2: Antimicrobials 1 Flashcards

(43 cards)

1
Q

3 targets of antimicrobials

A

Peptigolycan layer of cell wall

Inhibition of bacterial protein synthesis

DNA gyros and other prokaryote specific enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what are the 2 types of inhibitors of cell wall synthesis and examples of them, differences

A

B-lactam abx = penicillins, cephalosporins, carbapenems

  • Broad spectrum

Glycopeptides = vancomycine, teicoplanin

  • Gram +ve
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Gram +ve vs Gram -ve

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How do B-lactams work?

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 haveno effect**

  • Ineffective against bacteria lacking peptidoglycan cell walls (mycoplasma, chlamydia)
  • Cause cell lysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Give examples of penicillins (5)

A

Penicillin

Amoxicillin

Flucloxacillin

Piperacillin

Clavulanic acid + amoxicillin (co-amoxiclav) and tazobactam (tazocin/piptazobactam)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Penicillin

A

gram +ve, streptococci, clostridia

  • Broken down by beta lactamase (produced by SA and many other gram -ve organisms)
  • Allergy – need to get a clear history
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Amoxicillin

A

broad-spectrum (enterococci to gram -ve)

  • Broken down by beta lactamase (produced by SA and many other gram -ve organisms)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Flucloxacillin

A

SA

  • Not broken down by beta-lactamase produced by SA
  • Similar to penicillin, less reactive
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Piperacillin

A

broad-spectrum (pseudomonas, non-enteric gram -ve)

  • Broken down by beta lactamase (produced by SA and many other gram -ve organisms)
  • Similar to amoxicillin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Co-amoxiclav and tazobactam

A
  • Clavulanic acid = beta lactamase inhibitors → protect penicillin from enzymatic breakdown
  • Increase coverage to include SA, gram -ve (i.e. E. coli), anaerobes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What bacteria (G+ve) produced b-lactamase?

A

Staph aureus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Give examples of cephalosporins (4)

A

Cefuroxime

Ceftriaxone

Ceftazidime

Cefotaxime

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Cefuroxime

A
  • Stable to many beta lactamases made by gram -ve
  • Similar cover to co-amox (less active against anaerobes)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Ceftriaxone

A
  • Associated with C. difficile
  • Treat meningitis (IM ceftriaxone)
  • NO COVER against Pseudomonas
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Ceftazidime

A
  • Activity against pseudomonas (HAIs often)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Cefotaxime

A

The paediatric ceftriaxone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Give examples of Carbapenems

A

Meorpenem, imipenem, ertapenem (STABLE TO ESBL enzymes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Give an example of monobactams

19
Q

Key features of beta lactase

A
  • 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
20
Q

Glycopeptides

A

Active against gram +ve (inhibit cell wall synthesis)

  • Large molecules so unable to penetrate gram -ve

Important uses:

  • MRSA infections (IV)
  • C. difficile infection (oral – Vancomycin, teicoplanin)

Slowly bactericidal

Nephrotoxic – must monitor for accumulation

21
Q

Gove 5 examples of inhibitors of protein synthesis

A

Aminoglycosides

Tetracyclines

Macrolides

Chloramphenicol

Oxazolidinones

22
Q

Give 3 examples of aminoglycosides

A

Gnetamicin, amikacin, tobramycin

G-ve action

23
Q

Aminoglycoside MoA

A
  • Bind to amino-acyl site of 30s ribosome subunit
  • Rapid, concentration-dependent bactericidal
  • Require specific transport mechanisms to enter
    • Accounts for some intrinsic resistance
    • Ototoxic and nephrotoxic – monitor levels
    • Gentamicin and tobramycin are particularly active against pseudomonas aeruginosa
    • Synergistic combination with beta lactams
      • Endocarditis treatment, pneumonia
    • No activity against anaerobes
24
Q

tetracylines MoA

A

Broad spectrum, activity against intracellular pathogens – chlamydia, rickettsia, mycoplasma

Bacteriostatic (stops bacteria from reproducing)

Widespread resistance now

Deposited in growing bone

  • Don’t give to children, pregnant women
  • SE: photosensitivity rash (summer effect)

