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4 - Y5 a Path lectures 2021/22 > Microbiology 2: Antimicrobials 1 > Flashcards

Microbiology 2: Antimicrobials 1 Flashcards

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1
Q

What are some targets of antimicrobials?

A
  • Peptidoglycan layer of cell wall
  • Inhibition of bacterial protein synthesis
  • DNA gyrase and other prokaryote specific enzymes
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2
Q

What are some antibiotic classes that inhibit peptidoglycan synthesis

A

beta-lactam antibiotics, glycopeptides

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3
Q

Give some examples of Beta lactam antibiotics

A

penicillins, cephalosporins, carbapenems

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4
Q

Give some examples of Glycopeptides antibiotics

A

vancomycin, teicoplanin

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5
Q

Do Beta lactam antibiotics target gram positive or gram negative bacteria?

A

broad spectrum

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6
Q

Do Glycopeptides antibiotics target gram positive or gram negative bacteria?

A
  • Gram-positive
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7
Q

What is the difference between gram positive and gram negative bacteria?

A
  • Gram-positive cell wall = thick peptidoglycan cell wall (made of NAG and NAM components)
  • Gram-negative cell wall = thinner peptidoglycan cell wall, outer membrane conferring resistance to some antibiotics
    • Can be more resistant and harder to treat due to outer membrane
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8
Q

What is beta lactam antibiotics’ mechanism of action?

A
  • Inactivate enzymes involved in terminal stages of cell wall synthesis = transpeptidases / penicillin binding proteins
    • Beta lactam is a structural analogue of the enzyme substrate
  • Bactericidal (active against rapidly dividing bacteria) – if cell wall has already been formed, they have no effect
    • Ineffective against bacteria lacking peptidoglycan cell walls (mycoplasma, chlamydia)
    • Cause cell lysis
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9
Q

What type (gram positive or gram negative) of bacteria does penicillin target? Give some examples

A
  • gram +ve,
  • streptococci, clostridia
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10
Q

What is penicillin broken down by?

A
  • beta-lactamase
  • produced by S. aureus (SA) and many other gram -ve organisms
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11
Q

What type (gram positive or gram negative) of bacteria does amoxicillin target? Give some examples

A
  • broad-spectrum
  • (enterococci to gram -ve)
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12
Q

What is amoxicillin broken down by?

A
  • beta-lactamase
  • produced by S. aureus (SA) and many other gram -ve organisms
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13
Q

What type (gram positive or gram negative) of bacteria does flucloxacillin target? Give some examples

A
  • gram negative, ONLY S. aureus
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14
Q

What is flucloxacillin broken down by?

A
  • Not broken down by beta-lactamase produced by SA
  • used to treat SA infections (S. aureus)
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15
Q

Compare flucloxacillin and penicillin

A
  • Similar to penicillin, less reactive
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16
Q

What type (gram positive or gram negative) of bacteria does Piperacillin target? Give some examples

A
  • broad-spectrum
  • (pseudomonas, non-enteric gram -ve)
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17
Q

What is Piperacillin broken down by?

A
  • Broken down by beta lactamase
  • (produced by SA and many other gram -ve organisms)
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18
Q

Which antibiotic is Piperacillin similar to?

A

amoxicillin

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19
Q

What is the antibiotic name for Clavulanic acid

A

Co-amoxiclav

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20
Q

What is the antibiotic name for tazobactam?

A

Tazocin / Piptazobactam

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21
Q

What is clavulanic acid and how does it work?

A

beta lactamase inhibitors –> protect penicillin from enzymatic breakdown

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22
Q

What is the point of combining Clavulanic acid (Co-amoxiclav) and tazobactam (Tazocin / Piptazobactam)?

