Bind to Penicillin Binding Proteins
 
Resistant to Penicillinase, but not other classes of β-lactamases (e.g. Extendend Spectrum Beta-Lacatamases or ESBLs)
 
Renal excretion
 
Side Effects
  • Hypersensitivity reactions (Cross-hypersensitivity with penicillins 1-3%)
  • Superinfections: Enterococci, Enterobacter and Candida

THE CEPHALOSPORIN FAMILY

THE CEPHALOSPORINS
CATEGORY PARENTERAL AGENTS ORAL AGENTS
First Generation Cefazolin Cephalexin
Second Generation Cefotetan, Cefoxitin, Cefuroxime Cefuroxime axetil, Cefaclor
Third Generation Cefotaxime, Ceftazidime, Ceftriaxone Cefixime, Cefdinir
Fourth Generation Cefepime  
Fifth Generation Ceftaroline  

Generational Coverage

Generation Gram Negatives Gram Positives β-Lactamase Stability
1st + +++ +/-
2nd ++ ++ +
3rd +++ + ++
4th +++ ++ +++
5th +++ +++ ++++

Note: There are generational shifts from gram-positive to gram-negative coverage & resistance to β-lactamases.

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1st Gen Cephalosporin Coverage & Indications

  • Cefazolin - iv
  • Cephalexin - po

Spectrum

  • Gram Positive Cocci, including MSSA (Does NOT cover Enterococcus)
  • Gram Negative Rods
  • No CNS penetration

Coverage

  • MSSA
  • Streptococci Grp A,B,C,G
  • Strep viridans
  • S. pneumoniae
  • H. influenzae
  • E. coli
  • Klebsiella pneumoniae
  • Proteus mirabilis

Common Uses

  • Skin & Soft Tissue Infections (SSTI)
  • Upper Respiratory Tract Infections
  • Surgical Prophylaxis

Cephalexin

  • Trade Names: generic, Keflex ®
  • Drug Class: Cephalosporin 1st generation (oral)
  • Mechanism of Action:
    • Similar to penicillins. Cephalosporins are generally resistant to penicillinase.
  • Indications:
  • Side Effects:
    • hypersensitivity
  • Pharmacokinetics:
    • orally effective, renal clearance
  •  

Cefazolin

  • Trade Names: generic, Kefzol, Ancef ®
  • Drug Class: Cephalosporin 1st generation (parenteral: iv or im)
  • Indications:
  • Pharmacokinetics:
    • parenteral administration (injection) only; elimination via the kidney.
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2nd Gen Cephalosporin Coverage & Indications

  • Cefuroxime - iv or po
  • Cefaclor - po
  • Cefoxitin - iv
  • Cefotetan - iv (MMT)
    • MMT = methyl-thio-tetrazole (can cause disuliram-like reaction)
Half life = 1hr (except Cefotetan = 4 hrs)
 Coverage
Same as 1st Generation Plus:
  • β-lactamase positive H. influenzae
  • Moraxella catarrhalis
  • Neisseria meningitidis
  • E. coli
  • Klebsiella pneumoniae
  • Proteus
  • Oral anaerobes
  • Cefoxitin & Cefotetan cover B. fragilis

Holes in Coverage

  • No CNS Penetration
  • Cefuroxime does not have good coverage of gut anaerobes

Common Uses

  • Community Acquired Pneumonia
  • Bronchitis, Sinusitis, Otitis
  • Skin & Soft Tissue Infections (SSTI)
  • MSSA
  • Abdominal Surgical Prophylaxis
  • Cefoxitin or Cefotetan can be used as monotherapy of mild intra-abdominal & pelvic infections
    • Coverage includes many gut anaerobes (e.g. B. fragilis)
  • Cefuroxime
    • Covers pneumococcus & H. influenzae
    • Community Acquired Pneumonia, Sinusitis & Otitis
    • Does NOT cover gut anaerobe 

Cefaclor

  • Trade Names: generic, Ceclor ®
  • Drug Class: Cephalosporin 2nd generation (oral)
  • Indications:
  • Pharmacokinetics:
    • oral absorption, renal clearance
       

Cefotetan

  • Trade Names: generic
  • Drug Class: Cephalosporin 2nd generation (parenteral)
  • Indications:
  • Pharmacokinetics:
    • parenteral absorption, renal clearance
  • Major drug interactions:
    • The methylthiotetrazole ring of some cephalosporins (cefamandole, cefotetan, cefmetazole, and cefoperazone) may cause severe disulfiram-like reactions; so alcohol and medications containing alcohol should be avoided.
       

