Microbiology 2 Flashcards
1
Q
List the protein synthesis targeting antibiotics
A
- Aminoglycosides
- Nitrofurans
- tetracyclines
- Chloramphenicol
- Macrolides
- Lincosamides
- Pleuromutilins
2
Q
List the bacteriocidal protein synthesis targeting antibiotics
A
- Aminoglycosides (streptomycin, neomycin)
- Nitrofurans
3
Q
List the bacteriostatic protein synthesis targeting antibiotics
A
- Tetracyclines (oxytetracyline, doxycycline)
- Chloramphenicol
- Macrolides (erythromycin, tylosin)
- Lincosamides
- Pleuromutilins
4
Q
Compare eukaryotic and bacterial ribosomes
A
- Eukaryote has 80s: 40s and 60s subunits
- Prokaryote has 70s : 30s and 50s subunits
5
Q
What is the mechanism of resistance against ribosome targeting antibiotics?
A
- intrinsic:Ribosome sequence alterations leading to alterations in binding sites for drug
- Extrinsic: Acquisition of degradative enzymes that modify the drug
6
Q
Describe the structure of nitrofurans
A
Furan ring with nitro group is the defining structural feature
7
Q
Describe the mechanism of action of nitrofurans
A
- Unique
- Reduced by bacterial flavoproteins to reactive intermediates that inhibit bacterial ribosomes and other macromolecules
8
Q
Describe the mechanism of action of aminoglycosides
A
Bind 30s subunit and affect number of steps in protein synthesis, leading to non-functional proteins
- Irreversibl inhibition
9
Q
Describe the activity and pharmacology of aminoglycosides
A
- Gram -ve
- Not absorbed orally
- Poor tissue penetration (hydrophilic)
- Eliminated by renal filtration
10
Q
Describe the mechanism of action of tetracyclines
A
- Enter cell by active process, bind to receptors on 30s subunit
- Block tRNA attachment
11
Q
Describe the activity and pharmacology of tetracyclines
A
- Many Gram -ve and +ve
- Atypical bacteria e.g. Ricketssia, Borellia, Chlamydia, Mycoplasma
- Can be absorbed orally but varies in group
- Dairy and ant-acids impair use
- Concentrate in liver, significant biliary secretion
- Can cause GIT imbalances
12
Q
Describe the mechanisms of action of chloramphenicol
A
Binds 50s subunit, prevents linking of amino acids to growing peptides
13
Q
Describe the activity and pharmacology of chloramphenicol
A
- Broad spectrum
- Clinically ineffective against Chlamydia
- Good distribution incl CNS and eye
- Banned from use in food animals
14
Q
Describe the mechanism of action of macrolides
A
Block 50s activity
15
Q
Describe the activity and pharmacology of macrolides
A
- Active against Gram +ve nad anaerobic bacteria
- High lipid solubility, good distribution
- Bacteriostatic, but erythromycin can kill at high concentrations
- Chromosomal resistance can develop
16
Q
Describe the mechanism of action of lincosamides
A
Bind 50s subunit and block peptidyl transferase activity
17
Q
Describe the activity and pharmacology of lincosamides
A
Primarily Gram +ve but some -ve
- Basic, lipid soluble
- Wide distribution in body
- Facultative aanaerobic bacteria are intrisincally resistant due to methylation of 50S binding site
18
Q
Describe the toxic effects of lincosamides
A
Serious fatal diarrhoea in horses, rabbits, guinea pigs and other herbivores, can cause problems in cattle. Caused by rapid bacterial overgrowth
19
Q
List the DNA disruption and RNA synthesis targeting classifications
A
- Nucleic acid targeting
- Non-ribosome blocking of protein synthesis
- DNA precursor affecting
- DNA packaging
- DNA destruction
20
Q
List the antibiotics that affect DNA in some way
A
- Sulphonamide/trimethoprim
- Quinolones, novobiocin
- Nitroimidazoles
21
Q
Name the antibiotic that affects RNA synthesis
A
Rifampicin
22
Q
Describe the mechanism of action of sulphonamides/trimethoprim
A
- Affect nucleotide synthesis
- Competitive inhibitors of dihydropteroate synthase
- Cell lacks dihydrofolate synthesis which is required for DNA synthesis
23
Q
How does sulphonamide exert its action?
