Cell Wall Inhibitors Flashcards
Are β-Lactams bactericidal or bacteriostatic?
Bactericidal
What is the mechanism of action of β-Lactams?
Inhibit cell wall synthesis
What is the generic structure of cephalosporins comprised of?
A = dihydrothiazine ring B = β-lactam ring R = acyl side chain adaptations
What is the mechanism of action of cephalosporins?
Interfere with cell wall synthesis by binding to penicillin-binding proteins (PBPs) located in bacterial cell walls. Inhibition of PBPs leads to inhibition of the final transpeptidation step of peptidoglycan synthesis.
What are the 3 mechanisms of resistance to cephalosporins?
- Production of ß-lactamase
- Alteration of PBPs
- Alteration of outer membrane permeability that interferes with PBP access by the drug
What is the general action of 1st generation cephalosporins?
Best activity against gram-positive aerobes, with good activity against a few gram-negative aerobes
What Gram (+) do 1st Gen cephalosporins hit?
Meth-susc S. aureus*
Pen-susc S. pneumoniae
Group streptococci
Viridans streptococci
What Gram (-) do 1st Gen cephalosporins hit?
PEK
P. mirabilis
E. coli
K. pneumoniae
What are the main examples of 1st Gen cephalosporins?
Cefazolin
Cephalexin
What is the general action of 2nd generation cephalosporins?
In general, slightly less active against gram-positive aerobes, but more active against gram-negative aerobes
Do 2nd generation cephalosporins have action against anaerobes?
The cephamycins of the second generation agents have activity against anaerobes.
What Gram (+) do 2nd Gen cephalosporins hit?
Meth-susc S. aureus*
Pen-susc S. pneumoniae
Group streptococci
Viridans streptococci
What Gram (-) do 2nd Gen cephalosporins hit?
HENPEK H. influenzae Enterobacter spp. (some) Neisseria spp. P. mirabilis E. coli K. pneumoniae
What are examples of 2nd Gen cephalosporins?
Cefuroxime
Cefprozil
Cefoxitin
Cefotetan
What are the cephamycins (2nd Gen)?
Cefoxitin
Cefotetan
Cefmetazole
What are the cephamycins useful for?
Anaerobes. They are the only cephalosporins that have activity against anaerobes
Bacteroides fragilis
What is the general action of 3rd generation cephalosporins?
In general, are less active against gram- positive aerobes, but have greater activity against gram-negative aerobes, including some β-lactamase-producing strains
What Gram (+) do 3rd Gen cephalosporins hit?
Less Gram (+) action
What Gram (-) do 3rd Gen cephalosporins hit?
HENPECKSSS H. influenzae E. coli Neisseria spp. P. mirabilis E. coli Citrobacter spp. K. pneumoniae Serratia marcescens Salmonella spp. Shigella spp.
What are examples of 3rd Gen cephalosporins?
Ceftriaxone
Ceftazidime
Cefpodoxime
What are the 3rd Gen cephalosporins that have activity against P. aeruginosa?
Ceftazidime
Cefoperazone
What is the general action of 4th generation cephalosporins?
Extended spectrum of activity
▪ Gram-positives: similar to ceftriaxone
▪ Gram-negatives: similar to ceftazidime, including Pseudomonas aeruginosa*; also covers β-lactamase producing Enterobacter spp.
What is the only 4th Gen cephalosporin?
Cefepime
What is the general action of 5th generation cephalosporins?
Extended activity vs
▪ Respiratory pathogens: H. influenzae, Strep pneumoniae, Moraxella, Staph aureus
▪ Gram + pathogens of SSSI: Strep pneumoniae, MRSA.
What are cephalosporins generally ineffective against?
MRSA Enterococcus spp. Listeria monocytogenes Stenotrophomonas maltophilia Clostridium difficile Atypical bacteria, including Legionella
What is the absorption of oral cephalosporins?
Oral cephalosporins are well absorbed, but achieve lower serum concentrations than parenteral
Who does cephalosporin allergy occur most frequently in?
Hypersensitivity reactions to cephalosporins occur most frequently in patients with a history of penicillin allergy.
What is the mechanism of action of carbapenems?
Inhibition of PBP-2 prevents cell wall synthesis and it penetrates the cell wall well.
Are carbepenems bacteriostatic/cidal?
Time-dependent bactericidal
What is the general use of carbapenems?
The carbapenems are currently the most broad-spectrum antibiotics, with good
activity against many gram positive AND gram-negative aerobes AND anaerobes.
What do carbapenems NOT have activity against?
The carbapenems do NOT have activity against methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, some enterococci, Clostridium difficile, Stenotrophomonas maltophilia, Nocardia, and atypical bacteria.
What carbapenem does not have P. aeruginosa activity?
Ertapenem
What can be administered with Imipenem to reduce renal toxicity?
Cilastatin
Do carbapenems require dosage adjustment in renal failure patients?
All carbapenems require dosage adjustment in patients with renal dysfunction
What is the clinical use of carbapenems?
Polymicrobial infections
What is the mechanism of action of monobactams?
Like bicyclic β-lactam antibiotics, aztreonam is bactericidal because of its ability to bind to and inhibit PBPs and ultimately inhibit peptidoglycan synthesis, which is essential for the synthesis, assembly and maintenance of bacterial cell walls.
What is the only monobactam?
Aztreonam
What is the spectrum of aztreonam action?
Aztreonam preferentially binds to PBP-3 in gram-negative aerobic bacteria; therefore, aztreonam only has activity against gram-negative aerobes.
Is aztreonam P. aeruginosa active?
Yes
Do monobactams penetrate the CNS?
Yes
What is the major clinical use of aztreonam?
Aztreonam is especially useful for the treatment of gram-negative infections in patients with a history of a severe penicillin allergy.
Do monobactams need to be adjusted for renal failure patients?
Yes
What is the clinical use of Gen 1 Ceph?
Skin infections
Some UTIs
What is the clinical use of Gen 2 Ceph?
Cephamycins VS Gram (-) anaerobes
What is the clinical use of Gen 3 Ceph?
Meningitis
Pneumonia
What is the clinical use of Gen 4 Ceph?
P. aeruginosa
What is the clinical use of Gen 5 Ceph?
Skin and Soft Tissue Infection