TETRACYLINE, DOXYCYCLINE

25
Give examples of Macrolides and their MoA
***Erythromycin**, **lincosamides** – **clindamycin**, **streptogramins** – **synercid** – **MLS group*** * Bacteriostatic * Useful agent for treating mild staphylococcal or streptococcal infections in pen-allergic patients * Active against campylobacter species, legionella, pneumophilia * Newer agents include ***clarithromycin*** and ***azithromycin*** due to a better half-life * Little activity against gram -ve bacteria (membrane) Useful to inhibit toxins produced by bacteria
26
Chloramphenicol use and MoA
*(if pen-allergic, used for meningitis)* * Bacteriostatic * **Broad** antibacterial activity * **_Rarely used_** apart from eye preparations * Risk of aplastic anaemia * Risk of grey-baby syndrome in neonates because of inability to metabolise the drug
27
Oxazolidinones (Linezolid) use and MoA
* Highly active against **gram +ve** (MRSA & VRE) * **Not active** against most gram -ve * Expensive, may cause _thrombocytopenia_ & _optic neuritis_; should only be used with micro/ID approval * Binds to 23S component of 50s subunit → prevents formation of a functional 70s initiation complex
28
Give 2 examples of inhibitors of DNA synthesis
Quinolones/Fluoroquinolones Nitroimidazoles
29
Quinolones/fluoroquinolones
Ciprofloxacin, levofloxacin, moxifloxacin * Act on alpha unit of **DNA gyrase**, bactericidal * **Broad antibacterial activity** versus gram -ve (pseudomonas aeruginosa) * Newer agents (levofloxacin, moxifloxin) better against gram +ve and intracellular bacteria (Chlamydia spp.) * Well absorbed after PO administration (good bioavailability) * Use for *_UTI*_, _*pneumonia*_, _*atypical pneumonia*_, _*bacterial gastroenteritis_*
30
Nitroimidazoles
Metronidazole, tinidazole * Under anaerobic conditions, an active intermediate is produced which causes **DNA strand breakage** * Rapidly bactericidal * Active against anaerobic bacteria and protozoa (Giardia) * Nitrofurans are related compounds (nitrofurantoin is good for cystitis and lower UTIs)
31
What is an inhibitor of RNA synthesis?
**Rifamycins** – *rifampicin and rifabutin*
32
How do Rifamycins work?
* Inhibits protein synthesis by binding to **DNA-dependent RNA polymerase**, inhibiting initiation * Bactericidal * Active against mycobacteria and chlamydia * Interactions with other drugs metabolised in the liver (OCP) and so need to **monitor LFTs** * Turns secretions orange (urine and contacts) – can check compliance **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
33
Give 2 examples of cell membrane toxins
Daptomycin and colistin
34
Daptomycin
* Cyclic lipopeptide with activity limited to gram +ve * MRSA and VRE infections as an alternative to linezolid and synercid
35
Colistin
* Polymyxin antibiotic; not absorbed PO though * Active against gram -ve including pseudomonas aeruginosa, Acinetobacter baumannii, klebsiella pneumoniae * Nephrotoxic and reserved for use against multi-resistant organisms
36
Give 2 examples of inhibitors of folate metabolism
Solphonamdes and diaminopyrimidines
37
4 mechanisms of abx resistance
1. Bypass antibiotic-sensitive step 2. Enzyme chemical modification/inactivation of abx 3. Accumulation reduced of abx (impaired uptake, enhanced efflux) 4. Target modification or replacement
38
what are the three ways beta lactams are inactivated?
1. **Beta-lactamases** (SA and gram-ve bacteria aka coliforms) 2. **MRSA resistance** (altered target) * mecA gene encodes _novel PBP2A_ * low affinity for binding beta lactase * substitutes for essential functions of high affinity PBPs at otherwise lethal concentrations of antibiotics **3. Streptococcus pneumonia** * penicillin resistance is the result of stepwise mutations in PBP genes * lower level resistance can be overcome by increasing dose of penicillin used
39
What is the mechanism of macrolide resistance?
* Adenine-N6 methyltransferase modifies 23S rRNA → **_reduces binding of MLS antibiotics_** and results in resistance * Encoded by **erm** (erythromycin ribosome methylation) genes.
40
ESBL-based resistance (extended spectrum beta lactamases)
* ESBLs can enzymatically break down **cephalosporins** (cefotaxime, ceftazidime, cefuroxime) as well as **penicillins** * But, **not carbapenems** * More common in *E. coli* and *Klebsiella* * **Treatment failures reported** with beta lactam and beta lactamase inhibitor combinations – augmentin/tazocin * Aminoglycoside used in combinations * New beta-lactamases are **spreading MDR instead of just the ESBL-component of resistance** (big problem) * If something is erythromycin-resistant, be careful about giving clindamycin (may make the bacteria MDR) * HPA guidance:
41
By which mechanism is an ESBL E. coli resistance to ceftriaxone?
Enzymatic inactivation of the antibiotics
42
Which mechanism mediates flucloxacillin resistance in S. aureus?
alteration of the target (flucloxacillin is stable to b-lactamases and its PBP2A alteration of target instead)
43
Oxazolidinones (Linezolid) use and MoA
* Highly active against **gram +ve** (MRSA & VRE) * **Not active** against most gram -ve * Expensive, may cause _thrombocytopenia_ & _optic neuritis_; should only be used with micro/ID approval * Binds to 23S component of 50s subunit → prevents formation of a functional 70s initiation complex