1-Selective Toxicity

(Antimicrobial drugs have selective toxicity)

2-MIC

1 -The ability of a drug to kill invading microorganisms w/out harming the cells of the host

-Cancer drugs dont have selective toxicity, they kill host cells almost as well as they kill cancer cells

2-MIC-minimum inhibitory concentration- min dose of drug that will get the job done

1.Bacteriostatic

2.Bactericidal

3. Pt. Factors

1-Bacteristatic: these limit the reproduction and growth of bacteria, so that the hosts immune system can dominate the bacteria.  Don´t work well in immunocompromised pts. used for common infections, eg-ENT, Sinus

2-Bactericidal: Kill the pathogens themselves, more aggressive. used in immunocompromised pts…these drugs don’t depend on host immune system to kill.

3-Pt factors: Age, Preg./lactation, Liver/kidney function, immune status, allergy, location of infection, $$ (don’t give antibiotics that are eliminated by an organ that isn’t functioning.)

Bacterial statics-educated guesses about what organism is causing a person’s ailment based on the fact that certain, common, organisms are usually found in certain body areas

-If a patient is severely ill and hospitalized the MD would not do this, they would get a culture and sensitivity test to ID the organism and then prescribe an antibiotic with specificity for it.

1-Emperic/Initial therapy- Used in critically ill, no time to figure out the pathogen, so you use a broad spectrum antibiotic and hope it kills the one causing the illness

2-Definitive therapy-when you ID an organism and choose abx specific for it

1-Name and describe Gram + bacteria

2-Name and describe Grame - bacteria

1-Staph and Strep

Corina Likes Bad Clocks

Corinebacterium, Listeria, Bacillus-(in the name, not just the shape), Clostridium

-Thick cell wall, Purple

2-everything else

-Thin cell wall with extra (outer) LPS layer (endotoxin), RED/Pink

1-Bacterial cell wall synthesis (3 stages)

2-How do drugs work

1-  Stage 1-bacteria synthesize 2 different 5 amino acid chains in cytoplasm, NAG and NAM

Stage 2-Formation of peptidoglycan chain, NAG-NAM-NAG-NAM etc

Stage 3-different peptidoglycan chains are crossed-linked together by Transpeptidase enzymes (aka PBP's-penecilin binding protiens)

2- Drugs bind to Transpeptidase and inhibit it

Beta-Lactam Antibiotics

1-name 4 classes

2-MOA

1- Penicillins, Cephalosporins, Carbapenems, Monobactams

2-MOA-Inhibit stage 3 of bacterial cell wall synthesis

-these drugs have a square ring that inhibits stage 3, bacteria are hypertonic so when the cell wall becomes weak, osmosis-water rushes into bacteria-> lysis

-bacteria also kill themselves when they are damaged

Bacterial Resistance(R)

Tell 4 ways bacteria are resistant (against B-Lactum Antibiotics?)

1- Some bacteria have Beta-lactamases-(an enzyme that breaks open the square ring (eg-penicillinases and cephalosporinases)

2-bacteria have Modified Transpeptidase that reduce drug binding

3-Decreased entry of drug thru outer membrane/porins

4-bacteria have Efflux pumps that activly pump the drug out of the bacteria

Penicillin

1-general info

2-first through fourth generation

3-Penicilline allergy

1- Are Beta-Lactam Antibiotics (have a 4-sided Beta-Lactam Ring which is their key structure that binds the drugs to the bacterial Transpeptidase Enzymes) (inhibit cell wall)

-Cause the most amount of allergies of all the Bacterial Cell Wall Inhibitors

-Are all water soluble, excreted almost unchanged in urin, short half life, 30-60 minutes, usually given 4 times a day, people w/ kidney disease have a longer half life, up to 10 hours, be careful with PCN and people with kidney disease.

