Antibiotics Symposium Flashcards by Neil Srivastava

Define antibiotic

Agents produced by micro-organisms that kill or inhibit the growth of other micro-organisms in high-dilution

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Why are antibiotics more correctly called antimicrobials

Because most agents are semi-synthetic derivative of antibiotics

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How do antibiotics work

They are molecules that bind a target site on a bacteria which are crucial to the survival of the bacterium

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What does penicillin binding protein bind to

Cell was to inhibit cell wall synthesis

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Role of beta lactams

Bind to the transpeptidase active site

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Examples of beta lactams

Penicillins
Cephalosporins
Carbapenems

GLYCOPEPTIDES

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Mechanism of beta-lactams in the body

Block transpeptidase activity and interrupts cross-linking and cell wall synthesis

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What antibiotics interfere with nucleic acid synthesis or function

METRONIDAZOLE

2. RIFAMPICIN

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How does Fluroquinolones inhibit DNA synthesis

Inhibit DNA Gyrase

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5 antibiotics that inhibit ribosomal activity and protein synthesis

Aminoglycosides
Tetracyclines
Lincosamides
Macrolides
Chloramphenicol

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Two antibiotics that inhibit folate synthesis and carbon unit metabolism

SULPHONAMIDES

TRIMETHOPRIM

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What drug effects bacterium cell membranes

Polymyxins

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What part of the ribosome do tetracycline and ahminoglycosides inhibit

30S subunit

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What part of the ribosome do macrocodes, Clindamycin, Linezolid, Chloramphenicol, Streptogramins inhibit

50S subunits

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What is the role of bacteriostatic antibiotics

Prevent growth of bacteria (stop multiplication)

Reduce exotoxin production

Exotoxin surge is less likely from Gram negative bacteria

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How long does it take for bacteriostatic antibiotics to kill 90% of bacteria

18-24 hours

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What do we do with bacteriostatic antibiotics before giving them to patients

Produce a minimum inhibitory concentration

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How do we carry out a minimum inhibitory concentration

Tube dilution with antimicrobial agent
Incubate for 24 hours
Determine MIC based on turbidity

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Define turbidity

Cloudiness of fluid caused by presence of bacteria

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Three reasons why bactericidal antibiotics are useful

Good during poor tissue penetration
Good when difficult to read infections (TB)
Eradicates infections quickly

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Bacteriostatic vs Bactericidal antibiotics in mechanism

Bacteriostatic - prevents growth of bacteria
Bactericidal - agent skill bacteria
Bacteriostatic - kill more than 90% in 18-24 hours
Bactericidal - Kill more than 99.9% in 18-24 hours
Bacteriostatic - inhibit protein synthesis, DNA replication, metabolism
Bactericidal - inhibits cell wall synthesis
Bacteriostatic - Reduces toxin production, endotoxin surge less likely, reduced bacterial component release
Bactericidal - Useful if poor penetration, difficult to treat infections or need to treat quickly

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Does a low MIC mean its a better antibiotic than those that are higher

No, drugs have to also occupy enough binding sites (high conc/ in microorganism) + STAY there for a sufficient period of time in order for metabolic processes of bacteria to be inhibited

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What are two major determinants of anti-bacterial effects

Concentration

2. Time

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Define ‘concentration-dependant killing’

Key parameters how high the concentration is above MIC

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Define 'time-dependant killing'

Key parameter is the time that serum concentrations remain above MIC during dosing interval

How is the value of concentration-dependant killing calculated

Peak conc. / MIC ratio

How is the value of time-dependant killing calculated

t>MIC

What does the antibiotics ability to reach and remain at the site of bacterial infection rely on

Pharmacokinetics

Define pharmacokinetics

The movement of a drug from its administration site to the place of its pharmacological activity and elimination from the body RELEASE ABSOPTION DISTRIBUTION ELIMINATION

What three factors effect the distribution of an antibiotic

1. Which antibiotic will penetrate that site 2. pH of the site 3. Is the antibiotic lipid-soluble

What other key consideration is there when deciding what antibiotic to use

WHAT IS SAFE FOR THE PATIENT

How do bacteria resist antibiotics

1. Change antibiotic target 2. Destroy antibiotic 3. Prevent antibiotic access 4. Remove antibiotic from bacteria

How do bacteria change antibiotic target

Change molecular configuration of antibiotic binding site or masks it

How has Methicillin (Flucloxacillin) been affected by a change in antibiotic target

