Antimicrobial Chemotherapy + Drug Resistance

lysozyme

• enzyme that breaks down bacterial cell walls

• found in mucosal secretions (tears, saliva, mucous)

selective toxicity

ability of drug to kill/inhibit pathogen while damaging host as little as possible

therapeutic dose

drug level required for clinical treatment

toxic dose

drug level at which drug becomes too toxic for patient (produces side effects)

therapeutic index

ratio of toxic dose to therapeutic dose

side effects

undesirable effects of drugs on host cells

narrow-spectrum drugs

attack only a few different pathogens

broad-spectrum drugs

attack many different pathogens

cidal agent

kills microbes

static agent

inhibits growth of microbes

minimal inhibitory concentration (MIC)

lowest concentration of a drug that prevents growth of particular organism

minimal lethal concentration

lowest concentration of a drug that kills the pathogen

dilution susceptibility test

• antimicrobial agent is diluted in different concentrations of broth to determine the minimal inhibitory or lethal concentration

• Mueller-Hinton broth usually used

Kirby-Bauer method

fresh bacteria inoculated off of Mueller-Hinton plate → dried for 5 min → antibiotic disks are added

E-test

• strips with a gradient of antibiotic

• intersection of elliptical zone of inhibition with strip indicates minimal inhibitory concentration (MIC)

• convenient for use with anaerobic pathogens

penicillin

antibiotic that is derivates of 6-aminopenicillanic acid

penicillin

• has similar structure to D-Ala - D-Ala in pentapeptide chains of peptidoglycan

• blocks the enzyme transpeptidase which links the peptide chains (looks for D-Ala-D-Ala to cleave)

penicillin binding protein (PBP)

• transpeptidase that penicillin blocks

• rather than cleaving the D-ala-D-ala, it opens the β-lactam ring of pencillin because of similar structure

beta-lactam antibiotics

antibiotics with a β-lactam ring that tricks transpeptidase into thinking it’s D-Ala-D-Ala (prevents peptidoglycan synthesis)

beta-lactamases

enzyme produced by some bacteria that degrades β-lactam antibiotics

clavulanic acid

inhibitor of the enzyme β-lactamase in bacteria which degrades β-lactam antibiotics

cephalosporins

β-lactam antibiotic that has 4 broad generations

avibactam

non-β-lactam β-lactamase inhibitor that isn’t targeted by β-lactamases

vancomycin

• glycopeptide antibiotic that binds to D-ala-D-ala and prevents transpeptidation

• “last resort drug”

vancomycin resistance

bacteria swap D-Ala-D-Ala with D-Ala-D-lactate preventing antibiotic from binding and blocking transpeptidation

protein synthesis inhibitors (antibiotics)

aminoglycosides, tetracyclines, macrolides

aminoglycosides

• protein synthesis inhibitor antibiotics with cyclohexane ring and amino sugars

• binds to 30S ribosomal subunit

aminoglycoside resistance

• acetylation of an amino group

• ATP-dependent adenylation of hydroxyl group

• ATP-dependent phosphorylation of a hydroxyl group

• works because the drug has cyclohexane rings and amino sugars

tetracyclines

• protein synthesis inhibitor antibiotics with common 4 ring structure

• bind to 30S ribosomal subunit just like aminoglycosides

macrolides

• protein synthesis inhibitor antibiotics with lactone rings linked to sugars

• ex) erythromycin binds to 23S rRNA of 50S subunit

metabolic inhibitors

sulfonamides and trimethoprim

sulfanilamide

metabolic inhibitor antibiotic that is an analog of p-aminobenzoic acid (PABA)

trimethoprim

metabolic inhibitor antibiotic that is an analog of dihydrofolic acid

quinolones

nucleic acid synthesis inhibitor antibiotic