Bacterial cell wall synthesis inhibitors Flashcards
Name 2 classes of bacterial cell wall synthesis inhibitors.
Beta-lactams, Glycopeptide
Beta lactams bind to the active side of which enzyme?
Transpeptidase (penicillin binding protein)
Name 4 types of beta lactams
Penicillins, cephalosporins, carbapenems, monobactam
Name the 4 classes of penicillins
natural penicillins (Pen G and Pen V),
penicillinase resistant penicillins (cloxacillin),
aminopenicillins (amoxicillin, ampicillin),
antipseudomonal penicillins (piperacillin)
Which natural penicillin is administered parenterally?
Penicillin G
Syphilis caused by Treponema pallidum can be treated with which penicillin?
Penicillin G
Which natural penicillin is administered orally?
Penicillin V (not IV)
Which bacteria are natural penicillins effective against?
Mostly against Gram positive (streptococci and bacillus diphtheriae)
And some gram negative (meningococci and gonococci)
beta-lactamase negative strains
What is cloxacillin effective against?
It is a Penicillinase-resistant Penicillin (anti-staphylococcal Penicillin)
effective against Penicillinase producing staphylococci and other gram positive.
Ineffective against Gram negative
What are Ampicillin and amoxicillin effective against?
have additional hydrophilic group, allowing penetration into Gram-negative bacteria
Also effective against many beta-lactamase negative strains of Gram negative/positive microorganisms
What are Ampicillin and amoxicillin ineffective against?
Pseudomonas and Klebsiella
How is piperacillin administered?
Intravenously
Which class of penicillins has coverage against Pseudomonas, Proteus and Klebsiella?
Anti-pseudomonal penicillins (piperacillin)
How are penicillins cleared?
Renal excretion
Which of the aminopenicillins (amoxicillin or ampicillin) has better oral absorption?
Amoxicillin
Are aminopenicillins effective against beta lactamase producing strains of bacteria?
No
Name the 2 aminopenicillins
Ampicillin, amoxicillin
Which class of penicillin is commonly used against methicillin sensitive Staphylococcus aureus?
Penicillinase resistant penicillins
How does methicillin sensitive Staphylococcus aureus acquire resistance against the natural penicillins?
They produce penicillinases
Which bacteria is cloxacillin effective against?
Methicillin Sensitive Staphylococcus aureus (MSSA)
How do beta-lactamase inhibitors work?
They either covalently bind at or near the active site of the β-lactamase and restructures it, permanently inactivating. In doing so, they protects other beta-lactam antibiotics from beta-lactamase catalysis.
Name 3 beta lactams-beta-lactamase inhibitor combination drugs.
Augmentin (Amoxicillin + clavulanic acid)
Unasyn (ampicillin + sulbactam)
Zosyn (piperacillin + tazobactam)
Which beta-lactamase combination drugs can be administered orally?
Augmentin (Amoxicillin + clavulanic acid)
Name a microbe that commonly causes nosocomial infections and is resistant to all penicillins.
MRSA (methicillin resistant Staphylococcus aureus)
Name at least 2 penicillins related life-threatening allergic reactions.
1.Anaphylaxis
2. Stevens Johnson syndrome
3. Toxic epidermal necrolysis
Which generation of cephalosporins does cefazolin and cephalexin belong to?
First generation
Which generation of cephalosporins are primarily administered orally? Any exceptions?
First and second generation cehalosporins. Cefazolin (first generation) is an exception.
How are the 3rd, 4th and 5th generation cephalosporins administered?
Parenterally
Name at least 3 types of microbes against which 1st -4th generation cephalosporins are ineffective?
LAME
1. Listeria monocytogenes,
2. Atypicals (Mycoplasma, Chlamydia, Legionella spp.),
3. MRSA, and
4. Enterococcus species
Ceftriaxone belongs to which generation of cephalosporins?
Third generation
Cefuroxime belongs to which generation of cephalosporins?
Second generation
Name one cephalosporin from the third and fourth generation each which is effective against Pseudomonas aeruginosa.
Third generation – Ceftazidime
Fourth generation - Cefepime
Which generation of cephalosporins has coverage against MRSA?
Fifth generation (ceftaroline)
How are most cephalosporins cleared? Any exceptions?
Renal clearance except ceftriaxone which is cleared hepatically
Explain the mechanism of resistance underlying MRSA.
MRSA expresses an altered penicillin binding protein (PBP2a) with reduced affinity for the penicillins
Name 3 advantages the third generation and fourth generation cephalosporins have over the first and second generations.
- Higher activity against Gram-negative bacteria
- Greater resistance against the beta-lactamase producing strains
- Greater CSF penetration
What are 2 adverse reaction to cephalosporins?
- Hypersensitivity (CI with patients w penicillin allergy)
- GI symptoms (broad spectrum antibiotics kill normal gut flora, allowing overgrowth of toxin producing Clostridioides difficile resulting in Clostridioides difficile-associated disease (CDAD)
Name the class of antibiotics that are commonly used against extended spectrum beta-lactamase (ESBL) producing bacteria?
Carbapenems
How are carbapenems administered?
Parenterally
Name 3 carbapenems.
- Imipenem,
- meropenem,
- ertapenem
How are carbapenems administered?
Parenterally
Imipenem is combined with __________, which works by __________.
cilastatin,
inhibiting dehydropeptidase 1 (DHP1) found in the brush border of the proximal renal tubule. (DHP1 is necessary for the hydrolysis (breakdown) of imipenem–> increase active form of imipenem It is not a beta lactamase inhibitor.)
Which carbapenems is ineffective against Pseudomonas and Enterococcus?
Ertapenem
Can carbapenems be used to treat MRSA?
No
How are carbapenems excreted?
Renal
What are 3 adverse reaction to carbapenems?
- Hypersensitivity (CI with patients w penicillin allergy) (new research suggest cross reactivity is quite low)
- GI symptoms (broad spectrum antibiotics kill normal gut flora, allowing overgrowth of toxin producing Clostridioides difficile resulting in Clostridioides difficile-associated disease (CDAD)
- Neurotoxity: seizures
Which drug class does aztreonam belong to?
Monobactam
Aztreonam is effective against Gram-
negative bacteria (no activity against Gram positive and anaerobic microbes)
Does aztreonam have cross-sensitivity to penicillin?
No, suitable for treating Gram negative infections that normally would be treated with a beta lactam were it not for a prior allergic reaction
How is aztreonam administered?
IM/IV
Vancomycin is useful against Gram ___________
positives
How is vancomycin commonly administered?
Intravenously
When is oral vancomycin preferred instead of its usual IV form?
Clostridium difficile-associated diarrhea (CDAD) or the more severe antibiotic-associated pseudo-membranous colitis.
What is the first line of antibiotics for CDAD?
Vancomycin
Vancomycin interferes with cell wall synthesis by inhibiting ___________
transglycosylation
How is vancomycin cleared?
Renal clearnace
What must be noted before giving vancomycin?
whether patient has renal impairment; dose adjustment required
Name 2 antibiotics that work by inhibiting bacterial cell wall synthesis, and are effective against MRSA?
- ceftaroline (Fifth generation cephalosporins)
- Vancomycin
Name 3 adverse effects related to vancomycin
1.Nephrotoxicity,
2.Ototoxicity,
3.Red man syndrome due to histamine release; can be prevented by prolonging the duration of infusion to 1-2 hours.