A
  • Inhibit beta lactamase from being broken down by bacteria (protect penicillins from breaking down)
  • Increase coverage to include SA, gram -ve (i.e. E. coli), anaerobes
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23
Q

Which organisms are resistant to cephalosporins? What should be used instead

A

ESBL producing organisms resistant to cephalosporins –> use carbapenems

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24
Q

Give some examples of cephalosporins antibiotics

A
  • Cefuroxime
  • Ceftriaxone
  • Ceftazidime
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25
What is Cefuroxime broken down by?
* _Stable_ to many beta lactamases made by gram -ve
26
Compare co-amox and Cefuroxime
* Similar cover to co-amox (less active against anaerobes) * if anaerobes suspected, add metronidozole to cefuroxime
27
What is **ceftriaxone** associated with?
* C. difficile
28
What is **ceftriaxone** used to treat?
* Treat meningitis (IM ceftriaxone)
29
Which organism does c**eftriaxone** NOT cover against?
* **NO COVER** against *Pseudomonas*
30
Which organisms does c**eftazidime** provide cover against?
* Activity against *pseudomonas* (HAIs often)
31
What is the advantage of using **Ceftazidime** over **Ceftriaxone?**
* **Ceftazidime** = activity against *pseudomonas* (HAIs often) * **Ceftriaxone** = no activity against *pseudomonas*
32
Which type of patients is Cefotaxime used to treat?
* Cefotaxime = the _paediatric_ ceftriaxone
33
Are ESBL producing organisms resistant to carbapenems?
ESBL producing organisms **NOT resistant** to carbapenems
34
Give some examples of carbapenem antibiotics
* **Meropenem, imipenem, ertapenem**
35
Why do MDR organisms pose a threat to carbapenem use?
production of carbapenemase enzymes becoming more widespread
36
Which bacterial species are becoming more multi-drug resistant (MDR)?
Acinetobacter and klebsiella species
37
Give an example of a **Monobactam** antibiotic
* Carumonam
38
What are the key features of beta lactam antibiotics?
* Relatively non-toxic * Renally excreted so decrease dose if renal impairment * Short T1/2 (many are type 2 drugs so aim to maximise the **time \> MIC**) * Will not cross BBB * Cross allergenic – penicillin has 10% cross reactivity with cephalosporins and carbapenems
39
Do Glycopeptides antibiotics target gram positive or gram negative bacteria?
gram +
40
What is the mechanism of action for glycopeptide antibiotics?
inhibit cell wall synthesis (hence target gram +tive)
41
Why are glycopeptide antibiotics unable to target gram -tive bacteria?
* Large molecules so unable to penetrate gram -ve
42
What are the important uses of glycopeptide antibiotics?
* MRSA infections (IV) * *C. difficile* infection (oral – Vancomycin, teicoplanin)
43
What is the major complication/risk of using glycopeptide antibiotics?
* Nephrotoxic – must monitor for accumulation
44
Which antibiotic classes are inhibitors of Protein Synthesis?
* Aminoglycosides * Tetracyclines * Macrolides * Chloramphenicol * Oxazolidinones
45
Give some examples of **Aminoglycoside** antibiotics
**gentamicin, amikacin, tobramycin**
46
\*\*Give some examples of tetracycline antibiotics
??
47
Give some examples of macrolide antibiotics
erythromycin, lincosamides – clindamycin, streptogramins – synercid – MLS group
48
Describe the mechanism of action of Aminoglycoside antibiotics
* Bind to amino-acyl site of 30s ribosome subunit * Rapid, concentration-dependent bactericidal * Require specific transport mechanisms to enter * Accounts for some intrinsic resistance
49
What are some possible complications of aminoglycoside antibiotics?
* Ototoxic and nephrotoxic – monitor levels
50
Which of the 3 aminoglycoside antibiotics are particularly active against pseudomonas aeruginosa?
**Gentamicin** and **tobramycin**
51
When combined with beta lactams, what can aminoglycosides be used to treat?
* **Synergistic combinaton** with beta lactams * Endocarditis treatment, pneumonia
52
Do aminoglycosides have any activity against aenerobes?
no
53
What type (gram positive or gram negative) of bacteria does **Tetracyclines** target?
Broad spectrum
54
