acute Prostatitis (STD): Neisseria gonorrhea, Chlamydia, Enterobacteriaciae

Chronic Prostatitis: Enterobacteraciae, Pseudomonas, enterococcus

Urethritis: Neisseria gonorrhoeae, Chlamydia, Tichomonas, Ureaplasma, Mycoplasma
What microbes cause STDs?
Urethritis/Cervicitis/Prostatitis: Neisseria gonorrhaeae, Chlamydia

PID: Neisseria gonorrhea, Chlamydia trachomatus, Entric gram neg, Ureaplasma, Bactroides

Genital Herpes: HSV-1/2

Chancroid: Haemophilus ducreyi

Lymphogranulopa venerum: Chlamydia

Syphilis: Treponema palladum
**Very sensitive to penicillin (spirochete)

Ghonorrhea: Neisseria gonorrhea

Epididymitis: Neisseria gonorrhea, Chlamydia, E. coli

Vaginosis: Gardnerella vaginalis. Bacterpodes. {e[tpccis

Vaginalis: Trichomonas vaginalis
*Metronidazole

Genital Warts: Human Papillovirus
What microbes do you need to cover for with surgery?
Clean Surgeries
-Cardiothoracic, Orthopedic, Neurosurgery, Ophthalmic, Vascular/Graft Surgery, Breast: Treat for Staph

-Ophthalmic, Head/neck Surgery: Treat for Staph and Strep

Dirty Surgeries
Gastroduodenal, Biliary tract/Laparoscope/Cholecystectomy, Genitourinary, Obstetric/Gynecoloic, Colorectal, Appendectomy: Treat for Staph, Strep, GNB or anaerobes
What are some of the terminology used in antimicrobial therapy?
antibacterial agents: drugs directed against bacteria

antifungal agents: drugs directed against fungi

antiprotozoal agents: drugs directed against protozoa

antihelminthic agents: drugs directed against nematods

antiviral agents: drugs directed against viruses

antiseptics: compounds used topically to limit microbial growth; too toxic to unse internally

disinfectants: compounds used on inanimate objects (counter tops) to destroy microbes; too toxic for internal or external use

Germicides: disinfectants that can kill microbes rapidly

"cidal": kills (ex. RTI drugs)

"static": limits growth of population (uses immune system)
What are the natural antibiotics?
These have resistance to them.

PCNs (Pen-G)
Cephalosporins (Cephalosporin C)
Carbapenems (thienamycin)
Monobactams (aztreonam)
Glycoptides (vancomycin)
Lipopeptides (daptomycin)
Aminoglycosids (streptomycin)
Macrolides, Azalides, Ketolides (erythromycin)
Lincomycins (lincomycin)
Streptogramins ("synercid")
Tetracyclines (chlortetracycline)
What are the synthetic antibiotics?
Fluroquinolones (ciprofloxacin)
Oxazolidinones (linezolid)
Nitroimidazols (metronidazole)
Trimethoprim
Sulfonamides (sulfamethoxazole)

**Synthetic drugs don't get deactivated...that's why they are so popular!!!
What's the spectrum of activity for drugs?
Fluoroquinolones: BROADEST spectrum!
-treats Mycobacteria, Gram negative bacteria, Gram positive bacteria, Chlamydias, Rickettsias, and Mycoplasmas

Tetracycline:Gram negative bacteria, Gram positive bacteria, Chlamydias, Rickettsias, and Mycoplasmas

Erythromycin: Gram positive bacteria, Chlamydias, Rickettsias, and Mycoplasmas

Aminoglycosides: Mycobacteria, Gram negative bacteria, Gram positive bacteria

Cephalosporins, Penicillins, Sulfonamides: Gram negative and Gram positive bacteria

Isoniazid: Mycobacteria

Aztreonam: Gram negative bacteria

Vancomycin: Gram positive bacteria
What is the MOA of PENs, Cephalosporins, Carbapenems, and Monobactams?
These inhibit cell wall synthesis by binding to PBP enzymes

**Note: Microbes alter or make a new PBP site to block beta-lactams from binding ex. MRSA and PRSP (Penicillin Resistant Strep. pneumoniae). This is an example of altering the target site to develop resistance.

Microbes can also produce Beta-lactamases to develp resistance. This inactivates the drug.

