Red/Bolded Words/Review - Deck 1 Flashcards by Rebecca Lea

What is unique about chemotherapy?

Selectively toxic against infectious agent

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Every time you prescribe, you are selecting for

resistance

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Chemotherapy resistance can be

natural or acquired

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Natural chemotherapy resistance means that:

Example?

the antiobiotic cannot get into inner membrane –>

enterococci - penicillins can weakly bind to penicillin-binding protein and aminoglycosides can get inside the cell

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Bacteriostatic drugs work how?

They keep infectious agent from growing so host immune system can take care of infectious agent

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Good example of drug synergy?

Penicillins and aminoglycosides

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Transferring resistance

transduction

transformation

conjugation

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How does conjugation work?

requires direct contact with pilus

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How does transformation work?

incorporates free DNA information from environment

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How does transduction work?

bacteriophages passes resistance from one bacteria to another

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Bacteriostatic pharmacokinetic important property

Maintain blood level because they are static –> as soon as blood level drops below threshold, the growth of the bacteria will start again

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Empirical therapy

Don’t know what is going on, use clinical judgment. If they need antibiotics, you may need to change antibiotic when you find out lab results.

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If septic, what kind of empirical therapy is used?

Broad spectrum - parenteral

Carbapenims,
Cefapime, combine aminoglycoside (good G-) with parenteral G+ (like Pen G)

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Cidal v static

Cidal = cell death

Static = growth inhibition

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Immunocompromised patient should be on what kind of antibiotic?

Cidal

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Concentration-dependent killing

Example?

high concentration to have effect

Aminoglycosides

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Time-dependent killing

Must be in system for a certain amount of time to be effective

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Minimum inhibitory concentrations

smallest concentration to keep cells from growing

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Minimum bactericidal concentrations

smallest concentration to kill cells

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Serial Dilution Susceptibility Test (MIC and MBC)

Bacteria is growing –> MIC occurs –> innoculate MIC cultures into antimicrobial-free media –> MBC occurs

MIC tells us when growth will be inhibited, but MBC tells us when cell death occurs

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Post-antibiotic effect

Example

Why is this important/beneficial?

Persistent suppression of bacterial growth –> extension of antimicrobial effect even when concentration is below threshold but there is still inhibition of growth.

PAE –> less you have to dose –> less adverse side effects

Aminoglycosides

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Synergism

What bacteria do we always treat with synergism?

Use multiple drugs together

Pseudomonas

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Drug antagonism

Drugs do not work well together

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Why do static and cidal drugs not work well together?

Static drug require cell growth and cidal drugs inhibit cell wall synthesis (cell growth)

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Development of superinfections more common with what kind of spectrum of antibiotics? Why? Example

broad spectrum antibiotics disturbance of flora C. diff.

Overgrowth of C.Diff leads to

pseudomembranous colitis | also a superinfection

What are the beta-lactams (inhibitors of cell wall synthesis)?

1. Penicillins 2. Cephalosporins 3. Carbapentims 4. Monobactims

How do beta-lactams inhibit cell wall synthesis ?

Bind to penicillin-binding protein which affects cell wall which is integral to the integrity of cell --> cell blows up

Inhibitors of cell wall synthesis: static of cidal

Cidal

Entire penicillin group is susceptible to penicillinase BESIDES:

pencillinase-resistant penicillins

Penicillinase is only a problem for

penicillins (besides penicillinase resistant penicillins)

Difference between bacterial and mammalian cells is

rigid cell wall

Cell wall protects bacterial cells from

osmotic rupture

Structure conferring cell wall rigidity and resistance to osmotic lysis in both G+ and G- is

peptidoglycan

G+ peptidoglycan

only layered structure external to cell membrane and is thick

G- has an outer membrane external to what?

very thin peptidoglycan layer

What does transglycosylation do?

joins NAM and NAG

What does transpeptidation do?

cross links pentapeptides

Transglycosulation and transpeptidation are enzymatic actions performed by:

penicillin binding proteins

If antibiotic targets penicillin binding proteins, what does/does not occur?

transglycosulation and transpeptidation

Beta-lactams prevent

transpeptidation

What do autolysins do to initiate cell death/lysis?

