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Pharmacology > Principles of Antibacterials > Flashcards

Principles of Antibacterials Flashcards

1
Q

Bacteriostatic

A

Reversible inhibition of growth of bacteria

Does not kill the bacteria but stops bacteria from growing and relies on host immune mechanisms to clear the bacteria from body.

Bacteria can regrow when bacteriostatic antibiotic is removed.

Used in patients that are immune-competent or for treatment of mild infections.

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2
Q

Bactericidal

A

Irreversible inhibition of growth –> kill the bacteria and do not depend on the host immune system

Used in immune-compromised patients or to treat life-threatening infections.

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3
Q

Selective Toxicity

A

Ability to injure or kill an invading microorganism without harming host cells –> less adverse effects

Ideally target sites unique to infecting organism

Or taget site suitably different compared to host equivalent

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4
Q

Postantibiotic Effect

A

When the killing action continues once the drug plasma levels are below measurable levels

Mechanisms:

  • lag time required to synthesise new enzymes or cell components
  • persistence of agent at target site
  • Enhanced susceptibility of bacteria to phagocytic/defence mechanisms
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5
Q

Broad spectrum antibiotics uses and disadvantages

A

Antimicrobial drugs which are effective against several groups of micro-organisms (eg: Gm+ and Gm - bacteria)

Uses:

  • empiric therapy
  • mixed infections
    eg: peritonitis (intraabdominal infections) post surgery normally present with many different bacterial infections

Disadvantages:

  • selection of multi-drug resistant bacteria
  • disruption of normal flora
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6
Q

Narrow spectrum antibiotics uses and disadvantages

A

Antimicrobial drugs which are effective against only a specific group of bacteria (usually target one or 2 classes)

Use: treating infections of known origin

Disadvantages:

  • must know causative agent
  • not useful for empiric therapy
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7
Q

Extended spectrum antibiotics uses and disadvantages

A

Antimicrobial drugs which are effective against Gm + bacteria and some Gm - bacteria due to chemical modifications

Uses:

  • empiric therapy
  • mixed infections

Disadvantages:

  • selection of multi-drug resistant bacteria
  • disruption of normal flora
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8
Q

MIC

A

Minimum inhibitory concentration - lowest concentration of antibiotic that prevents visible growth

Measured using - broth or tube dilution method or disk sensitivity test

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9
Q

MBC

A

Minimum bactericidal concentration - lowest concentration of antibiotic that results in a 99.9% decline in colony count after overnight broth dilution incubation

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10
Q

MIC vs MBC of a truly bactericidal agent

A

MBC will be equal to or just slightly above its MIC

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11
Q

MIC vs MBC of a bacteriostatic agent

A

MBC will be way higher than the MIC. MBC is usually not clinically achievable as they are not designed to kill the bacteria

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12
Q

Criteria for selecting the right antibiotic (6)

A

1) Organisms identity and susceptibility to an agent
2) Necessity of empiric therapy
3) Site of infection
4) Pharmacology
5) Patient factors
6) Cost of therapy

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13
Q

Factors that influence drug penetration of blood brain barrier

A

Lipid solubility of drug - fluoroquinolone and metronidazole are lipid soluble but penicillin has low lipid solubility

Molecular weight

Protein binding of the drug

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14
Q

Bacterial cell walls - gram positive vs. negative

A

Gram positive bacteria have a thick mesh-like cell wall made of peptidoglycan + lipoteichoic acid and an inner cell membrane –> stain purple with gram stain

Gram negative bacteria have an extra out membrane with porins and LPS They have a narrow cell wall –> stain pink with gram stain

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15
Q

Examples of Gm - bacteria

A 
E.coli 
Salmonella 
Shigella 
Psuedomonas 
Helicobacter 
Legionella 
Enterobacter 
Niesseria (meningitis, gonorrhea)
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16
Q

Examples of Gm+ bacteria

A 
Staphylococcus 
Streptococcus 
Clostridium 
Listeria 
Actinobacteria 
Mycoplasma 
Bacillus 
Entercoccus
17
Q

Advantages of giving combination therapy

A

To achieve synergistic effects

In emergency situations

To delay development of resistance

To treat mixed infections

To treat immunosuppressed

18
Q

Disadvantages of combination therapy

A

Some agents will only act on multiplying bacteria. If combined with another agent that causes bacteriostasis, they will be less effective.
(eg: b-lactams and tetracyclines)

Can select for multi-drug resistant bacteria

19
Q

Mechanisms of synergism caused by combination therapy

A

1) Sequential blockage - blocking two enzymes in the same cascade will maximise probability of killing bacteria (trimethoprim + sulfamethoxazole)
2) Blockade of drug-inactivavting enzymes (clavulanic acid + amoxicillin)
3) Enhanced drug uptake (increased permeability to aminoglycosides after b-lactam treatment which breaks down cell wall and allows aminoglycosides to get to ribosomes)

