Cephalosporins First Generation Cephalosporins Second Generation Cephalosporins Third Generation...
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Transcript of Cephalosporins First Generation Cephalosporins Second Generation Cephalosporins Third Generation...
Cephalosporins
• First Generation Cephalosporins
• Second Generation Cephalosporins
• Third Generation Cephalosporins
• Fourth Generation Cephalosporins
Cephalothin (IV) G1
SpectrumSimilar to ampicillin except effect against:
• KlebsiellaKlebsiella 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
KlebsiellaKlebsiella infections (80%) - not DOC
Alternative for penicillinase-resistant staph.
infection (NOT MRS or PRSP)
Staph. infections in most PCN allergic pts
NOT FORNOT FOR - MRS, PRSP, enterococcal/listeria/B. frag, or CNS infections or meningitis
Cefazolin (IV) G1
SpectrumSimilar to ampicillin except effect against:
• KlebsiellaKlebsiella 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
Cefazolin - elim. GF > RTS; longer t/2
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
KlebsiellaKlebsiella infections (80%) - not DOC
Alternative for penicillinase-resistant staph.
infection (NOT MRS or PRSP)
Staph. infections in most PCN allergic pts
NOT FORNOT FOR - MRS, PRSP, enterococcal/listeria/B. frag, or CNS infections or meningitis
Cephalexin (PO) most used oral (Keflex)
G1Spectrum
Similar to ampicillin except effect against:• KlebsiellaKlebsiella 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
KlebsiellaKlebsiella infections (80%) - not DOC
Alternative for penicillinase-resistant staph.
infection (NOT MRS or PRSP)
Staph. infections in most PCN allergic pts
NOT FORNOT FOR - MRS, PRSP, enterococcal/listeria/B. frag, or CNS infections or meningitis
Cefadroxil (PO) G1
SpectrumSimilar to ampicillin except effect against:
• KlebsiellaKlebsiella 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
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
KlebsiellaKlebsiella infections (80%) - not DOC
Alternative for penicillinase-resistant staph.
infection (NOT MRS or PRSP)
Staph. infections in most PCN allergic pts
NOT FORNOT FOR - MRS, PRSP, enterococcal/listeria/B. frag, or CNS infections or meningitis
Cefadroxil (PO) G1
SpectrumSimilar to ampicillin except effect against:
• KlebsiellaKlebsiella 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
KlebsiellaKlebsiella infections (80%) - not DOC
Alternative for penicillinase-resistant staph.
infection (NOT MRS or PRSP)
Staph. infections in most PCN allergic pts
NOT FORNOT FOR - MRS, PRSP, enterococcal/listeria/B. frag, or CNS infections or meningitis
Second Generation Cephalosporins
(Cefamandole-Like)
Note some have MTT side chains
Cefamandole (IV) prototype
G2
SpectrumSimilar 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
Special Properties
Can be used with caution in pts allergic to
PCNs but not those with immediate
hypersensitivity rxn
Clinical Uses
Above the diaphragm drugs
"Day Care Drugs"
Primarily for ampicillin-resistant
H.influenzae infections (sinusitis, otitis
media, URIs,
Cefuroxime (IV)Cefuroxime Axetil (PO)
G2Spectrum
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 meningitisCSF 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
SpectrumSimilar to first generation cephalosporins plus:
Two to 8X greater activity against H. influenzae
(including ampicillin resistant)
More active against KlebsiellaKlebsiella, E. coli, and indole +
proteus
NOT effective against enterococci, listeria, or MRS
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
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)
Cefaclor (PO) oral equiv. of cefamandole
G2
Cefprozil and Loracarbef (PO) G2
SpectrumSimilar to first generation cephalosporins plus:Two to 8X greater activity against H. influenzae(including ampicillin resistant)More active against Klebsiella, E. coli, and indole +proteusNOT effective against enterococci, listeria, or MRSCefprozil - may be more stable against betalactamase producing strains of staph, H. flu, andMorazella
Pharmoco-kinetics
Inadequate CSF penetration for meningitis
Elimination - primarily RTS
Cefprozil and Loracarbef - better PO absorption
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
