Infection pt 1 (copy)

Inadequate Immune response (immune deficiency)

* (1) exaggerated against noninfectious environmental substance (allergy)
* (2) Misdirected against the body’s own cells (autoimmunity)
* (3) directed against beneficial foreign tissues, such as transfusions or transplants (alloimmunity)

Communicability

* The ability to spread from one individual to another.

(higher communicability = easily spread ex. measles spread through touch, low communicability = not easily spread ex. HIV through sexual intercourse)

Infectivity

* The ability for the pathogen to invade and multiply in the host.

(herpes virus can survive long periods of time in the latent stage).

Virulence

* The capacity of a pathogen to cause severe disease.

(ex. Ebola is highly virulent)

Pathogenicity

* the ability of an agent to produce disease-success depends on communicability, infectivity, extent of tissue damage, and virulence.

(ex. HIV can cell T-cells)

Portal of entrance

* the route by which a pathogen infects the host.

(ex. direct contact, inhalation, ingestion, or bite from animal)

Toxigenicity

The ability to produce soluble toxins (endotoxins), which are factors that influence the pathogens degree of virulence.

Biofilms

* multicellular mass which consists of mixed species such as bacteria, viruses, fungi.
* Biofilms increase the survival of these pathogens from the hosts responses and exposure of antibiotics.

Exotoxin

* Polypeptide proteins excreted by living gram

(-/+) bacteria

* Is released by cells
* Highly toxic
* elicits inflammatory response

Endotoxin

* LPS complexes produced at the time of gram (-) bacteria death
* moderately toxic
* Part if the bacteria chromosomal genes

Anaerobic bacteria

* Producing energy without oxygen

Aerobic bacteria

* produces energy with oxygen

Bacteraemia

* occurs when bacteria is present in the bloodstream.
* When bacteria is growing in the bloodstream they release endotoxins which may lead to endotoxic shock
* Gram (-) in blood stream produce sepsis

Antimicrobial Stewardship

The appropriate selection, dosing, choice of route, and duration of antibacterial drugs

Antiseptic

inhibits the growth and reproduction of microorganisms but doesn’t necessarily kills them, known as a static agent

Prophylactic therapy

there use of antibiotics before infections have occurred to prevent them (before surgeries)

Empiric Therapy

The treatment with a antibiotic for a assumed bacteria before cultures are available to not delay treatment

disinfectant

Kills microorganisms

Superinfection

* (1) development of a infection while treating a different one as it is resistant to the antibiotics being used
* (2) A second infection occurs due to a patients weekend immune system

Shapes of Bacteria

* Spirilla (like a spring)
* Bacilli (rod)
* Cocci (round)
* +
* Coccobacillus (oval)
* Vibrio (boomerang)
* Spirochete (spiral)

Gram (+)

* purple staining (because there is less layers so the stain penetrates more)
* Releases exotoxins = local tissue damage

Gram (-)

* Stains pink (because there are more layers)
* releases endotoxins (stays in bacteria much longer so is able to reproduce and spread around the body before bursting so hard to detect)
* harder to treat with antibiotics as they tend to be more resistant as their cell walls are thicker, and harder to penetrate.

Definitive therapy

when the bacteria culture is complete so specific antibiotics can be used to destroy it

Pseudomembranous colitis

* c-difficile
* antibiotic acquire diarrea

Sulfonamides

* Bacteriostatic, inhibits synthesis of folate acid in bacteria


* One of the first groups of antibiotics


* often combined with other antibiotics
* Most common in allergic reactions
* Broad spectrum (gram + & - )
* Used for upper respiratory and UTIs

(can’t be used with anti-diabetic, oral contraceptive, or phenytoin drugs)

Beta-Lactam antibiotics

* penicillins
* carbapenems
* Monobactams
* Cephalosporins

Cephalosporins

Beta-Lactam Antibiotics

* Bacteriocidal
* Beta-lactam ring can be susceptible to beta-lactamase


* Potential cross-sensitivity with penicillins if an allergy exists, due to having similar mechanisms to penicillins and being cousins
* Semisynthetic broad spectrum antibiotics (good gram (+) coverage, poor gram (-) coverage, better coverage as you increase generations, and more potent.
* You have to go in a sequence of generations can’t use generation 4th then 2nd.

1) 1st Generation: used for surgical prophylaxis and susceptible staph infections.

2) 2nd Generation: Better gram (-) coverage then 1st.

3) 3rd Generation: most potent gram (-) coverage, less active gram (+) coverage.

4) 4th Generation: Broader spectrum then 3rd generation, especially gram (+), used for UTI’s.

Macrolides

* common to treat strep throat infections
* Bacteriostatic but can become bactericidal in high concentration.
* Treats upper & lower respiratory infections, syphilis, Lyme disease, gonorrhea, chlamydia
* Inhibits bacteria synthesis by tightly coiling its DNA so it can’t uncoil it.
* Used if someone is allergic to penicillin

(erythromycin is popular)

(Fidaxomicin is one of the only drugs to treat c-difficle)

Monobactams

B-Lactam Antibiotics

* not commonly used
* Bactericidal primarily for gram (-)

(cayston is the drug of choice for cystic fibrosis patients with chronic pulmonary infections)

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Carbapenems

B-Lactam Antibiotics

* Broadest spectrum antibiotic to date
* Reserved for large body cavity infections
* Must be infused over 60 mins
* If any irritation at the site of infusion slow down the rate
* May cause seizure activity (avoid with proper dosing)

Penicillins

B-Lactam antibiotics

* used to treat gram (+) bacteria (strep, staph, entero)
* if allergic to penicillins maybe allergic to all b-lactam antibiotics, especially cephalosporins,

(Interactions; Warfarin, NSAID’s, Oral Contraceptives)

