Cephalosporins

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

2. Cephalothin (IV) 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 Special Properties Can be used with caution in pts allergic to PCNs but not those with immediate hypersensitivity rxn 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 (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 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 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

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 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 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. 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, 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 Special Properties Can be used with caution in pts allergic to PCNs but not those with immediate hypersensitivity rxn 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 NOTeffective 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 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 NOTeffective against enterococci, listeria, or MRS 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 ·     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) prototypeG2 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 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 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 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 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 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) 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 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     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

21. Moxalactam disodium (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 ·     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

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 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 withMTT 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