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Microbiology > Antimicrobial AgentsActivity, Action and Resistance > Flashcards

Antimicrobial AgentsActivity, Action and Resistance Flashcards

1
Q

Aim of Treatment

To consider not only the outcome of the immediate infection but the effect of currently administered antibiotics on ………. that could precipitate ………………. infections”

A

Aim of Treatment

To consider not only the outcome of the immediate infection but the effect of currently administered antibiotics on flora that could precipitate future infections”

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2
Q

The goal of antimicrobial therapy

Achieve maximum eradication.

  • Of the causative organism.
  • From the site of the infection.
A

The goal of antimicrobial therapy

Achieve maximum eradication.
Of the causative organism.
From the site of the infection.

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3
Q

Considerations - Patient

Epidemiological considerations

  • Ag…., se….., occu……….
  • Location of infection
  • Local knowledge about dis……… prev………

History of ove………… travel

Pre-existing me………. problems or treatments

A

Considerations - Patient

Epidemiological considerations

  • Age, sex, occupation
  • Location of infection
  • Local knowledge about disease prevalence

History of overseas travel

Pre-existing medical problems or treatments

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4
Q

Laboratory Considerations

Confirmation of diagnosis
Identification of Organism

Selection of antimicrobial chem………………
Evidence of likely clinical response

Local epidemiological knowledge of bug-drug susceptibility patterns

M…… determination

A

Laboratory Considerations

Confirmation of diagnosis
Identification of Organism

Selection of antimicrobial chemotherapy
Evidence of likely clinical response

Local epidemiological knowledge of bug-drug susceptibility patterns

MIC determination

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5
Q

Antibiotic Considerations

Mode of Administration

  • O……..
  • Oi……………
  • Intr………………
Target Site
- Inhibitors of cell ........... synthesis
- Protein synthesis ..................
- Metabolic anta....................
- Nu....... acid synthesis inh.
............
When to use
- Abso..............
- Distri..............
 -Ex...............
- Concentration at site of infection

Complications with treatment

  • Resistan………
  • Toxici………..
A

Antibiotic Considerations

Mode of Administration

  • Oral
  • Ointment
  • Intravenous

Target Site

  • Inhibitors of cell wall synthesis
  • Protein synthesis inhibitors
  • Metabolic antagonists
  • Nucleic acid synthesis inhibitors

When to use

  • Absorption
  • Distribution
  • Excretion
  • Concentration at site of infection

Complications with treatment

  • Resistance
  • Toxicity
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6
Q

Methods of determining sensitivity/resistance to antimicrobial agents

Di……… tes…….

s………… me…………

B………….. Meth……….

A

Methods of determining sensitivity/resistance to antimicrobial agents

Disc testing

stoke method

BSAC Method

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7
Q

Stokes Method

Compares test s……… with c………. strain

Measure difference between test and control
2mm less than control strain = res…………

Very sub…………….

Requires accurate measurements
Prone to e…………..

Gives 3 results:

  • Int…………….
  • Se………………
  • Resi…………….
A

Stokes

Compares test strain with control strain

Measure difference between test and control
2mm less than control strain = resistant

Very subjective

Requires accurate measurements
Prone to errors

Gives 3 results:

  • Intermediate
  • Sensitive
  • Resistant
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8
Q

BSAC Method

L…….. prone to er…….

Compares zo…….. si……. to a st……….. set of
measurements of known se……… strains

Allows mo………… re………….. to be monitored

Need to spe………….. bacteria

E.coli sensitivity may be different from other G…… .negative bacilli

Can relate zone size to the min……… inhibi……….. concentration

A

BSAC Method

Less prone to error

Compares zone size to a standard set of measurements of known sensitive strains

Allows moving resistance to be monitored

Need to speciate bacteria

E.coli sensitivity may be different from other Gram negative bacilli

Can relate zone size to the minimum inhibitory concentration

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9
Q

Problems With Disc Diffusion Techniques

Depth of ……………

D………… concentration

Si……….. of an………………. molecule

Pre inc………….

Poor att………….. to zone measurements
Plate stacking

Variations in m……….. content (ca………. and mag…………..)
Disc storage

A

Problems With Disc Diffusion Techniques

Depth of media

Disc concentration

Size of antibiotic molecule

Pre incubation

Poor attention to zone measurements
Plate stacking

Variations in media content (calcium and magnesium)
Disc storage

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10
Q

Minimum inhibitory concentration (MIC)

Qua………………. methodology

L………….. concentration required to i…………. visible growth in v………

Serial dil………….. of test antibiotic prepared in broth or agar

Inoculate with bacterial sus…………..
Incubate overnight

MIC is the highest dil……….. showing no visible gr……………

Important for mana………….. of difficult infe……….

End……………..

