Catapult Pharmacology

Catapult Pharmacology

Cephalosporins

Cephalosporins are another grouping of beta-lactam antibiotics. Cephalosporins work by inhibiting cell wall synthesis through various mechanisms including inhibition of transpeptidation, weakening cell wall structure by binding to penicillin binding proteins, and promotion of autolysin activity.

Cephalosporins are separated into generations. The first generation of cephalosporins has activity against gram positives including non-MRSA staphylococcus species and streptococcus species.  First generation cephalosporins also have activity against some gram negative rods including klebsiella, e. coli, and proteus.  Later generations, 2nd through 5th, generally add more more activity against gram negatives.  

Adverse effects include diarrhea, hypersensitivity reactions, and more rarely, nephritis.

Class Drugs

First Generation

  • Cefazolin

  • Cefadroxil

  • Cephalexin

Second Generation

  • Cefaclor

  • Cefotetan

  • Cefoxitin

  • Cefprozil

  • Cefuroxime

Third Generation

  • Cefdinir

  • Cefditoren

  • Cefixime

  • Cefotaxime

  • Cefpodoxime

  • Ceftazidime

  • Ceftibuten

  • Ceftriaxone

Fourth Generation

  • Cefepime

Fifth Generation

  • Ceftaroline

Class Mechanism of Action

Three mechanisms of action:

  • Cell wall inhibitor

Inhibits transpeptidation, which decreases cell wall strength/integrity

  • Only effective against rapidly growing bacteria

  • Inactivation of penicillin binding proteins (PBPs)

Bacteria have proteins on the surface that bind to cephalosporin, resulting in morphologic changes to the bacteria and weakening the structure of the cell wall

  • Certain bacteria can develop resistance to cephalosporins by altering their surface proteins to decrease interaction of drug with bacteria

  • Autolysins

Many bacteria naturally produce autolysins that usually assist in performing "maintenance" function for the bacteria by degrading the cell wall.  If new cell wall is not being produced in the presence of a cephalosporin, the autolysins aid in destruction of the cell wall.

Class Applications

Treatment of gram negative and gram positive infections

First Generation Cephalosporin Coverage

  • Gram (+) Cocci:

MSSA (methicillin sensitive staph. aureus)

  • Staph. epidermidis

  • Strep. pneumoniae

  • Strep. pyogenes

  • Gram (-) rods

E. coli

  • Klebsiella pneumoniae

  • Proteus mirabilis

Second Generation Cephalosporin Coverage

Treatment of gram negative and gram positive infections - extended gram negative coverage when comparing to 1st gen

  • Gram (+) Cocci:

MSSA (methicillin sensitive staph. aureus)

  • Strep. pneumoniae

  • Strep. pyogenes

  • Anaerobic strep

  • Gram (-) Rods

E. coli

  • Klebsiella pneumoniae

  • Proteus mirabilis

  • H. influenzae

  • Enterobacter

  • Gram (-) Cocci

N. gonorrhoeae

Third Generation Cephalosporin Coverage

Treatment of gram negative and gram positive infections - extended gram negative coverage when comparing to 2nd generation

  • Gram (+) Cocci:

Relatively poor coverage

  • Strep. pneumoniae

  • Strep. pyogenes

  • Anaerobic strep

  • Gram (-) Rods

E. coli

  • Klebsiella pneumoniae

  • Proteus mirabilis

  • H. influenzae

  • Enterobacter

  • Gram (-) Cocci

N. gonorrhoeae

Fourth Generation Cephalosporin Coverage

Treatment of gram negative and gram positive infections - extended gram negative coverage including pseudomonas when comparing to 3rd generation

  • Gram (+) Cocci:

MSSA

  • Strep. pneumoniae

  • Strep. pyogenes

  • Anaerobic strep

  • Gram (-) Rods

E. coli

  • Klebsiella pneumoniae

  • Proteus mirabilis

  • H. influenzae

  • Enterobacter

  • P. aeruginosa

Fifth Generation Cephalosporin Coverage

Treatment of gram negative and gram positive infections: Includes MRSA coverage

  • Gram (+) Cocci:

MRSA

  • Strep. pneumoniae

  • Strep. pyogenes

  • Anaerobic strep

  • Gram (-) Rods

E. coli

  • Klebsiella pneumoniae

  • Proteus mirabilis

  • H. influenzae

  • Enterobacter

  • Serratia marcescens

Class Adverse Effects

Resistance

  • Beta-lactamase

Enzyme produced by some bacteria that hydrolyzes the beta-lactam ring, which renders the cephalosporin ineffective

Gram positive organisms secrete beta-lactamase

  • Gram negative organisms have beta-lactamase in the periplasmic space

  • Cephalosporins are less sensitive to beta-lactamase than penicillins

  • Decrease penetration of drug

Some organisms' cell membrane is resistant to penetration of the cephalosporins, so the cephalosporin cannot bind to PBPs.

  • Efflux pumps

Pumps decrease intracellular concentration of drug

  • Modified PBPs

Alterations of the binding proteins structure, limits ability of cephalosporins to bind to the BPs.

Hypersensitivity

  • Rashes, angioedema, anaphylaxis

Diarrhea

  • Alteration of normal gut flora causes diarrhea

  • Clostridium difficile can also cause a severe form of diarrhea with use of antibiotics

Neurotoxicity

Cytopenia in long term therapy

Drug Table

First Generation Cephalosporins

Drug Name Application Comments Image
Cefazolin "UNICEF Logo" "Asshole Lint"
Cefadroxil "UNICEF Logo" "Ad" "Rocks"
Cephalexin "UNICEF Logo" "Alex"

Second Generation Cephalosporins

Drug Name Application Comments Image
Cefaclor "UNICEF Logo" "Clorox"
Cefotetan "UNICEF Logo" "Tetons"
Cefoxitin "UNICEF Logo" "Ox" "Tin"
Cefprozil "UNICEF Logo" "Pro"
Cefuroxime "UNICEF Logo" "Ox" "Lime"

Third Generation Cephalosporins

Drug Name Application Comments Image
Cefdinir "UNICEF Logo" "Dinner"
Cefditoren "UNICEF Logo" "Dice" "Toe" "Wren"
Cefixime "UNICEF Logo" "Lime"
Cefotaxime "UNICEF Logo" "Tax" "Lime"
Cefpodoxime "UNICEF Logo" "Pod" "Ox" "Lime"
Ceftazidime Pseudomonas aeruginosa "UNICEF Logo" "Tasmanian Devil" "Lime"
Ceftibuten "UNICEF Logo" "Butte"
Ceftriaxone "UNICEF Logo" "Tri Headed Axe"

Fourth Generation Cephalosporins

Drug Name Application Comments Image
Cefepime "UNICEF Logo" "Prime"

Fifth Generation Cephalosporins

Drug Name Application Comments Image
Ceftaroline "UNICEF Logo" "Tar" "Line"
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