Antibiotics: Cell Wall Synthesis inhibitors Flashcards
what are the cell wall synthesis inhibitor drugs?
- Beta lactam antibiotics
- Penicillins *
- Cephalosporins*
- Carbapenems
- Monobactam
- Vancomycin*
- Bacitracin
ß-lactams will work on what bacteria?
actively synthesizing peptidoglycan or in the log phase
how do ß-lactams work?
bind and inactivate bacterial enzymes essential for cross-linking between peptidoglycan chains
(inactivates transpeptidases and carboxypeptidases)
inactivation of enzymes for bacterial cross linking by ß-lactams will cause activation of what?
it will activate Autolysins that degrade cell wall and eventually kill the bacteria
ß-lactams drugs are considered what type of drugs?
bacteriocidal drugs
what are 3 ways that bacteria have adapted to evade ß-lactams?
- Hydrolysis of antibiotic by Beta-lactamases
- (cleave beta-lactam ring and destroy the antibitotic)
- Alteration of PBPs (penicillin-binding proteins)
- bacteria can alter their PBPs so that beta-lactams cannot bind them
- Reduced permeability of Gram negative outer membrane
- bacteria alter their porins and size of porin channels
- Prevent the large molecules of the beta-lactam drug from penetrating the cell wall
what are the enzymes that inactivate ß-lactams antibiotics?
1) Penicillinases – specific for penicillins
2) Cephalosporinases – target cephalosporins
3) Carbapenemases – inactivate carbepenems
4) Extended-Spectrum B-lactamases (ESBLs) - inactivate cephalosporins and penicillins
what is important about the penicillin structure?
it contains a ß-lactam ring
what is penicillin’s mode of action?
Inhibition of transpeptidases (PBPs) with subsequent Inhibition of cell wall synthesis & bacterial cell death
what side effects can penicillin have?
hypersensitivity
name the different types of penicillin.
1) Penicillin G, Penicillin V
2) Aminopenicillins
3) Extended spectrum Penicillins (Anti-pseudomonal
4) Penicillinase-Resistant Penicillins
5) Beta-lactamase Inhibitors
6) Penicillin + Beta-lactamase inhibitor
what penicillins are susceptible to penicillinase (ß-lactamase)?
penicillin G and V
Aminopenicillins
Extended spectrum Penicillins (Ureidopenicillins)
what are the penicillins that are penicillinase resistant?
Methicillin
Nafcillin
Oxacillin
Cloxacillin
Dicloxacillin
how is penicillin G administered?
through IV
how is penicillin V administered?
orally
how is penicillin G and V’s spectrum?
narrow
penicillin G and V are used for what type of bacteria?
gram positive bacteria
Methicillin, Nafcillin, Oxacillin, Cloxacillin, Dicloxacillin are used only for what bacteria?
staph infections
aminopenicillins like ampicillin and amoxicillin have this side effect…
diarrhea
name the aminopenicillins?
ampicillin and amoxicillin
how are Aminopenicillins: Ampicillin, amoxicillin, taken?
orally
what is another term for penicillinase?
ß-lactamase
Aminopenicillins: Ampicillin, amoxicillin, are used for what infection?
enterococci and listeria infections
what is an important anti-psudomonal penicillin?
pipercacillin
What are the penicillinase resistant penicillins?
Methicillin,
Nafcillin
Oxacillin
Cloxacillin
Dicloxacillin
how are cloxacillin and dicloxacillin administered?
orally
how are Methicillin, Nafcillin, Oxacillin administered?
Intavenous
what bacteria have developed resistance to methicillin?
MRSA, MRSE
methicillin resistance refers to resistance against what drugs?
met, naf, oxa, clox, diclox
what is the drug of choice for staph infection?
Methicillin, Nafcillin, Oxacillin, Cloxacillin, Dicloxacillin
(Naf for Staph)
what is the drug of choice to treat MRSA or methycillin resistance?
vancomycin
what is an example of a common staph infection?
abcesses
what is the drug of choice for listeria infections?
Aminopenicillins
what do ß-lactamase inhibitors do?
Inactivate some types of beta-lactamase enzymes produced by bacteria
Give an example of a ß-lactamase inhibitors
Clavulanic acid (clavulanate)
are they effective working alone? what do you do to correct this?
no, always used in combination penicillin
how effective are beta lactamase inhibitors when administered alone?
inactive at inhibiting bacteria on their own
how do you increase the effectivity of ß-lactamase inhibitors?
administer in conjunction with penicillin
do beta lactamase inhibitors all work will all beta lactamases
no
what is a Beta lactam + beta lactamase inhibitor combination?
penicillins that have been combined with beta lactamase inhibitors to increase effectiveness
what are the Beta lactam + beta lactamase inhibitors?
Amoxicillin + clavulanate (Augmentin)
Piperacillin + tazobactum
how is the antibiotic spectrum of Beta lactam + beta lactamase inhibitors?
broad
beta lactam + beta lactamase inhibitor has improved activity against?
Improved activity against beta-lactamase producing staphylococci and selected gram negative rods*
what is another name for cephalosporins?
ß lactam antibiotics
what type of antibiotic are cephalosporins?
bacteriocidal
why do bacteria develop reistance to cephalosporins?
Production of beta-lactamases and cephalosporinases
what are cephalosporins less susceptible to?
penicillinases
do cephalosporins target only a limited amount or a wide amount of bacteria?
cephalosporins target a wide antibacterial spectrum
cephalosporins are more resistant to what?
to many ß-lactamases
how are the cephalosporins classified?
