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Infection > Antimicrobialsl > Flashcards

Antimicrobialsl Flashcards

1
Q

What are the classifications of antimicrobials?

A

• Antibacterial, antifungal, antiviral &
antiprotozoal (against parasites) agents
• Antibacterial agents can be classified:
– Bactericidal (kill bacteria) or bacteriostatic (stop replication so they eventually die)
– Spectrum – ‘broad’ (eg gram pos only) v. ‘narrow’ (eg certain types of gram pos only)
– Target site (mechanism of action)
– Chemical structure (antibacterial class)

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2
Q

What are the ideal features of antimicrobial agents?

A
  • Selectively toxic - to bacteria but not to host
  • Few adverse effects - dont want patient to experience side effects
  • Reach site of infection - need to know where site is
  • Oral/IV formulation - ideal want both but some only exist in one form
  • Long half-life (infrequent dosing)
  • No interference with other drugs
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3
Q

Name some classes of antibacterials and their mechanism of action

A

Cell wall synthesis:

  • beta-lactams
  • glycopeptides

Cell membrane function
- polymixins e.g. colistin

Protein synthesis

  • tetracyclines
  • aminoglycosides
  • macrolides

Nucleic acid synthesis
- quinolones - trimethoprim, riampicin

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4
Q

Explain the mechanism of action of penicillin

A

Penicillin binding protein helps to build bacterial cell walls
Penicillin binds to this which prevents it from building/maintaining the bacterial cell wall

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5
Q

Explain the action of vancomycin

A

Vancomycin sits on gly-ala residues - the cell wall cross-linking enzyme cannot link them together so cell wall synthesis is disrupted

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6
Q

What is the mechanism of action of fluoroquinolones

A

They bind to 2 nuclear enzymes (DNA gyrase and Topoisomerase IV) which inhibits DNA replication)

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7
Q

What are 3 types of antimicrobial resistance?

A

• Intrinsic
– No target or access for the drug - drug doesnt have access to bacteria
– Usually permanent
• Acquired
– acquires new genetic material or mutates
– Usually permanent
• Adaptive - some bacteria only have gene which is expressed in the presence of antimicrobial, e.g. codes for an enzyme that breaks down the antibiotic
– The organism responds to a stress (e.g. sub-inhibitory level of antibiotic)
– Usually reversible

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8
Q

What are mechanism of antimicrobial resistance?

A

• Drug inactivating enzymes
– e.g. Β-lactamases, aminoglycoside enzymes
• Altered target
– Target enzyme has lowered affinity for antibacterial e.g. resistance to meticillin, macrolides & trimethoprim
- target changed via mutation - antibiotic cant bind to the site
• Altered uptake
– ↓permeability (e.g. Β-lactams) – or ↑efflux (e.g. tetracyclines)
- antibiotic cant get in, or if they do get in, upreglte the efflux pump

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9
Q

What is teh genetic basis for antibiotic resistance?

A

Resistance can be passed on in 2 ways

  • chromosomal gene mutation
  • horizontal gene transfer
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10
Q

What is chromosomal gene mutation?

A
  • one bacterial cell may have a mutated gene conferring resistance
  • in the presence of antibiotics cells without the gene will die
  • the gene is an evolutionary advantage - bacteria with it will survive and replicate so subsequent generations all have the resistance
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11
Q

What is horizontal gene transfer?

A

Mutation can be in chromosome or plasmid 0 it can be transferred by

  • conjugation of 2 bacteria cells
  • phages
  • can be free bits of DNA taken up and integrated

Then when these replicate the subsequent generations have the gene

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12
Q

How can antibiotic activity be measured using disc sensitivity testing?

A

Resistance = smaller zone size
sensitive = larger zone size
vary for different bacteria against different antibiotic
zone sizes nee to be measured - compared to a preset table

Antibiotic disc placed on agar - antibiotic diffuses through agar

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13
Q

How can antibiotic activity be measured using the minimum inhibitory concentration method?

A

Wells on a dish - each contain different concentration of antibiotic
No organism = negativecontrol
Organism in positive control
Various concs of antibiotic going up in doubles each with a set amount of bacteria
Minimum inhibitory concentration is the first well where antibiotic growth is inhibited

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14
Q

What are beta lactams

A

Inhibition of cell wall synthesis. This particular group is characterized by its four-membered, nitrogen-containing beta-lactam ring at the core of their structure, which is key to the mode of action of this group of antibiotics.

