Mechanisms of Antimicrobial Action and Resistance 1 Flashcards
PBP 1a and 1b, what is their activity and function?
Transpeptidase activity
Peptidoglycan synthesis and cell wall elongation
Molecular weight of Penicillin Binding Proteins goes ______ as the number increases (i.e. PBP 1a vs PBP 6)
Molecular weight is inversely proportional to the PBP #
PBP 2 activity and function?
Transpeptidase activity
Maintains rod shape
PBP 3 activity and function?
Transpeptidase activity
Peptidoglycan synthesis and septum formation
PBP 4, 5, and 6 activity and function
D-alanine carboxypeptidase activity
Control extent of cross-links
Are beta-lactams toxic to humans?
Targets of beta-lactams are uniquely bacterial so they are selectively toxic
What is superinfection and why does it occur?
Overgrowth in large intestine with clostridium difficile (pseudomembranous colitits)
Its a nonspecific side effect of beta-lactams
Hypersensitivity is a serious problem in response to what?
Beta-lactams
When does haptene formation occur?
Reaction of beta-lactams with serum proteins
Which group of bacteria are still highly sensitive to beta-lactams/penicillin G?
Group A streptococcus (beta-hemolytic)
What is the largest mechanism of resistance to beta-lactams/penicillin G?
beta-lactamases
Beta-lactamases of staphylococci act primarily as what?
Penicillinases
The inoculum size has a large effect on what?
The MIC
What are 3 limitations of early penicillins?
No oral administration
Resistant important groups of pathogens
Narrow antibacterial spectrum
What happens if penicillin G is taken orally? What have we done to compensate for this?
Hydrolyzed by acid in the stomach
Give a much larger dose
Which penicillin is acid-stable? How is it made?
Penicillin V
Made by adding phenoxyacetic acid to medium of mold producing penicillin
Methicillin is _________ to beta-lactamase hydrolysis
refractory/resistant (?)
Penicillin G can’t pass through what of which gram bacteria?
Outer membrane of gram negative bacteria
What can pass through the outer membrane of gram negative bacteria due to its charged amino group? Is it acid-stable?
Ampicillin
Yes, ampicillin is acid stable
Are there broad spectrum beta-lactamase refractory penicillins? What is the solution
No, so we add a broad spectrum penicillin with a beta-lactamase inhibitor
Is methicillin refractory to beta-lactamases?
Yes, because if its large side chains… but that means that it also can’t cross the outer membrane of gram negative bacteria
What are two active site directed inhibitors of beta-lactamases?
Clavulanic acid Sulbactam
Methicillin resistant staph aureus: what is the resistance carried on? Is it intrinsic?
Yes, it is intrinsically carried on a transposon, meaning it is easily transmitted to other bacteria
What is a haptene?
Antibiotic + serum protein that can cause formation of antibodies
1st generation cephalosporin?
Cefazolin - antibacterial spectra and potency like penicillins
2nd generation cephalosporin?
Cefoxitin - more potent and better against gram negatives (than cefazolin, 1st gen)
What percent of people that are hypersensitive to penicillins are also hypersensitive to cephalosporins?
8%
Are haptenes more commonly formed by penicillins or cephalosporins?
Penicillins (drug plus serum protein)
Can bacteria have more than one beta-lactamase? Can they be effective against penicillins or cephalosporins?
Yes they can have more than one
Beta-lactamases can be effective against both penicillins and cephalosporins
What is an advantage of carbapenems?
Resistant to many beta-lactamases
Which bacteria can produce carbapenemases?
Enterobacteria
What are 2 bacterial mechanism of resistance against carbapenems?
Active transport out of cell
Porin mutations preventing influx
3rd generation cephalosporins?
Cefotaxime, Ceftazidime - even more potent (than 1st and 2nd gen) and highly effective against gram negatives but at the expense of being less effective against gram positives
4th generation cephalosporins?
Cefepime - enhanced activity against gram negatives without loss of potency for gram positives
5th generation cephalosporins?
Ceftaroline, Ceftobiprole - effective against MRSA and psuedomonas
What percent of the population are hypersensitive to cephalosporins?
2%