Download Cephalosporins

Cephalosporins
• First Generation Cephalosporins
• Second Generation Cephalosporins
• Third Generation Cephalosporins
• Fourth Generation Cephalosporins
Cephalothin (IV)
G1
Spectrum
Adverse
Reactions
Special
Properties
Pharmoco-kinetics
Drug
Clinical
Reactions
Uses
Similar
to ampicillin
except
effectPCNs);
against:pain
Common
allergic
rxn
(less
than
Klebsiella
Inadequate
infections
CSF penetration
(80%) - notfor
DOC
meningitis
• Klebsiella
pneumoniae
and
absess
at
IM
inj
site
(less
with
Can
be
usedfor
with
pts
allergic
to
Alternative
Possible
potentiation
penicillinase-resistant
ofinnephrotoxicity
staph.
Elimination
-caution
primarily
RTS
• Penicillinase-producing
staphylococci
(not
MRSA
or
cefazolin);
NVD;
+ coombs test
PRSP)
and
many
gram
+
(proximal
necrosis)
with concurrent
PCNs
but(NOT
nottubular
those
with
immediate
infection
MRS
or
PRSP)
• E. coli, P. mirabilis
use
of
aminoglycosides,
loop
diuretics,
or
hypersensitivity
rxn
• Somewhat
against H.
Staph.
infections
ininfluenzae
most PCN allergic pts
• NOT for enterococci,probenecid
listeria, or MRS
NOT
FOR
MRS,
PRSP,
• Staphylococci (and other gram +) - cephalothin > cefazolin
enterococcal/listeria/B.
frag,
or
CNS
• Gram - bacilli - cefazolin > cephalothin
infections or meningitis
Cefazolin (IV)
G1
Adverse
Drug
Reactions
Reactions
Pharmoco-kinetics
Special
Properties
Spectrum
Clinical
Uses
Common
allergic
rxn except
(less than
Inadequate
CSF penetration
forPCNs);
meningitis
Similar- to
ampicillin
effect
against: pain
Klebsiella
infections
(80%)
- notwith
DOC
and
absess
at
IM
inj
site
(less
• Klebsiella
pneumoniae
Possible
potentiation
ofinnephrotoxicity
Can
be
used
with
caution
pts allergicstaph.
to
Alternative
for
penicillinase-resistant
cefazolin);tubular
NVD;necrosis)
+ coombswith
test
• (proximal
Penicillinase-producing
staphylococci
(not concurrent
MRSA or
Cefazolin
- gram
elim.
> RTS; longer t/2
PRSP)
andnot
many
+ GFimmediate
PCNs
but
those
with
infection
(NOT MRS or PRSP)
use
of
aminoglycosides,
loop diuretics, or
• E. coli, P. mirabilis
hypersensitivity
rxn
probenecid
Staph.
infections
most PCN allergic pts
• Somewhat against H.in
influenzae
•NOT
NOTFOR
for enterococci,
or MRS
- MRS,listeria,
PRSP,
• Staphylococci (and other gram +) - cephalothin > cefazolin
enterococcal/listeria/B. frag, or CNS
• Gram - bacilli - cefazolin > cephalothin
infections or meningitis
Cephalexin (PO)
most used oral (Keflex)
G1
Spectrum
Adverse
Pharmoco-kinetics
Reactions
Special
Drug
Clinical
Reactions
Properties
Uses
Similar to ampicillin except effect against:
Common
Inadequate
-infections
allergic
CSF rxn
penetration
(less- than
for
PCNs);
meningitis
pain
Klebsiella
(80%)
not
DOC
• Klebsiella pneumoniae
and
absess
at
IM
inj
site
(less
with

Elimination
primarily
RTS
Can
Alternative
Possible
be usedfor
potentiation
with
penicillinase-resistant
caution
ofinnephrotoxicity
pts (not
allergic
staph.
to
• Penicillinase-producing
staphylococci
MRSA
or
cefazolin);
NVD;
+ coombswith
test concurrent
PRSP) and many
gram +necrosis)
(proximal
tubular
PCNs
infection
but(NOT
not those
MRS
with
or PRSP)
immediate
• E. coli, P. mirabilis
use
of
aminoglycosides,
loop
diuretics,
or
•
Somewhat
against
H.
influenzae
hypersensitivity
Staph.
