Cephalosporins

1
Cephalosporins

• First Generation Cephalosporins
• Second Generation Cephalosporins
• Third Generation Cephalosporins
• Fourth Generation Cephalosporins

2
Cephalothin (IV) G1
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 gt
  cefazolin
• Gram - bacilli - cefazolin gt cephalothin

Special Properties Can be used with caution in
pts allergic to PCNs but not those with
immediate hypersensitivity rxn
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
3
Cefazolin (IV) G1
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
Pharmoco-kinetics     Inadequate CSF penetration
for meningitis Cefazolin - elim. GF gt 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 gt
  cefazolin
• Gram - bacilli - cefazolin gt 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 gt
  cefazolin
• Gram - bacilli - cefazolin gt 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
5
Cefadroxil (PO) 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
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 gt
  cefazolin
• Gram - bacilli - cefazolin gt 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
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 gt
  cefazolin
• Gram - bacilli - cefazolin gt 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

Pharmoco-kinetics           Elimination -
primarily RTS
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
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

Pharmoco-kinetics     CSF penetration for
meningitis      Elimination - primarily RTS
Special Properties Cefuroxime - only 2G with
adequate CSF penetration longer t/2 no MTT side
chain
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
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

• 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

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 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
  gt
• cefotetan)
• N. Gonorrhoeae (including PPNG)
• Gram - enteric aerobic bacilli (Klebsiella, E.
  coli,
• some serratia) cefotetan gt cefoxitin
• NOT effective against enterococci, listeria, or
  MRS
• lt 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
• Similar to first generation cephalosporins but
  with enhanced
• activity against
• Bacteroides fragilis
• Other bacteroides species -anaerobes - (cefoxitin
  gt cefotetan)
• N. Gonorrhoeae (including PPNG)
• Gram - enteric aerobic bacilli (Klebsiella, E.
  coli, some serratia)
• cefotetan gt cefoxitin
• NOT effective against enterococci, listeria, or
  MRS
• Less active against H. flu and enterobacter than
  cefamandole

Drug Reactions Possible potentiation of
nephrotoxicity (proximal tubular necrosis) with
concurrent use of aminoglycosides, loop
diuretics, or probenecid
Special Properties Expensive cefotetan may
have cost advantage since it can be administered
less frequently
Pharmoco-kinetics     Inadequate CSF penetration
for meningitis      Elimination - primarily
RTS Cefotetan - has long t/2 (4.5 hrs)
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
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
• Similar to first generation cephalosporins but
  with enhanced
• activity against
• Bacteroides fragilis
• Other bacteroides species -anaerobes - (cefoxitin
  gt cefotetan)
• N. Gonorrhoeae (including PPNG)
• Gram - enteric aerobic bacilli (Klebsiella, E.
  coli, some serratia)
• cefotetan gt cefoxitin
• NOT effective against enterococci, listeria, or
  MRS
• Less active against H. flu and enterobacter than
  cefamandole

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
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)
Adverse Reactions Common - allergic rxn (less
than PCNs) pain and absess at IM inj site (less
with cefazolin) NVD coombs test
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
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
Drug Reactions Possible potentiation of
nephrotoxicity (proximal tubular necrosis) with
concurrent use of aminoglycosides, loop
diuretics, or probenecid
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

• 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
Pharmoco-kinetics     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 (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
Pharmoco-kinetics           Elimination -
primarily RTS
Clinical Uses Cefixime - PPNG via single oral
dose
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 withMTT Side Chain

• G2 Cephalosporins
• Cefamandole
• Cefotetan
• Cefmetazole
• G3 Cephalosporins
• Moxalactam
• Cefoperazone

25
Cephalosporin activity against Gram Positives

• G1gt G2gtG3gtG4

26
Cephalosporin activity against Gram
Negatives/Stability to GN Blases

• G4gt G3gtG2gtG1