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1
Q

What is an example of an antibiotic with a high chemotherapeutic index value? Low value?

A

Penicillin – high

Aminoglycosides – lower

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2
Q

MIC and MBC related to which type of agents?

A

MIC: minimum inhibitory concentration
MBC: minimum bactericidal concentration

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3
Q

Name 3 bacteriostatic drugs:

A

Chloramphenicol, clindamycin, macrolides

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4
Q

Name 3 bactericidal drugs:

A

Penicillin & cephalosporin, vancomycin, rifampin

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5
Q

Direct toxic damage caused by the following drugs:

A

Aminoglycosides – kidney, nerves
Chloramphenicol – bone marrow
Vancomycin – kidneys
Antifungal drugs – liver
Tetracycline – teeth (avoid in children under 8)
Quinolones – bones and cartilage (especially Achilles tendon)
Cephalosporin – may cause gall stones

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6
Q

Which are the beta-lactam antibiotics?

A

Penicillin, cephalosporin, carbapenem, monobactam

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7
Q

What is the penicillin mechanism of action?

A

Penicillin molecules bind penicillin binding protein & transpeptidation is inhibited, cell wall synthesis is blocked so autolytic enzymes are activated

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8
Q

Which penicillin generation is acid sensitive? What is the consequence?

A

Ist, only injectable

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9
Q

Which bacteria lacks a cell wall and therefore is resistant to penicillin?

A

Mycoplasm tb

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10
Q

Which bacteria are resistant to penicillin due to beta-lactamase production?

A

Staphylococcus, Neisseria, enteric bacteria (ESBL)

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11
Q

Which bacteria are resistant to penicillin due to lack or alteration of binding protein

A

Streptococcus pneumoniae, MRSA

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12
Q

Which penicillin derivative is a narrow spectrum antibiotic, primarily to gram + cocci and bacilli? How is it administered?

A

Penicillin G, paraenterally

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13
Q

Which penicillin is used to treat oral infections?

A

Penicillin V (has higher serum concentration)

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14
Q

What are penicillin derivatives (G, V) effective against?

A

Streptococcus, Neisseria, Treponema, Bacillus anthracis

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15
Q

What are the penicillin with extended spectrum and what are they effective against?

A

Aminopenicillins: wide spectrum, G+/-
Carboxypenicillin: Proteus, Pseudomonas (ineffective against S. aureus, enterococcus)
Ureidopenicillin: Pseudomonas
ALL are sensitive to beta-lactamase

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16
Q

Give examples of beta lactamase inhibitors:

A

Clavulanic acid, sulbactam, tazobactam (Unasyn, Augmentin)

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17
Q

Which penicillin derivatives are penicillinase (=beta-lactamase) resistant? What is their downside?

A

Methicillin, oxacillin, cloxacillin, nafcillin

Less effective

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18
Q

What are mechanisms of cephalosporin resistance?

A

Difficult penetration, lack of penicillin binding protein, broken down by beta-lactamase enzyme

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19
Q

What is the cephalosporin spectrum?

A

Broad, bactericidal

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20
Q

What are the synthetic derivatives of cephalosporins?

A 
1st gen – Gram + cocci
2nd gen – Gram -
3rd gen – Gram - 
4th gen – Gram + and gram - 
5th gen  - MRSA (ceftarolin), pseudomonas (ceftobiprole)
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21
Q

What are monobactams (aztreonam) used for?

A

Gram-negative aerobic bacteria: neisseria, pseudomonas

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22
Q

What are carbapenems (impenem, meropenem) used for?

A

Gram + and Gram - (mostly for MDR bacteria, but ineffective against MRSA)

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23
Q

Which are the glycopeptide antibiotics?

A

Vancomycin, teicoplanin

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24
Q

glycopeptide antibiotics

What is a side effect? Why are they important?