Gram negative microbes can also alter the antibiotic accumulation by altering their porins in the outer membrane.
What is the MOA of Glycopeptides (vancomycin), Bacitracin, Isoniazid?
These inhibit cell wall synthesis

**Note: Microbes can alter their target site to block Vancomycin from binding ex. VRE (Vacomycin-Resistant Enterococci). This is an example of altering the target site to develop resistance
What is the MOA of Aminoglycosides, Tetracyclines, Macrolides, Azalides, Ketolides, Lincosamides, Chloramphenicol, Streptogramins, and Oxazolidinones?
These inhibit protein synthesis inside the cell by binding to ribosomes in the cytoplasm

**Note: Microbes can alter their ribosomal protein to block the actions of Aminoglycosides and methylate the RNA on their ribosome to block the actions of Macrolides, Clindamycin and Tetracycline. This is an example of altering the target site to develop resistance.

Microbes can also produce acetyltransferases, nucleotidyltransferases, and phophotransferases which are enzymes that change the drug structure of Aminoglycosides, Clindamycin, and Chloramphenicol to inactivate them.

Gram negative microbes can also alter the accumulation of Chloramphenicol by altering their porins in the outer membrane (ex. Pseudomonas).

Microbes can also have P-gp pumps in their inner membrane that actively efflux drug as a new or redirected transport system in order to alter Macrolides and Tetracycline accumulation (ex. Pseudomonas).
What is the MOA of Fluoroquinolones, Nitroimidazoles, and Rifampin?
These inhibit nucleic acid synthesis inside the cell by binding to enzymes (DNA gyrase, RNA polymerase)

**Note: Microbes can alter their DNA gyrase to block actions of FQ and alter RNA polymerase to block actions of Rifampin. This is an example of altering the target site to develop resistance.

Gram negative microbes can also alter the FQ accumulation by altering their porins in the outer membrane (ex. Pseudomonas)

Microbes can also have P-gp pumps in their inner membrane that actively efflux drug as a new or redirected transport system in order to alter FQ accumulation (ex. Pseudomonas).
What is the MOA of Trimethoprim and Sulfonamides?
These target the folate pathway by inhibiting enzymes (RNA polymerase, dihydrofolate reductase) so all purine synthesis is blocked and dUMP can't be converted to dTMP

**Note: Microbes can become insensitive to dihydrofolate reductase or increase production of the normal enzyme. This is an example of altering the target site to develop resistance.

Gram negative microbes can also alter the Trimethoprim accumulation by altering their porins in the outer membrane (ex. Pseudomonas)
What is the MOA of Polymyxins and Lipopeptides?
These disrupt the cytoplasmic membrane function/integrity outside the cell
What is the MOA of Polyenes: Amphoteracin B, Nystatin and what are they used to treat?
Antifungals: These are large, extremely polar and you can't take orally so have to be injected. They are EXTREMELY TOXIC!

These bind to ergosteral and cause fungal memberane disruption. These cause NEPRHOTOXICITY and INFUSION RXNS!!

Amphoteracin B: effective against every fungus (Dermatophytosis/TEM, Blastomycosis, Coccidiomycosis, Histoplasmosis, Aspergillosis, Candiasis, and Cryto/Coccosis) but very TOXIC!! This can be injected but causes HYPERSENSITIVITY RXNS AND NEPHROTOXICITY IN 50% OF PATIENTS (REVERSIBLE)!! ONLY USED FOR IMMUNOCOMPROMISED PATIENTS!!

Nystatin: effective against every fungus (Dermatophytosis/TEM, Blastomycosis, Coccidiomycosis, Histoplasmosis, Aspergillosis, Candiasis, and Cryto/Coccosis) but it is the too TOXIC! YOU CAN'T INJECT NYSTATIN!! ONLY USED TO TREAT CANDIDIASIS!
What is the MOA of Imidazoles: Clotrimazole, Ketoconazole, Miconazole?
Antifungals: These were made first. They were made to retain the efficacy of Amphotericin B but are not as toxic. These block ergosterol biosynthesis by inhibiting CYPs. These attack ergosterols in a different way. They are large and lipophillic so they require acidity to solubilize. DO NOT TAKE WITH PPI'S!!! They have good oral activity.

They are powerful CYP INHIBITORS!!!

ALL IMIDAZOLES CAN TREAT ALL FUNGI BUT LESS POTENT THAN TRIAZOLES!!!

KETOCONAZOLE CAUSES GYNECOMASTIA BECAUSE IT INHIBITS HUMAN STEROID BIOSYNTHESIS!!!
What is the MOA of Triazoles: Fluconazole, Itraconazole, Voriconazole, Posaconazoles and what are they used to treat?
Antifungals: These block ergosterol biosynthesis by inhibiting CYPs. These attack ergosterols in a different way. They are large and lipophillic so they require acidity to solubilize. DO NOT TAKE WITH PPI'S!!! They have good oral activity.

They are powerful CYP INHIBITORS!!!