infectionsrxn
in most PCN allergic pts
• NOT for enterococci,probenecid
listeria, or MRS
NOT
FOR
MRS,
PRSP,
• Staphylococci (and other gram +) - cephalothin > cefazolin
enterococcal/listeria/B. frag, or CNS
• Gram - bacilli - cefazolin > cephalothin
infections or meningitis
Cefadroxil (PO)
G1
Drug
Reactions
Special
Adverse
Properties
Reactions
Spectrum
Pharmoco-kinetics
Clinical
Uses
Similar
to ampicillin
except
effect
against:pain
Common
allergic
rxn
(less
than
PCNs);
Inadequate
CSF
penetration
for
meningitis
Klebsiella infections (80%) - not DOC
•
Klebsiella
pneumoniae
and
absess
at IM
inj site
(less
with to
Possible
potentiation
of
nephrotoxicity
Can
be
used
with
caution
in
pts
allergic

Elimination
primarily
RTS
Alternative
for penicillinase-resistant
staph.
• Penicillinase-producing
staphylococci
(not
MRSA
or
cefazolin);
NVD;
+
coombs
test
(proximal
tubular
necrosis)
with
concurrent
PRSP)
andnot
many
gram
+ t/2
PCNs
but
those
with
immediate
Cefadroxil
-MRS
longer
for less frequent
infection
(NOT
or
PRSP)
aminoglycosides, loop diuretics, or
• E.use
coli,of
P. mirabilis
dosing
hypersensitivity
rxn
Staph.
infections
inprobenecid
most PCN allergic pts
• Somewhat against H.
influenzae
• NOT
for enterococci,
NOT
FOR
- MRS,listeria,
PRSP,or MRS
• Staphylococci (and other gram +) - cephalothin > cefazolin
enterococcal/listeria/B. frag, or CNS
• Gram - bacilli - cefazolin > cephalothin
infections or meningitis
Cefadroxil (PO)
G1
Spectrum
Similar to ampicillin except effect against:
Pharmoco-kinetics
• Klebsiella pneumoniae
• Penicillinase-producing
staphylococci
(not MRSA or
Adverse
Reactions
Inadequate
CSF
penetration
for
meningitis
PRSP) and many gram +
Drug
Reactions
allergic
rxn
(less RTS
than PCNs); pain
•Common
E.
coli,
P.
mirabilis
 Elimination - primarily
Special
• Somewhat
against
and absess
at H.
IMinfluenzae
injProperties
site (less with
• NOT
for enterococci,
listeria,
or MRS test
cefazolin);
NVD;
+
coombs
ClinicalofUses
Possible potentiation
nephrotoxicity
• Staphylococci (and other gram +) - cephalothin > cefazolin
(proximal
tubular
necrosis)
concurrent
Can
be -used
with
caution
in pts
allergic
to
infections
-with
not
DOC
•Klebsiella
Gram
bacilli
- cefazolin
>(80%)
cephalothin
use
of
aminoglycosides,
loop
diuretics,
or
PCNs
but
not
those
with
immediate
Alternative for penicillinase-resistant staph.
Second Generation
Cephalosporins
(Cefamandole-Like)
Note some have MTT side
chains
Cefamandole (IV)
prototype
G2 Uses
Clinical
Special
Properties
Above the diaphragm
drugs
Pharmoco-kinetics
Adverse
Reactions
Spectrum
Drug
Reactions
stgeneration
Similar
toto
first
cephalosporins
plus:
"Day
Care
Similar
1Drugs"
generation
except:
Two
to
8X
greater
activity
against
H.allergic
influenzae
Can
be
used
with
caution
in
pts
toto
Primarily
for
ampicillin-resistant
Cefamandole
may
cause
bleeding
(due
 Possible
Elimination
primarily
RTS
potentiation of nephrotoxicity
(including
ampicillin
resistant)
PCNs
but
not
those
with
immediate
H.influenzae
infections
(sinusitis,
otitis
(proximal
tubular
necrosis)
with concurrent
vit. K inhibition) and
disulfuram-like
rxn;
More
active
against
Klebsiella,
E.
coli,
and
indole
+
use
of
aminoglycosides,
loop
diuretics,
or
hypersensitivity
media,
URIs,
these are
due to rxn
MTT side chain at R2
proteus
probenecid
NOT effective against enterococci, listeria, or MRS
Cefuroxime (IV)
Cefuroxime Axetil (PO)
G2
Spectrum
Special
Pharmoco-kinetics
Properties
Drug
Adverse
Reactions
Reactions
Clinical
Uses
Similar to first generation cephalosporins plus:
CSF
penetration
forthan
meningitis
Common
allergic
rxn
(less
PCNs); pain
Above
the
diaphragm
drugs
Two to 8X greater activity against H. influenzae
and
absess
at resistant)
IM
injwith
site
(less
Cefuroxime
- only
adequate
 Possible
Elimination
- 2G
primarily
RTSwithCSF
potentiation
of nephrotoxicity
"Day
Care
Drugs"
(including
ampicillin
cefazolin);
NVD;
+t/2;
coombs
test
penetration;
longer
side+chain
More
activefor
against
Klebsiella,
E.no
coli,MTT
and
indole
(proximal
tubular
necrosis)
with
concurrent
Primarily
ampicillin-resistant
H.