What kind of organisms (intracellular or extracellular) do tetracyclines target? Gice some examples
* activity against intracellular pathogens – * chlamydia, rickettsia, mycoplasma
55
What is the mechanism of action of tetracyclines?
* Bacteriostatic (stops bacteria from _reproducing_)
56
What are the problems with using tetracyclines?
* Widespread **_resistance_** now * Deposited in growing bone * Don’t give to children (\<12 yrs), pregnant women * **SE**: photosensitivity rash (summer effect)
57
What is the mechanim of action of macrolides?
* Bacteriostatic (stops bacteria from _reproducing_)
58
What are the benefits of using macrolides?
* Useful agent for treating mild staphylococcal or streptococcal infections in pen-allergic patients * Active against campylobacter species, legionella, pneumophilia
59
What are some newer macrolide agents, and why are they useful?
* Newer agents include ***clarithromycin*** and ***azithromycin*** * due to a better half-life
60
Are macrolides useful against gram -tive bacteria?
* Little activity against gram -ve bacteria (membrane)
61
What type (gram positive or gram negative) of bacteria does chloramphenicol target?
broad spectrum
62
What is the mechanism of action of chloramphenicol?
* Bacteriostatic
63
How often is chloramphenicol used? What are the risks/complications of its/their use?
* **_Rarely used_** apart from eye preparations * Risk of aplastic anaemia * Risk of grey-baby syndrome in neonates because of inability to metabolise the drug
64
What is the main antibiotic in the Oxazolidinone class?
*Linezolid*
65
What type (gram positive or gram negative) of bacteria does Oxazolidinones target?
* Highly active against **gram +ve** (MRSA & VRE) * **Not active** against most gram -ve
66
What are the downsides of Oxazolidinones?
* Expensive, * may cause _thrombocytopenia_ & _optic neuritis_; * should only be used with micro/ID approval
67
What is the mechanism of action of Oxazolidinones ?
* Binds to 23S component of 50s subunit à prevents formation of a functional 70s initiation complex
68
Name the antibiotic classes that are inhibitors of DNA synthesis
* Quinolones / Fluoroquinolones * Nitroimidazoles
69
Name some examples of Fluoroquinolones
* *ciprofloxacin (old),* * *levofloxacin (new),* * *moxifloxacin (new)*
70
What type (gram positive or gram negative) of bacteria do Fluoroquinolones target?
* **Broad antibacterial activity** versus gram -ve (pseudomonas aeruginosa)
71
What is the mechanism of action of Fluoroquinolones
* Act on alpha unit of **DNA gyrase**, bactericidal
72
What are the newer agents of fluroquinolones? Which organisms are they better against?
* Newer agents (levofloxacin, moxifloxin) * better against gram +ve and intracellular bacteria (Chlamydia spp.)
73
What are Fluoroquinolones used to treat?
* UTI, * pneumonia, * atypical pneumonia, * bacterial gastroenteritis
74
Name some examples of Nitroimidazoles
* **metronidazole**, * tinidazole
75
What is the mechanism of action of Nitroimidazoles?
* Under anaerobic conditions, an active intermediate is produced which causes **DNA strand breakage** * Rapidly bactericidal
76
Which organisms are Nitroimidazoles active against?
* Active against anaerobic bacteria and protozoa (Giardia)
77
What are nitrofurans? What are they used to treat?
* Nitrofurans are related compounds to Nitroimidazoles * nitrofurantoin is good for cystitis and lower UTIs – take after voiding bladder
78
Which classes of antibiotics are inhibitors of RNA Synthesis?
Rifamycins
79
Name some examples of **Rifamycins**
* *rifampicin* * *rifabutin*
80
What is the mechanism of action of Rifamycins?
* Inhibits protein synthesis by binding to **DNA-dependent RNA polymerase**, inhibiting initiation * Bactericidal
81
Which organisms are Rifamycins active against?
* mycobacteria * chlamydia
82
Where is rifamycin metabolised? And hence which bloods must be done regularly?
* Interactions with other drugs metabolised in the liver (e.g. OCP) * and so need to **monitor LFTs**
83
How might you check compliance with Rifamycins?
* Turns secretions orange (urine and contacts) – can check compliance
84
Which of the Rifamycin antibiotics have bacteria developed resistance to? And how?
