Ch 43 - Cephalosporins and Other Cell Wall Synthesis Inhibitors Flashcards
Where did cephalosporins originate?
From the Cephalosporium acremonium fungi
How does the cephalosporins work?
They are analogous to penicillins in:
- binding to specific PBPs
- inhbition of cell wall synthesis by blocking the transpeptidase step of peptidoglycan synthesis
- activation of autolytic enzymes
Are cephalosporins bactericidal or bacteriostatic?
bactericidal
How are cephalosporins subdivided?
Into first, seconds, third, and fourth generations.
- these classification are based on general features of antimicrobial activity
In general, how do the characteristics of cephalosporins change from first- to fourth-generation agents?
- a decrease in gram-positive coverage
- an increase in gram-negative coverage
- an increase in CNS penetration
- an increase in resistance to β-lactamase
First generation cephalosporins are active against which organisms?
- gram-positive cocci, including pneumococci, streptococci, and staphylococci.
- some gram-negative bacilli, including Preoteus mitabilis, Escherichia coli, and Klebsiella -> PEcK.
Which drugs are in the first-generation cephalosporins, and what is the route of administration?
- cefadroxil -> oral
- cephalexin -> oral
- cephradine -> oral
- cefazolin -> IV
Name some second-generation cephalosporins and state the route of administration:
- cefaclor -> PO
- cefuroxime axetil -> PO
- loracarbef -> PO
- cefprozil
- cefotetan -> IV
- cefoxitin -> IV
- cefuroxime -> IV
What infections can be treated with second-generation cephalosporins?
- they cover the same organisms as first-generation cephalosporins, but they also have somewhat increased activity against Gram-negative organisms including Haemophilus influenzae, Neisseria, and Enterobacter.
- cefoxitin, cefmetazole, and cefotetan canbe used to treat anaerobic and aerobic infections, such as those that affect the intra-abdominal area
Name third-generation cephalosporins and state the route of administration:
- cefoperazone -> IV
- cefotaxime -> IV
- ceftazidime -> IV
- ceftizoxime -> IV
- ceftriaxone -> IV
- cefpodoxime -> PO
- cefdinir -> PO
- ceftibuten -> PO
What infections can be treated with third-generation cephalosporins?
- they provide expanded Gram-negative coverage but poor gram positive coverage
- good against Enterobacter, Citrobacter, and Providencia as well as β-lactamase-producing strains of Neisseria and Haemophilus.
- Pseudomonas infection can be treated with ceftazidime and cefoperazone
Name fourth-generation cephalosporins and state the route of administration:
cefepine -> IV only
What is the spectrum of fourth-generation cephalosporins?
- an expanded range of Gram-positive and Gram-negative organisms over third generation
- better Pseudomonas coverage
- more stable against β-lactamase
- not active against MRSA, enterococci, B. fragilis, or L. monocytogenes
What are the cephalosporins inactive against?
all cephalosporins are inactive agains enterococci, methicillin-resistant staphylococci, Listeria monocytogenes, and Clostridium difficile
How are the cephalosporins primarily excreted?
- through glomerular filtration
- cefoperazone and cetriaxone are exceptions, they are excreted in bile
Are cephalosporins metabolized extensively?
they are excreted largely unchanged
How does resistance occure (cephalosporins)?
through the same mechanisms as penicillin
In general, what are the adverse effects of the cephalosporins?
- hypersensitivity
- nephrotoxicity
- intolerance to alcohol
- positive Coomb´s test result
- hypothrombinemia
- intolerance to alcohol
(a disulfiram type reaction) with cefotetan and cefoperazone
- positive Coomb´s test result
but rarely associated with hemolytic anemia
- hypothrombinemia
with cefoperazone due to vitamin K inhibition
Monobactams =
aztreonam
Describe the mechanism of action of the monobactams:
monobactams disrupt bacterial cell wall synthesis by binding to PBPs and inhibiting peptidoglycan synthesis
Describe the pharmacokinetics of aztreonam:
aztreonam is administered via IV or IM routes and is excreted in urine
What are the clinical indications of aztreonam?
primarily aerobic Gram-negative rods (pseudomonas, klebsiella, serratia)
What are the adverse effects of aztreonam?
- skin rash
- elevated liver function enzymes
- GI distress (nausea, vomiting)
What are carbapenems?
- they are synthetic β-lactam antibiotics that are structurally related to the penicillins
- they are resistant to β-lactamase
Give two examples of carbapenems:
- imipenem, prototype
- meropenem
How are the carbapenems administered?
IV
What is the antibacterial spectrum of carbapenems?
- Imipenem: is a bactericidal agent active against virtually all Gram-positive, Gram-negative, and anaerobic organisms
- Methicilin-resistant Staph, vancomycin-resistant enetrococci (VRE), and Clostridium difficile are important exceptions
