1. Cephalosporins First Generation Cephalosporins
Second Generation Cephalosporins
Third Generation Cephalosporins
Fourth Generation Cephalosporins

2. Similar to ampicillin except effect against:
Cephalothin (IV) G1
Adverse Reactions
Common - allergic rxn (less than PCNs); pain and absess at IM inj site (less with cefazolin); NVD; + coombs test
Special Properties
Can be used with caution in pts allergic to
PCNs but not those with immediate
hypersensitivity rxn
Spectrum
Similar to ampicillin except effect against:
Klebsiella pneumoniae
Penicillinase-producing staphylococci (not MRSA or PRSP) and many gram +
E. coli, P. mirabilis
Somewhat against H. influenzae
NOT for enterococci, listeria, or MRS
Staphylococci (and other gram +) - cephalothin > cefazolin
Gram - bacilli - cefazolin > cephalothin
Drug Reactions
Possible potentiation of nephrotoxicity (proximal tubular necrosis) with concurrent use of aminoglycosides, loop diuretics, or probenecid
Clinical Uses
Klebsiella infections (80%) - not DOC
Alternative for penicillinase-resistant staph.
infection (NOT MRS or PRSP)
Staph. infections in most PCN allergic pts
NOT FOR - MRS, PRSP, enterococcal/listeria/B. frag, or CNS infections or meningitis
Pharmoco-kinetics
    Inadequate CSF penetration for meningitis
·     Elimination - primarily RTS

3. Cefazolin - elim. GF > RTS; longer t/2
Cefazolin (IV) G1
Drug Reactions
Possible potentiation of nephrotoxicity (proximal tubular necrosis) with concurrent use of aminoglycosides, loop diuretics, or probenecid
Adverse Reactions
Common - allergic rxn (less than PCNs); pain and absess at IM inj site (less with cefazolin); NVD; + coombs test
Pharmoco-kinetics
    Inadequate CSF penetration for meningitis
Cefazolin - elim. GF > RTS; longer t/2
Special Properties
Can be used with caution in pts allergic to
PCNs but not those with immediate
hypersensitivity rxn
Spectrum
Similar to ampicillin except effect against:
Klebsiella pneumoniae
Penicillinase-producing staphylococci (not MRSA or PRSP) and many gram +
E. coli, P. mirabilis
Somewhat against H. influenzae
NOT for enterococci, listeria, or MRS
Staphylococci (and other gram +) - cephalothin > cefazolin
Gram - bacilli - cefazolin > cephalothin
Clinical Uses
Klebsiella infections (80%) - not DOC
Alternative for penicillinase-resistant staph.
infection (NOT MRS or PRSP)
Staph. infections in most PCN allergic pts
NOT FOR - MRS, PRSP, enterococcal/listeria/B. frag, or CNS infections or meningitis

4. Cephalexin (PO) most used oral (Keflex) G1
Spectrum
Similar to ampicillin except effect against:
Klebsiella pneumoniae
Penicillinase-producing staphylococci (not MRSA or PRSP) and many gram +
E. coli, P. mirabilis
Somewhat against H. influenzae
NOT for enterococci, listeria, or MRS
Staphylococci (and other gram +) - cephalothin > cefazolin
Gram - bacilli - cefazolin > cephalothin
Adverse Reactions
Common - allergic rxn (less than PCNs); pain and absess at IM inj site (less with cefazolin); NVD; + coombs test
Pharmoco-kinetics
    Inadequate CSF penetration for meningitis
·     Elimination - primarily RTS
Drug Reactions
Possible potentiation of nephrotoxicity (proximal tubular necrosis) with concurrent use of aminoglycosides, loop diuretics, or probenecid
Clinical Uses
Klebsiella infections (80%) - not DOC
Alternative for penicillinase-resistant staph.
infection (NOT MRS or PRSP)
Staph. infections in most PCN allergic pts
NOT FOR - MRS, PRSP, enterococcal/listeria/B. frag, or CNS infections or meningitis
Special Properties
Can be used with caution in pts allergic to
PCNs but not those with immediate
hypersensitivity rxn