2-first gen.- Benzyl, narrow spectrum gram +

second gen-Amino, extended spectrum

third gen-Carboxy increased spectrum into more gram-

fourth gen-Uride broad spectrum

-Abx used in animal feed, when people eat the animal they can develop an allergy

-minor antigenic determinant-intact ring low % of allergies but very serious (anaphylaxis)

major antigenic determinant-broken ring allergy, higher %, but less severe, delayed rxn like a rash (unfortunatly even if its not an allergy it is still marked as an allergy, all antibiotics can cause a rash)

1st generation (Natural PCN)

1-main drugs

2-excretion

3-duration

4-spectrum

PCN G(different Preps)-IV,IM

PCN V (Pen VK)-Oral

2-Urin via tubular secretion, drug is mostly unchanged

3-t 1/2=30to60 minutes

-almost all PCN is water soluble, short duration

4-Narrow spectrum, mostly Grm+ ENT and Strep infections, (not effective for Grm- eg-E.coli)

2nd generation (semisynthetic)

1-2 main drugs

2-advantage of 2nd gen.

1-Ampicillin (PO, IM/IV)

-Amoxicillin (PO)

2-reliable oral bioavailability

-extended spectrum GM+ same as Pen G also effective against some common Gm -

3-Not resistant to B-lactamases

3^rd Generation

PCN

Less Grm+ than 1^st and 2^nd, but works against more serious Grm-

-Proteus Vulgaris

-Pseudomonas Aeruginosa

-not resistant to B-Lactimases

Made of Disodium salts, 2 salts, compared to the other PCN, watch in people w/ heart disease

4th Generation

PCN

-Parenteral

-not resistant to B-Lactimases

-Very broad spectrum, almost all Grm+ and Grm- and also Anaerobes

- Proteus Vulgaris

-Pseudomonas Aeruginosa

-Eneterobacter

PCN Hypersensitivity Reactions

MINOR ANTIGENIC DETERMINANT: 

MAJOR ANTIGENIC DETERMINANT: 

MINOR ANTIGENIC DETERMINANT:  You can become allergic to the intact drug that has not had its bond broken.-Less common but reaction is way worse

MAJOR ANTIGENIC DETERMINANT:  You can become allergic to the drug in its broken molecule form.-More common but reaction is only minor, rash etc.

*All antibiotics can cause rash, not all rashes caused by antibiotics are allergic

Hypersensitivity Type I

-timing

-mediated by

-symptoms

-Occurs within the hour, immediately

-Mediated by IgE antibodies

-Uticaria, Angioedema, Anaphlaxis

Hypersensitivity Type II

-timing

-mediated by

-symptoms

Delayed (could occur within days)

Cytotoxic Antibodies of IgG

Hemolytic Anemia

Hypersensitivity Type III

-timing

-mediated by

-symptoms

Delayed (could occur within days)

Formation of immune complexes of IgG or IgM

Serum Sickness

Hypersensitivity Type IV

-timing

-Sx

Delayed (could occur within days)

Occurs after 72 hours

Dermatitis, Rash

*Most Common Type Of Hypersensitivity RX

this is a class of drugs that looks similar to Penicillin in its chemical structure These drugs have a great attraction to Beta Lactamases enzymes and so are paired or combined with a penicillin so that the Beta Lactamase Inhibitor can bind to the Beta Lactamases and the penicillin can work effectively.

Bind to and Inhibit Beta Lactamase Enzymes

Amoxicillin + Clavulanic Acid = Augmentin

Ampicillin + Sulbactam = Unisyn

Cephalosporins

-type of antibiotic

-MOA

-Resistance

-excretion

-Beta-Lactam Antibiotics-meaning they have a 4-sided Beta-Lactam ring which is their key structure that binds the drugs to the bacterial transpeptidase enzymes

-Similer to PCN

MOA-inhibit bacteria cell wall synthesis

-same adverse effects ass PCN

-affected by the same resistance mechanism as pcn but are more resiliant against beta-lactamases, so if pcn isnt working you can try cephalosporins

-same excretion as PCN (excreted unchanged in urin via tubular secretion)

Cephalosporins

-cross-allerginicity

-about 5-10% of people allergic to pcn, are also allergic to cephalosporins

-generally you can give cephalosporins to people who are allergic to pcn, unless they have developed an immediae type I hypersensitivity rxn to pcn, if they had a delyed, just rash rxn they can use them.

