Antibacterial Drugs that Inhibit Cell Wall Synthesis

penicillin G

penicillin V

representative natural penicillins

methicillin

ampicillin

amoxicillin

representative semisynthetic penicillins

cephalothin

representative natural cephalosporin

cefaclor

cephalexin

monobactam

representative semisynthetic cephalosporin

Penicillium (penicillins) and Cephalosporium (cephalosporins, e.g., cephalothin)

Large number of natural and semisynthetic derivatives from …bind to, and deactivate, the enzyme that cross links the NAM subunits of peptidoglycan

monobactams

single ring

beta- lactams

two rings

natural drugs

have limited action against most G- bacteria because they do not readily cross the outer membrane;

semisynthetics

have broader spectra of action

monobactams

have a limited spectrum of action, affecting only aerobic, G- bacteria

oral

Route of Administration: Pencillin V, a few cephalosporins (e.g., cephalexin), and monobactams

IM or IV

penicillin G, and many semisynthetics (e.g., methicilin, ampicillin, carbenicilin, cephalothin)

beta-lactams

allergic reactions are seen in some adults

monobactams

least allergenic

G- bacteria

change their outer membrane structure to prevent entrance of the drug

G- bacteria

modify the enzyme so that the drug no longer binds to it

G- bacteria

synthesize beta-lactamases that cleave the functional lactam ring of the drug;

R-plasmids

genes for lactamases are often carried on

vancomycin

produced by Streptomyces orientalis;

vancomycin

directly interferes with the formation of alanine-alanine crossbridges between NAM subunits

IV

route of administration for vancomycin

vancomycin

Adverse Effects: Damage to ears and kidneys, allergic reactions

G- bacteria (vancomycin)

are naturally resistant because the drug is too large to pass through the outer membrane

G+ bacteria (vancomycin)

(e.g, Ersipelothrix, Lactobacilus) are naturally resistant because they do not form alanine-alanine bonds between NAM subunits

cycloserine

Analog of alanine that interferes with the formation of alanine-alanine crossbridges between NAM subunits

cycloserine

Spectrum of Action: Some G+ bacteria, mycobacteria

oral

route of administration for cycloserine

cycloserine

Adverse Effects: Toxic to nervous system, producing depression, aggression, confusion, and headache

bacitracin

Isolated from Bacillus licheniformis growing on a patient named Tracy

bacitracin

interference with the movement of peptidoglycan precursors through the bacterial cell membrane to the cell wall

bacitracin

inhibition of RNA transcription

bacitracin

damage to the bacterial cytoplasmic membrane

bacitracin

The latter two modes of action have not been proven definitely

bacitracin

Spectrum of Action: G+ bacteria

topical

route of administration for bacitracin

bacitracin

Adverse Effects: Toxic to kidneys

bacitracin

Resistance most often involves changes in bacterial cell membranes that prevent it from entering the cell

isoniazid

Blocks the gene for an enzyme that forms mycolic acid

isoniazid

analog of the vitamins nicotinamide and pyridoxine

isoniazid and ethambutol

Spectrum of Action: Mycobacteria, including M. tuberculosis and M. leprae

oral

route of administration for isoniazid

isoniazid

Adverse Effects: Occasionally toxic to liver

isoniazid and ethambutol

Resistance is due to random mutations of bacterial chromosomes that result in reduced drug uptake or alteration of target sites

ethambutol

Prevents the formation of mycolic acid;

ethambutol

used in combination with other antimyco-bacterial drugs

oral

route of administration for ethambutol

ethambutol

adverse effects: none