Can't bind to PBP of staphylococci (MRSA)

How has Vancomycin been effected by a change in antibiotic target site

1. Wall components change in enterococci and reduces binding

How has rifampicin activity been effected by a change in antibiotic target site

Reduced by changes to RNA polymerase in MTP

How have bacteria been able to disable the effect of penicillin

Hydrolysis by the bacterial enzyme beta lactase of beta lactic ring in penicillin and cephalosporins

What is the product of penicillin destruction after B-lactam is removed

Penicilloic acid

Does penicillinase produced by staphylococci inactivate flucloxacillin

How do Gram negative bacteria effect ahminoglycosides

Phosphorylate and acetylate them

How do bacteria prevent antibiotic access

Modify the bacterial membrane prone channel, size, number and selectivity

Give an example of prevention of antibiotic access

1. Pseudomonas aeruginosa against imipenem | 2. Gram negative bacteria against aminoglycosides

How can proteins in bacterial membrane reduce effects of antibiotics

1. Proteins in bacterial membranes act as an export or efflux pumps

Example of efflux pumps for antibiotics in S.aureus and s. pneumonia

1. Fluoroquinolones

What are Enterbacteriacae resistant to

Tetracyclines

Three ways horizontal gene transfer can take place

1. Conjugation 2. Transduction 3. Transformation

What three ways can bacteria develop resistance

1. Naturally 2. Spontaneous gene mutation 3. Horizontal gene transfer

Define intrinsic resistance

All subpopulations of a species will be equally resistant

Effect of Vancomycin on gram negative bacteria

Can't penetrate outer membrane

Effect of cephalosporins on enterococci

1. PBP not effectively bound

Define acquired resistance

A bacterium which was previously susceptible obtains the ability to resist the activity of a particular antibiotic

What is spontaneous gene mutation

New nucleotide base pair in AA sequence change to enzyme or cell structure reduced affinity or activity of antibiotic

Define conjugation

Sharing extra-chromosomal DNA plasmids

Define transduction

Insertion of DNA by bacteriophages

Define transformation

Picking up naked DNA

In what way has MRSA developed resistance

Transduction of mecA genes

What species is MRSA

S. Aureus

Why is MRSA resistant

Chromosome me contains mecA mecA encodes penicillin-binding protein 2a Resistance to all Beta lactic antibiotics + methicillin

How are Vancomycin-resistant enterococci formed

1. Plasmid mediated acquisition of gene encoding altered AA on peptide chain preventing vancomycin binding

What increases the resistance of Vancomycin by enterococci

Cephalosporin

How has gram-negative bacteria developed resistance

1. Beta-lactamase hydrolyses penicillin | 2. Typically remain sensitive to beta-lactamase inhibitors

Describe how resistance has developed ESBL (extended spectrum beta lactase)

Mutation at active site of extended range of antimicrobial resistance inhibits ESBL and allows oxyamino beta-lactam and monobactam inhibition so more extended beta-lactam resistance

When is beta-lactam most sensitive

In vitro NOT in vivo

How is ESBL spread

Plasmid

How has AmpC beta-lactamase resistance developed

1. Beta-lactamas inhibitor resistant in vitro and in vivo

What bacteria express AmpC beta-lactamase resistance

Enterobacter and citrobacter

What are bacteria with AmpC Beta-lactamase resistant to

Penicillin

When is AmpC beta-lactamase resistance expressed

Only in the presence of the antibiotic

What are carbapenems

Antimicrobials of last resort to treat infection s due to ESBL or plasmid-mediated AmpC-producing organisms of the enterobacteriaceae family s

What property do carbapenems have

Highly resistant to degradation by beta-lactamases or cephalosporinases

What bacteria developed carbapenemases

Gram-Negative bacteria

How do we test for resistance

1. Amount of antibacterial that inhibits visible growth of the microorganism - MIC

What are breakpoint plates

Plates with a specific breakpoint conc. of antibiotic to see if a given inoculum grows or not

Formula for breakpoint conc.

(Cmax/et) x f x s Max = maximum serum conc. following a state dose at steady state s = shift factor t= factor to allow for serum elimination half-life e = factor by which the Cmax should exceed MIC