* Patients with a history of hives, throat swelling with penicillin, should not take cephalosporins

Aminoglycosides

* Bactericidal to most gram (-) & some gram (+)
* very potent, high risk of toxicity (must monitor through blood levels)
* Not given orally due to poor absorption
* Often given with other antibiotics for a synergistic effect
* Reserved for large infections
* If trough levels are too high, withhold the next dose for adequate renal clearance
* Antibiotic resistance can occur as bacteria can develop enzymes to stop its successfulness
* Given to people with kidney disease as a last-ditch effort, also half-life is doubled if the kidneys don’t work properly
* May cause ototoxicity or nephrotoxicity
* Must be carful with older patients who may have natural kidney disfunction
* if used with drugs such as loop diuretics that are ototoxic may cause more damage

Tetracyclines

* Bacteriostatic
* Broad spectrum gram (+) & (-)
* Should not be used in children under 8yrs, pregnant, breast feeding, or with diary products.
* Will discolour teeth and deform fetal skeletons as it binds to calcium.
* Treats acne

Ototoxicity

* toxicity to the ears

Nephrotoxicity

* Toxicity to the kidneys

Synergistic effect

* Drug interaction in which the bacterial killing effect of two antibiotics given together is greater than the sum of the individual effects of the same drugs given alone.

Therapeutic drug monitoring

monitoring of plasma drug concentrations and dosage adjustments based on lab values.

Vancomycin

* similar to ahminoglycosides
* Treats c-difficle
* usually given through IV, gets in cerebral spinal fluid and cross blood brain barrier, placenta barrier
* Ototoxicity = first symptom (tinnitus) = ringing
* Very caustic = high PH. (will burn tissue if leaves blood vessels)
* Given through central line into superior vena cava where blood volume is 2L/min so it can dilute compared to the hand which is 30mL/min
* Will cause red man syndrome = slow down perfusion
* if turning red at 30mins slow down to 45mins

Miscellaneous Antibiotics

* Clindamycin: (necrotizing bacteria)
* Metronidazole (flagly): c-difficle/ bacteriostatic
* Fluoroquinolone’s: bactericidal, broad spectrum used for bacteria that is resistant

Quinolone

* Very potent
* also known fluroquinolones
* broad spectrum
* used for complicated bone infections

The complement system and infection:

1. the complement system makes plasma proteins that attach to microbes and opsonize them. this increases the chance that they will be phagocytized and killed. it’s like putting a red flag on them.
2. small pieces of some of the plasma proteins act as chemoattractants and draw more phagocytes to the site of the activation and also activates these phagocytes
3. the terminal complement components damage certain bacteria by putting pores in the bacterial membrane. the pores allow extracellular contents to enter and kill the bacteria

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what is a pathogen?

it is a microbe that can produce a disease, most common being bacteria and viruses.

they must be able to find to specific human cell receptors to cause disease.

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they can cause disease by either: destroying the cell, exposing the cell to toxins or messing with the cells metabolism.

what is an obligate parasite?

it needs a host to survive it can’t live independently.

what are facultative parasites?

they can live either in the host or outside the host independently in water or dirt for example.

bacteria structure

single-celled organisms that may be aerobic or anaerobic.

bacterial structure:

they have an indiscrete nucleus meaning it’s not separate from the cytosol (cytoplasm of bacteria)

they have ridgid cell walls and a flagella for movement

what are the 3 shapes of bacteria?

cocci (circles), bacilli (rods) or spirochetes (spirals)

bacteria: endotoxins and exotoxins

Endotoxins: gram-negative bacteria. have them as they have a thicker cell wall. Endotoxins cause a massive inflammatory response and clotting. they also stay in the bacteria a lot longer, and it is harder to break the cell wall of gram -, so when it does release it releases a lot of toxins all at once. often what leads to sepsis. there is more as the bacteria have more time to replicate before releasing endotoxins.

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Exotoxins: released by gram-positive bacteria, released into the surrounding tissue to cause damage. the toxins are released more locally at the site while it enters. but it spreads quickly. this causes tissue damage.

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some bacteria also produce enzymes that have similar effects to exotoxins.

What is sepsis normally caused by?

endotoxic shock, by gram negative bacteria.

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when the membrane of gram negative bacteria erupt (lysis) they release the endotoxins within. they release into circulation in moe of lipopolysaccharide. then it binds to the LPS binding protein.

what aspects of bacterial activity would be effective for pharamacologic treatment?

the cell wall of the bacteria.

flagellum so it’s can’t move around

it’s ability to replicate.

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viruses

obligate intracellular microbes: meaning they need a host to survive and they live in the cells of the host rather than the outside feeding off resources like bacteria

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the virus attaches to a host cell and its viral genetic material enters the cell, it takes control of the host cell nucleus.

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it then uses this cell to synthesize viral proteins and nucleic acids.

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it then replicates itself and the virons get released by host cell lysis but sometimes also budding form the host cell.

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viruses can mess with our DNA. they can cause dna mutation which can lead to alliterated differentiation and proliferation. which can cause cancer.

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virus structure

**they have genetic material** they can have either DNA or RNA.

**they have a membrane envelope and capsid.**

a layer of fatty acids that cover them, they usually get it from the membrane of the host cell.

**they have ligands on their surface** which are proteins that stick out, they act as keys to recognize the cell to be infected and invade that cell.

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steps of viral replication:

1. virus enters
2. attachment to host cell and penetration
3. uncoating of viral DNa or rna enters the host cell nucleus and takes control of the host cell DNa.
4. host cell synthesizes the viral compounds
5. assemble new viruses (replicating)
6. release of many new viruses and host cell lysis. (cell breaks open, dies and viruses spill out).