5. Similar to ampicillin except effect against:
Cefadroxil (PO) G1
Drug Reactions
Possible potentiation of nephrotoxicity (proximal tubular necrosis) with concurrent use of aminoglycosides, loop diuretics, or probenecid
Special Properties
Can be used with caution in pts allergic to
PCNs but not those with immediate
hypersensitivity rxn
Adverse Reactions
Common - allergic rxn (less than PCNs); pain and absess at IM inj site (less with cefazolin); NVD; + coombs test
Spectrum
Similar to ampicillin except effect against:
Klebsiella pneumoniae
Penicillinase-producing staphylococci (not MRSA or PRSP) and many gram +
E. coli, P. mirabilis
Somewhat against H. influenzae
NOT for enterococci, listeria, or MRS
Staphylococci (and other gram +) - cephalothin > cefazolin
Gram - bacilli - cefazolin > cephalothin
Pharmoco-kinetics
    Inadequate CSF penetration for meningitis
·    Elimination - primarily RTS
Cefadroxil - longer t/2 for less frequent dosing
Clinical Uses
Klebsiella infections (80%) - not DOC
Alternative for penicillinase-resistant staph.
infection (NOT MRS or PRSP)
Staph. infections in most PCN allergic pts
NOT FOR - MRS, PRSP, enterococcal/listeria/B. frag, or CNS infections or meningitis

6. Similar to ampicillin except effect against:
Cefadroxil (PO) G1
Spectrum
Similar to ampicillin except effect against:
Klebsiella pneumoniae
Penicillinase-producing staphylococci (not MRSA or PRSP) and many gram +
E. coli, P. mirabilis
Somewhat against H. influenzae
NOT for enterococci, listeria, or MRS
Staphylococci (and other gram +) - cephalothin > cefazolin
Gram - bacilli - cefazolin > cephalothin
Pharmoco-kinetics
    Inadequate CSF penetration for meningitis
·     Elimination - primarily RTS
Adverse Reactions
Common - allergic rxn (less than PCNs); pain and absess at IM inj site (less with cefazolin); NVD; + coombs test
Drug Reactions
Possible potentiation of nephrotoxicity (proximal tubular necrosis) with concurrent use of aminoglycosides, loop diuretics, or probenecid
Special Properties
Can be used with caution in pts allergic to
PCNs but not those with immediate
hypersensitivity rxn
Clinical Uses
Klebsiella infections (80%) - not DOC
Alternative for penicillinase-resistant staph.
infection (NOT MRS or PRSP)
Staph. infections in most PCN allergic pts
NOT FOR - MRS, PRSP, enterococcal/listeria/B. frag, or CNS infections or meningitis

7. Second Generation Cephalosporins
(Cefamandole-Like)
Note some have MTT side chains

8. Cefamandole (IV) prototype G2
Clinical Uses
Above the diaphragm drugs
"Day Care Drugs"
Primarily for ampicillin-resistant
H.influenzae infections (sinusitis, otitis
media, URIs,
Special Properties
Can be used with caution in pts allergic to
PCNs but not those with immediate
hypersensitivity rxn
Spectrum
Similar to first generation cephalosporins plus:
Two to 8X greater activity against H. influenzae
(including ampicillin resistant)
More active against Klebsiella, E. coli, and indole +
proteus
NOT effective against enterococci, listeria, or MRS
Adverse Reactions
Similar to 1st generation except:
Cefamandole - may cause bleeding (due to
vit. K inhibition) and disulfuram-like rxn;
these are due to MTT side chain at R2
Pharmoco-kinetics
    
·     Elimination - primarily RTS
Drug Reactions
Possible potentiation of nephrotoxicity (proximal tubular necrosis) with concurrent use of aminoglycosides, loop diuretics, or probenecid

