Lecture 9: Drugs that target the Cell Membrane and Sulfonamides

Drugs that target Cell Membrane

Daptomycin- I.V.

Polymyxin B- Topical

Colistin- Topical

Daptomycin

binds bacterial membranes to cause a rapid depolarization of membrane potential → bacterial cell death

bactericidal

aerobic and anaerobic G+

IV

empiric therapy in patients with serious G+ infections

Polymyxin B and Colistin

Polypeptide Antibiotics

bind to G- bacterial cell membrane phospholipids (lipid A of endotoxin)

bactericidal against most G- bacilli, with the exception of Proteus and Neisseria species

No effect in G+ (lack lipid A)

Topical in combination with neomycin and bacitracin

Sulfonamides Drugs

Sulfamethoxazole + Trimethoprim, Co-trimoxazole, TMP-SMX

Sulfonamides Mechanism of Action

sulfamethoxazole competes with PABA in the synthesis of bacterial folic acid

trimethoprim prevents reduction of dihydrofolate to tetrahydrofolate → avoid use in first trimester of pregnancy

Sulfamethoxazole + Trimethoprim Resistance

Increased production of PABA

Alternative metabolic pathway for synthesis of essential metabolite (plasmid)

Active efflux or decreased permeability

Sulfamethoxazole + Trimethoprim Spectrum

sulfa drugs inhibit both G+ and G- organisms (poor anaerobic activity)

generally bacteriostatic

in the urinary tract, bactericidal

UTI infections (first attack)- Co-trimoxazole is DOC

avoid use near term or in nursing premature or jaundiced infants

Sulfamethoxazole + Trimethoprim Adverse effects

aplastic anemia (G6PD deficiency) – high risk near term

Hypersensitivity

Stevens Johnson syndrome

Kernicterus

Photosensitivity

sulfa drugs should not be given to infants less than two months of age

avoid weeks 36-40 gestation