A
Similar structure to PABA, substitutes it in the synthesis of dihydrofolate
24
Q
How does trimethoprim exert its action?
A
Inhibits dihydrofolate reductase preventing production of THF and thus the production of nucleotides
25
Why are sulphonamide and trimethoprim used together?
Some production of DHF can still occur where sulphonamide is used alone, addition of trimethoprim prevents conversion of this to THF and then nucleotide
26
Describe the mechanism of action of quinolones
- Inhibits DNA gyrase activity, needed for supercoiling of DNA to be packaged in bacteria
27
How can resistance to quinolones develop?
Single point mutation
28
Describe the pharmacokinetics of quinolones
- Low activity on gut anaerobes
- Rapid oral absorption (poor in ruminants)
- Excretion via urine after partial metabolism in liver
- Large volume of distribution
- Good penetration into CSF, bronchial secretions, bone, cartilage, prostatic tissues
29
Give an example of a side effect of quinolones
Cartilage erosion in horses
30
Describe the mechanism of action of nitroimidazoles
- Reduction products of imidazole group are reactive with DNA
- Cause DNA strand breaks
- Require reduction environment so ineffective on aerobic bacteria
31
Name members of the fluoroquinolone group
- Nalidixic acid
- Erofloxacin
- Neomycin
32
Describe the spectrum of activity of nitroimidazoles
- Effective only on anaerobes
| - Some Gram +ve, all Gram -ve
33
Describe the pharmacokinetics of nitroimidazoles
- Absorbed rapidly after oral admin
- Wide distribution (lipophilic)
- Will cross placenta and into milk
- Functional in abscesses
34
List the adverse effects of nitroimidazoles
- Carcinogenic and mutagenic
- Hepatotoxicity
- Neurotoxicity including seizures
- Ataxia
35
Describe the spectrum of activity of pleuromutlins
Mainly Gram +ve, moderate against some fastidious Gram -ve bacilli, Mycoplasma and Campylobacter, inactiva against Enterobacteriaceae
36
Define narrow spectrum of activity
Few bacterial groups targeted, usually only effective on Gram +ve bacteria
37
What are potential outcomes of combined antibacterial therapy?
- Additive effect (purely summative)
- Synergistic effect
- Indifference
- Antagonistic effect
38
Give an example of where combined antibacterial therapy may have an antagonistic effect
Combination of bacteriostatic drug with a bacteriocidal drug
39
List the potential mechanisms of antibiotic resistance
- Modification/breakdown of drug
- Efflux
- Reduced permeability
- Modified pathways
- Altered target site
40
Explain how efflux pumps lead to antibacterial resistance
- Pumps on bacteria, reduce intracellular concentration of the antibiotic
- Not inhibiting every component of the cell
41
Explain how bacteria may be able to modify/breakdown a drug before it enters the cell
Secretion of enzymes into the cytoplasm or out of the cell, altering the structure of the antibiotic and thus preventing function
42
List the ways in which genetic make up of bacteria can change
- New genes (insertion, inheritance on plasmids)
- Loss of genes (deletions)
- Modification of function by genes by deletion, inheritance or point mutation
- Modification of promotors leading to altered expression (point mutations)
43
Explain transferable acquired resistance in bacteria
- Based on genetic transfer through plasmids
| - Transposons can hop between chromosomes and plasmids
44
Define intrinsic resistance
Innate ability of group to resist activity of a particular antimicrobial agent through inherent structure or functional characteristics which allow tolerance of the drug (e.g. lack or altered target)
45
Define acquired resistance
When a microorganism obtains the ability to resist the activity of a drug, allowing alteration of drug, alteration of target, or provides bypass mechanism