Cephalosporins

-Generations

The Generations are based on the drug’s ability to affect GRAM – organisms. As you go from the 1st generation to the 4th generation:There is a gradual decrease in GRAM + coverage There is an increase in GRAM – coverage

There is an increase in CNS penetration The 3rd and 4th generation cephalosporins are lipid soluble (unlike the penicillins) and so can get into the brain.

There is an increase in resistance to inactivation by Beta Lactamases

1st Generation Cephalosporins 

Gram + spectrum is similar to Penicillin G, Mostly used common Gram+,  Strep and StaphCan be used on Staph that Penicillin cannot work on

Gram – spectrum is similar to Penicillin’s first generation in that they work against common Gram – organisms

E. Coli

Proteus Mirabilis

Klebsiella Pneumoniae

Are drug of choice to treat Klebsiella Pneumoniae

DO NOT affect H. Influenza

 eg-Cefazolin  IM/IV, Cephalexin  PO

2nd  Generation Cephalosporins 

Gram + activity goes down a little bit, not as potent as 1st generation Have increased Gram – activity

ARE effective against H. Influenza

Neisseria Gonorrhea  (cefaclor)

Neisseria Menigitidis  (cefoxitin)

Anaerobes (cefoxitin)

Bacteroids Fragillis

Cefoxitin  (Mefoxin)IM/IV,Cefaclor  (Ceclor)   PO

Has less of a Gram + spectrum but because the lipid solubility of the drugs increases they can be used to treat Gram + Meningitis (cn cross blood brain barrier).

They are the drug of choice for CNS gram + infections

Covers most Gram – organisms, even the serious ones

Pseudomonas Aeruginosa

Has increased resistance against Beta Lactamases

 Cefoperazone  (Cefobid)IM/IV, Ceftriaxone  (Rocephin) IM/IV

Excellent penetration into brain

Increased stability against Beta Lactamases

Good activity against all Gram – rods and Gram + organisms

Indicated for moderate to severe complicated infections

Must be administered parentally

 Cefepime (Maxipime) IV

A.      Beta-Lactamase Inhibitors

-similar to Penicillin in its chemical structure and has antibiotic activity.

These drugs have a great attraction to Beta Lactamases enzymes and so are paired or combined with a penicillin so that the Beta Lactamase Inhibitor can bind to the Beta Lactamases and the penicillin can work effectively.

Bind to and Inhibit Beta Lactamase Enzymes

Amoxicillin + Clavulanic Acid = Augmentin

Ampicillin + Sulbactam = Unisyn

Cephalosporin Adverse Effects:

Similar to Penicillin

Bleeding

Disulfiram Reactions

Carbapenems

Moa

type

administraion

Same MOA as the Penicillins and Cephalosporins

Are Beta-Lactam Antibiotics

Only used Parentally

Broad Spectrum for Gram + and Gram – and Anaerobes

So they are mainly indicated for serious infections

Demonstrates good resistance to Beta Lactamases but are not effective against MRSA

Imipenem Cilastin  (Primaxin)  IV, Meropenem  (Merrem)  IV

Vancomycin

-Type

-how does it work

*NOT a Beta Lactam Antibiotic-This antibiotic interferes with the bacterial cell wall synthesis in step two of the process, the formation of the peptidoglycan chains.

-it Is Bacteriocidal

-(Has a more limited spectrum) Gram + organisms=Staph (including lactamase producers)

MRSA and C-Diff

Resistant Strep

Resistant Enterococci

Mostly used to treat MRSA and Clostridum Difficile, which is an organism that lives in the GI tract and can cause a super infection called Pseudomembranous Colitis, which can give you severe diarrhea and cause death.

Usually administered parentally, except when dealing with C-Diff

Resistance is increasing

Vancomycin

Adverse Effects:

Ototixicity (deafness)

Nephrotoxicity

Red Man Syndrome

Rapid IV administration provokes histamine release in upper body and you get flushing, rash, urticaria.

Serious Rashes like Bullous Dermatosis or Steven Johnson Syndrome

Otitis Media

Drug of choice

1st-Amoxocillin

2nd-Augmentin, if it doesn't work

3rd-Zythromycin if that doesn't work

Pharyngitis

-drug of choice