Autolysins are remodeling enzymes that cleave peptidoglycan bonds in normal course of cell growth. In presence of inhibitors of cell wall synthesis, autolysis proceeds without normal cell-wall repair --> lysis

In order for autolysis to occur, what needs to be happening?

cell needs to be growing

Natural Pencillins have the highest antibacterial activity against certain gram (___) bacterial including anaerobic/aerobic

G+, anaerobic

Do natural penicillins have any G- coverage?

Some

Natural penicillins are readily inactivated by

beta-lactamase (penicillinase)

Natural penicillins have/do not have anti-pseudomonal actviity?

Do not have

Penicillinase-Resistant Penicillins have increased/decreased activity against G+ bacteria compared to natural penicillins

lower activity

Penicillinase resistance penicillins have increased/decreased G- coverage compared to natural penicillins?

increased

Penicillinase-Resistant penicillins are the DOC for

penicillinase-producing S. aureus - MSSA

What kind of metabolism and excretion do penicillinase-resistant penicillins have?

hepatic metabolism and renal excretion

How does MRSA work?

MRSA produces alternate penicillin-binding protein which decreases affinity of beta-lactam antibiotics to PBPs

ONLY beta-lactam that is used to treat MRSA?

ceftaroline

Extended spectrum penicillins have increased/decreased G+ coverage compared to natural penicillins?

decreased

Extended spectrum have increased G (__) coverage

G- coverage

Do extended spectrum penicillins have antipseudomonal activity?

DOC for lysteria?

ampicillin (oral)

Is the ampicillin rash a sign of hypersensitivty?

No - does not preclude future use of penicillin

Antipseudomonal penicillins have what kind of spectrum?

extended plus some enteric gram negative bacilli

What are the two major uses of antipseudomonal penicillins?

P. aeruginosa and acinetobacter

What do we use antipseudomonal penicillins in combo with? Why?

Aminoglycosides prevent resistance

3 Beta-lactamase inhibitors:

clavulanic acid, sulfactam, tazobactam

What four penicillins are beta-lactamase given in conjunction with?

ampicillin, amoxicillin, ticarcillin, piperacillin

Combination products are/are not effective agaisnt MRSA?

Are not - MRSA does not affect beta-lactamase - it affects PBP

5 ways cell wall synthesis is inhibited?

``` Transglycosylation Transpeptidation NAG reduction to NAM Transport across inner membrane Amino acid mimicry - pentapeptide chain ```

Which of the natural penicillins (Pen G, Benzathine penicillin, procraine penicillin, or Pen V) are used only orally?

PEN V

Gold standard for G+ infections?

Pen G

Which natural penicillin would you use if you needed treatment to start immediately?

Pen G d/t parenteral administration

Only group of penicillins that has anti-pseudomonal properties and is used to treat pseudomonas?

Anti-pseudomonal penicillins

If you have a bacteria that produces penicillinase, what group is completely out?

Natural penicillins

Which drug (ONLY ONE) in penicillinase resistant penicillins are give parenterally? Other two given orally

Naficillin

Penicillinase resistant penicillins are DOC for

MSSA (produces penicillinase)

How does MRSA occur?

MRSA produces alternate PBP which decreases affinity of beta-lactam antibiotics. Has nothing to do with beta-lactamase itself.

Amoxicillin and Ampicillin are both adminstered

orally

Ampicillin and amoxicillin can have inhibitor of beta-lactamase added to them. Amoxicillin becomes what? And is it oral or parenteral? Ampicillin becomes what? Oral or parenteral?

Augmentin - oral Ampicillin - parenteral (hospital use)

Ampicillin and amoxicillin both have lower ____ and higher ____ coverage than natural penicillins.

Lower G+ and higher G-

____ rash: NOT a hypersensitivity reaction

Ampicillin

Anti-pseudomonal penicillins are used with what?

aminoglycosides (beta lactamase inhibitors)

Bacterial resistance: penicillins inactivation of penicillin by:

bacterial beta-lactamase

Bacterial resistance: penicillins ______ ______ of bacterial cell to penicillins (G-)

decreased permeability

Bacterial resistance: penicillins Alteration inf _____ which prevents penicillin from binding (MRSA)

PBPs

Bacterial resistance: penicillins ____ enzymes not being activated thus forming tolerant organisms or non-growing persistent bacteria which are recalcitrant to antibiotics

activated

Bacterial resistance: penicillins No ____ ____

cell wall

permeability is really only an issue for

gram negatives

Toxicity to worry about with penicillins?

allergies