* **Rifampicin** resistance (never used as a single): * Resistance due to chromosomal mutation * Causes **single amino acid change in beta subunit of RNA polymerase** which fails to bind rifampicin
85
Which classess of antibiotics act by releasing **Cell Membrane Toxins?**
* **Daptomycin** * **Colistin**
86
What type (gram positive or gram negative) of bacteria does **Daptomycin** target?
activity limited to gram +ve
87
What is the molecular structure of **Daptomycin?**
Cyclic lipopeptide
88
What can **Daptomycin** be used to treat? When may this be necessary?
* MRSA and VRE infections * as an alternative to linezolid and synercid (e.g. if patient is intolerant)
89
How is **Colistin** administered?
IM/IV
90
What is the structure of **Colistin?**
Polymyxin antibiotic
91
What type (gram positive or gram negative) of bacteria does **Colistin** target? Give some examples
* Active against gram -ve including: * pseudomonas aeruginosa, Acinetobacter baumannii, klebsiella pneumoniae
92
What are some possible complications of **Colistin** use? Hence, what is it reserved for?
* Nephrotoxic * reserved for use against multi-resistant organisms
93
Which classes of antibiotics are Inhibitors of Folate Metabolism?
* **Sulphonamides** * **Diaminopyrimidines**
94
How do antibiotics that are Inhibitors of Folate Metabolism work?
These **act** **indirectly on DNA** through interference with folic acid metabolism
95
Give an example of synergistic action between 2 drug classes (**Synergistic action** between 2 drug classes because they act on sequential stages in the same pathway)
* I.E. co-trimoxazole = sulphamethoxazole + trimethoprim
96
What is the problem with **Sulphonamides**
Resistance is common
97
What combination is important in treating pneumocystis jiroveci pneumonia? (PCP – HIV-defining disease)
Combination of sulphamethoxazole + trimethoprim (co-trimoxazole)
98
Give an example of a Diaminopyrimidines
trimethoprim
99
What is trimethoprim (Diaminopyrimidine) used to treat?
Used as treatment for community acquired UTIs
100
What is the acronym for methods of antibacterial resistance?
**BEAT**
101
Which antibiotic classes are susceptible to inactivation?
* beta lactams * aminoglycosides * chloramphenicol
102
103
Which antibiotic classes are susceptible to altered targets (method of antibiotic resistance)?
104
Which antibiotic classes are susceptible to reduced accumulation (of the antibiotic)?
105
Which antibiotic classes are susceptible to bypass antibiotic-sensitive step (method of antibiotic resistance)?
* trimethoprim * sulphonamides
106
Which organisms produced beta lactamases as a major mechanism of resistance to beta lactam ABx?
SA and gram -ve bacilli (coliforms)
107
Which organisms are not penicillin resistant?
* group A (strep pyogenes), B, C, or G beta haemolytic streptococci
108
What is MRSA's method of antibiotic (methicillin) resistance?
* **altered target** * *mecA* gene encodes novel penicillin binding protein (PBP)(2A) / novel PBP 2a * Low affinity for binding beta lactams * Substitutes for essential functions of high affinity PBPs at otherwise lethal concentrations of antibiotics
109
How is **Streptococcus pneumoniae** resistant to penicillin?
* Penicillin resistance is the result of acquisition of stepwise mutations in PBP genes * Lower level resistance can be overcome by **increasing dose** of penicillin used
110
How is resistance to macrolides acquired by bacteria?
* Adenine-N6 methyltransferase modifies 23S rRNA à **_reduces binding of MLS antibiotics_** and results in resistance * Encoded by **erm** (erythromycin ribosome methylation) genes.
111
What is ESBL-based Resistance?
Extended spectrum beta lactamases
112
Which antibiotic classes can ESBLs break down?
* **cephalosporins** (cefotaxime, ceftazidime, cefuroxime) as well as **penicillins** * _But, **not carbapenems**_
113
Which organisms produce ESBLs?
* More common in *E. coli* and *Klebsiella*
114
What are new beta lactamases spreading?
New beta-lactamases are spreading MDR instead of just the ESBL-component of resistance

4 - Y5 a Path lectures 2021/22 (37 decks)

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