ALL TRIAZOLES CAN TREAT ALL FUNGI!!!
What is the MOA of Allylamines: Terbinafine and what are they used to treat?
Antifungals: These block ergosterol biosynthesis by inhibiting CYPs. These attack ergosterols in a different way. They are large and lipophillic so they require acidity to solubilize. DO NOT TAKE WITH PPI'S!!! They have good oral activity.

They are powerful CYP INHIBITORS!!!

ALLYLAMINES ARE THE MOST EFFECTIVE AGAINST DERMATOPHYTOSIS (TEM)!!!
What is the MOA of Echinocandins: Caspofungin and what are they used to treat?
Antifungals: These inhibit fungal cell wall (beta-1,3-glucan). They have a narrow spectrum and have less ADRs than Polyenes.

NO CYP DIs!!!

ECHINOCANDINS ARE ONLY EFFECTIVE AGAINST YEAST INFECTIONS (APERGILLOSIS, CANDIDIASIS)!!!
What is the MOA for antimetabolites: 5-Fluorocytosine and what are they used to treat?
Antifungals: It behaves like a MECHANISM BASED INHIBITOR where it inhibits DNA and protein synthesis by blocking biosynthisis of dTMP. The side effect is that they suppress bone marow and GI. THESE HAVE RAPID RESISTANCE SO YOU HAVE TO USE WITH AMPHOTERICIN B.

ANTIMETABOLITES ARE ONLY EFFECTIVE AGAINST YEAST INFECTIONS (CANDIDIASIS AND CRYTO/COCCOSIS) WITH COMBINATION THERAPY!!!
What is the MOA of metronidazole and what is it used to treat?
Antiprotozoal: Used to treat Entamoeba histolytica, Giardia intestinalis, and Trichomonas vaginalis
What is the MOA of Quinolines: chloroquine, hydroxychloroquine, mefloroquine, and priquine and what are they used to treat?
Antiprotozoal agents: They work as ANTIMALARIALS and are used to treat Plasmodium
What is the MOA of Pyrimethamine in combination with Sulfonamides or Clindamycin?
Antiprotozoal agents: They block the folate pathway and prevent the production of dTMP. They are used to treat Toxoplasma
What is the MOA of Trimethoprim-Sulfamethoxazole and what are they used to treat?
Antiprotozoal agents: They block the folate pathway and prevent the production of dTMP. They are used to treat Cryptosporidium parvum, Isospora belli, Pneumocystis carinni (a fungus)
Which RNA viruses have vaccines?
Poliovirus
Hepatitis A
Dengue fever and yellow fever virus
Eastern equine encephalitis
Rubella virus
Rotavirus
Influenza
Rabies
Measles
Mumps
Which DNA viruses have vaccines?
Chronic Hepatitis B
Condyloma acuminatum (genital warts)
Varicella (chicken pox)
Variola (small pox)
Which DNA viruses have drugs for treatment? "ovir"
Herpes
CMV
EBV
HHV-6
Varicella
Which bacteria have vaccines?
Tetanus
Diphtheria
Pertussis
Strep. pneumoniae
Neisseria meningitidis
Haemophilus influenza
Salmonella typhi
Bacillus anthracis
Vibrio cholerae
Yersinia pestis
What is microbial resistance?
the natural or acquired capacity of a pathogenic microorganism to survive the deleterious effects of an antimicrobial agent

It is a function of:
*the pathogen
*the antibacterial agent
*the concentration of the antibacterial agent
What are MDROs?
Multidrug-Resistant Organisms

1. Methicillin-Resistant Staph. aureus (MRSA): also includes HA-MRSA and CA-MRSA

2. Multi-Drug Resistant Strep. pneumoniae (MDRSP)

3. Vancomycin-Resistant Enterococci (VRE)

4. Gram-Negative Bacilli (GNB)
*Escherichia coli (ESBLs) - produce beta-lactamases
*Klebsiella pneumoniae (ESBLs) - produce beta-lactamases
*Acinetobacter baumannii (multiple mechanisms)

*Pseudomonads: (Multi-Drug Resistant)
***Pseudomonas aeruginosa (Amp C resistance)
***Stenotrophomonas maltophilia (CPases)
***Burkholderia cepacia
What contributes to resistance?
Over-prescribing of antibiotics

Inappropriate use of antibiotics

Out-patient care and transmission (MRSA)

Implanted medical devices

Increases in patients with immunologic diseases

Increased travel, trans-continental exposure

Agriculture use of antimicrobials as "growth promoters" (99% of antibitics go here)

Biocide use: "Home Hygiene Products"

Animals

Resistance transmission from environment and microflora
How do microbes acquire resistance?
1. Innately/Inherently
a. Viruses, Fungi and Protozoa are resistant to beta-lactams
b. Gram negative pathogens are resistant to Vancomycin because they have pores and Vancomycin is big