A

Minimum inhibitory concentration (MIC)

Quantitative methodology

Lowest concentration required to inhibit visible growth in vitro

Serial dilutions of test antibiotic prepared in broth or agar

Inoculate with bacterial suspension

Incubate overnight

MIC is the highest dilution showing no visible growth

Important for management of difficult infections

Endocarditis

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11
Q

Minimum bacteriocidal concentration (MBC)

Extend the MIC test to determine the MBC

………….. concentration required to …………….. the organism

Sub culture the n……………. wells from the
MIC tubes onto an……………… free media

In…………………. overnight

MBC is the highest dil……….. where there is no vis………… gr………..

A

Minimum bacteriocidal concentration (MBC)

Extend the MIC test to determine the MBC

Lowest concentration required to kill the organism

Sub culture the negative wells from the MIC tubes onto antibiotic free media

Incubate overnight

MBC is the highest dilution where there is no visible growth

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12
Q

Inhibitors of cell wall synthesis

Primary structure of cell wall is peptidoglycan

Composed of repeating sugar molecules

  • N-acetyl glucos………… (…….)
  • N-acetyl muramic a…….. (………)

Meshwork is held together with small pe………. chains

Linking together of NAG and NAM subunits facilitated by several en……….
- Penicillin b……….. proteins (PBPs)

A

Inhibitors of cell wall synthesis

Primary structure of cell wall is peptidoglycan

Composed of repeating sugar molecules

  • N-acetyl glucosamine (NAG)
  • N-acetyl muramic acid (NAM)

Meshwork is held together with small peptide chains

Linking together of NAG and NAM subunits facilitated by several enzymes
- Penicillin binding proteins (PBPs)

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13
Q

Inhibitors of cell wall synthesis

b-lactams, vancomycin, daptomycin “crossbows”

b-lactams

  • Penic……….
  • Cepha…………..
  • Carb……………
  • Mono…………………
A

Inhibitors of cell wall synthesis

b-lactams, vancomycin, daptomycin “crossbows”

b-lactams

  • Penicillins
  • Cephalosporins
  • Carbapenems
  • Monobactams
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14
Q

b-lactams – how they work

Essential core = b-lactam ring

Mechanism of action is same for ALL

  • Inhibitors of PBPs
  • b-lactam ring resembles D-alanyl-D- alanine portion of pe………….. side chains
  • PBP binds with ri………. and not s………. chain
  • Disruption of peptid……….. layer
  • Lys……
A

b-lactams – how they work

b-lactams – how they work

Essential core = b-lactam ring

Mechanism of action is same for ALL

  • Inhibitors of PBPs
  • b-lactam ring resembles D-alanyl-D- alanine portion of peptide side chains
  • PBP binds with ring and not side chain
  • Disruption of peptidoglycan layer
  • Lysis
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15
Q

b-lactams - resistance

Intrinsic resistance
- Resistance is int………. to structure or physiology of bacterial species

Acquired resistance
- A previously sensitive ba………….. acquires a mut………. or e……….. genetic material allowing it to resist activity of the a……..

A

b-lactams - resistance

Intrinsic resistance
- Resistance is intrinsic to structure or physiology of bacterial species

Acquired resistance
- A previously sensitive bacterium acquires a mutation or exogenous genetic material allowing it to resist activity of the agent

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16
Q

Six potential pitfalls
Penetration
- b-lactams penetrate po………. into ce……….(intracellular pathogens)

Porins
- Needs to ac……… PB……

Pumps
- Efflux pu……… transport antibiotics out of the peri…………. space

Penicillinases (b-lactamases)
- Enzymes that degrade b-lact…….. rin……
Many “flavours”

PBPs
-Low affi……… binding

Peptidoglycan
-Some organisms do not produce peptid…………

A

Six potential pitfalls
Penetration
- b-lactams penetrate poorly into cells (intracellular pathogens)

Porins
- Needs to access PBPs

Pumps
- Efflux pumps transport antibiotics out of the periplasmic space

Penicillinases (b-lactamases)
- Enzymes that degrade b-lactam ring
Many “flavours”

PBPs
-Low affinity binding

Peptidoglycan
-Some organisms do not produce peptidoglycan

17
Q

Inhibitors of Cell Wall Synthesis

Non b-lactams – glyco……………..

  • Glycopeptide antibiotics are derived from Streptomyces organisms
  • Vancomycin is a glycopeptide antibiotic.

They inhibit cell …………… synthesis by forming a complex with the substrates that make up peptid…………….

Cannot penetrate the po………. of Gram-…………. cells
- Narrow spectrum antibiotics restricted to Gram-positive bacteria

Work on different parts of peptidog………… to penicillin

A

Inhibitors of Cell Wall Synthesis

Non b-lactams – glycopeptides
= Glycopeptide antibiotics are derived from Streptomyces organisms
= Vancomycin is a glycopeptide antibiotic.