These include penicillins, cephalosporins, carbapenams, and monobactams

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15
Q

What are penicillins? Give some examples

A

Penicillins
Penicillin v, benzylpenicillin, amoxicillin, flucloxacillin, co-amoxiclav (amoxicillin + clavulanate), tazocin (piperacillin + tazobactam)

• Penicillin
– Mainly active against streptococci

• Amoxicillin
– Also some activity against Gram-negatives
- slightly wider spec than penicillin

• Flucloxacillin
– Active against staphylococci & streptococci
- choice for cellulitis

• Β-lactamase inhibitor combinations - prevent beta lactamase enzymes from breakin it down (acts as protection)
– Co-amoxiclav (all of above +anaerobes + ↑Gneg
– Piperacillin/tazobactam (as above + ↑↑ Gneg incl
pseudomonas)

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16
Q

What are cephalosporins?

A

1st - cefalexin, 2nd - cefuroxime, 3rd - cefotaxime ceftriaxone and ceftazidime

  • ‘Generations’ with ↑Gneg and ↓Gpos (increasing generations - increasing Gneg)
  • ↑broad-spectrum but no anaerobe activity
  • Cetriaxone has good activity in the CSF
  • Concern over association with C. difficile
17
Q

What are carbapenams?

A

Carbapenems - meropenam, imipenam

• Carbapenems: Meropenem (& imipenem)
– Very broad spectrum (incl anaerobes)
– Active against most (not all) Gram negs, also work against Gpos
– Generally safe in penicillin allergy
- cover big range of infections
- penetrate rly well to skin

18
Q

Give an example of a monobactam

A

Monobactams e.g. aztreonam

19
Q

What are glycopeptides?

A

• Vancomycin
– Active against most Gram pos (not Gnegs)
– Some enterococci resistant (VRE)
– Resistance in staphs rare
– Not absorbed (oral for C. difficile only)
– Therapeutic drug monitoring (TDM) required (narrow therapeutic window)

• Teicoplanin
– Similar activity to vancomycin
– Easier to administer

20
Q

What are tetracyclines?

A

Tetracyclines
• Tetracycline & doxycycline
– Similar spectrum, both oral only
– Broad-spectrum but specific use in penicillin allergy, usually for Gram pos
- very versatile - active against atypical pathogens
– Active in atypical pathogens in pneumonia
– Active against chlamydia & some protozoa
– Shouldn’t be given to children <12 years bc irreversible staining of teeth and boens

21
Q

What are aminoglycosides?

A
  • Most common agent is gentamicin
  • Profound activity against Gram negs But not active against Gpos
  • Good activity in the blood/urine
  • Potentially nephrotoxic/ototoxic - toxic to kidneys at high levels
  • Therapeutic drug monitoring (TDM) required - if levels too high increase interval length
  • Generally reserved for severe Gram neg sepsis
  • Can lead to autotoxicity
22
Q

What are macrolides?

A

Macrolides
• e.g. erythromycin (& clarithromycin)
• Well distributed including intracelleluar penetration
• Alternative to penicillin for mild Gram pos infections
• Also active against atypical respiratory pathogens
Gets into cells very well - work against atypical organisms and organisms what survive very well in host cells

23
Q

What are quinolones?

A

Quinolones
• Commonest example ciprofloxacin
• Inhibit DNA gyrase so inhibit DNA replication
• Very active against Gram negs
• Also active against atypical pathogens
• Increasing resistance and risk of C. difficile
• penetrates bones and other tissues well - bioavailability about 70%
• can cause tendinitous or tendon rupture during several month treatment - try not to give long term

24
Q

What are trimethoprim and sulphonamides?

A

Trimethoprim & sulphonamides

• Inhibitors of folic acid synthesis 
• Trimethoprim used alone in the UK for UTI 
• When combined with sulphamethoxazole
– Co-trimoxazole 
– Used to treat PCP 
– Has activity against MRSA
25
Q

What are antifungals?

A

Antifungals
• Azoles (active against yeasts +/- molds
– Inhibit cell-membrane synthesis
– Fluconazole used to treat Candida
• Itra/vori/posaconazole also active against Aspergillus

Candida is most common fungal infection
candida is a yeast
systemic funcgal infections happen in very immunosuppressed patients

• Polyenes (nystatin and amphotericin)
– Inhibit cell membrane function
– Nystatin for topical treatment of candida
– Amphotericin for IV treatment of systemic fungal infections (e.g. aspergillus)

26
Q

What are antivirals?

A

• Aciclovir
– When phosphorylated inhibits viral DNA polymerase
– Herpes simplex
– genital herpes (give orally), encephalitis (give IV)
– Varicella zoster
– chicken pox & shingles
- give very early - past 48 hours effect is a lot less

• Oseltamivir (‘Tamiflu’)
– Inhibits viral neuraminidase
– Influenza A & B
• Specialist agents for HIV, HBV, HCV, CMV

27
Q

What is metronidazole?

A

Metronidazole: an antibacterial and Antiprotozoal agent
• Active against anaerobic bacteria
• Also active against protozoa:
– Amoebae (causes dysentery & systemic)
– Giardia (causes diarrhoea)
– Trichomonas (causes vaginitis)

Infection (14 decks)

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