cell wall II Flashcards
Structurally, the cephalosporins have a ___ membered ring attached to the beta-lactam moiety in contrast to the 5-membered ring of the penicillins.
6
cephalosporins are
bactericidal- inhibit bacterial cell wall synthesis exhibiting time-dependent killing
cephalosporins activity against enterococci
not active
which cephalosporins is the only one active against MRSA
5th generation- ceftaroline
- Active against gram positive cocci
- Gram negative coverage: active against some Escherichia coli, Proteus spp., Klebsiella spp.
- oral form is cephalexin
- Cephalosporin of choice for S. aureus that is not Methicillin resistant
Used in PCN (oxacillin) allergic patients
Cefazolin
_____ today is most commonly used to treat gram positive infections such as skin and soft tissue infections or bacteremias caused by susceptible S. aureus in patients who are allergic to oxacillin and for surgical antibiotic prophylaxis when MRSA is of low concern.
Cefazolin
when should we never use cephalosporins in a patients
history of pcn anaphylaxis
*** caphalosporins have a cross-reactivity rate with penicillins of approx. 5-8%
What organisms are considered part of the skin microbiota?
S. epididermis
- Active against gram positive cocci
- Active against β-lactamase producing Haemophilus influenzae
- Active against Eschericia coli, Klebsiella, Proteus (some gram (-))
cefuroxime- 2nd generation
- Slightly less active than first generation against gram + cocci
- Active against gram negative organisms including E. coli, Proteus, Klebsiella
- **True strength is activity against Bacteroides fragilis (bowel anaerobe)
cefoxitin- second generation
- Less active against S. aureus than first generation cephalosporins
- Excellent activity against Streptococci
- Excellent activity against gram neg. rods - (more stable to beta-lactamases)
- ****More effective penetration into CNS
- Modest activity against bowel anaerobes
- No activity against Pseudomonas
ceftriaxone- 3rd generation
Ceftraixone has good activity against streptococcus pneumoniae and gram negatives but not to
yep but NOT pseudomonas
cefrtriaxone may complex with calcium leading to
precipitation- stones
** associated with formation of biliary sludge/ pseudo biliary pseudolithiasis
BROAD Spectrum:
- Active against gram positive organisms
- Active against gram negative organisms including Pseudomonas aeurginosa
- No anaerobic activity
Clinical Use
Hospital acquired infections
Hospitalized neutropenic patients with fever and we don’t know the organism
cefepime- 4th generation
- Poor gram positive activity
- NO anaerobic activity
- ****Special role is in infections due to Pseudomonas aeruginosa (gram negative rod)
- Excellent penetration into central nervous system
ceftazidime- 3rd generation
ceftraixone but with MRSA activity
ceftaroline
what types of tox associated with cefepime if you have renal failure
neurotoxicity
________ binds PBP 1-4 and has a high affinity for PBP2a (mecA) which is associated with methicillin resistance
Little clinical experience with VRE
Broad gram positive activity with some gram negative activity
Ceftaroline
weird factor of ceftaroline and positive direct Coombs test
positive but not hemolysis
cephalosporins is associated with what type of infection
C. difficile
Aztreonam- is a monocyclic beta lactam – beta lactam ring is not fused to another ring
- excellent activity against ___ thus it is
excellent activity against gram negative esp. P. aeruginosa thus it is a narrow spectrum agent
aztreonam is usually reserved for
PCN allergic patients with GNR infections
carbapenems are broad or narrow spectrum activity
broad
carbapenems are active against MRSA
nope- active against gram negative, gram positive and anaerobes but not MRSA
Carbapenems share common beta-lactam ring with penicillins
yes however clinical studies have shown low rate of cross-reactivity
Non-Beta Lactam Cell Wall and Cell Membrane Inhibitors (2)
- vancomycin
2. daptomycin
vancomycin is a bactericidal that has a narrow spectrum oonly active against
gram positive esp. those that are resistant to other antibiotics
MOA of Vancomycin
Blocks peptidoglycan synthesis, prevents cross linking
however note mechanism of action is distinct from that of beta lactams. vancomycin binds D-ala-D-ala preventing binding of transpeptidase and cross linking
while beta lactams inhibit transpeptidases
vancomycin is only used orally to treat for
C. difficile colitis
Red man syndrome
it is a adverse effect of vancomycin caused by a fast infusion
tox. associated with vancomycin
kidney tox
MOA of daptomycin
binds to the bacterial cell membrane and forms a potassium channel leading to an efflux and destroys the gradient causing cell death
*** cell membrane potential is inhibited
daptomycin is not used to treat pneumonia… why?
it is inactivated by alveolar surfactant
daptomycin is used against
gram positive organisms
very good for resistant GNRs (ESBL) and anaerobes
imipenem-cilastatin
Which beta lactams is able to bind Penicillin Binding Protein 2a?
ceftaroline