Antimicrobials And Anitviral - Facts

Front 1

What is the minimum conc that will cause complete inhibition of cell division of the organism.

What is the minimum concentration that causes complete (99.9%) killing of the bacteria?

Back 1

MInimum Inhibitory Concentration (MIC)

Minimum Bactericidal Concentration (MBC)

Front 2

What do you call a drug that has selectivity against a microorganism ONLY?

Back 2

antimicrobial.

Front 3

How are MIC and MCB related in regards to bacteriocidal drugs?

Back 3

Bacteriocidal Drugs: MIC = MBC (Inhibiting it kills it. ) The conc will drop dramatically.

Bacteriostatic Drugs: MBC >> MIC
(Inhibiting it weakens it...it stop dividing...then the pts own immune system kills it. The conc will plateau. )

Front 4

Define Selective Pressure

How do you avoid it>

Back 4

Continued use of antimicrobials selects for resistant microorganisms....it causes an AQUIRED RESISTANCE.

To avoid selective pressure, treatment must be consistent (do not skip doses) and complete.

Front 5

Discern natural vs acquired resistance with antibiotics.

Back 5

Natural - via mutations
* Random Substitutions
* Single-Step (fast) - Rifampin
* Multi-step (slow ) - zidovudine

Acquired - via selective pressure - not finishing full dose of antibiotics. Once this resistance occurs, it is peramanent.
* This can occur via Natural Selection or via Plasmids: small circular DNA that are separate from normal DNA that encode resistance, and are shared/ transferred by existing bacteria. Even across species.

Front 6

DNA Replication occurs via the enzyme ____________.

DNA Transcription occurs via the enzyme ___________________.

DNA Translation occurs via ______________.

Back 6

DNA replication occurs via the enzyme DNA Polymerase

DNA transcription occurs via the enzyme RNA Polymerase.

DNA translation allows for protein synthesis.

Front 7

Mechanisms of Resistance (once it has developed)

Back 7

1) DECR CELLULAR UPTAKE OF DRUG
* Ex: mutation of the transport protein.

2) ENZYMATIC DEACTIVATION OF DRUG
* This is how plasmids cause resistance.

3) ALTERED METABOLIC PATHWAY OF THE PATHOGEN (so that the drug cannot attack via the metabolic pathway).

4) ALTERED AMOUNT OR AFFINITY OF DRUG TARGET/ RECEPTOR

Front 8

Explain the mechanism of superinfections with antimicrobials.

Back 8

BROAD SPECTRUM antibiotics will kill the natural bacterial flora. This allows the species that causes the superinfection to proliferate. This secondary infection is resistant to the antibiotic used for the primary infection.

Front 9

Antibiotic- Associated Pseudomembranous Colitis....what causes it, what are the symptoms, and what do you do?

Back 9

Caused by C difficile. - A superinfection in the GI tract from antibiotic use.

S/S: EXTREME, life threatening diarrhea. Yellow-white plaques on the intestinal mucosa.

TX:
* D/C Antibiotics
* Support with IVF
* Stool Test for C. Difficile x 2
* Metrondiazole
* AVOID antidiarheal drugs....they decrease the transit of the C-diff).

Front 10

Desired effects of an antimicrobial agent:

Back 10

Selectivity (avoids superinfections)
Present in the site of infection.
Minimal adverse effects on the patient.
Low Cost.

Front 11

Precise Therapy

Back 11

EXACT DRUG USED: Antibiotic tx when a SPECIFIC org has been identified and you have done a lab test to determine the EXACT suspectibility to the org to the drug.

Use a NARROW SPECTRUM DRUG to tx. May have to use COMBO's.

Front 12

Gram POSTITIVE Cocci and their PRECISE therapy....

Back 12

* Enterococcus
--> PCN G/Ampicillin + Gentamycin
--> PCN allerg: Vanc + gent
--> Vanc resistant: Linezolid

* Staphylococcus aureus
--> Methicillin-susceptible: Oxacillin
--> Methicillin-resistant: vanc + gent
--> Vanc. Resistant: Linezolid

* Streptococcus pyogenes (GrpA)
--> PCN G/ PCN V
--> PCN Alleg: Macrolide or Clindamycin

* Streptococcus (anaerobic)
--> PCN G
--> PCN allerg: Clindamycin

* Streptococcus viridians
--> PCN G + gent
--> PCN Alleg: Cephalosporin or Vanc

* Streptococcus pneumoniae (pneumococcus)
--> PCN G
--> PCN resistant: vanc + ceftriaxone or levofloxacin (not for CNS).

Front 13

Gram NEGATIVE Cocci and their precise therapy:

Back 13

Neisseria meningitidis (meningococcus)
--> PCN G

Neisseria gonorrheoeae (gonococcus)
--> Ceftriaxone

Front 14

What two antimicrobials in combination have a synergistic effect?

Back 14

Trimethoprim + Sulfamethoxazole

(both have meth in them)

Front 15

When is combination therapy of antibiotics most useful?

Back 15

Mixed bacterial infections
Ex: Abscesses

Synergistic therapy
Trimethoprim + sulfamethoxazole

Prevent emergence of resistant organisms
Tuberculosis
HIV

Front 16

Presumptive (empiric) therapy

Back 16

Tx before you know what the pathogen is. Target the most likely org based on pt's hx, gram stain of drainage, site and origin of infection, etc. A choice is then made based on drug spectrum and the distribution of the drug.