A

Oto- and nephrotoxicity

Used against MRSA, VRE

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25
glycopeptide antibiotics | What is their spectrum? Mode of action?
* Narrow – only against gram + b/c CANNOT cross outer membrane and penetrate inside because too big, bacteria, bactericidal * Bind terminal D-ala-D-ala (D-ala-D-lactate) and block crosslink with pentagylcin bridge to inhibit cell wall synth
26
What is fosfomycin spectrum, what is it used for? What is its mechanism?
Broad, UTI (single dose) | Inhibits early stage synthesis of peptidoglycan
27
What is bacitracin and what is it used for?
Polypeptide, inhibits peptidoglycan synthesis (translocation of precursor across membrane), effect against gram - and gram + (especially MRSA!)
28
Which are protein synthesis inhibitors? Which ribosomal subunit do they act on?
30S: Aminoglycosides, tetracyclines 50S: chloramphenicol, macrolides (streptogramins, linezolid)
29
Some examples of aminoglycosides?
Streptomycin (used against TB), gentamicin (used parenterally or in eye drops), neomycin (eye drops)
30
How do aminoglycosides work?
Bind 30S subunit, don’t allow tRNA to bind ribosome which is bactericidal
31
What is the resistance mechanism of aminoglycosides?
Changing receptor on ribosome – mutation Breaking down by enzymes – encoded on plasmids Efflux pump Side molecule can’t penetrate into cell (aerobic)
32
What are side effects of aminoglycosides?
Oto and nephrotoxic, neurotoxic at high doses
33
Which was the first broad spectrum antibiotic (against gram - and +)
Cloramphenicol
34
What is the mechanism of chloramphenicol?
Binds 50S subunit of ribosome, so peptidyl transferase is inhibited
35
What is the side effect of chloramphenicol?
Defective bone marrow function, gray-syndrome, aplastic anaemia
36
What is the resistance mechanism of chloramphenicol?
Acetyl-transferase
37
Which antibiotics disrupt the cell membrane?
Polymixins, lipopeptides
38
Which is the mode of action of the macrolide antibiotics?
Binds 50S subunit of ribosome, bacteriostatic | Bind peptidyl transferase center
39
What is the spectrum of macrolides?
Gram + cocci, legionella, mycoplasma, chlamydia trachomatis
40
What is the resistance mechanism of macrolides?
Target modification | Efflux pump
41
What is the side effect of tetracyclines? What is their resistance mechanism?
Forms complex with Ca2+ which colorizes enamel, shouldn’t be used in children! Mutations
42
Which antibiotic is good to use against intracellular bacteria? Which bacteria?
Tetracycline, chlamydia, mycoplasma, rickettsia
43
What is the action of clindamycin? What is it an antagonist of?
50 S subunit | Macrolides
44
Which bacteria is linezolid NOT effective against?
Gram negative
45
What are streptogramins effective against?
VRE and VRSA
46
Which antibiotics inhibit nucleic acid synthesis?
Quinolons Inhibitors of folate synthesis Metronidazol RNA synthesis inhibitor (Rifampin
47
Inhibitors of folic acid synthesis include:
P-amino-benzol-sulfonamides – p-Amino benzoic acid (PABA) antagonist Trimethoprim – dihydrofolate reductase inhibitor
48
Which antibiotic inhibits DNA gyrase enzyme?
Nalidix acid and fluoroquinolons (inhibit DNA gyrase enzyme)
49
What is the original compound in quinolons?
Nalidixic acid
50
Rifamycin B (rifampin) mechanism and spectrum?
mRNA synthesis inhibition, Gram + cocci, mycobacterium (URT infections)
51
Mechanism of action of nitroimidazole – metronidazole? Limitations?
Damages DNA – no DNA synth | Bactericidal, effective only in anaerobic conditions
52
Spectrum of polymyxin and mode of action?
Narrow, gram -, bactericidal | Binds membrane phospholipids and inhibits membrane transport
53
Which antibiotic that alters membrane functions is antifungal and toxic (therefore has to be administered locally)?
Nystatin (steroid of membrane binding disintegrates PM)
54
When do we use daptomycin? Why is it limited?
Used against vancomycin resistant enterococci and staphylococcal infections ONLY active against gram + (b/c cannot cross outer membrane of gram negatives)
55
Mechanisms of daptomycin:
Mutations in genes that involve synthesis of phosphatidylglycerol Some phenotypes of staphylococcus aureus with VISA phenotype are less susceptible b/c of thicker wall less access
56
Which antibiotics should be completely avoided in pregnancy and young children?
Quinolon
57
Which are some important “synergies” or combinations of antibiotics that can be used?
Sumetrelim: TMX (tetramethoprim) + SMX (sulfamethoxazole) Synercid: quinopristin + dalfopristin Penicillin + gentamycin
58
Which antibiotics are contraindicated to be used together?
Beta-lactams and macrolides | Ciprofloxacin+ tetracycline
59
Which antibiotics can be used to treat MRSA?
Vancomycin, teicoplanin Bacitracin 5th generation cephalosporin (cephtarolin)
60
Which are the problem bacteria/problems associated with the following straings: Staph. Aureus Enterococcus faecalis, faecium Mycobacterium TB
Staph. Aureus – MRSA, VRSA Enterococcus faecalis, faecium – VRE Mycobacterium TB – MDR, XDR
61
Which are the carbapenem resistant gram-negative bacteria?
Acinobacter baumanni, pseudomonas aeruginosa, Klebsiella spp, stenotrophomonas maltophila Enterobacteriaceae