2. Aquired
a. Mutation: ex. Staph. areus ad Psuedomonas altered their DNA gyrase so FQ can't bind

b. Acquisition
**Transformation: uptake of "naked" DNA from outside of the cell that gets incorporated into bacterial chromosome (e. Strep. pneumoniae, Neisseria gonnorrheae, and Haemophilus influenzae.
**Transduction: infecton of the cell by a virus (bacteriophage) vector that carries new DNA. This is the least important in resistance. (ex. Staph. aureus)
How do microbes acquire resistance?
b. Acquisition (cont.)
**Conjugation: a direct, unidirectional transfer of DNA from once cell to another via physical contact between sex pilli. It is mediated by plamsids (small, independently replicated, circular DNA molecules which carry nonchromosomal genes that allows for environmental adaptation). Plasmids are used for fertility (transfer of genetic info), antibacterial resistance, production of virulence factors such as exotoxins and adhesions, and utilization of nutritional sources.
**Transposon/Integrons (Jumping Genes): this is when genetic elements are moved from on part of the chromosome to another. Also genetic information can be shared beween plasmids and chromosomes within the same cell. This now is a permanent part of the chromosome.

MUTATION AND CONJUGATION ARE THE 2 MAIN WAYS THAT BACTERIA ACQUIRE RESISTANCE!!!
What is horizontal transmission vs. vertical transmission?
Vertical transmission is replication species (1 cell --> 2 cells --> 4 cells, etc.).

Horizontal transmission is conjugation between 2 different species (they share genetic info between plasmids). They only have to be in the same environment to do this.
What are the major bacterial resistance determinants for Staph aureus?
MRSA (modified PBP target and produces Penicillinases)
What are the major bacterial resistance determinants for Streptococcus pneumoniae?
altered PBP target (PCNs)
decreased binding (Tetracycline)
methylated ribosome (Erythromycin)
What are the major bacterial resistance determinants for Neisseria gonorrheae?
beta-lactamases (PCNs)
alterned DNA gyrases (Quinolones, Cephalosporins)
What are the major bacterial resistance determinants for Mycobacterium tuberculosis?
resistant to antituberculosis drugs (several mechanisms)
What are the major bacterial resistance determinants for Enterococcus faecium/faecalis?
beta-lactamases (PCNs)
altred binding site (Vancomycin/VRE)
What are the major bacterial resistance determinants for Staph. epidermidis?
altered PBP target (MRSE)
What are the major bacterial resistance determinants for Acinetobacter baumanii?
All 3 mechanisms: altered binding site, beta-lactamase enzyme production, and efflux
What are the major bacterial resistance determinants for Enterobacter cloacae?
produce beta-lactamases against AmpC and Cephalosporins
What are the major bacterial resistance determinants for Klebsiella pneumonia?
produce beta-lactamases against AmpC and Cephalosporins
What are the major bacterial resistance determinants for Pseudomonas?
All 3 mechanisms: altered binding site, beta-lactamase enzyme production, and efflux
What are the major bacterial resistance determinants for Stenotrophomonas maltophilia?
produce carbapenemases which chop up all PCNs and beta-lactams
What is breakpoint?
Antibacterial drug breakpoints represent the highest MIC (90)for which the unbound plasma concentrations of the antimicrobial drug (following standard doses) are sufficient to achieve the PK/PD target against a defined organism and for which adequate clinical data support their use.

It is calculated by multiplying the Avg Cpx (peak concentration of drug) by Pbf (extent of protein binding of drug) and then dividing that value by the half-life factor of the drug multipled by (MIC 90 x 4).

The half-life ranges between 0.5 and 2.

4 is a shift factor.
How do you use breakpoint?
Those with a "low" breakpoint would fall in the "susceptible" range. Here, the infecting organism should respond to therapy with the antibiotic in question. (ex. PSSP - Penicillin Susceptible Strep. pneumoniae)

Those with between "low" and "high" breakpoint fall within the intermediate range. Here the MIC of the infecting organism either falls into a range inwhich it apporaches or exceeds the concentreation of the antibiotic which can ordinarily be achieved. In this case, increase the dose. (ex. ISSP - Intermediate Susceptible Strep. pneumoniae)

Those who are esistant have an infecting organism which would not respond to herapy no matter how much drug is given. In this case, find another drug to treat with. (ex. PRSP - Penicillin Resistant Strep. pneumoniae)
What is TI?
Therapeutic Index = Toxic dose for humans / Toxic dose for "bugs"
What determines the activity of antibiotics?
MICs and Breakpoints

Aminoglycosides/Fluroquinolones have high Cmax/MIC

FQ/B-lactams/Vanco. have to have AUC>MIC

Vanco/Beta-lactam have Time>MIC