46
Give examples of intrinsic resistance
- Poor permeability due to outer membrane (Gram-ve intrinsically resistant to vancomycin)
- Target different to other genera (e.g. Enterococci resistant to cephalosporins, have low affinity for enterococal PBPs)
- Lack target (e.g. Gram +ve bacteria are resistant to LPS targeting antibiotics e.g polymyxin)
47
Describe acquired resistance through mutation
- Common
- Ribosome, or ribosomal proteins, such that the antibiotic does not bind target
- Mutation of DNA gyrase so it tolerates fluoroquinolones
48
Give examples of acquired resistance genes
- beta-lactamases
- Aminoglycoside modifying enzymes
- Alternate targets MRSA (add variant of target)
- Efflux systems (new gene, or upregulation of existing)
49
Describe the alternate target resistance of MRSP
- have mecA gene, encodes alternate penicillin binding protein (PBP2a)
- Low affinity for beta lactam
- Outcome is strains which can tolerate most of beta-lactam antibiotics, as anitbiotic only binds PBP1 not PBP2a
50
Describe resistance to vancomycin via the modification of the cell wall
- Production of altered peptidoglycans
- Method of vancomycin resistance in enterococci
- Alteration of terminal amino acid residues of NAM/NAG-peptide subunits
- Mediated by van genes found on transposon
- van gene can be transferred via plasmids
51
Describe the resistance to antibiotic by efflux
- New genes or upregulation of existing
- Antibiotic efflux transporters classified into 5 superfamilies based on amino acid sequence and energy source used to export substrates
- All transport groups of compounds with similar chemical properties so may lead to cross-resistance
52
Name the 5 superfamilies of bacterial antibiotic efflux transporters
- Major facilitator superfamily (MFS)
- ATP- binding cassette superfamily (ABC)
- Small multidrug resistance family (SMR)
- Resistance -nodulation-cell-division superfamily (RND)
- Multi-antimicrobial extrusion protein family (MATE)
53
List the antibiotics and other agents exported by the major facilitator superfamily transporters
- Tetracycline, fluoroquinolones, erythromycin, lincosamides, rifampicin, chloramphenicol, aminoglycosides
- QACs, basic dyes, phosphonium ions
54
List the antibiotics and other agents exported by the resistance-nodulation-cell division superfamily transporter
- Tetracyclines, fluoroquinolones, erythromycin, rifampicin, beta-lactams,fusidic acid, chloramphenicol, aminoglycosides
- Basic dyes, detergents, fatty acids
55
List the antibiotics and other agents exported by the small multidrug resistance family transporters
- Tetracycline, erythromycin, sulfadiazine
| - QACs, antiseptics, tratrphynly compounds, phosphonium, ethidium
56
List the antibiotics and other agents exported by the ATP-binding cassette superfamily transporter
- Tetracycline, fluoroquinolones, erythromycin, rifampicin, macrolides, beta-lactams, fusidic acid, chloramphenicol, aminoglycosides
- Ionophors, ethidium, akaloids, phospholipids
57
List the antibiotics and other agents exported by the mutli antimicrobial extrusion protein superfamily transporters
- Tetracycline, fluoroquinolones, erythromycin, rifampicin, chloramphenicol, beta-lactams, fusidic acid, aminoglycosides
- Dyes
58
What are the major mechanisms of resistance against beta-lactams?
Cleavage by beta-lactamases
| - Altered PBPs, aternate PBPs
59
What are the major mechanisms of resistance against aminoglycosides
- Enzymatic modification
- Efflux
- Ribosomal mutations
- 165 rRNA methylation
60
What are the major mechanisms of resistance against quinolones?
- Efflux
- Modification
- Target mutations
61
What are the major mechanisms of resistance against vancomycin?
- Altered cell walls
| - Efflux
62
What is the major mechanism of resistance against rifampicin?
