Antibacterials Flashcards

1
Q

Sterilise

A

To kill all microbes

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2
Q

Sanitise

A

To kill most microbes

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3
Q

Aseptic

A

Absence of microbes

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4
Q

Disinfectant

A

o Non-selective chemical for killing microbes
o Unsuitable for use on living tissue
o High concentrations required
o E.g. sodium hypochlorite

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5
Q

Antiseptic

A

o Non-selective chemical for killing microbes
o Appropriate for use on living tissue, usually skin
o High concentrations required
o E.g. betadine

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6
Q

Antibiotics

A

o Target particular pathways
o Pathways are unique to bacteria or group of bacteria
o Very small concentrations required
o For use on or in living tissues

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7
Q

Broad spectrum antibiotics

A

Effective against many bacterial groups

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8
Q

Narrow spectrum antibiotics

A

Effective against only a few bacterial groups

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9
Q

Bactericidal antibiotics

A

Kill bacteria

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10
Q

Bacteriostatic antibiotics

A

Inhibit growth of microbes, immune system kills.

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11
Q

Complication in the definition of bactericidal and bacteriostatic.

A

Decreasing concentration: bactericidal becomes bacteriostatic.
Increasing concentration: bacteriostatic becomes bacteriocidal.

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12
Q

Prophylactic therapy

A
  • Before the infection risk occurs e.g. surgery
  • Antimicrobial choice based on known or likely pathogen
  • Use only if: there is evidence for effectiveness or an infection is disasterous
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13
Q

Empirical therapy

A

• Best guess
• Use only when:
o Bacterial infections are very likely
o Treatment has substantial benefit
o ID, sensitivity unknown
• Use narrowest spectrum antibiotic for most likely pathogen
• First obtain specimens for MC&S testing
• Change to directed therapy when laboratory results are available.

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14
Q

Directed therapy

A

• Antimicrobial therapy with evidence from laboratory testing
o Microbial pathogen has been identified
o Antimicrobial sensitivity has been determined
• Then choose the antimicrobial that is:
o Most effective
o Least toxic
o Narrowest spectrum
• Directed therapy is the most desirable antimicrobial therapy

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15
Q

The antimicrobial creed

A

Microbiology guides therapy wherever possible
Indications should be evidence-based
Narrowest spectrum required
Dosage appropriate to the site and type of infection
Minimise duration of therapy
Ensure monotherapy in most situations

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16
Q

Oral antimicrobial administration

A
  • Preferred
  • Less serious adverse effects
  • Cheaper products
  • Lower costs to administer
  • Just as ‘powerful’ as injections
  • Drugs must have good oral bioavailability
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17
Q

Parenteral antimicrobial administration

A

• When oral administration is ineffective
o Poor oral bioavailability
o Swallowing difficulties
o Absorption problems (e.g. vomiting, diarrhoea)
o Higher concentrations are required than possible oral route
o Time critical (rare)
• Reassess daily and convert to oral ASAP

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18
Q

Topical antimicrobial administration

A
  • Use only when effectiveness is proven

* Antimicrobial different from oral and parenteral types, for avoidance of resistance

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19
Q

Adverse effects

A

• All microbials can cause adverse effects
• Adverse effects are usually mild, self-limiting
• Adverse effects more likely in:
o Elderly
o Patients with renal or hepatic impairment

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20
Q

Antimicrobial hypersensitivity (allergy)

A
  • Very commonly reported, esp. to penicillin
  • 5 to 10% of patients
  • But often vague details, inaccurate
  • Usually from parenteral administration
  • True anaphylaxis in 0.01% to 0.04% of courses of penicillin
  • 10% of anaphylaxis fatal
21
Q

When can a patient be given allergy causing antibiotics?