Cefoxitin

  • Trade Names: Mefoxin ®
  • Drug Class: Cephalosporin 2nd generation (parenteral)
  • Mechanism of Action:
    • Similar to penicillin
    • Increased activity against Gram negative bacilli and greater stability against beta-lactamase inactivation
  • Indications:
  • Pharmacokinetics:
    • parenteral, injection, renal clearance
  •  
 

Cefuroxime

  • Trade Name: Cefuroxime, Cefuroxime axetil (Ceftin ®)
  • Drug Class: Cephalosporin 2nd generation (oral or parenteral)
  • Indications:
  • Pharmacokinetics:
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3rd Gen Cephalosporin Coverage & Indications

  • 3rd Generation:
    • Cefotaxime - iv
    • Ceftazidime - iv
    • Ceftriaxone - iv
    • Cefixime - po
    • Cefdinir - po
  • Half life = 2hrs (except Ceftriaxone = 8 hrs)
  • Ceftriaxone must NOT be administered with calcium containing solutions. Potentially fatal calcium precipitates can form in the lungs & kidney.

3rd Generation Coverage

Same as 1st Generation Plus:
  • Expanded gram-negative coverage
  • Oral anaerobes
  • S. aureus (OSSA)
  • Strep pneumoniae
  • Strep Grp A,B,C,G
  • Strep viridans
  • Gram negative rods
  • N. gonorrhea
  • All cover B. fragilis EXCEPT cefotaxime & ceftazidime
  • P. aeruginosa - ceftazidine only

Holes in 3rd Generation Coverage

  • Poor gram-positive coverage
  • E. faecium
  • MRSA
  • All cover OSSA EXCEPT ceftazidime
  • Legionella / atypicals
  • Listeria
  • Acinetobacter
  • Not all cover Pseudomonas

3rd Generation Common Uses

  • Community acquired pneumonia
  • Bacterial MENINGITIS (except Listeria) (3rd & 4th Gen cross the BBB to enter the CSF)
  • UTIs (3rd & 4th Gen penetrate into tissues reasonably well)
  • Anogenital gonorrhea: ceftriaxone or cefixime
  • Lyme disease
  • Viridans strep endocarditis
  • Intra-Abdominal & Pelvic Infections: ceftriaxone + metronidazole or clindamycin
  • Hospital Acquired Pneumonia: ceftazidime only

Cefotaxime

  • Trade Name: Claforan ®
  • Drug Class: Cephalosporin 3rd generation (parenteral)
  • Indications:
  • Pharmacokinetics:
    • parenteral administration
    • renal clearance
       

Ceftriaxone

  • Trade Name: Rocephin ®
  • Drug Class: Cephalosporin 3rd generation (parenteral)
  • Indications:
    • A drug of choice for treatment of bacterial meningitis
    • Treatment of Pyelonephritis (UTIs)
    • Uncomplicated gonorrhea (cervical/urethral and rectal) caused by Neisseria gonorrhoeae
    • See 3rd Generation Coverage & Uses
  • Pharmacokinetics:
    • Longer half-life (7-8 hr), parenteral administration
    • excreted via the bile tract, no dosage adjustment required in renal insufficiency
       

Cefixime

  • Trade Names: Suprax ®
  • Drug Class: Cephalosporin 3rd generation (oral)
  • Indications:
  • Pharmacokinetics:
    • oral administration  

Ceftazidime

  • Trade Names: generic, Fortaz, Tazdime, Ceptaz ®
  • Drug Class: Cephalosporin 3rd generation (parenteral)
  • Indications:
  • Pharmacokinetics:
    • parenteral administration
  •  
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4th Generation - Adds Pseudomonas Coverage

 
  • Cefepime
    • Good gram-positive & gram-negative coverage
    • Anti-Pseudomonal (including ceftazidime resistant isolates)
    • Penetrates CSF
    • Limited anaerobic coverage
 

Cefepime

  • Trade Name: Maxipime ®
  • Drug Class: Cephalosporin 4th generation (parenteral)
  • Indications:
    • Good gram-positive & gram-negative coverage
    • Anti-Pseudomonal (including ceftazidime resistant isolates)
    • Penetrates CSF
    • Limited anaerobic coverage
  • Pharmacokinetics:
    • parenteral administration
    • renal clearance
  •  
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5th Generation - Very Broad Spectrum

 

Ceftaroline

Fifth Generation Cephalosporin
  • Ceftaroline fosamil is newly FDA approved prodrug formulation of ceftaroline
  • Effective against gram-positive bacteria, and retains the activity of later-generation cephalosporins with broad-spectrum activity against gram-negative bacteria
  • it has increased affinity for PBP2a that mediates methicillin resistance in Staphylococci
  • indicated for treating:
    • ORSA
    • skin & soft tissue infections
    • community-acquired pneumonia