med micro chapter 20

Antibiotics

Drugs produced naturally by microorganisms

Antimicrobials

Drugs produced synthetically

Spectrum of antimicrobial activity

Range of microorganisms a drug affects

Narrow-spectrum drugs

Affect only a limited group of microorganism

Broad-spectrum drugs

Affect many Gram+ and Gram– organisms; useful when pathogen unknown but can cause superinfection

Selective toxicity

Ability to harm the microorganism without harming the host

Thrombocytopenic purpura

Drug binds to platelet → hapten complex → immune response → platelet destruction

Why prokaryotes are easier to treat

Their cells differ greatly from human (eukaryotic) cells

Why fungi & protozoa are harder to treat

They are eukaryotic like humans, making selective toxicity difficult

Why viruses are hardest to target

They multiply inside host cells

Paul Ehrlich

Proposed the “magic bullet” concept

Alexander Fleming (1928)

Discovered penicillin from Penicillium notatum

Florey & Chain (1940)

Conducted first penicillin clinical trials

Source of most potent penicillin strain

Penicillium chrysogenum from an Illinois cantaloupe

Therapeutically ideal drug traits

Selective toxicity, low hypersensitivity, rapid penetration and retention in tissues, low resistance development

Penicillins

β-lactam antibiotics (~50 types)

Natural penicillins

Penicillin G and V

Semisynthetic penicillins

Methicillin, ampicillin, amoxicillin, oxacillin

β-lactamases / Penicillinases

Enzymes that destroy penicillins

Extended-spectrum penicillins

Ampicillin, amoxicillin, carbenicillin, azlocillin

Augmentin

Amoxicillin + clavulanic acid (β-lactamase inhibitor)

Carbapenem

Primaxin = Imipenem + cilastatin

Cephalosporins

Penicillin-like drugs grouped into “generations”

Vancomycin

Toxic; last-line defense for MRSA; overuse caused VRE & VRSA

Isoniazid (INH)

Treats tuberculosis; inhibits mycolic acid; used with ethambutol

Aminoglycosides

Change shape of ribosomes; streptomycin/gentamicin/neomycin/tobramycin; risk of hearing & kidney damage

Tetracyclines

Prevent amino acid addition; broad-spectrum; GI issues, liver damage, teeth staining

Chloramphenicol

Prevents peptide bond formation; can cause aplastic anemia

Macrolides

Penicillin alternatives; erythromycin & azithromycin

Streptogramins (Synercid)

Two bacteriostatic agents become bactericidal together; expensive/side effects

Polymyxin B

Targets Pseudomonas; in OTC triple-antibiotic ointments

Antifungals

Amphotericin B, miconazole, ketoconazole; disrupt fungal plasma membranes

Sulfonamides (sulfa drugs)

Treat UTIs; silver sulfadiazine for burns; structural competitor to PABA

TMP-SMZ

Trimethoprim + sulfonamide; synergistic

Antagonism example

Tetracycline + penicillin less effective together

Rifamycins

Inhibit mRNA synthesis; Rifampin colors secretions orange-red

Fluoroquinolones

Inhibit DNA replication; ciprofloxacin/norfloxacin; avoid in children due to cartilage issues

Disk diffusion assay

Tests drug effectiveness using inhibition zones

E-test

Determines minimum inhibitory concentration (MIC)

Broth dilution test

Determines MIC and minimum bactericidal concentration (MBC)

Prudent antibiotic use

Preserve drug effectiveness by preventing misuse

New development strategies

New drug sources, new molecular targets, virulence-factor drugs, phage therapy, scientific discovery