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