PoD - Antimicrobial Chemotherapy Flashcards

1
Q

define bactericidal

A
  • antimicrobial that kills bacteria
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2
Q

define bacteriostatic

A
  • antimicrobial that inhibits growth of bacteria
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3
Q

what does it mean if an organism is ‘sensitive’ to an antimicrobial?

A
  • organism is sensitive if it is inhibited or killed by the antimicrobial available
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4
Q

what does it mean if an organism is ‘resistant’ to an antimicrobial?

A
  • organism is resistant if it is not inhibited or killed by the antimicrobial
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5
Q

what does minimal bactericidal concentration mean?

A
  • MBC is the minimum concentration of antimicrobial needed to kill a given organism
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6
Q

what does minimal inhibitory concentration mean?

A
  • MIC is the minimum concentration of antimicrobial needed to inhibit growth of a given organism
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7
Q

list the main routes of administration

A
  • topical
  • systemic
  • parenteral (injection)
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8
Q

what are the 3 methods antibiotics use to inhibit/kill bacteria?

A
  • inhibition of cell wall synthesis
  • inhibition of protein synthesis
  • inhibition nucleic acid synthesis
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9
Q

what are the main differences between gram +/-ve bacteria?

A
  • gram positive = thick peptidoglycan layer = PURPLE

- gram negative = thin peptidoglycan layer = PINK

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10
Q

what antibiotics inhibit cell wall synthesis?

A

Penicillins & cephalosporins (beta-lactams)
- bactericidal antibiotics
- effective against most gram-positive bacteria
- disrupt peptidoglycan synthesis by inhibiting the enzymes (penicillin binding proteins) responsible for cross-linking the carb chains needed to create cell wall
Glycopeptides
- bactericidal antibiotics
- only act on gram-positive bacteria
- inhibit assembly of peptidoglycan precursor. Prevent the binding of proteins to PBPs
- need to be given parenterally, can’t absorbed from GI tract (vancomycin - toxicity is common)

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11
Q

what antibiotics are given to inhibit protein synthesis?

A

Aminoglycosides - bactericidal antibiotics
- used in treatment of serious gram negative
- binding impairs translation ‘proof-reading’ so leads to RNA being mis-read, premature termination or inaccuracy of product
(gentamicin - toxicity is common)
Macrolides - bactericidal or static depending on conc
- useful alternative to penicillin
Tetracyclines - bacteriostatic
- gram positive infections
- a significant percentage of staph.aureus/strep.pyogenes/strep.pneumoniae are resistant
Oxazolidones - bacteriostatic or cidal
- treatment of gram positive infection
- prevents formation of complex required for bacterial reproduction
(linezolid - new class, given orally, serious infection)

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12
Q

what antibiotics inhibit nucleic acid synthesis?

A

co-trimoxazole - bacteriostatic
- inhibit purine synthesis
- inhibit DNA synthesis directly or indirectly
fluroquinolones - bactericidal
- gram-negative organisms
- direct inhibition of DNA synthesis
- used orally/parenterally can’t be used with children

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13
Q

define bacterial resistance

A
  • an organism is considered resistant to a given drug when it is unlikely to respond to attainable levels of that drug in tissue
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14
Q

what is intrinsic resistance? give examples

A
  • all strains of a given species are naturally resistant to an antibiotic
  • streptococci resistant to aminoglycosides
  • gram-negative organisms always resistant to vancomycin
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15
Q

what is acquired resistance?

A
  • an example of ‘natural’ selection that may or may not be present in strains
  • can occur by spontaneous mutation (change in structure or function which prevents the antibiotic from acting) or spread of resistance (resistant gene spread via plasmids or transposons)
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16
Q

how does b-lactamase cause antibiotic resistance?

A
  • bacterial enzyme cleaves the B-lactam ring of the antibiotic (penicillin/cephalosporin), rendering it inactive
  • staph.aureus produces B-lactamase (also g -ve)
17
Q

how do we combat b-lactamase in bacteria?

A
  • modify the antibiotic side chain, producing new antibiotic resistant to actions of B-lactamase
    (co-amoxiclav - amoxicillin (b-lactam) plus b-lactamase inhibitor clavulanic acid)
  • introduce second component to the antibiotic protecting it from enzymatic degradation (flucloxacillin - modified form of penicillin)
  • extended spectrum B-lactamases (ESBLs) - problem in hospitals by some g -ve bacteria)
18
Q

what is carbapenemase producing enterobacteriaceae (CPE) or Carbapenem-resistant-E (CRE)?

A
  • carbapenems are highly effective antibiotic agents used for treatment of severe/high-risk or suspected multi-drug resistant bacterial infections
  • carbapenems = B-lactam ring
  • carbapenemase = enzyme
19
Q

how does altering the PBP site cause resistance?

A
  • mutations in PBP genes result in a modified target site to which B-lactams can no longer bind
  • methicillin resistant staph.aureus (MRSA) - multiple drug resistance to B-lactam antibiotics
  • combated with vancomycin (inhibit cw synthesis) or linezolid (inhibit p synthesis)
20
Q

what does vancomycin resistant enterococci (VRE) mean?

A
  • in VRE (faecalis/faecium), the peptidoglycan precursor to PBP which vancomycin normally binds to has altered structure
  • major problem with infection control…potential to spread to staph.aureus
21
Q

can antimicrobials cause adverse reactions?

A
  • most have potential
  • incidence dependent on dose and duration of therapy
  • most adverse reactions are trivial and reversible upon withdrawal of antimicrobial
  • some cases can be severe or fatal
22
Q

what antibiotics are likely to develop adverse reactions?

A
  • commonly associated with B-lactams

- true penicillin hypersensitivity is rare

23
Q

what is immediate hypersensitivity?

A
  • anaphylactic shock
  • IgE mediated reaction occurs within minutes administration
  • itching, nausea, wheezing, shock
24
Q

what is delayed hypersensitivity?

A
  • immune response takes hours or days to develop
  • immune complex or cell mediated mechanism
  • rashes, fever, serum sickness
25
Q

what are common GI/abdo side effects?

A
  • nausea and vomiting
  • diarrhoea associated with toxic production by clostridium difficile
  • thrush
  • liver toxicity
  • renal toxicity
26
Q

what are common neurological toxic side effects?

A
  • ototoxicity (ear)
  • optic neuropathy
  • peripheral neuropathy
  • encephalopathy/convulsions
27
Q

what are common haematological toxic side effects?

A
  • toxic effect on the bone marrow resulting in selective depression of one cell line or unselective depression of all bone marrow elements
28
Q

when should antimicrobials be prescribed?

A
  • prophylaxis
  • preventative against future infections
  • patient exposed to other patients with highly communicable disease
  • patients about to be subjected to surgical procedures
  • most abdominal operations
  • when the organism(s) causing infection is not known - empirical antimicrobial therapy commenced if urgent