9. Cefuroxime (IV) Cefuroxime Axetil (PO) G2
Spectrum
Similar to first generation cephalosporins plus:
Two to 8X greater activity against H. influenzae
(including ampicillin resistant)
More active against Klebsiella, E. coli, and indole +
proteus
Cefuroxime also effective for PPNG
NOT effective against enterococci, listeria, or MRS
Special Properties
Cefuroxime - only 2G with adequate CSF penetration; longer t/2; no MTT side chain
Pharmoco-kinetics
    CSF penetration for meningitis
·     Elimination - primarily RTS
Drug Reactions
Possible potentiation of nephrotoxicity (proximal tubular necrosis) with concurrent use of aminoglycosides, loop diuretics, or probenecid
Adverse Reactions
Common - allergic rxn (less than PCNs); pain and absess at IM inj site (less with cefazolin); NVD; + coombs test
Clinical Uses
Above the diaphragm drugs
"Day Care Drugs"
Primarily for ampicillin-resistant H. influenzae
infections (sinusitis, otitis media, URIs, cefuroxime
for pneumonias)
Cefuroxime for H. influenzae meningitis (not DOC)
Cefuroxime is alternative drug for PPNG

10. Cefaclor (PO) oral equiv. of cefamandole G2
Adverse Reactions
Common - allergic rxn (less than PCNs); pain and absess at IM inj site (less with cefazolin); NVD; + coombs test
Spectrum
Similar to first generation cephalosporins plus:
Two to 8X greater activity against H. influenzae
(including ampicillin resistant)
More active against Klebsiella, E. coli, and indole +
proteus
NOT effective against enterococci, listeria, or MRS
Drug Reactions
Possible potentiation of nephrotoxicity (proximal tubular necrosis) with concurrent use of aminoglycosides, loop diuretics, or probenecid
Pharmoco-kinetics
    Inadequate CSF penetration for meningitis
·     Elimination - primarily RTS
Special Properties
Can be used with caution in pts allergic to
PCNs but not those with immediate
hypersensitivity rxn
Cefaclor - cheapest
Clinical Uses
Above the diaphragm drugs
"Day Care Drugs"
Primarily for ampicillin-resistant H. influenzae infections (sinusitis, otitis media, URIs, cefuroxime for pneumonias)

11. Cefprozil and Loracarbef (PO) G2
Drug Reactions
Possible potentiation of nephrotoxicity (proximal tubular necrosis) with concurrent use of aminoglycosides, loop diuretics, or probenecid
Spectrum
Similar to first generation cephalosporins plus:
Two to 8X greater activity against H. influenzae
(including ampicillin resistant)
More active against Klebsiella, E. coli, and indole +
proteus
NOT effective against enterococci, listeria, or MRS
Cefprozil - may be more stable against beta
lactamase producing strains of staph, H. flu, and
Morazella
Pharmoco-kinetics
    Inadequate CSF penetration for meningitis
·     Elimination - primarily RTS
Cefprozil and Loracarbef - better PO absorption
Special Properties
Can be used with caution in pts allergic to
PCNs but not those with immediate
hypersensitivity rxn
Adverse Reactions
Common - allergic rxn (less than PCNs); pain and absess at IM inj site (less with cefazolin); NVD; + coombs test
Above the diaphragm drugs
"Day Care Drugs"
Primarily for ampicillin-resistant H. influenzae infections (sinusitis, otitis media, URIs, cefuroxime for pneumonias)

12. Second Generation Cephalosporins
(Cefoxitin-Like)
Note some have MTT side chains

13. Cefoxitin (IV) prototype G2
Spectrum
Similar to first generation cephalosporins but with
enhanced activity against:
Bacteroides fragilis
Other bacteroides species -anaerobes (cefoxitin >
cefotetan)
N. Gonorrhoeae (including PPNG)
Gram - enteric aerobic bacilli (Klebsiella, E. coli,
some serratia) cefotetan > cefoxitin
NOT effective against enterococci, listeria, or MRS
< active against H. flu and enterobacter than cefamandole
Pharmoco-kinetics
    Inadequate CSF penetration for meningitis
·     Elimination - primarily RTS
Adverse Reactions
Common - allergic rxn (less than PCNs); pain and absess at IM inj site (less with cefazolin); NVD; + coombs test
Drug Reactions
Possible potentiation of nephrotoxicity (proximal tubular necrosis) with concurrent use of aminoglycosides, loop diuretics, or probenecid
Special Properties
Expensive
Clinical Uses
Below the diaphragm drugs
PPNG
Tx of abdominal and gynecologic infections
where B. fragilis is suspected
Urinary tract, lower respiratory tract, soft
tissue infections (cefotetan)