Altered beta-subunit of RNA polymerase
63
What are the major mecahnisms of resistance against antibioics that inihibit cell wall synthesis (e.g. streptogramins such as virginiamycins, quinupristin, dalfopristin)
Enzymatic cleavage, modification, efflux
64
Name some bacterial antibiotic susceptibility tests
- Dilution test (for MIC)
- Kirby-Bauer Disc diffusion
- E strip diffusion (rapid simple MIC)
65
Explain the principles of the Kirby-Bauer resistance test
- Assessment of the diffusion gradient around an antibacterial disc
- Measure, compare ot known values
- Allows establishment of susceptibility and MIC
66
Describe the use of Evaluator (E) strips in assessing bacterial resistance
- Strip has gradient of antibiotic content
- Compaire amount of bacterial growth with demarkation on strip
- Allows determination of susceptibility and MIC
67
Outline the interpretation of a disc diffusion and dilution assays
- Resistant = small inhibitory zone on disc diffusion and high MIC by dilution
- Susceptible = very large inhibitory zone on disc diffusion and low MIC by dilution
68
Outline how resistance can spread
- Selective pressure leading to survival of resistant bacteria
- Eventually end up with fully resistant populations
69
What is multi-drug resistance?
- Acquired non-susceptibiltiy to at least one agent in 3 or more categories
- Antimicrobial category list based on clinical break points for drugs that are listed for use against that organism
70
What is XDR?
- Extensively drug resistant
| - Acquired non-susceptibility to at least one agent in all but 2 or fewer antimicrobial categories
71
What is PDR?
- Pan-drug resistant
| - Acquired non-susceptibility to all agents in all antimicrobial categories
72
How can MDR, XDR and PDR develop?
- Plasmid transfer of resistance
- Cassettes and transposable elements allowing increased mobility of complex collections of genes to express resistances and ability to hop in chromosomes and plasmids between
- TN3 transposon gene
- Plasmid conjugation
- Transduction (bacteriophage)
- Transformation (uptake of naked DNA from environment)
73
Explain how the TN3 transposon gene can lead to the transfer of resistance between bacteria
- Genes are on mobile elements
- Taken up by other bacteria
- Selected for and maintained
- Big problem for lots of Gram -ve
74
When may prophylactic treatment with antibiotics be advantageous?
When started within 3 hours of contamination
75
What are the disadvantages of prophylactic antibiotic use?
- Toxicity
- Encouragement of drug resistance
- Residues in food animals
- Cost
76
Give examples of deleterious use of antibiotic prophylaxis
- Growth promotion with fluoroquinolones increases resistant pathogens
- Neomycin used in calves predisposes to diarrhoea
- Tetracyclines given to feedlot calves increases mortality
- Inter-uterine treatment e.g. neomycin to prevent post-partum metritis may affect fertility
77
Give examples of prophylactic antibiotic use
- Feedlot pneumonia of calves on arrival
- Leptospira in cows (remove carriers)
- Strangles in horses (treat at risk horses, quarantine)
- Broilers at known risk of colibacillocis or chronic respiratory disease
78
Outline where antimicrobial combination therapy may be used
- Mixed bacterial infections
- Therapy in severe conditions where aetiology unknown
- Treating life threatening cases prior to susceptibility data
- Treating unusual pathogens incl. Mycobacterium
- Syntergistic effects e.g. sulphonamide and trimethoprim
79
Give examples of adjunctive therapy that may be used with antimicrobials
- Fluids
- Surgery
- Drugs to improve effectiveness e.g. modifying urine pH
- Glucocorticoid treatment to reduce trauma while drugs act (but also leads to immune suppression)
80
What is the importance of the MIC in clinical use?
- Need to reach MBC, as only reaching MIC may allow overgrowth of resistant bacteria
- Need to maintain this for particular period of time with most drugs
81
When should culture and sensitivity be carried out?
Always, in order to prescribe specific drug for specific pathogen
82
What is an important consideration when giving antibiotics to ruminants?
Cannot be administered orally as will knock out the rumen microflora
83
Give the points of the 7 point plan for responsible use of antimicrobials in veterinary practice
- Work with clients to avoid need for antimicrobials
- Avoid inappropriate use
- Choose right drug for right bug
- Monitor antimicrobial sensitivity
- Minimise use
- record and justify deviation from protocols
- Report suspected treatment failure to the VMD
84
What is a potential consequence of antimicrobial resistance through veterinary use?