Above the diaphragm drugs
"Day Care Drugs"
Primarily for ampicillin-resistant H. influenzae infections (sinusitis, otitis
media, URIs, cefuroxime for pneumonias)
Second Generation Cephalosporins
(Cefoxitin-Like)
Note some have MTT side chains
SpectrumSimilar to first generation cephalosporins but withenhanced activity against:
Bacteroides fragilisOther bacteroides species -anaerobes (cefoxitin >cefotetan)N. Gonorrhoeae (including PPNG)Gram - enteric aerobic bacilli (Klebsiella, E. coli,some serratia) cefotetan > cefoxitinNOT 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)
Cefoxitin (IV) prototype
G2
Cefotetan (IV) G2
SpectrumSimilar to first generation cephalosporins but with enhancedactivity against:Bacteroides fragilisOther bacteroides species -anaerobes - (cefoxitin > cefotetan)N. Gonorrhoeae (including PPNG)Gram - enteric aerobic bacilli (Klebsiella, E. coli, some serratia) –cefotetan > cefoxitinNOT effective against enterococci, listeria, or MRSLess active against H. flu and enterobacter than cefamandole
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
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
Clinical Uses
Below the diaphragm drugs
PPNG
Tx of abdominal and gynecologic infections
where B. fragilisB. fragilis is suspected
Urinary tract, lower respiratory tract, soft
tissue infections (cefotetan)
Cefmetazole (IV) G2
SpectrumSimilar to first generation cephalosporins but with enhancedactivity against:Bacteroides fragilisOther bacteroides species -anaerobes - (cefoxitin > cefotetan)N. Gonorrhoeae (including PPNG)Gram - enteric aerobic bacilli (Klebsiella, E. coli, some serratia) –cefotetan > cefoxitinNOT effective against enterococci, listeria, or MRSLess 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
Cefmetazole - 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
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) infections or 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
SpectrumMore active against many enteric gram - aerobes;DOC for E. coli, Indole positive proteus,Providencia, SerratiaGenerally less active against gram + organisms than1st generationVery effective against H. influenzae and N.gonorrhoeae (including PPNG), NOT effectiveagainst 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
Cefotaxime sodium (IV)&
Ceftizoxime sodium (IV G3
SpectrumMore active against many enteric gram - aerobes; DOC for E.
coli, Indolepositive proteus, Providencia, SerratiaGenerally less active against gram + organisms than 1st
generationVery effective against H. influenzae and N. gonorrhoeae
(includingPPNG)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
Ceftazidime pentahydrate (IV) G3
SpectrumMore active against many enteric gram - aerobes;DOC for E. coli, Indole positive proteus,Providencia, SerratiaGenerally less active against gram + organisms than G1Very effective against H. influenzae and N.gonorrhoeae (including PPNG), NOT effectiveagainst enterococci, listeria, or MRS
Ceftazidime - most active cephalosporin against P.aeruginosa (cefoperazone also good but not given
alone)
Pharmoco-kinetics
Same as 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
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
Cefoperazone (IV) G3
SpectrumMore 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
Cefoperazone - excreted in bile (OK for CRF); poor CNS penetration than other G3s
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
Moxalactam disodium (IV) G3
SpectrumMore 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
Elimination - primarily RTS
Adverse Reactions
moxalactam - have MTT side chain and may have increased bleeding and disulfuram-like rxn
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
Cefixime (PO) G3
SpectrumMore 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
Pharmoco-kinetics
Elimination - primarily RTS
Adverse Reactions
Cefixime - diarrhea Clinical Uses
Cefixime - PPNG via single oral dose
Cefepime (IV) G4
Parenteral only
“Broadest” Gram neg and Gram Pos
Spectrum of cephalosporinsLow affinity for gram Neg blases, does
not induce blases
100% renal excretion
T1/2 – 2.2 hrs
Cephalosporins withMTT 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