62
What do extended spectrum beta lactamases (ESBL) do? Which type of bacteria are they?
Hydrolyze penicilins, cephalosporins Do not hydrolyze carbapenems, monobactams Gram negative
63
What does metallo beta-lactamase do? Which type of bacteria are they?
Hydrolyze carbapenems | Gram negative bacteria
64
What are other antibiotics that work through enzyme inactivation?
Aminoglycoside (N-acetyltransferase, O-phosphotransferase, O-adenylotransferase) Chloramphenicol (acetyltransferase)
65
Which are antibiotic resistance problems seen in gram + bacteria?
MRSA – methicillin resistant staphylococcus aureus PRP – penicillin resistant pneumococcus VRE – vancomycin resistant enterococcus
66
Why is MRSA resistant to all beta-lactams?
PBP2a has low affinity to all beta-lactams
67
What does vancomycin bind in its process of inhibiting cell wall synthesis?
D-alanine D-alanine
68
Which kinds of bacteria are resistant to vancomycin?
All gram-negative bacteria!
69
Why can’t vancomycin be given per os? When should it be given per os?
No absorption in GI | To kill gram + bacteria in GI that overgrow after other antibiotics were taken
70
What is the mechanism of vancomycin resistance? (VRE)
Vancomycin can’t bind to the D-ala-D-lactate structure
71
What are the most important MDR bacteria?
``` ESKAPE: Enterococcus, S. aureus, Klebsiella, Acinetobacter, p. aeruginosa, Enterobacter spp. ```
72
What are the fundamental mechanisms of extrinsic (acquired) resistance?
1. Receptor is absent 2. Resistance against the antibiotic which was produced by themselves 3. Cell wall barrier (gram negatives) or lack of a cell wall (mycoplasma) 4. Lack of a transport system 5. Antibiotic concentration is low at the receptor
73
How is resistance described clinically?
MIC is higher than maximal dose tolerable by the host
74
Which type of resistance results from the following: Absence of sterols in cell membrane of bacteria Mycoplasms have no cell wall Isoniazid inhibits synthesis of mycolic acid Gram-negative bacteria have complex cell wall Some bacteria need energy from the membrane potential to be absorbed
1. Absence of sterols in cell membrane of bacteria resistance to antifungal polyenes (amphotericin B, nystatin) 2. Mycoplasms have no cell wall beta-lactams are ineffective 3. Isoniazid inhibits synthesis of mycolic acid only works on mycobacteria, nothing else has mycolic acid in cell walls 4. Gram-negative bacteria have complex cell wall penicillin G can’t reach penicillin-binding-protein 5. Some bacteria need energy from the membrane potential to be absorbed inhibition of transport results in resistance to aminogylcosides
75
What is virulence?
The degree of pathogenicity of a microbe, depends on presence/absence of certain structures, exotoxins and endotoxins
76
Which bacteria are toxin producing?
Clostridium tetani, Corynebacterium diphtheriae
77
Which bacteria produce the following toxins? | Neurotoxins, Cyotoxins
Neurotoxins – clostridium botulinum, tetani | Cyotoxins – staphylococci, streptococci, clostridia toxins (cause non-specific necrosis)
78
What is a superantigen?
Binds MHC class II molecules at a location outside the groove normally bound by antigenic peptides, then binds part of the beta-chain of the T-cell which can trigger T—cell activation
79
What is the function of non-toxic virulence factors:
Capsule: macrophages and neutrophils can’t phagocytose Flagella: motility, chemotaxis Pili (fimbrae): adherence Biofilm: binding of prosthetic devices Invasin: provides most direct and efficient manner of host cell invasion Extracellular enzymes: antiphagocytic effect (coagulase, haemolysins, proteases), fascilitate invasion (streptokinase, collagenase, hyaluronidase)
80
Why are there only vaccines for viruses and bacteria?
Immune responses against them are antibody mediated
81
What are the types/components of vaccines?
Inactivated, attenuated, toxoid, subunit, conjugate
82
Which vaccine contains pathogens grown in culture and destroyed by chemical, heat, radioactivity or antibiotics? Examples?
Inactivated vaccines | Cholera, bubonic plague, pertussis
83
Which vaccine contains live pathogens? Examples?
Attenuated | Typhoid, TB (BCG - modified strain), typhus
84
What Is a toxoid vaccine? Examples?
Contains bacterial toxin components that have been inactivated (chemically or by heat) Botulism, tetanus, diphtheria
85
What is a subunit vaccine? How can they be made more immunogenic and T-dependent?
Contains a subcomponent of the pathogenic organism (proteins or polysaccharides) Conjugation with proteins
86
Which vaccines contain capsular polysaccharide?
- HiB, haemophilus influenzae type B - Prevenar 13/Pneumovax 23 - Meningococcus vaccines (against ACWY – not B)
87
Which infections require passive immunity?
Diphtheria, tetanus, measles, rabies, botulism
88
What are examples of anti-phagocytotic substances on the bacterial surface?
``` Polysaccharide capsules M protein and fimbrae Surface slime (polysaccharides) O antigen associated with LPS K antigen of E coli Cell bound or soluble protein A ```

micro (9 decks)

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