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Respiratory > Antimicrobials 2 > Flashcards

Antimicrobials 2 Flashcards

1
Q

What does prophylaxis mean in clinical human use>

A

To prevent infection e.g. around some surgical procedures (perioperative)

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2
Q

What is clinical resistance (treatment failure) dependent on?

A
  • Concentration of antibiotic at site of infection (PK)
  • Activity v infecting organism there (PD)
  • Host defences
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3
Q

What are the types of resistance?

A
  • Acquired

- Intrinsic

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4
Q

What resistant bacteria are in the community?

A
  • Penicillin and multi-resistant pneumococci (PRP)
  • Erythromycin resistant Group A strep
  • Multi-resistant salmonellae (Cipro R)
  • N. gonorrhoea (PPNG, cipro, cefixime R)
  • Community acquired MRSA
  • Drug resistant TB global issue
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5
Q

What resistant bacteria are in hospitals?

A
  • Methicillin resistant S. aureus (MRSA)- Glycopeptides resistant as well
  • Glycopeptide resistant enterococci (VRE)
  • Extended spectrum beta lactamase (ESBL) producing Klebsiella pneumoniae
  • Klebsiella pneumoniae carbapenemases (KPC) and others, carbapenemases producing Enterobacteriaceae (CPE) usually multi resistant to other agents too
  • Other multi-drug resistant Gram negatives (Enterobacter, Serratia, Acinetobacter spp)
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6
Q

What resistance is there in other pathogens?

A
  • Antivirals: HSV, HIV, CMV
  • Antiprotozoals: P. falciparum
  • Antifungals: azole and echinocandin resistant yeasts
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7
Q

What are the factors that promote the success of Antibiotic Resistance?

A
  1. Antibiotic usage- too much/ too little antibiotic
  2. Effective Genetic Mobility- plasmid carriage, transposons, integrins
  3. Efficient Resistance Mechanism- bacterial factors
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8
Q

What antibiotic dose is needed to prevent emergence of resistance?

A

Between 32 to 64 mg/L

Around 48

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9
Q

What is the evidence for association between use of antibiotics and resistance?

A
  • Multi-R bacteria hospitals> community
  • Pre-antibiotic era: hospital infections: Streptococcus pneumoniae and Streps A, antibiotic era: hospital infections more resistant: Pseudomonas, E coli, Klebsiella
  • Patients with resistant bacteria more likely t have had prior antibiotic
  • Restriction used to control outbreaks
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10
Q

Hoe does chromosome mutation select a resistant variant?

A

Spontaneous mutation- 1:10^6- 10^12 per generation

Usually independent of antibiotic usage= selection of mutation, often by the killing of antibiotic sensitive bacteria

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11
Q

What are the locations of resistance genes?

A
  • Chromosome
  • Plasmid
  • Transposon
  • Integron
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12
Q

How do plasmids relate to antibiotic resistance?

A
  • Agents of infectious resistance
  • Extra chromosomal double stranded DNA
  • Autonomous replication
  • Transferred by conjugation (sex pili)
  • Promiscuous
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13
Q

Describe plasmid transfer of Antibiotic Resistance genes

A

Bacterial cell resistant to ampicillin
R-plasmid transferred to bacterial cell sensitive to ampicillin by sex pilus
No resistant

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14
Q

How do plasmids acquire new genes?

A

Transposition (jumping genes)
Transposon go between plasmid and chromosome
Unable to replicate independently

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15
Q

How do transposons acquire new genes?

A

Integrons- gene capture and expression systems- “natural” genetic engineering

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16
Q

What is an integron?

A
  • Genetic element
  • Usually resides on transposon
  • Able to ‘poach’ resistant genes (extracts DNA segments and inserts into other DNA segments)
17
Q

What are the main mechanisms of resistance?

A
  1. Target site alteration
  2. Reduced access (efflux or impermeability)
  3. Drug inactivation
  4. Metabolic bypass
18
Q

What is modification?

A

-Bacterium modifies configuration of site so affinity is reduced- antibiotic can no longer bind to site

19
Q

Examples of modification (binding sites)

A
  • MRSA has altered penicillin binding protein (PBP) 2a instead of PBP 2
  • Ribosome (gentamycin)
  • DNA gyrase (quinolone) altered
20
Q

How is access to target sites reduced?

A

Efflux- tetracyclines, macrolides, quinolones (flow out via pump)
Impermeability- altered porins

21
Q

What enzymes result in drug inactivation/ destruction?

A
  • Beta lactamases
  • Aminoglycoside modifying enzymes
  • Erythromycin esterase
  • Chloramphenicol acetyltransferase
22
Q

Which antibiotics are involved in metabolic bypass?

A

Sulphonamides

Trimethoprim

23
Q

How are these antibiotics involved in metabolic bypass?

A

Effect compromised by hyperproduction or additional target site
Synthase- sulphonamides, extra target dihydropteroate synthetase
Reductase (hyperproduction)- trimethoprim

24
Q

What are the strategies for control of resistance?

A
  1. Conservation= remove devices (urinary and central catheters), drain abscesses (antibiotics don’t penetrate), source control
  2. Prudent use= antibiotic polices (VRE in RIE), good prescribing practice (discourage topicals) de-escalation and date to stop)
  3. Surveillance= use, R organisms, infection syndromes
  4. Infection control= hand decontamination and disinfectant policies

Respiratory (41 decks)

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