Drugs for RTI

Question 1

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

Answer 1

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

Question 2

drugs to treat pseudomembranous colitis?

Answer 2

metronidazole
vancomycin

Question 3

Groups of antibiotics with low risk of superinfection?

Answer 3

macrolides
tetracyclines
sulfonamides

Question 4

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

Answer 4

staphylococci
neisseria gonorrhea

Question 5

how to prevent antimicrobial resistance?

Answer 5

-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

Question 6

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

Answer 6

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

glycopeptides: vancomycin, teicoplanin

ALL inhibit cell wall synthesis

Question 7

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

Answer 7

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

Question 8

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

Answer 8

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

Question 9

Stages of bacterial cell wall synthesis?

Answer 9

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 )

Question 10

Beta lactam antibiotics target

Answer 10

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

Question 11

beta lactam antibiotics have no use against two things:

Answer 11

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

Question 12

MOA of beta lactam antibiotics

Answer 12

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]

Question 13

Bacterial resistance against beta lactam antibiotics due to two reasons:

Answer 13

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

Question 14

Types of penicillins

Answer 14

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

Question 15

ADR of penicillins

Answer 15

-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!!!

Question 16

inhibitors of beta-lactamase

THEY ARE NOT ANTIBIOTICS

Answer 16

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

Question 17

use of inhibitors of beta-lactamase

Answer 17

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

Question 18

Is AMOXICILLIN CLAVULANATE effective in treatment of MRSA?

Answer 18

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

Question 19

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

Answer 19

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

Question 20

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

Answer 20

Ceftaroline fosamil is used to treat MRSA infections

Question 21

Types of cephalosporins

Answer 21

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

Question 22

1st gen of cephalosporins

Answer 22

cefazolin
cephalexin

Question 23

2nd gen of cephalosporins

Answer 23

cefuroxime

Question 24

3rd gen of cephalosporins (can cross BBB)

Answer 24

cefotaxime
ceftriaxone

Question 25

4th gen of cephalosporins

Answer 25

cefepime

Question 26

5th gen of cephalosporins

Answer 26

Ceftaroline fosamil

Question 27

cefazolin (1st gen) spectrum

Answer 27

most active against gram + bac like staph NO ACTIVITY against gram - bac clinical use: mild/mod skin infection by staph

Question 28

cefuroxime (2nd gen) spectrum

Answer 28

enhanced activity against gram + some gram - clinical use: uncomplicated community acquired infection

Question 29

cefotaxime/ceftriaxone (3rd gen ) spectrum

Answer 29

broad spectrum (gram + and -) resistant to most beta-lactamase clinical use: severe CAI and HAI, w/ risk of secondary resistance

Question 30

cefepime (4th gen) spectrum

Answer 30

most active against gram - like P. aeruginosa resistant to beta lactamase clinical use: severe CAI and HAI, w/ risk of secondary resistance

Question 31

ceftaroline fosamil (5th gen) spectrum

Answer 31

active against gram + like aureus, INCLUDING MRSA, strep pneumonia gram - like E.coli, haemophilus influenza, klebsiella pneumonia clinical use: CAI with risk of MRSA

Question 32

ADR of cephalosporins

Answer 32

do not take with alcohol ethanol=disulfiram will inhibit **aldehyde dehydrogenase**, acetaldehyde which is toxic cannot be metabolised into acetate (non-toxic)

Question 33

Examples of carbapenem

Answer 33

imipenem meropenem

Question 34

Carbapenem has modified beta lactam ring and highly resistant to

Answer 34

beta lactamases Most MRSA strains are resistant to it.

Question 35

pharmacokinetics of carbapenem

Answer 35

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

Question 36

Carbapenem is a ______ line drug.

Answer 36

second line drug used only in **SEVERE CAI and HAI**

Question 37

Example of monobactam

Answer 37

aztreonam

Question 38

monobactam>aztreonam is very resistant to

Answer 38

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 -

Question 39

under group of glycopeptides, examples of drugs are?

Answer 39

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

Question 40

MOA of vancomycin

Answer 40

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

Question 41

clinical use of vancomycin

Answer 41

gram + only **gram + anaerobes Clostridium difficile which cause pseudomembranous colitis** used in serious, life threatening gram + infections MRSA pseudomembranous colitis

Question 42

why vancomycin has no effect on gram - bac?

Answer 42

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

Question 43

ADR of vancomycin

Answer 43

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

Question 44

treatment of MRSA infections

Answer 44

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

Question 45

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

Answer 45

COMMUNITY ACQUIRED PNEUMONIA (CAP)