1st, 2nd, 3rd, 4th generation
1st generation cephalosporins will attach what bacteria?
gram positive and some gram negative
what gram negative bacteria are targeted by using 1st gen. cephalosporins?
proteus
e. coli
klebsiella pneumonie
cephalexin
cefuzzlin
what are some of the 2nd gen. cephalosporins?
cefotoxin
cefuroxime
what is an example of a bacteria targeted by cefuroxime, cefuclor, cefuman?
H. Inlfuenza
E.Coli
2nd generation cephalosporins will target what bacteria?
gram negative and some anaerobes
give an example of an anaerobic bacteria targetted by 2nd gen cephalosporins?
bacteroides fragilis
what can inhibit 2nd generation cephalosporins?
beta-lactamases
what will 3rd gen. cephalosporins target?
gram positive bacteria mostly
some gram negative bacteria
what are some of the 3rd gen. cephalosporins?
Cefotaxime, Ceftriaxone, Ceftazidime
what is special about the 3rd gen cephalosporins?
they can cross the Blood-Brain Barrier
what gram negative bacteria can 3rd generation cephalosporins target?
pseudomonas
when are 3rd generation cephalosporins used?
- Empiric therapy for Bacterial meningitis***
- Gonorrhoeae
- Pseudomonas infections
how susceptible are 3rd generation cephalosporins to beta-lactamases?
they are Very resistant to some beta-lactamases*
what cephalosporin do you give for adults with meningitis?
Ceftriaxone
what cephalosporin do you give for children with meningitis?
Cefotaxime
what is the drug of choice for Pseudomonas infection?
ceftazidime
what is the drug of choice for gonorrhoeae?
ceftriaxone
what is an example of a 4th gen cephalosporine?
Cefepime
4th gen cephalosporins are resistant to what?
ß-lactamases
4th gen cephalosporins will be excellent against what bacteria?
pseudomonas
what gram neg. bacteria will 4th gen cephalosporins attack very effectively?
psudomonas aureginosa
what infection are 4th generation cephalosporins used for?
treatment of nosocomial infections by suspected beta-lactamase-producing bacteria*
what is the 5th generation cephalosporins?
Ceftaroline
how is the antibiotic spectrum of 5th gen. cephalosporins?
broad
against what infection is 5th generation cephalosporins used against?
MRSA and MRSE
what is the drug of choice for methycilin resistant staph infections?
vancomycin
what are the side effects of cephalosporins?
hypersensitivity
Cross-sensitivity between penicillins & cephalosporins
what organisms not covered by cephalosporins?
Listeria monocytogenes****
Atypical bacteria (Chlamydia, Mycoplasma)
MRSA (exception; ceftaroline coveres MRSA)
Enterococci
what are cabapenems?
ß lactams
what is an example of a carbapenems?
imipenem
carbapenems are always used with what other drug?
cislastatin (a dihydropeptidase inhibitor)
carbapenems are what type of drugs?
reserve drugs
carbapenems are used against what?
anaerobic and gram neg. rods
what is an example of monobactam?
aztreonam
monobactams are resistant to what?
ß lactamases
how is the spectrum of monobactam drugs?
narrow spectrum
Monobactam drugs used for what?
- Can be given to patients allergic to penicillin*
- treatment of hospital-acquired multi-drug resistant Gram-negative bacteria
can this type of drugs be given to people with allergies to penicillin?
yes
monobactam is used on what type of bacteria (+ or -)?
gram neg aerobic only
what is vancomyicin?
a bacteriocidal glycoprotein
how does vancomyicin work?
binds to (D-Ala)-(D-Ala) of peptidoglycan chain and inhibits the cross linking
how is the spectrum for vancomyicin?
narrow
when will you administer vancomyicin?
for serious infection caused by drug resistant gram positive organisms
give an example of an organism which can be treated with this antibacterial (vancomyisin)
MRSA
penicillin resistant pneumococci
penicillin resistant clostridium difficile
how can bacteria increase resistance to vancomyicin?
changing its peptidoglycan chains:
D-Ala-D-Ala to D-Ala-D-Lac
there will be decreased affinity to vancomyicin in binding site
These bacteria are resistant to vancomyicin…
enterococci and staphylococci (VRE and VRSA)
what are some adverse reactions that can occur by using vancomyicin?
nephrotoxicity, orotoxicity, thrombophebitis
red man syndrome (due to continuous release of histamine)
(prevented through pre-treatment with antihistamines)
what 2 other drugs work as cell wall synthesis inhibitors?
bacitracin = very nephrotoxic
cycloserine = gram pos and neg bacteria
cycloserine is used exclusively to treat what bacteria?
tuberculosis
vancomycin is administered orally or intravenously for treatment of pseudomembranous colitis?
Oral
what drugs do you use to treat VRE and VRSA?
- Quinupristin-dalfopristin***
- Linelozid
what does bacitracin do?
inhibit cell wall synthesis
why is bacitracin not used so frequently?
it is nephrotoxic
how do you administer bacitracin?
topically only
for what infections do you use bacitracin?
Staphylococcal & Streptococcal skin infections *
what do Anti-Mycobacterial agents do?
inhibit synthesis of mycolic acid
where do you find mycolic acid?
mycobacterial cell wall
what are examples of anti-mycobacterial agents?
Isoniazid
Ethambutol
Ethionamide
Cycloserine