A
  • The antibiotics is clearly the most effective
  • Patient is carefully observed
  • Patient undergoes desensitisation therapy
22
Q

Multi-drug resistant bacteria

A
o	Myobacterium tuberculosis 
o	Staphylococcus aureus
o	Enterococcus
o	Enterics (E. coli, Klebsiella, Enterobacter) 
o	Pseudomonas aeruginosa
23
Q

Antibiotic resistant mechanisms

A
  • Enzymes that degrade antibiotics e.g. beta-lactamases
  • Decreased inner cell membrane permeability
  • Decreased outer membrane permeability
  • Efflux pumps removing antibiotic from inside cells
  • Alteration of the binding site e.g. MRSA
24
Q

How to bacteria gain resistance genes?

A

• Inherent (natural) e.g. many Gram-negs to penicillin
• Vertical gene transfer
o Mutations after selection pressure of antibiotics
o Then transferred ‘vertically’ to progeny
• Horizontal gene transfer
o Genes transferred to related bacteria
o Mechanisms

25
Horizontal gene transfer mechanisms
• Conjugation o Related bacteria in direct contact o Plasmid (ring of DNA) containing the gene transferred o Main mechanisms of antibiotic resistance transfer • Transformation o DNA from external environment (dead bacteria) taken up • Transduction o Bacteriophages transfer DNA between closely related bacteria
26
Research into new antibiotics
``` • To overcome problems with resistance? • Previously much research. • Now very limited. • Only one new antibiotic (Lipopeptides) with a novel mechanism of activity discovered in past 50 years. • Not a good business: o Resistance develops too quickly o We expect antibiotics to be cheap ```
27
Overcoming antimicrobial resistance
``` • Change how we prescribe antibiotics o Prescribe only when absolutely necessary o Narrowest spectrum o Directed therapy when possible o Monotherapy o Correct dose o Only as long as necessary o Discuss antibiotic resistance with patients o Antimicrobial stewardship ```
28
Antimicrobial sterwardship
* Co-ordinated interventions designed to improve the appropriate use of antimicrobial therapy * All healthcare facilities in Australia now require to demonstrate they have an effective Antimicrobial Stewardship program.
29
RHH Antimicrobial stewardship
o Antimicrobials must be prescribed in accordance with the current version of Therapeutic Guidelines Antibiotic or local guidelines, where appropriate. o Patient’s medication chart shows for all prescriptions:  Dose, frequency and route  Indication  Proposed duration with a review date or stop date documented o Classification of antimicrobials  Class A: unrestricted  Class B: approval required  Class C: higher level approval required
30
Antibiotic sensitivity testing
• Patient specimens sent to the laboratory o Blood o Urine o Swabs o Aspirates • Microscopy, culture and sensitivity (MC&S) requested • If pathogen is isolated: o Tested for sensitivity to a variety of antibiotics o Tested for appropriate antibiotic concentration if required
31
Antibiotic sensitivity testing methods
Agar disc diffusion, Broth dilution assay, Epsilometer (E) test
32
Agar disc diffusion
o Make a ‘lawn’ of bacteria on agar plate o Stamp with antibiotic impregnated discs o Incubate then measure zones of inhibition (MM) o Compare zones of inhibition with predetermined ‘break points’ o Inhibition zone > breakpoint: sensitive (S) o Inhibition zone < breakpoint: resistant (R) o Qualitative only: result shows sensitive or resistant only
33
Broth dilution assay
o For when treatment concentration is required  Appropriate antibiotic already known  Make antibiotic dilution series  Add test bacteria and growth medium  Incubate. Cloudiness shows growth.  MIC = lowest antibiotic concentration with no growth o For minimum bactericidal concentrations (MBC):  Plate out concentration with no growth, incubate  MBC = lowest concentration with no growth
34
Epsilometer (E) Test
o For when a treatment concentration is required o E test strips: antibiotic concentration gradient on plastic strip o Make a ‘lawn’ of bacteria on again plate o Place E test strips for different antibiotics on bacterial lawn o Incubate o Intersection of clearing zone with scale shows minimum inhibitory concentrations (MIC) o Ensure antibiotic concentration in the blood is at least the MIC