influenzae
proteus
use of aminoglycosides,
loopURIs,
diuretics,
or
infections
(sinusitis, otitis media,
cefuroxime
Cefuroxime
also effective
for PPNG
probenecid
for pneumonias)
NOT
effective
enterococci,
listeria,
or DOC)
MRS
Cefuroxime
foragainst
H. influenzae
meningitis
(not
Cefuroxime is alternative drug for PPNG
Cefaclor (PO)
oral equiv. of cefamandole
G2
Adverse
Reactions
Drug
Reactions
Spectrum
Pharmoco-kinetics
Special
Properties
Clinical
Uses
Common
- allergic
rxncephalosporins
(less than
Similar
to first
generation
plus: pain
Inadequate
CSF penetration
for PCNs);
meningitis
Above
the
diaphragm
drugs
absess
at
IM
inj
site
(less
with
Twoand
to
8X
greater
activity
against
H. influenzae
Possible
potentiation
of
nephrotoxicity
 be
Elimination
-caution
primarily
RTS
Can
used
with
in
pts
allergic to
"Day
Care
Drugs"
cefazolin);
NVD;
+
coombs
test
(including
ampicillin
(proximal
tubularresistant)
necrosis) with concurrent
PCNs
but for
not
those
with immediate
Primarily
ampicillin-resistant
H.
More
active
against
Klebsiella,
coli,diuretics,
and indoleor+
use of aminoglycosides,E.
loop
hypersensitivity
rxnprobenecid
influenzae infections
(sinusitis, otitis
proteus
media,
cefuroxime
for listeria,
pneumonias)
Cefaclor
-URIs,
cheapest
NOT
effective
against
enterococci,
or MRS
Cefprozil and Loracarbef (PO)
G2
Spectrum
Drug
Reactions
Pharmoco-kinetics
Special
Properties
Adverse
Reactions
Above the diaphragm
drugs
Similar to first generation cephalosporins plus:
Inadequate
CSF
penetration
for meningitis
Common
allergic
rxn
(less
than
PCNs);
pain
"Day
Care
Drugs"
Two to 8X greater activity against H. influenzae
Possible
potentiation
ofinRTS
nephrotoxicity
and
absess
at
IM
inj
site
with H.
be
used
with
caution
pts allergic
to
Can
Elimination
primarily
(including
ampicillin
resistant) (less
Primarily
for ampicillin-resistant
(proximal
tubular
necrosis)
with
concurrent
cefazolin);
NVD;
+
coombs
test
PCNs
Cefprozil
but not
andthose
Loracarbef
with immediate
-(sinusitis,
PO indole
More
active
against
Klebsiella,
E.better
coli, and
influenzae
infections
otitis +
use
of
aminoglycosides,
loop
diuretics,
or
absorption
proteus
media, rxn
URIs, cefuroxime for
hypersensitivity
probenecid
NOT effective against
enterococci, listeria, or MRS
pneumonias)
Cefprozil - may be more stable against beta
lactamase producing strains of staph, H. flu, and
Morazella
Second Generation
Cephalosporins
(Cefoxitin-Like)
Note some have MTT side
chains
Cefoxitin (IV)
prototype
G2
Spectrum
Pharmoco-kinetics
Adverse
Reactions
Special
Drug
Clinical
Reactions
Properties
Uses
Similar to first generation cephalosporins
but with
Inadequate
CSF penetration
forPCNs);
meningitis
enhanced
activity
against:
Common
allergic
rxndrugs
(less than
pain
Below
the -diaphragm
Bacteroides
fragilis
and
absess
at IM
inj site
(less

Elimination
-Expensive
primarily
RTSwith
PPNG
Possible
potentiation
of
nephrotoxicity
Other bacteroides species -anaerobes (cefoxitin >
cefazolin);
NVD;
+
coombs
test
cefotetan)
(proximal
tubular
withinfections
concurrent
Tx
of abdominal
andnecrosis)
gynecologic
N. Gonorrhoeae
(including PPNG) loop diuretics, or
use
of
aminoglycosides,
where
B. fragilis
suspected
Gram - enteric
aerobicis
bacilli
(Klebsiella, E. coli,
probenecid
some serratia)
cefotetan
cefoxitin
Urinary
tract,
lower>respiratory
tract, soft
NOT effective against enterococci, listeria, or MRS
tissue
infections
(cefotetan)
< active against
H. flu and
enterobacter than cefamandole
Cefotetan (IV)
G2
Spectrum
Special
Drug
Reactions
Properties
Adverse
Pharmoco-kinetics
Reactions
Clinical
Uses
Similar to first generation cephalosporins but with enhanced
Common
Inadequate
- allergic
CSFrxn
penetration
(less
PCNs);
meningitis
pain
Below
the
diaphragm
drugsthanfor
activity
against:
Bacteroides
fragilis
and
absess
at IM- primarily
inj may
siteof(less
with
Expensive;
Possible
cefotetan
potentiation
have
nephrotoxicity
cost advantage
PPNG
Elimination
RTS
Other bacteroides species -anaerobes - (cefoxitin > cefotetan)
cefazolin);
NVD;
+
coombs
test
(proximal
since
it
can
tubular
be
administered
necrosis)
with
less
concurrent
frequently
Cefotetan
- has and
long
t/2 (4.5 hrs) infections
N.
