Chapter 7 Anti-infective agents - cephalosporins

Question 1

oral drugs:
cephalexin (keflex)
cefadroxil

parenteral drugs:
cefazolin (kefzol)

first gen - narrow spectrium, sensitive to beta lactamase

Answer 1

• b-lactam binds to penicillin binding proteins => stops cell wall forming + activate autolysins (in turn cause resistance by reducing drug permeability, mutating penicillin binding proteins, producing beta lactamase and cephalasporinases)
• clavulanate can circumvent this problem

spectrum
* gram positive cocci except enterococci + MRSA (staph. aureus)
* some gram neg enterics
* not effective against anaerobes

indication:
* surgical prophylaxis
* tx skin or soft tissue infections cause by staph or strep

pharmacokinetics
* cannot penetrate CSF
* penetrates bone (particularly cephazolin)
* cephalothin only admin as IV b/c painful w/ IM

effects
* hypersen (anaphylaxis, serum sickness [skin rash, joint stiffness, joint pain, facial and extremity swelling, and fever])
* Rare neurologic (sz, confusion) => cefazolin)
* neutropenia, thrombocytopenia, anemia — hematologic
* nephrotoxicity and liver enzyme abnormalities

cross allergy between cephalosporin and penicillins 10-15% of patients

Question 2

oral drugs
* cefaclor (ceclor)
* cefprozil

oral or parenteral
* cefuroxime (ceftin)

parenteral
* cefoxitin
* cefotetan

Answer 2

• b-lactam action
• more resistant to beta-lactamase

spectrum
* gram positive cocci
* extended gram-negative activity (h. flu, enterobacter, proteus, neisseria)
* NONE effective w/ pseudomonas

indication
* otitis media, pharyngitis (sore throat)
* skin, sinus, and respiratory infection

cefuroxime - used as single dose therapy for n. gonorhea + more effective than cefzolin in prophylaxis against MRSA wound infections

cefuroxime can reach CSF levels but 3rd gen preferred b/c greater penetration and more rapid sterilization

effects:
cefaclor – high incidence of serum sickness rxn
* hypersen (anaphylaxis, serum sickness [skin rash, joint stiffness, joint pain, facial and extremity swelling, and fever])
* Rare neurologic (sz, confusion) => cefazolin)
* neutropenia, thrombocytopenia, anemia — hematologic
* nephrotoxicity and liver enzyme abnormalities

Question 3

parenteral
ceftriaxone (rocephin)
cefotaxime
ceftazidime (fortaz)
cefepime
ceftaroline

oral
ceftibuten
cefpodoxime
cefdinir
cefditorin

later generation - broad spectrum, resistant to most cephalosporinases

Answer 3

• similar mech to 1st gen cephalosporin w/ b-lactam
• more resistant to beta lactamase produced by gram negative bacteria

spectrum
* gram negative bacilli (resistant to other cephalosporins, penicilins, and aminoglycosides)
* varying efficacy against pseudomonads (ceftazidime, cefepime, cefoperazone) — gram neg
* gram pos cocci (including staphlococcus and nonenteric streptococcus)

pharmaco
penetrates CSF (except cefoperazone and perhaps cefixime)

Ceftriaxone longest serum half life (ceftazidime lowest)

effects
* hypersen (anaphylaxis, serum sickness [skin rash, joint stiffness, joint pain, facial and extremity swelling, and fever])
* Rare neurologic (sz, confusion) => cefazolin)
* neutropenia, thrombocytopenia, anemia — hematologic
* nephrotoxicity and liver enzyme abnormalities
* Ceftriaxone associated with cholestasis (slowing or stalling of bile flow from your liver) + billrubin displacement from albumin —-> avoid neonate use and avoid in jaundiced infants

ceftriaxone and cefoperazone excreted in bile!

Question 4

Cefotetan (a cephamycin) and cefpodoxime (ester prodrug)

Answer 4

• improved gram negative coverage equivalent to many 3rd generation cephalosporins

Question 4

Cefotetan, cefmetazole, and cefoxitin

Answer 4

• cover bacteriodes (gram neg) and clostridium spp. (anaerobes