1) IN SERIOUS INFECTIONS
--> Meningitis, Sepsis

2) IN HARD TO SAMPLE INFECTIONS
--> Otitis Media

Front 17

Prophylactic (preventative) therapy...explain it and all examples

Back 17

* Those exposed to serious pathogens by other sick individuals or those with low immune systems that maybe exposed.

Front 18

List some common pathogens that require prophylactic tx against and the drug that tx's them

Back 18

MENINGITIS
* Haemophilus influenzae, type b Neisseria meningitidis
* Prophylactic Tx with RIFAMPIN

TUBERCULOSIS
* Mycobacterium tuberculosis
* Tx with ISONIAZID OR RIFAMPIN

ANTRAX
* Bacillus antracis
* Tx with FLUOROQUINOLONE OR DOXYCYCLINE

STD'S
* N. gonnorrhoeae, C. Trachematis, T. Pallidum
* Tx w. CEFTRIAXONE
* (if someone has gonorhea you should assume they have chylamidia and tx them accordingly).

* DENTAL PROCEDURES to pvt S. viridians induced endocarditis for those with:
---> Prosthetic cardiac valves/ material
---> Previous infective endocarditis
---> Congenital heart disease: especially with prothesis
---> Cardiac transplant recipients
---> Valve Disease
--> AMOXICILLIN (an amino pcn) pre-procedure. If allergic to PCN give CLINDAMYCIN or a MACROLIDE

* BEFORE SURGERY to pvt surgical infections.(aseptic tech only)
---> CEFAZOLIN: for heart, vasc, ortho, head/neck, C-section, implants. (Vanc if MRSA suspected). You are tx againt gram +/- bacteria.
---> CEFOXITIN: for colorectal, hysterectomy, appendectomy. You are tx against Gram +/- bacteria AND anaerobes.

Front 19

Drug dosing intervals for maintenance of MIC depends on ....

Back 19

the halflife of the drug.

Front 20

What types of antibiotics must be used in immunosuppressed pts?

Back 20

Bacteriocidal....they cannot kill the pathogen...the drug must kill it, not weaken it.

Front 21

Describe the bacterial cell wall and cell membranes of bacteria.

How does this differ in gram + and gram - organisms?

Back 21

INNER CELL MEMBRANE: Phospholipid bilayer. Contains PCN binding proteins, which synthesize 2 enzymes: transpeptidases and carboxypeptidases.

CELL WALL "Peptidoglycan (Murein)" : a rigid outer layer that surrounds the cell membrane. This wall maintains cell shape and integrity. Unlike human cells, bacterial cells do not lyse with high osmotic pressure (hypotonic environments.)
-->Has TWO PARTS:
1) Long carbohydrate chains "-glycan"
2) Peptide Crosslinks (connect the long carbohydrate chains). "Peptido-"
These cross-links are formed by the enzyme transpeptidase, which is synthesized by PBP's on the inner cell membrane.
---> Cell division is done by enzymes called "Murein Hydrolases or Autolysins", that make nicks in the cell wall and weaken it. REQUIRED FOR BACTERIA TO DIVIDE. (The transpeptidases follow behind and repair..making 2 cells from one.).

GRAM POS orgs have a outer cell wall and inner cell membrane only. GRAM NEG orgs have a cell membrane around BOTH the cell wall and the inner cytoplasm. These membranes are both phospholipid bilayers and the outer membrane includes porins that allow the passage of water sol. substances.

Front 22

What are the 3 types of Beta Lactam Drugs?

Explain the MOA of beta lactam drugs

Back 22

TYPES: PCN, Cephalosporins, Carbapenems

MOA: Bind to PCN binding proteins on the inner cell membrane of bacteria, inhibiting the synthesis of transpeptidase enzyme. This pvts formation of peptide linkages of the long chains in cell walls.

PVTS PRODUCTION AND REPAIR OF PEPTIDOGLYCAN CHAINS. So the wall leaks and the cell dies...BACTERIOCIDAL. (MOA is very dependent on the ability of the drug to get past the cell wall to the inner membrane...this is harder in gram neg bacteria d/t the outer cell membrane.).

Front 23

WHAT ARE THE FOUR WAY A BACTERIA CAN BE RESISTANT TO BETA LACTAMASES?

Back 23

1) Reduces PBP affinity for the drug
* Occurs in GRAM POS bacteria:
---> MRSA
---> PCN resistant S. Pneumoniae (give vanc and ceftriaxone)

2) Decreased membrane permeability
* GRAM NEG bacteria do this. Modify their porins to that water sol. drugs cannot get through.
---> Ex: P. aeruginosa (water-sol drugs are ineffective).

3) Bacteria can synthesize "Beta-lactamases": which bind the drug render it ineffective.
--> H. influenzae, Enterobacteriaceae.
* Give CLAVULANIC ACID with Beta Lactam (amino or extended spectrum PCN's). drugs to pvt inactivation by this enzyme.

4) DO NOT MAKE/ REQUIRE MUREIN HYDROLASE.
--> Beta lactamases are dependent on murein hydrolases to be BACTEROCIDAL (cell wall is weakened and cell dies). W/o them, beta lactams are only BACTEROSTATIC (inhibits cell division only.).
--> Enterococci.