May also have resistance in the human variant
85
Explain how vets can work with clients to avoid the need for antimicrobials
- Inform owners about benefits of regular health checks, educate on antibiotic use
- Use symptomatic relief or topical preparations where possible
- Use integrated disease programmes, biosecurity, monitoring of health status for early intervention, environmental modification to reduce infection risk
- Vaccination where possible
- Isolate infected animals
- Improve animal health and welfare
86
Explain how vets can avoid inappropriate use of antimicrobials
- Use for bacterial infections
- Restrict use to ill or at-risk animals
- Advise clients on correct administration of products and completion of course
- Avoid underdosing (consider formulation and site that needs dosing)
87
Explain how to choose the "right drug for the right bug"
- Identify likely target organisms and predict susceptibility
- Create practice based protocols for common infections based on clinical judgement and up to date knowledge
- Know how antimicrobials work and their pharmcodynamics
- Use as narrow spectrum as possible
- Have idea of pathogen likely prior to culture and sensitivity by using in house smears and microscopy
88
Explain the monitoring of antimicrobial sensitivity
- Must be determined so can implement change in treatment where necessary
- Monitor bacterial culture and sensitivity trends
89
Explain how to antimicrobial use can be minimised
- Use only when necessary, and evidence that usage will reduce morbidity/mortality
- Regularly assess antimicrobial use and develop written protocols for appropriate use
- Use alongside strict aseptic techniques and written practice guidelines
90
Explain the recording and justification of deviations from antimicrobial protocol
- Must be able to justify choice and dose
| - Accurate records allow evaluation of outcome of therapeutic regimens
91
Explain the reporting of suspected treatment failure of antimicrobials to the VMD
- May be first indication of resistance
| - report through Suspected Adverse Reaction Surveillance Scheme (SARSS)
92
Explain what is meant by narrow spectrum antibiotics
- Only treat specific groups of bacteria
- Gram +ve or Gram -ve
- or Gram +ve with some Gram -ve
- Anaerobic or aerobic
93
Explain what is meant by broad spectrum antibiotics
- Treat wide range of bacteria
- Often active against Mycoplasmas
- Gram +ve and Gram -ve
94
Which antimicrobials can be used to treat Gram +ve bacteria?
- Beta-lactams e.g. penicillin, cloxacillin, 1st gen cephalosporins
- Macrolides e.g. erythromycin, tylosin
- Lincomycin, tiamulin, novobiocin
95
Which antimicrobials can be used to treat Gram -ve bacteria
- Aminoglycosides (e.g. dihydrostreptomycin, framycetin, kanamycin, neomycin, streptomycin, gentamycin)
- Septinomycin, apramycin
96
Which antimicrobials can be considered broad spectrum?
- Beta-lactams except penicillin
- Sulphonamides
- Tetracyclines
- Fluoroquinolones (protected group)
97
What factors may affect the choice of antimicrobial?
- Pathogen to be treated
- Age of animal
- Pregnancy status
- Concurrent disease
- Immune status of patient
- Food or not food animal
- Licensing
- Toxicity and side effects
- Practical considerations e.g.practice stock
98
Why could efflux systems allow resistance to multiple antibiotics while an enzyme to degrade an antibiotic may only lead to resistance to that group?
Efflux is non-specific and leads to reduced intracellular concentrations of that antimicrobial. Enzymes need to be specific to that antibiotic and so can only provide resistance to that one drug
99
What is clavulanic acid?
A beta-lactamase inhibitor that allows the functioning of beta-lactam antibiotics where there is resistance to beta-lactam alone
100
What are the risks associated with antimicrobial resistance in commensals?
May be opportunistic pathogens and may be reservoirs for plasmid transfer of resistance genes
101
Describe fusidic acid
- Protein synthesis inhibitor preventing turnover of elongation factor G
- Resistance via: alterations in ribosomal structure or drug, chromosomal mutation
- Bacteriostatic
- Effective for Gram +ve
