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CRP 2 KCP 1 & 2 > Drugs for RTI > Flashcards

Drugs for RTI Flashcards

1
Q

Broad spectrum antibiotics have higher risk for superinfection like pseudomembranous colitis. Besides, antibiotic induced alteration of normal flora may cause invasion of opportunistic pathogens like Clostridium difficile (caused by clindamycin), Candida etc. Antibiotics with high risk of pseudomembranous colitis are

A

clindamycins
fluoroquinolones (ciprofloxacin, levofloxacin)
beta lactams (aminopenicillins like ampicillin, cephalosporins, carbapenems)

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2
Q

drugs to treat pseudomembranous colitis?

A

metronidazole
vancomycin

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3
Q

Groups of antibiotics with low risk of superinfection?

A

macrolides
tetracyclines
sulfonamides

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4
Q

penicillin’s activity is limited due to bacterial resistance, which microorganisms are resistant to it?

A

staphylococci
neisseria gonorrhea

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5
Q

how to prevent antimicrobial resistance?

A

-used only when indicated, in sufficiently high dose for sufficient time
-prefer rapidly acting & narrow spectrum drugs
-use combination of antibacterial agents whenever prolonged therapy

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6
Q

Groups of antibiotics commonly used for RTI? (sem 2)

A

beta lactams:
1. penicillin
2. cephalosporin
3. carbapenem
4. monobactam

glycopeptides: vancomycin, teicoplanin

ALL inhibit cell wall synthesis

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7
Q

RTI divided into bacterial and viral. Bacterial infection is subdivided into community-acquired & hospital-acquired. List the rational treatment of bacterial pneumonia.

A

listed below are all 1st line drugs

CAP:
outpatient>aminopenicillins (amoxicillin)
inpatient> aminopenicillins (amoxicillin)+macrolides (azithromycin)
HAP/VAP:
amoxicillin/clavulanate
cephalosporins 4th gen eg. cefepime
Aspiration pneumonia:
amoxicillin/clavulanate

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8
Q

Bacterial cell wall structure difference in gram-positive and negative?

A

+ thick peptidoglycan cell wall
- thin peptidoglycan cell wall with a outer membrane

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9
Q

Stages of bacterial cell wall synthesis?

A

first stage
synthesis of peptidoglycan monomer intracellularly
second stage
peptidoglycan monomers are joined to form peptidoglycan chains at the outer surface of membrane (glycopeptide)
third stage
peptidoglycan chains are cross-linked by transpeptidase (penicillin binding protein PBP) at the outer surface of membrane ( beta lactam )

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10
Q

Beta lactam antibiotics target

A

PBP, preventing final crosslinking of peptidoglycan, inhibiting peptidoglycan cell wall synthesis

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11
Q

beta lactam antibiotics have no use against two things:

A
  1. atypical bacteria like Legionella, Mycoplasma, Chlamydia as they do not have peptidoglycan cell wall
  2. MRSA except ceftaroline fosamil due to its ability to bind & block PBP2A in MRSA
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12
Q

MOA of beta lactam antibiotics

A
  1. PBP catalyses the last step of peptidoglycan synthesis/cross-linking
  2. beta lactam antibiotics irreversibly bind to active site of PBP
  3. inhibit PBP, prevent final crosslinking of peptidoglycan, prevent synthesis of bac cell wall
  4. disruption of bac cell [bactericidal effect]
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13
Q

Bacterial resistance against beta lactam antibiotics due to two reasons:

A
  1. beta-lactamase production
    -beta-lactamase/penicillinases hydrolyse beta lactam antibiotics
    -producers of the enzymes : staph, neisseria gonorrhoea, E.coli, pseudomonas aeruginosa
  2. alteration of PBP structure
    -MRSA have PBP2A (an altered struc of PBP)
    -most beta lactam antibiotics cannot bind to PBP2A hence not effective against MRSA
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14
Q

Types of penicillins

A
  1. natural penicillin
    Eg: penicillin G, penicillin V
    +/- (mostly +)
    ineffective against S. aureus
  2. anti-staphylococcal penicillin
    Eg: cloxacillin
    resistant to beta lactamases
    treat staph infection EXCEPT MRSA
  3. extended spectrum penicillin/aminopenicillin
    Eg: amoxicillin+clavalunate
    +/-
    treat non-complicated community acquired infection
    Empirical treatment for lung abscess pneumonia
  4. anti-pseudomonal penicillin
    Eg: piperacillin
    -
    treat P. aeruginosa infections, HAP
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15
Q

ADR of penicillins

A

-wide therapeutic index, safe
-no tetragenic, safe in pregnancy and breastfeeding
-anaphylaxis
-allergic cross-reactions with other beta lactams
-pseudomembranous colitis caused by Clostridium difficile!!!

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16
Q

inhibitors of beta-lactamase

THEY ARE NOT ANTIBIOTICS

A

clavulanic acid
sulbactam
tazobactam

  • most effective against plasmid-encoded beta lactamases
  • inactive against type I chromosomal beta-lactamases produced by gram - bac like enterobacter, acinetobacter, pseudomonas
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17
Q

use of inhibitors of beta-lactamase

A

to extend activity of beta-lactam antibiotics against the beta lactamse producing strain

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18
Q

Is AMOXICILLIN CLAVULANATE effective in treatment of MRSA?