14. Cefotetan (IV) G2 Spectrum Drug Reactions
Possible potentiation of nephrotoxicity (proximal tubular necrosis) with concurrent use of aminoglycosides, loop diuretics, or probenecid
Spectrum
Similar to first generation cephalosporins but with enhanced
activity against:
Bacteroides fragilis
Other bacteroides species -anaerobes - (cefoxitin > cefotetan)
N. Gonorrhoeae (including PPNG)
Gram - enteric aerobic bacilli (Klebsiella, E. coli, some serratia) –
cefotetan > cefoxitin
NOT effective against enterococci, listeria, or MRS
Less active against H. flu and enterobacter than cefamandole
Special Properties
Expensive; cefotetan may have cost advantage since it can be administered less frequently
Adverse Reactions
Common - allergic rxn (less than PCNs); pain and absess at IM inj site (less with cefazolin); NVD; + coombs test
Cefotetan- may cause bleeding (due to vit. K inhibition) and disulfuram-like rxn; these are due to MTT side chain at R2
Pharmoco-kinetics
    Inadequate CSF penetration for meningitis
·     Elimination - primarily RTS
Cefotetan - has long t/2 (4.5 hrs)
Clinical Uses
Below the diaphragm drugs
PPNG
Tx of abdominal and gynecologic infections
where B. fragilis is suspected
Urinary tract, lower respiratory tract, soft
tissue infections (cefotetan)

15. Cefmetazole (IV) G2 Spectrum Below the diaphragm drugs PPNG
Clinical Uses
Below the diaphragm drugs
PPNG
Tx of abdominal and gynecologic
infections where B. fragilis is suspected
Urinary tract, lower respiratory tract, soft
tissue infections (cefotetan) infections or meningitis
Spectrum
Similar to first generation cephalosporins but with enhanced
activity against:
Bacteroides fragilis
Other bacteroides species -anaerobes - (cefoxitin > cefotetan)
N. Gonorrhoeae (including PPNG)
Gram - enteric aerobic bacilli (Klebsiella, E. coli, some serratia) –
cefotetan > cefoxitin
NOT effective against enterococci, listeria, or MRS
Less active against H. flu and enterobacter than cefamandole
Adverse Reactions
Common - allergic rxn (less than PCNs); pain
and absess at IM inj site (less with cefazolin); NVD; + coombs test
Cefmetazole - may cause bleeding (due to vit. K inhibition) and disulfuram-like rxn; these are due to MTT side chain at R2
Pharmoco-kinetics
    Inadequate CSF penetration for meningitis
    Elimination - primarily RTS
Special Properties
Expensive
Drug Reactions
Possible potentiation of nephrotoxicity (proximal tubular necrosis) with concurrent use of aminoglycosides, loop diuretics, or probenecid

16. Third Generation Cephalosporins
Ceftriaxone (IV) - Rocephin
Cefotaxime sodium (IV)
Ceftizoxime sodium (IV)
Ceftazidime pentahydrate (IV)
Cefoperazone (IV)
Moxalactam disodium (IV)
Cefixime (PO)

17. Ceftriaxone (IV) Rocephin G3
Spectrum
More active against many enteric gram - aerobes;
DOC for E. coli, Indole positive proteus,
Providencia, Serratia
Generally less active against gram + organisms than
1st generation
Very effective against H. influenzae and N.
gonorrhoeae (including PPNG), NOT effective
against enterococci, listeria, or MRS
Pharmoco-kinetics
    Ceftriaxone - longest t/2 of all cephalosporins (8 hrs); excreted in bile (OK for CRF)
Clinical Uses
Ceftriaxone - DOC for PPNG but does not
cover chlymadia; PRSP; H. ducreyi and
Salmonella; Ampicillin-resistant H. flu
meningitis (good CSF penetration); pts in
renal failure
Adverse Reactions
Common - allergic rxn (less than PCNs); pain and absess at IM inj site (less with cefazolin); NVD; + coombs test