20
Q

Antibiotic resistance

A

Occurs if maximal level of antibiotic tolerated by host does not halt bacterial growth

21
Q

Antibiotic resistance mechanisms

A

Altered uptake of antibiotic - decrease in permeability, decrease in uptake mechanisms, increase in multi-drug resistance pumps

Altered target - change in receptor site affinity, modification of targeted metabolic pathway

Drug inactivation - bacterial production of enzymes that inactivate drug (e.g beta lactamases)

22
Q

Primary antibiotic resistance

A

Structural absence of target for drug to act on

By nature, mycoplasma lack a cell wall so are resistant to penicillins

23
Q

Acquired antibiotic resistance mechanisms

A

Spontaneous mutations of bacterial DNA

DNA transfer of drug resistance genes

Altered expression of proteins in drug-resistant organisms

24
Q

Ways that bacteria can acquire resistance genes and fate of new DNA

A

Conjugation
Transposition
Transduction
Transformation

Newly introduced DNA

  • Destroyed by bacterial endonucleases
  • Circularization and maintenance as a plasmid
  • Recombination and integration (recombination can be homologous or non-homologous)
25
Q

Transformation of resistance genes

A

Ability to uptake DNA that is released by cell lysis from the environment (also known as competence) –> homologous DNA will undergo recombination and incorporation

Usually occurs between related bacterial species

Facilitated by bacterial DNA binding proteins located on bacterial cell membrane

Requires Ca2+

26
Q

Conjugation of resistance genes

A

F+ plasmid (donor) contains genes required for sex pilus and conjugation. F factor (tra) plasmid encodes for the pilus which brings the donor and recipient cells into contact.

Recipient bacteria without this plasmid are F-

Pilus brings F+ and F- into contact –> single strand of plasmid DNA is transferred across the conjugal bridge –> synthesis of complementary strand and recircularization of plasmid in both –> completion of transfer and cells separate –> both bacteria are now F+ –> other genes like genes for antibiotic resistance can be only the F plasmid

**gram positive bacteria have no sex pilus so only occurs in gram negative –> are more difficult to treat and are more resistant

27
Q

Transposition of resistance genes

A

Transposons are mobile genetic elements –> can transfer genes from plasmid to chromosome and vice versa

When excision occurs, may include some flanking chromosomal DNA, which can be incorporated into a plasmid –> plasmid can then be transferred to another bacteria

28
Q

Transduction of resistance genes

A

Bacteriophage (virus that infects bacteria) injects DNA into host bacterial cell.

Can be generalised (random parts of the bacterial genome are transferred) or specialised (specific parts of the genome from immediate vicinity of prophage are transferred)

29
Q

Generalized transduction of resistance genes

A

Generalized/lytic:
Lytic phage infects bacterium –> bacterial DNA cleavage –> Parts of bacterial chromosomal DNA may become packaged in phase capsid (instead of phage DNA) –> New bacteriophage are released and infect new bacterium and transfer the bacterial chromosome fragment that can carry the resistance genes

Random parts of the bacterial genome are transferred

30
Q

Specialized transduction of resistance genes

A

Specialized/lysogenic:
Lysogenic phage infects bacterium –> viral DNA incorporates into bacterial chromosome at a specific location –> when phage excises, flanking bacterial genes may be excised with it –> DNA is packaged into phage capsid and can infect another bacterium, transferring the DNA

Specific parts of the genome from immediate vicinity of prophage are transferred

31
Q

General complication of antibiotic therapy (3)

A

Hypersensitivity - frequent (can range from urticaria to anaphylactic shock)

Direct toxicity - directly affects host cellular processes (eg: ahminoglycosides and ototoxicity)

Superinfection - new or secondary infection that occurs during antibacterial therapy of a primary infection

32
Q

Criteria for antimicrobial chemoprophylaxis

A

Giving antibacterial before patient acquires infection

  • Should always be directed towards specific pathogen
  • No resistance should develop
  • Use should be for limited duration
  • Conventional therapeutic doses should be given
  • Should only be used in situations of documented drug efficacy
33
Q

When should nonsurgical antimicrobial prophylaxis be given?

A

Prevention of CMV, HIV infections, influenza, meningococcal infections, TB

Animal or human bite wounds

Chronic bronchitis

34
Q

When should surgical antimicrobial prophylaxis be given?

A

Limited to procedures that are associated with infection in > 50% of untreated cases under optimal conditions

Eg: GI procedures, vaginal hysterectomy, C-section, going replacement, open fracture surgery

Pharmacology (20 decks)

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