Micro 20

• German physician and bacteriologist
• began searching for "magic bullet", a drug that would kill a microbial pathogen w/o harming the human host
• Was looking for sure for syphilis
• The 606 drug compound he tested proved highly effective in txing dx in lab animals
• Drug called Salvarsan

discovered red dye called Protosil which could be used to treat streptococcal infections in animals

chemicals used to treat disease

successfully purified penicillin compound

antimicrobial drugs naturally produced by microorganisms

exhibited by antimicrobial drugs, as they cause greater harm to microbes than to human host

the lowest dose toxic to patient divided by dose typically used for therapy

inhibits bacterial growth

kills bacteria

• resistance due to inherent characteristics of organism
• Ex: If a species lacks a cells wall, will be resistant to penicillin as that's what penicillin attacks

when sensitive organisms develop resistance by spontaneous mutation or horizontal gene transfer

• bactericidal against variety of bacteria
• Includes penicillins, cephalosporins, monobactams and carbapenems
• Competitively inhibit enzymes that catalyze formation of peptide bridges in peptidoglycan synthesis (for cell wall)
• These enzymes bind penicillin, which causes disruption in cell wall synthesis = weakens wall, causing cell to lyse
• *Are bactericidal only against growing bacteria, as these cells continually synthesize peptidoglycan

• Penicillin-binding proteins
• enzymes that are affected by β-lactam drugs

• the vary in their spectrum of activity
• The peptidoglycan of gram+ is exposed on outside, drug can reach target. But Peptidoglycan of gram- is on inside preventing drug from reaching target
• Another difference is PBP's...

an enzyme that breaks the critical β-lactam ring, destroying the activity of the antibiotic

The original penicillins produced naturally by the mold Penicillium chrysogenum

• Narrow-spectrum
• effective against gram+ & a few gram-
• *Bacteria that produce penicillinase are resistant to natural penicillins

• Lab developed in response to penicillinase-producing Staphylococcus aureus strains
• include methicillin and dicloxacillin

• *Unfortunately, some penicillinase-producing bacteria acquired ability to make altered PBP's to which β-lactam no longer bind
• S. aureus strains that can do this are called MRSA

• have modified side chains, giving them broad spectrum of activity
• retain their activity against penicillin sensitive gram+, yet also active against gram -
• Unfortunately, can be inactivated by β-lactamases

*Includes ampicillin and amoxicillin

• Have greater activity against Pseudomonas species - gram- bacteria that are unaffected by many antimicrobial drugs
• Has less activity against gram+ bacteria
• Include Ticarcillin and Piperacillin

• combo of agents
• inhibitor interferes with activity of some types of β-lactamases, thereby protecting the penicillin against enzymatic destruction

Includes Augmentin

• blocks peptidoglycan synthesis by binding to peptide side chain of NAM molecules being assembled to form glycan chains
• weakens cell, causing lysis
• Used to treat C diff infections

inhibits cell wall biosynthesis by interferring with transport of peptidogycan precursors across cytoplamsic membrane

• are bactericidal drugs that irreversibly bind to 30S ribosomal subunit, causing it to distort and malfunction
• blocks initiation of translation and causes misreading of mRNA by ribosomes that have already passed initiation step

reversibly bind to 30S ribosomal subunit, blocking the attachment of tRNA and preventing translation from continuing

related to tetracyclines, same mechanism of action and effect, but wider spectrum of activity

• reversibly bind to 50S ribosomal subunit and prevent the continuation of translation
• Often serve as drug of choice for pt's who are allergic to penicillin

binds 50S ribosomal subunit, preventing peptide bonds from being formed and blocking translation

bind to 50S ribosomal subunit and prevent continuation of translation

bind to 50S ribosomal subunit, interfering with the initiation of translation

• 2 streptogramins are administered together (quinupristin and dalfopristin) called Synercid
• act as synergistic combo, bonding 2 different sites on 50S ribosomal subunit and inhibiting distinct steps of translation