Jan Larmouth, MS, CIC

Director, Infection Prevention and IV Resource

SNHMC

Biochemistry is not scary.

We all live in a 3 dimensional world.

Life happens at the molecular level.

Wall, plasmid, DNA

Gram positive cocci Gram negative bacilli (rods)

Make things happen!

Different classes have different chemical structures

Penicillin (methicillin)

Glycopeptides (vancomycin)

Beta-lactams (cephalosporins)

Disrupt an essential process that is necessary for cell life: ◦ Cell wall synthesis

◦ DNA replication

Organisms change their structure and produce chemicals that protect them from the ABX

Gram positive cocci

Clonal organism – not many spontaneous mutations

Normal skin flora – 30% of population

Methicillin worked well until around 1960s

TP – transpeptidase

-lactam ring binds to TP (penicillin binding protein)

No cross links are formed = cell ruptures

MRSA are genetically slightly different - acquired the mec A gene - PBP = different

Methicillin doesn’t fit anymore

Gram positive cocci

Found in the gut – “fecal patina”

Some species – non-pathogenic and intrinsically resistant to many ABX

E. faecium/E. faecalis have acquired resistance to vancomycin

3 different mechanisms of action:

◦ Inhibits cross linking in the cell wall

◦ Interferes with RNA production

◦ Damages the plasma membrane

Nomenclature differs: ◦ not the bug but the enzyme

◦ Not one genus/species

Many species: E. coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, etc.

Most common: E. coli; K. pneumoniae

First Generation: cefazolin, cefalexin, cefadroxil

Second Generation: cefamandole, cefoxitin, cefaclor, cefuroxime, loracarbef, cefotetan

Third generation: cefotaxime, cefpodoxime, ceftizoxime, ceftriaxone, ceftazidime, cefoperazone

Fourth generation: cefepime, cefozopran, cefpirome, cefquinome

Activity is different

Generation1: ◦ Staph and Enterobacteriaceae

Generations 2, 3 and 4: ◦ Structure able to resist beta-lactamases – broader

spectrum