(including
PPNG)
TxGonorrhoeae
of abdominal
gynecologic
use
of aminoglycosides,
loop
diuretics,
Gram
- enteric
aerobic
bacilli (Klebsiella,
E. coli,
some
Cefotetanmay cause
bleeding
(due
to serratia)
vit.or
K–
where >B.
fragilis is
suspected
cefotetan
cefoxitin
probenecid
inhibition) and disulfuram-like rxn; these
NOT
effective
against
enterococci,
listeria, or MRS
Urinary
tract,
lower
respiratory
tract, soft
are
due
to
MTT
side
chain
at
R2
Less active against H. flu and enterobacter than cefamandole
tissue infections (cefotetan)
Cefmetazole (IV)
G2
Spectrum
Clinical
Uses
Adverse
Reactions
Pharmoco-kinetics
Special
Properties
Similar to first generation
cephalosporins
but with enhanced
Below
the diaphragm
drugs
Common
- allergic
rxn
(less than
PCNs); pain
activity
against:
Inadequate
CSF penetration
for meningitis
Bacteroides fragilis
PPNG
andElimination
absessspecies
at IM
inj site
(less
cefazolin);
--anaerobes
primarily
RTS>with
Other
bacteroides
- (cefoxitin
cefotetan)
Expensive
Gonorrhoeae
PPNG)
NVD;
+(including
coombs
test
TxN.
of
abdominal
and
gynecologic
Drug
Reactions
Gram - enteric aerobic bacilli (Klebsiella, E. coli, some serratia) –
Cefmetazole
- may
cause bleeding
(due to vit.
cefotetan
> cefoxitin
infections
where
B.
fragilis
is
suspected
Possible
potentiation
of nephrotoxicity
NOTK
effective
against
enterococci,
listeria,
or MRS
inhibition) and disulfuram-like
rxn; these
Less
active tract,
against tubular
H.lower
flu and enterobacter
thanwith
cefamandole
(proximal
necrosis)
concurrent
Urinary
respiratory
tract,
soft
are due to MTT side chain at R2
use
of
aminoglycosides,
loop
diuretics,
or
tissue infections (cefotetan) infections or
probenecid
meningitis
Third Generation
Cephalosporins
•
•
•
•
•
•
•
Ceftriaxone (IV) - Rocephin
Cefotaxime sodium (IV)
Ceftizoxime sodium (IV)
Ceftazidime pentahydrate (IV)
Cefoperazone (IV)
Moxalactam disodium (IV)
Cefixime (PO)
Ceftriaxone (IV)
Rocephin
G3
Spectrum
Pharmoco-kinetics
Adverse
Clinical
Reactions
Uses
More
active against
many enteric
gram
- aerobes;
Ceftriaxone
longest
t/2
of
all
Ceftriaxone
Common
-coli,
-allergic
DOC
for
rxn
PPNG
(less proteus,
than
but does
PCNs);
not pain
DOC
for
E.