18. Cefotaxime sodium (IV) & Ceftizoxime sodium (IV G3
Spectrum
More active against many enteric gram - aerobes; DOC for E. coli, Indole
positive proteus, Providencia, Serratia
Generally less active against gram + organisms than 1st generation
Very effective against H. influenzae and N. gonorrhoeae (including
PPNG)
NOT effective against enterococci, listeria, or MRS
Pharmoco-kinetics
    better CSF penetration for meningitis
·     Elimination - primarily RTS
Clinical Uses
Ceftriaxone - DOC for PPNG but does not
cover chlymadia; PRSP; H. ducreyi and
Salmonella; Ampicillin-resistant H. flu
meningitis (good CSF penetration); pts in
renal failure

19. Ceftazidime pentahydrate (IV) G3
Adverse Reactions
Common - allergic rxn (less than PCNs); pain and absess at IM inj site (less with cefazolin); NVD; + coombs test
Ceftriaxone - DOC for PPNG but does not cover chlymadia; PRSP; H. ducreyi and Salmonella; Ampicillin-resistant H. flu meningitis (good CSF penetration); pts in renal failure
Drug Reactions
Possible potentiation of nephrotoxicity (proximal tubular necrosis) with concurrent use of aminoglycosides, loop diuretics, or probenecid
Spectrum
More active against many enteric gram - aerobes;
DOC for E. coli, Indole positive proteus,
Providencia, Serratia
Generally less active against gram + organisms than G1
Very effective against H. influenzae and N.
gonorrhoeae (including PPNG), NOT effective
against enterococci, listeria, or MRS
Ceftazidime - most active cephalosporin against P.
aeruginosa (cefoperazone also good but not given
alone)
Pharmoco-kinetics
 Same as G1

20. Cefoperazone (IV) G3 Spectrum Pharmoco-kinetics Adverse Reactions
    Cefoperazone - excreted in bile (OK for CRF); poor CNS penetration than other G3s
Spectrum
More active against many enteric gram - aerobes; DOC for E. coli, Indole positive proteus, Providencia, Serratia
Generally less active against gram + organisms than 1st generation
Very effective against H. influenzae and N. gonorrhoeae (including PPNG), NOT effective against enterococci, listeria, or MRS
Adverse Reactions
Cefoperazone - have MTT side chain and may have increased bleeding and disulfuram-like rxn
Clinical Uses
Cefoperazone - Pseudomonas infection that is not in the CNS and pt has renal failure

21. Moxalactam disodium (IV) G3
Pharmoco-kinetics
    
·     Elimination - primarily RTS
Adverse Reactions
moxalactam - have MTT side chain and may have increased bleeding and disulfuram-like rxn
Spectrum
More active against many enteric gram - aerobes; DOC for E. coli, Indole positive proteus, Providencia, Serratia
Generally less active against gram + organisms than 1st generation
Very effective against H. influenzae and N. gonorrhoeae (including PPNG),
NOT effective against enterococci, listeria, or MRS
Clinical Uses
Ceftriaxone - DOC for PPNG but does not cover chlymadia; PRSP; H. ducreyi and Salmonella; Ampicillin-resistant H. flu meningitis (good CSF penetration); pts in renal failure

22. Cefixime - PPNG via single oral dose
Cefixime (PO) G3
Spectrum
More active against many enteric gram - aerobes; DOC for E. coli, Indole positive proteus, Providencia, Serratia
Generally less active against gram + organisms than 1st generation
Very effective against H. influenzae and N. gonorrhoeae (including PPNG),
NOT effective against enterococci, listeria, or MRS
Cefixime - poor activity against staph
Adverse Reactions
Cefixime - diarrhea
Clinical Uses
Cefixime - PPNG via single oral dose
Pharmoco-kinetics
    
·     Elimination - primarily RTS

23. Cefepime (IV) G4
Parenteral only
“Broadest” Gram neg and Gram Pos Spectrum of cephalosporins
Low affinity for gram Neg blases, does not induce blases
100% renal excretion
T1/2 – 2.2 hrs

24. Cephalosporins with MTT Side Chain
G2 Cephalosporins
Cefamandole
Cefotetan
Cefmetazole
G3 Cephalosporins
Moxalactam
Cefoperazone

25. Cephalosporin activity against Gram Positives
G1> G2>G3>G4

26. Cephalosporin activity against Gram Negatives/Stability to GN Blases
G4> G3>G2>G1