They inhibit cell wall synthesis by forming a complex with the substrates that make up peptidoglycan

Cannot penetrate the porins of Gram-negative cells
= Narrow spectrum antibiotics restricted to Gram-positive bacteria

Work on different parts of peptidoglycan to penicillin

18
Q

Protein synthesis inhibitors

Bacteria must constantly produce new biomolecules

  • Replace ……….. worn-out ones
  • Build new bac…………

Transcription
- Synthesis of m………. from DNA genes

Translation
- Gen……….. of new protein from mRNA

A

Protein synthesis inhibitors

Bacteria must constantly produce new biomolecules

  • Replace old worn-out ones
  • Build new bacteria

Transcription
- Synthesis of mRNA from DNA genes

Translation
- Generation of new protein from mRNA

19
Q

Protein synthesis inhibitors

many antibiotics bind specifically to the pro………… ribosome
- mbinding can be to 30S (small) or 50S (large) ribosomal subunit

other antibiotics inhibit a step in protein synthesis

  • amin……….l-tRNA binding
  • pe………… bond formation
  • mRNA re…………
  • transl…………..
A

Protein synthesis inhibitors

many antibiotics bind specifically to the procaryotic ribosome
- mbinding can be to 30S (small) or 50S (large) ribosomal subunit

other antibiotics inhibit a step in protein synthesis

  • aminoacyl-tRNA binding
  • peptide bond formation
  • mRNA reading
  • translocation
20
Q

Protein synthesis inhibitors

Aminoglycosides

  • bind to 3….S ribosomal subunit and interfere with pr……………. s…………… by directly in……….. the process and by causing misreading of the messenger RNA
  • Broad-spe………., especially useful against aer………. Gr……..-ne…………. rods and certain Gram-po………… bac……..

streptomycin –
= bubonic plague, tularemia, TB

Gentamicin
= less toxic, used against G………-negative rods

newer – tobramycin and amik………
= Gram-neg……… bacteria

A

Protein synthesis inhibitors

Aminoglycosides

  • bind to 30S ribosomal subunit and interfere with protein synthesis by directly inhibiting the process and by causing misreading of the messenger RNA
  • Broad-spectrum, especially useful against aerobic Gram-negative rods and certain Gram-positive bacteria

streptomycin –
= bubonic plague, tularemia, TB

Gentamicin
= less toxic, used against Gram-negative rods

newer – tobramycin and amikacin
= Gram-negative bacteria

21
Q

Protein synthesis inhibitors

Tetracyclines
- are broad spectrum, bacte…………

  • combine with 30S ribosomal subunit
    = inhibits bind of am……..-tRNA molecules to the A site of the ribosome
  • sometimes used to treat a………

Macrolides
- e.g., eryt……………

= broad spectrum, usually bacte………….

= binds to 2……S rRNA of ..0S ribosomal subunit
= inhibits peptide chain elon………….

  • used for patients allergic to pe……….
A

Protein synthesis inhibitors

Tetracyclines
- are broad spectrum, bacteriostatic

  • combine with 30S ribosomal subunit
    = inhibits bind of aminoacyl-tRNA molecules to the A site of the ribosome
  • sometimes used to treat acne

Macrolides
- e.g., erythromycin

= broad spectrum, usually bacteriostatic

= binds to 23S rRNA of 50S ribosomal subunit
= inhibits peptide chain elongation

  • used for patients allergic to penicillin
22
Q

Metabolic antagonists /Nucleic acid synthesis inhibitors

Bacteria vs. Human Immune Response
- Numbers = key!!

  • Rapid bacterial multiplication is essential for disease
    = Binary f…………..
    > Synthesis of deoxyn……………
    > Repl…………..
  • Antibiotics tip the balance -> HIR

Synthesis of deoxyn………….

  • Number of dif…………. pathways used
  • Tetrahy………. = essential for many of these
  • Humans absorb folate from diet
  • Bacteria must synt……….. THF
A

Metabolic antagonists /Nucleic acid synthesis inhibitors

Bacteria vs. Human Immune Response
- Numbers = key!!

