Cephalosporins

Question 1

MoA

Answer 1

Interfere with cell wall synthesis by binding to PBPs in bacterial cell walls
Inhibition of PBPs leads to inhibition of final transpeptidation step of peptidoglycan synthesis
ARE BACTERICIDAL

Question 2

MoR

Answer 2

Production of B-lactamase enzymes
Gram+: PenR s. aureus
Gram-: Kleb pneumoniae, H. influenze, M catarrhalis, E.coli, Enterobacer, N. gonorrhoeae
Anaerobes: B.fragilis

Cephalosporins display variable susceptibility to B-lactamase enzymes (4th gen most stable)

Some cephalosporins induce B-lactamase production (SPICE)

Alterations in PBPs leading to decreased binding affinity (MRSA, PRSP)

Alteration of outer membrane leading to decreased penetration to the PBPs

Question 3

First generation cephalosporins

Answer 3

Best against gram+ aerobes, some gram-

Gram+: meth-sus S.auerus, Pen-susc S. pneumoniae, group strep, viridans strep

Gram- (PEK): P. mirabilis, E. coli, K. pneumoniae

Question 4

Second Generation Cephalosporins

Answer 4

Cephalosporins, cephamycins, carbacephems

Less active against gram+ aerobes, but more active against gram-

Several have activity against anerobes (the cephamycins)

Question 5

Third Generation cephalosporins

Answer 5

Less active against gram+, greater activity against gram-

Question 6

Fourth Generation cephalosporins

Answer 6

Extended spectrum: Grm+ similar to ceftriaxone, Gram- similar to ceftazidime PLUS B-lactamase producing Enterobacter

Poor inducer of extended spectrum B-lactamase enzymes

Question 7

Fifth Generation cephalosporins

Answer 7

Extended activity against respiratory pathogens (H.influenzae, strep pneumo, moraxella, s. aureus) and gram+ pathogens of SSSI (Strep pneumoniae, MRSA)

Used for community acquired pneumonia, SSSI

Question 8

Generally not active against

Answer 8

MRSA, entercoccus, listeria monocytogenes, stenotrophomonas maltophilia, c. diff, atypical bacteria (legionella)

Question 9

Pharmacology

Answer 9

Orally well absorbed, lower serum concentrations

Distributed into tissues and fluid, CSF ONLY with parenteral cefuroxime, 3rd, 4th generation agents

Primarily kidney elimination, dosage adjustments necessary. CEFTRIAXONE and CEFOPERAZONE are not eliminated by kidney

Question 10

Adverse Effects

Answer 10

Hypersensitivity: cross- reactivity with penicillins

MTT side chain: Hypoprothrombinemia, due to enzyme inhibition of VitK metabolis or reduction in vitK producing bacteria in GI tract -> ethanol intolerance

Hematologic, leukopenia, thrombocytopenia

GI, c.diff

Other- IV calcium and ceftriaxone precipitates