CEPHALOSPORINS

Attention--this is one of the older files in the Peripheral Brain, mostly based on a lecture I heard as a resident in 1994. Take it with several grains of salt--ER 1/99

• Taste good
• More stable beta-lactam bond than PCN's
• Some cross-allergy with PCNs; avoid if + PCN allergy
• NO GOOD for inf. w/ ENTEROCOCCI or LISTERIA

All listed below are IM & IV unless otherwise indicated:

1st Generation:

• Cephaloridine (Loridine)--?route
• Cefazolin (Ancef, Kefzol)
• Cefadroxil (Duracef)-PO
• Cephadrine (Anspor, Velosef)-PO/IM/IV
• Cephalexin (Keflex)-PO
• Cephalothin (Keflin)
• Cephapirin (Cefadyl)

1. These last 4 are therapeutic & pharmacokinetic equivalents)
2. Coverage:

1. Gram +: better than 2g/3g

1. Staph: covers all except MRSA
2. Strep: covers all except enterococci (S. Fecalis; Gp. D)

2. Gram - rods:

1. Covers E. Coli, Proteus Mirabilis (indole -), Neisseria sp., Salmonella, Shigella
2. Not very good for Klebsiella or H. Influenza
3. Not effective for Pseudomonas, Enterobacter, Serratia, or indole + Proteus

3. Anaerobes:

1. Good for gm + (supradiaphragmatic) anaerobes
2. Not effective for Bacteroides fragilis

3. Clinical use

1. Alternative to PCN for Staph. & Strep.
2. URIs, soft tissue inf. 2? to mixed flora
3. UTIs
4. Surg. prophylaxis
5. Can use for Klebsiella along w/aminoglycoside
6. Cefazolin is a good workhorse: cheap, effective, less frequent (TID) dosing, high pk lvl 2? to small Vd., more activity than Cephalothin against E. Coli, Klebsiella, less painful IM than Keflex
7. But Cephalithin may be better than Cefazolin in inf. with ?-lactamase producing organisms, e.g. Staph endocarditis (more restistant to ?-lactamase)
8. Both Cefazolin & Cephalothin are 70-80% protein-bound, eliminated un-G'd by kidneys, & don't penetrate CSF adequately for use in meningitis
9. The PO's have excellent urine levels; good serum, tissue, bone, synovial fluid levels achieved when used in mod-hi dose
10. Cefaclor
    1. More active against gm-'s, esp. H. Flu (inc. ampi-resistant) than cephalexin
    2. Used in otitis, URI; should reserve for bacteria resistant to ampi + bactrim
    3. Expensive

2nd generation:

• Cefamandole (Mandol)
• Cefonocid (Monocid)
• Ceforanide (Precef)
• Cefuroxime (Zinacef)-PO (axetil); IM/IV (sodium)

• Cefoxitin (Mefoxin)
• Cefotetan (Cefotan)

• Cefmetazole (Zefazone)
• Cefaclor (Ceclor)
• Cefprozil (Cefzil)
• Loracarbef (Lorabid)

Divided into 2 groups as above; all agents within a group essentially equivalent

Cefamandole group:

1. Coverage:

1. Same gram + coverage as 1g's
2. Possibly good for coag - Staph (better than PCN)
3. Gram - same as 1g's plus indole + Proteus, H. flu. (so can use in comm.-acq'd pneumonia in COPD pts), some Citrobacter, Providencia, Enterobacter
4. Anerobes same as 1g's

2. Cefuroxime

1. (.75-1.5g)TID for cure; BID for surg. prophylaxis
2. Good CNS penetration
3. More resistant to Beta-lactamase-producing H. Flu than cefamandole--good for peds.
4. Renally excreted; must adjust dose in RF

3. Cefonocid, Ceforanide

1. QD-BID dosing
2. Less Staph. coverage than others in this group

Cefoxitin group:

1. Coverage:

1. Gram - aerobes: less than other group at H. flu., Enterobacter, Citrobacter, Providencia
2. Gram - anaerobes: modest activity (1g's & other 2g's have none)

2. Cefotetan

1. Cheap
2. BID dosing
3. Better gram - coverage than Cefoxitin; same anaerobic activity
4. Has MTTZ side ring which can PT; avoid if pt on Coumadin!

Cliinical use:

1. Cefamandole group

1. 2nd line for community-acquired pneumonia, except for "high-risk" pts, e.g. CHF, COPD, EtOH
2. Tx. of ampi-resistant H. flu (as above)
3. CV-surg prophylaxis

2. Cefoxitin group

1. OB/GYN infections
2. Diabetic foot infections
3. Surg prophylaxis (OB/GYN, biliary)
4. Formerly for intra-abdominal infections, but now too much resistance

3rd generation

• Cefotaxime (Claforan)
• Ceftriaxone (Rocephin)
• Ceftizoxime (Cefizox)

• Cefoperazone (Cefobid)
• Ceftazidime (Fortaz)

Divided into 2 groups as above; all agents within a group essentially equivalent; other agents:

• Cefixime (Suprax) 400mg PO Q24h
• Cefpodoxime (Vantin) 200mg PO Q12h
• Ceftibuten (Cedax) 400mg PO Q24h
• Moxalactam (Moxam)
• Cefinir (Omnicef)--PO (600mg/d divided QD-BID in adults; 14mg/kg/d divided QD-BID in kids; BID probably better)
• Cefditoren (Spectracef) 200-400mg PO Q12h
• Cefepime

*3g's contraindicated in neonates (<10do) because displace bilirubin from serum proteins*

Cefotaxime group:

1. Coverage:

1. Gram +: less for Staph than 1g/2g's; poor against Enterococci & MRSA
2. Gram - aerobes: excellent for most except Pseudomonas, Listeria; excellent for Neisseria sp., H. Flu (inc. ?-lactamase producers)
3. Anaerobes: poor activity

2. Ceftriaxone

1. QD dosing (1-2g) except in meningitis (2g Q12?)
2. Cleared through kidneys & liver, so don't need to adjust dose in renal failure
3. Theoretical risk of cholecystitis
4. Drug of choice for gonorrhea (125-250 IM x 1)

3. Others

1. Both have renal excretion
2. -taxime 1-2g Q6-8?; -zoxime 1-2g Q8?

Cefoperazone group:

1. Coverage:

1. Same as cefotaxime group except:
2. Anti- P. Aeruginosa activity, ceftaz>cefoperazone

2. Cefoperazone

1. Biliary clearance; no adjustment of dose in RF
2. BID dosing (2g Q12?)
3. MTTZ side ring: can PT
4. Disulfiram-like reaction

3. Ceftaz

1. Better CNS penetration than Cefoperazone
2. Good against Acinetobacter
3. Poor for gram +'s and anaerobes
4. 1-2g Q8h

Cllinical use:

1. Gram - meningitis (cefotaxime group); though you'd miss Listeria; give meningitis-dose PCN G if suspect
2. Empiric tx of febrile neutropenic host: double ?-lactam tx. Some use Ceftaz + Vanco (to cover Staph.)
3. Severe gram - pneumonia
4. Cefixime (PO)--2nd-line for otitis, also against resistant E. Coli