A

no, MRSA have altered structure of PBP called PBP2A. Beta lactam cannot inhibit site of synthesis of peptidoglycan, it can only inhibit PBP

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19
Q

Things to note about cephalosporins:
1. It has no use against?
2. Could cephalosporins be used as the first line for treatment of IE?

A
  1. ALL cephalosporins have no activity against Enterococci.
  2. NO, because it does not cover ALL causative agent for IE, only can be given for emergency. IE should be treated with penicillin as it is associated with enterococci, staph, strep
20
Q

Which drug is a single beta- lactam that can bind and block PBP2A?

A

Ceftaroline fosamil is used to treat MRSA infections

21
Q

Types of cephalosporins

A

1st gen: cefazolin
2nd gen: cefuroxime
3rd gen: cefotaxime
4th gen: cefepime
5th gen: ceftaroline fosamil

22
Q

1st gen of cephalosporins

A

cefazolin
cephalexin

23
Q

2nd gen of cephalosporins

A

cefuroxime

24
Q

3rd gen of cephalosporins (can cross BBB)

A

cefotaxime
ceftriaxone

25
Q

4th gen of cephalosporins

A

cefepime

26
Q

5th gen of cephalosporins

A

Ceftaroline fosamil

27
Q

cefazolin (1st gen) spectrum

A

most active against gram + bac like staph
NO ACTIVITY against gram - bac

clinical use: mild/mod skin infection by staph

28
Q

cefuroxime (2nd gen) spectrum

A

enhanced activity against gram +
some gram -

clinical use: uncomplicated community acquired infection

29
Q

cefotaxime/ceftriaxone (3rd gen ) spectrum

A

broad spectrum (gram + and -)
resistant to most beta-lactamase

clinical use: severe CAI and HAI, w/ risk of secondary resistance

30
Q

cefepime (4th gen) spectrum

A

most active against gram - like P. aeruginosa
resistant to beta lactamase

clinical use: severe CAI and HAI, w/ risk of secondary resistance

31
Q

ceftaroline fosamil (5th gen) spectrum

A

active against gram + like aureus, INCLUDING MRSA, strep pneumonia
gram - like E.coli, haemophilus influenza, klebsiella pneumonia

clinical use: CAI with risk of MRSA

32
Q

ADR of cephalosporins

A

do not take with alcohol

ethanol=disulfiram will inhibit aldehyde dehydrogenase, acetaldehyde which is toxic cannot be metabolised into acetate (non-toxic)

33
Q

Examples of carbapenem

A

imipenem
meropenem

34
Q

Carbapenem has modified beta lactam ring and highly resistant to

A

beta lactamases

Most MRSA strains are resistant to it.

35
Q

pharmacokinetics of carbapenem

A

imipenem needs to be given with cilastatin to prevent extensive renal breakdown & toxicity. Cilastatin can inhibit dipeptidase, preventing breakdown of imipenem

36
Q

Carbapenem is a ______ line drug.

A

second line drug
used only in SEVERE CAI and HAI

37
Q

Example of monobactam

A

aztreonam

38
Q

monobactam>aztreonam is very resistant to

A

beta lactamases produced by gram -

no gram + activity including MRSA
no activity against anaerobes
high gram - including pseudomonas

used in severe CAI and HAI caused by gram -

39
Q

under group of glycopeptides, examples of drugs are?

A

vancomycin
teicoplanin

HAVE BIG MOLECULAR SIZE
not absorbed from GIT, need parenteral administration

40
Q

MOA of vancomycin

A
  1. it binds with D-alanine of peptidoglycan precursors
  2. prevent following addition of new units to peptidoglycan and peptidoglycan chain formation
  3. inhibit cell wall synthesis
  4. bactericidal effect
41
Q

clinical use of vancomycin

A

gram + only
gram + anaerobes Clostridium difficile which cause pseudomembranous colitis

used in serious, life threatening gram + infections
MRSA
pseudomembranous colitis

42
Q

why vancomycin has no effect on gram - bac?

A

must penetrate via porins
structure too big to pass
cannot reach peptidoglycan

43
Q

ADR of vancomycin

A

nephrotoxicity
ototoxicity
red-man/red-neck syndrome!!!! ONLY FOR VANCOMYCIN , THIS IS NOT ALLERGIC RXN. IT IS DUE TO NON-SPECIFIC MAST CELL DEGRANULATION AND HISTAMINE RELEASE

44
Q

treatment of MRSA infections

A

1st LINE: glycopeptide antibiotic>vancomycin
2ns line: oxazolidinones>linezolid

45
Q

5th gen cephalosporin CEFTAROLINE FOSAMIL has no enough evidence to be used of MRSA, it is currently used for?

A

COMMUNITY ACQUIRED PNEUMONIA (CAP)

CRP 2 KCP 1 & 2 (8 decks)

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