Indole
positive
cephalosporins
(8inj
hrs);
excreted
in bile (OK
and
absess
at
IM
site
(less
with
cover
chlymadia;
PRSP; H. ducreyi and
Providencia,
Serratia
for
CRF) NVD; + coombs test
cefazolin);
Generally lessAmpicillin-resistant
active against gram + H.
organisms
than
Salmonella;
flu
st generation
1
meningitis (good CSF penetration); pts in
Very effective against H. influenzae and N.
renal
failure
gonorrhoeae (including PPNG), NOT effective
against enterococci, listeria, or MRS
Cefotaxime sodium (IV)
&
Ceftizoxime sodium (IV
G3
Spectrum
Pharmoco-kinetics
Clinical
Uses
More active against many enteric gram - aerobes; DOC for E.
better
CSF- DOC
penetration
for meningitis
Ceftriaxone
for PPNG
but does not
coli,
Indole
positive
proteus, Providencia,
Serratia
cover
Elimination
- PRSP;
primarily
chlymadia;
H. RTS
ducreyi and
Generally less active against gram + organisms than 1st
Salmonella;
generation Ampicillin-resistant H. flu
Very effective against H. influenzae and N. gonorrhoeae
meningitis
(good CSF penetration); pts in
(including
PPNG)
renal failure
NOT effective against enterococci, listeria, or MRS
Ceftazidime pentahydrate (IV)
G3
CeftriaxoneAdverse
-Drug
DOC
Reactions
for
Reactions
PPNG but does not
Spectrum
More
active-chlymadia;
against
manyrxn
enteric
gram
- aerobes;
cover
PRSP;
H.
ducreyipain
and
Common
allergic
(less
than
PCNs);
DOCSalmonella;
for E. coli, Indole
positive proteus,
Ampicillin-resistant
H.
flu
and
absess
at
IM
inj
site
(less
with
Pharmoco-kinetics
Possible
potentiation of nephrotoxicity
Providencia,
Serratia
meningitis
(good
CSF
penetration);
pts
in
cefazolin);
NVD;
+
coombs
test
(proximal
tubular
necrosis)
with concurrent
Generally
less active
against
gram
+ organisms
than G1
Same
as G1
renal
failure
Veryuse
effective
against
H.
influenzae
N. diuretics, or
of aminoglycosides, and
loop
gonorrhoeae (including PPNG),
NOT effective
probenecid
against enterococci, listeria, or MRS
Ceftazidime - most active cephalosporin against P.
aeruginosa (cefoperazone also good but not given
alone)
Cefoperazone (IV)
G3
Pharmoco-kinetics
Spectrum
Adverse
Reactions
Clinical
Uses
More
active against
manyMTT
enteric
gram
- aerobes;
Cefoperazone
-have
excreted
in bile
(OK
for
Cefoperazone
side
chain
and
may
Cefoperazone
Pseudomonas
infection
that is
DOC
for
E.
coli,
Indole
positive
proteus,
CRF);
poor CNSbleeding
penetration
than
other G3s
have
increased
and
disulfuram-like
not
in the CNS
and pt has renal failure
Providencia,
Serratia
rxn less active against gram + organisms than
Generally
1st generation
Very effective against H. influenzae and N.
gonorrhoeae (including PPNG), NOT effective
against enterococci, listeria, or MRS
Moxalactam disodium (IV)
G3
Pharmoco-kinetics
Adverse
Reactions
Spectrum
Clinical
Uses
More active against
enteric
gram
- may
aerobes;
moxalactam
havemany
MTTPPNG
side chain
and
Ceftriaxone
- -DOC
for
but
does
not
DOC
for E. coli,
Indoleand
positive
proteus,
have
increased
bleeding
disulfuram-like
chlymadia;
PRSP;Serratia
H.
ducreyi and
 cover
Elimination
- primarily
RTS
Providencia,
rxn
Salmonella;
Ampicillin-resistant
H. flu than
Generally
less active
against gram + organisms
meningitis (good1stCSF
penetration); pts in
generation
renal
Veryfailure
effective against H. influenzae and N.
gonorrhoeae (including PPNG),
NOT effective against enterococci, listeria, or MRS
Cefixime (PO)
G3
Spectrum
Adverse
Reactions
Pharmoco-kinetics
Clinical
Uses
More active against many enteric gram - aerobes;
Cefixime
- diarrhea
Cefixime
PPNG
single
dose Serratia
DOC
for E. -coli,
Indolevia
positive
proteus,oral
Providencia,
less active
against gram
+ organisms than
Generally
Elimination
- primarily
RTS
1st generation
Very effective against H. influenzae and N.
gonorrhoeae (including PPNG),
NOT effective against enterococci, listeria, or MRS
• Cefixime - poor activity against staph
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
Cephalosporins with
MTT Side Chain
• G2 Cephalosporins
– Cefamandole
– Cefotetan
– Cefmetazole
• G3 Cephalosporins
– Moxalactam
– Cefoperazone
Cephalosporin activity
against Gram Positives
G1> G2>G3>G4
Cephalosporin activity
against Gram
Negatives/Stability to GN
Blases
G4> G3>G2>G1