35
Beta-lactams
• Most widely used group • Cabapenams, cephalosporins, monobactams, penicillins • All have beta-lactam ring structure • Well tolerated (unless hypersensitive) • Interfere with cell wall synthesis • Mechnisms of activity o Target Penicillin Binding Proteins (PBPs) o PBPs are enzymes that catalyse the cross-linking of peptidoglycan in bacterial cell walls o Beta-lactam antibiotics bind to and inactivate PBPs o Cross0linking of peptidoglycans is inhibited o Peptidoglycan precursors accumulate in cell o Autolysis signal o Cells die
36
Aminoglycosides
* Very effective against gram-negatives * Aerobes and facultative anaerobes only * Potential serious side effects * Binds to bacterial ribosomes * Bacteria fail to make proteins – death * E.g. gentamcin, tobramycin, amikacin streptomycin, paromycin, neomycin, framycetin
37
Chloramphenicol
* Very effective, broad spectrum * Binds to ribosomes – inhibit protein synthesis * Potential serious side effects * Systemic use only if no alternative * Mainly topical use: eye and ear infections * Chloramphenicol only
38
Daptomycin
* Effective against gram-positives only * Attaches to and disrupts bacterial cell membrane * Alternative t glycopeptides * Skin and soft tissue infections * S. aureus bacteraemia * Daptomycin only
39
Glycopeptides
* Effective against gram-positives only * Inhibit cell wall synthesis, like beta-lactams * Bind to precursor peptidoglycan units inside cells * Prevents formation of peptidoglycan chains and prevents peptidoglycan chains cross linking * No cell wall formed, new cells die * E.g. vancomycin, teicoplanin
40
Lincosamides
* Effective on gram-positive aerobes and anaerobes * Bind to ribosomes, inhibit protein synthesis * Significant adverse effects * Only use if non others appropriate * Clindamycin and lincomyin only
41
Macrolides
* Wide spectrum activity, except gram-negative rods * Binds to ribosomes, inhibiting protein synthesis * Binding is reversible: bacteriostatic only * Erythromycin, azithromycin, clarithromycin
42
Nitroimidazoles
* Bacteria and protozoa: anaerobes only * Damage to microbial DNA * Metronidazole, tinidazole only
43
Oxazolidonones
* Excellent against antibiotic resistant gram-positives * Reserved for antibiotic resistant staphylococcal, streptococcal and enterococcal infections * Binds to ribosomes, inhibiting protein synthesis * Some potential for adverse reactions * Linezolid only
44
Polymyxins
* Gram-negative rods * Insert into bacterial outer membrane * Increase cell permeability – death * Potential serious side effects * Mainly used externally * Polymixin B, polymyxin E (colistin)
45
Quinolones
* Very widely used * Excellent activity against aerobic gram-negatives * Extended spectrum types are effective against gram-positives, intracellular bacteria and anaerobes * Inhibit DNA replication and repair * Ciprofloxacin, moxifloxacin, norfloxacin, ofloxacin
46
Rifamycins
* Gram-positives only, especially staph., strep. * Effective against Myobacterium tuberculosis * Inhibits RNA synthesis – no proteins made * Combination use only – resistance develops rapidly * Rifampin and rifabutin only
47
Streptogramins
* Gram-positives only: reserved for vancomycin resistant Staphylococcus, Enterococcus infections * Bind to ribosomes – inhibit protein synthesis * Synergistic combination: quinupristin-dalfopristin * Pristinamycin is effective against Gram-negatives as well as Gram-positives
48
Sulfonamides and Trimethoprim
* Broad spectrum * Potential serious side effects * Only for serious infections: MRSA, L. monocytogenes * Inhibit folate synthesis * Sulfamethoxazole-trimethoprim * Very effective synergistic combination
49
Tetracyclines
* Broad spectrum. Also Plasmodium * Reasonably safe * Bind to ribosomes – protein synthesis inhibited * Binding is reversible – bacteriostatic only * Doxycycline, minocycline, tigecycline