- Rapid bacterial multiplication is essential for disease
= Binary fission
       > Synthesis of deoxynucleotides
       > Replication 
- Antibiotics tip the balance -> HIR

Synthesis of deoxynucleotides

  • Number of different pathways used
  • Tetrahydrofolate = essential for many of these
  • Humans absorb folate from diet
  • Bacteria must synthesize THF
23
Q

Metabolic antagonists /Nucleic acid synthesis inhibitors

Replication
- Requires many different enzymes
= DNA poly………….
> Replicates bacterial chro………….
= Topoiso……………..
> Regulate super…………… of D………. strands

A

Metabolic antagonists /Nucleic acid synthesis inhibitors

Replication 
- Requires many different enzymes
= DNA polymerase
    > Replicates bacterial chromosome
= Topoisomerases 
     > Regulate supercoiling of DNA strands
24
Q

Metabolic antagonists /Nucleic acid synthesis inhibitors

Quinolones
- Broad-spectrum, synthetic drugs containing the dual 4-quinolone rings
- Act by inhibiting topo…………….
= DNA gy………….
= Topois……………….. IV
- Ciprofloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin

Metronidazole 
 -Nitro group on core ring
 -Must be reduced for activity
- Anaerobes – donate elec........... to nitro group (low redox potential electron transport proteins)
- Free radi............
   = Damage to DNA
   = Cell d............
A

Metabolic antagonists /Nucleic acid synthesis inhibitors
Quinolones
- Broad-spectrum, synthetic drugs containing the dual 4-quinolone rings
- Act by inhibiting topoisomerases
= DNA gyrase
= Topoisomerase IV
- Ciprofloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin

Metronidazole 
 -Nitro group on core ring
 -Must be reduced for activity
- Anaerobes – donate electrons to nitro group (low redox potential electron transport proteins)
- Free radicals
   = Damage to DNA
   = Cell death
25
Q

Evaluating Antibiotic Efficacy UsingPharmacokinetics and Pharmacodynamics

Pharmacokinetics (PK):

  • Reflects how a drug is ab……….., dist………… and elim…………. in the body
  • These factors, along with the dosing regimen of the drug, determine the time course of drug conc………… in the serum, tissues and body fluid

Pharmacodynamics (PD):

  • The relationship between a drug’s serum concentrations and its pharmacological and toxicological effects
  • In other words, P…. inte………. P……. with drug pote…………. (measured by the drug’s minimum inh………. conce………… [MIC] against a bacterium)
A

Evaluating Antibiotic Efficacy UsingPharmacokinetics and Pharmacodynamics

Pharmacokinetics (PK):

  • Reflects how a drug is absorbed, distributed and eliminated in the body
  • These factors, along with the dosing regimen of the drug, determine the time course of drug concentration in the serum, tissues and body fluid

Pharmacodynamics (PD):

  • The relationship between a drug’s serum concentrations and its pharmacological and toxicological effects
  • In other words, PD integrates PK with drug potency (measured by the drug’s minimum inhibitory concentration [MIC] against a bacterium)
26
Q

Synergy and antagonism

  • Patients often receive more than one ant………….
  • May interact with one an…………
  • Syn………… if their activity is greater than the sum of the individual acti……….
  • Anta……… if the activity of one drug is compromised by the presence of another
A

Synergy and antagonism

  • Patients often receive more than one antibiotic
  • May interact with one another
  • Synergistic if their activity is greater than the sum of the individual activities
  • Antagonistic if the activity of one drug is compromised by the presence of another
27
Q

Synergy and antagonism

Combinations:

  • Peni……… and an amino……….. (gentamicin) in treating endocarditis
  • Prevent the emergence of resis……… (TB therapy)
  • Polym………….. infections (abscess)
  • Serious infect…….. before cause has been identified

Ant…………. seen if bacte. and bacter……….. antibiotic used in combination

A

Synergy and antagonism

Combinations:

  • Penicillin and an aminoglycoside (gentamicin) in treating endocarditis
  • Prevent the emergence of resistance (TB therapy)
  • Polymicrobial infections (abscess)
  • Serious infections before cause has been identified

Antagonism seen if bacteriostatic and bacteriocidal antibiotic used in combination

28
Q

Drug Resistance

An increasing problem

Once resistance originates in a population it can be tran………… to other ba………..

A particular type of resi………. mechanism is not confined to a si………. class of drugs

Resistance mut……….arise spont………and are then selected

A

Drug Resistance

An increasing problem

Once resistance originates in a population it can be transmitted to other bacteria

A particular type of resistance mechanism is not confined to a single class of drugs

Resistance mutants arise spontaneously and are then selected

29
Q

Mechanisms of Drug Resistance

Prevent entrance of drug

  • drug can’t bind to or penetrate pathogen
  • bacterial decrease in perm,,,,,,,,,,,,,,

Pump drug out

Inactivation of drug
- chemical mo………… of drug by pathogen

Alteration of target enzyme or orga………….

Use of alternative p…………… or increased production of target meta………….

A

Mechanisms of Drug Resistance

Prevent entrance of drug

  • drug can’t bind to or penetrate pathogen
  • bacterial decrease in permeability

Pump drug out

Inactivation of drug
- chemical modification of drug by pathogen

Alteration of target enzyme or organelle

Use of alternative pathways or increased production of target metabolite

Microbiology (13 decks)

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