G4: Beta-Lactam Antibiotics Cephalosporins

What is the MOA of cephalosporins?

Inhibit cell wall synthesis at PBPs

What are the characteristics of cephalosporins?

• Time dependent (T > MIC), bactericidal activity

• Generations: gram (+) → Gram (-)

• NONE reliably cover Enterococcus spp.

• Renal elimination & dose-adjustment for renal dysfunction

What are the ADRs of cephalosporins?

• Allergic reaction, rash

• Thrombocytopenia

• Gastrointestinal upset

• C. Difficile-associated diarrhea

• Seizures (rare)

What are the drug interactions of cephalosporins?

• Warfarin (mild)

• Birth control (controversial)

What are the agents of 1st generation cephalosporins?

• Cefazolin (Ancef, Kefzol) (IV)

• XX cephalothin (Keflin) & cephradine (Velocef) (IV)

• Cephalexin (Keflex) (PO)

• Cefadroxil (Duricef) (PO)

What is the spectrum of 1st generation cephalosporins?

Penicillinase-producing Streptococci & Staphylococci, some P. Mirabilis, E. Coli, K. Pneumoniae

What is the notes of 1st generation cephalosporins?

• DOC for MSSA

• Use for Gm(-) only if have susceptibilities

What is the agents of 2nd generation cephalosporins?

• Cefuroxime (Zinacef) (IV) & Cefuroxime acetyl (Ceftin) (PO)

• Cefprozil (Cefzil) (PO)

• Cefaclor (Ceclor) (PO)

• XX Loracarbef (Lorabid) (PO)

• Cefoxitin (Mefoxin) (IV)

• Cefotetan (Cefotan) (IV)

What is the spectrum of 2nd generation cephalosporins?

• Adds respiratory Gm (-), H. Influenzae, Neisseria, M. Catarrhalis

• Slightly less Gm (+) activity

What is the notes of 2nd generation cephalosporins?

• Cefoxitin, Cefotetan are cephamycins w/ some anaerobic activity

• Cefotetan w/ MTT side chain

What is the agents of 3rd generation cephalosporins (group A)?

• Ceftriaxone (Rocephin) (IV) (IM)

• Cefotaxime (Claforan) (IV)

What is the spectrum of 3rd generation cephalosporins (group A)?

Enhanced Gm (-) activity, some w/ less Gm (+) activity

What is the notes of 3rd generation cephalosporins (group A)?

• IV formulations w/ good CSF penetration

• DOC for S. Pneumoniae

• No renal dosing adjustments (Ceftriaxone)

• Once daily administration for most indications (Ceftriaxone)

What is the agents of 3rd generation cephalosporins (group B)?

• Ceftazidime (Fortaz) (IV)

• XX Cefoperazone (Cefobid) (IV)

What is the spectrum of 3rd generation cephalosporins (group B)?

Enhanced Gm (-) activity, with less Gm (+) activity

What is the notes of 3rd generation cephalosporins (group B)?

• IV formulations w/ good CSF penetration

• Covers P. Aeruginosa

• Lacks reliable Staphylococcus & Streptococcus coverage

What is the agents of 3rd generation cephalosporins (PO)?

• Cefixime (Suprax) (PO)

• Cefpodoxime (Vantin) (PO)

• Cefdinir (Omnicef) (PO)

What is the spectrum of 3rd generation cephalosporins (PO)?

Enhanced Gm (-) activity, some w/ less Gm (+) activity

What is the notes of 3rd generation cephalosporins (PO)?

• Used mostly as “step-down” therapy from IV 3rd generation cephalosporins

• Cefixime less reliable for S. Pneumoniae

• No P. aeruginosa coverage for all

What is the agents of 4th generation cephalosporins?

Cefepime (Maxipime) (IV)

What is the spectrum of 4th generation cephalosporins?

Enhanced Gm (+) & Gm (-) activity w/ enhanced SPACE & P. Aeruginosa coverage

What is the notes of 4th generation cephalosporins?

• Broad spectrum cephalosporin

• DOC for enterobacter spp.

• Does not cover anaerobes

What is the agents of 5th generation cephalosporins?

Ceftaroline (Teflaro) (IV)

What is the spectrum of 5th generation cephalosporins?

• Enhanced Gm (+) including MRSA & enhanced S. Pneumoniae

• Some Gm (-) coverage

What is the notes of 5th generation cephalosporins?

• First (& only) beta-lactam to cover MRSA

• NO p. aeruginosa cvg

• FDA indications for CAP, SSTIs