Chapter 20: Antimicrobial Drugs

most common source of antibiotics

streptomyces

why are eukaryotic infections harder to treat?

eukaryote microbes are similar to human cells; low selectivity, high toxicity

bactericidal

kill microbes directly

bacteriostatic

prevent microbes from growing

synergistic drug interactions

more effective in combination (penicillin damages cell wall, helps streptomycin enter cell)

antagonistic drug interactions

one drug stops the other; tetracyline stops bacterial growth, preventing penicillin from being effective

major action modes of antimicrobial drugs

• inhibition of cell wall synthesis

• inhibition of protein synthesis

• inhibition of nucleic acid replication

• injury to plasma membrane

• inhibition of essential metabolite synthesis

oxacillin

narrow spectrum, only gram positives, but resistant to penicillinase

ampicillin

extended spectrum, many gram negatives

penicillinase inhibited by

clavulanic acid

cephalosporins

inhibition of cell wall synthesis; 4 generations

first gen cephalosporins

narrow spectrum; act against gram positive bacteria

second gen cephalosporins

extended spectrum includes gram negative bacteria

third gen cephalosporins

includes pseudomonads; injected

fourth gen cephalosporins

oral

polypeptide antibiotics

bacitracin, vancomycin

bacitracin

inhibition of cell wall synthesis; topical application; against gram-positives

vancomycin

inhibition of cell wall synthesis; glycopeptide (made from Streptomyces orientalis); important last line against MRSA

antimycobacterial antibiotics

isoniazid (INH); ethambutol

isoniazid (INH)

inhibition of cell wall synthesis; inhibits mycolic acid synthesis

ethambutol

inhibition of cell wall synthesis; inhibits incorporation of mycolic acid

streptomycin

inhibition of protein synthesis; changes shape of 30S portion, causing code on mRNA to be read incorrectly

tetracyclines

inhibition of protein synthesis; interfere w/ attachment of tRNA to mRNA-ribosome complex

chloramphenicol

inhibition of protein synthesis; binds to 50S portion & inhibits formation of peptide bond

lipopeptides

injury to plasma membrane; membrane depolarization (destroys proton gradient); daptomycin used for MRSA

polymyxin B

injury to plasma membrane; topical; combined w/ bacitracin & neomycin in OTC prep

rifamycin

• inhibitors of nucleic acid

• mycobacterium

• inhibits RNA synthesis

• antituberculosis & leprosy

• penetrates tissues & abscesses

• side effect: orange-red body fluids

quinolones & fluoroquinoloes (FQ)

• inhibitors of nucleic acid

• nalidixic acid

• ciprofloxacin (next gen, broader spectrum)

• inhibit DNA gyrase

• uti

sulfonamides (sulfa drugs)

inhibit synthesis of essential metabolites; competitive inhibitors; inhibit folic acid synthesis, broad spectrum

polyenes

disruption of cell membranes; amphotericin B

azoles & allylamines

inhibition of ergosterol synthesis; imidazoles like clotrimazol

echinocandins

inhibit cell wall synthesis; inhibit synthesis of beta glucan

antiviral treatments

• inhibitors of entry/fusion, nucleic acid synthesis, genome integration (retroviruses), assembly & exit

• interferon

early inhibitors of antiviral drugs

amantadine (influenza)

fusion inhibitors of antiviral drugs

• prevent membrane-envelope fusion and/or budding

• zanamivir, tamiflu: neuraminidase inhibitors (influenza)

• enfuvirtide (HIV)

acyclovir

structurally resembles nucleoside deoxyguanosine; interferes with viral nucleic acid synthesis; prevents virus from replicating

interferons (antiviral drugs)

prevents spread of viruses to new cells (alpha interferon: viral hepatitis)

imiquimod

promotes interferon production

antibiotic misuse

selects for resistance mutants

• outdated or weakened antibiotics

• antibiotics for common cold & other inappropriate conditions

• antibiotics in animal feed

• failing to complete the prescribed regimen

• using someone else’s leftover prescription

antibiotic overuse

selects for multidrug resistant bacteria

• hand soap, toothpaste, deodorant, surgical scrubs, etc

bacterial resistance to antibiotics

• blocking entry

• inactivation by enzyme

• alteration of target molecule

• efflux of antibiotic

phage therapy

use phage to kill bacteria