MI04: Antibiotics and Resistance

What defines a good antibiotic target?

• Selective toxicity: bringing greater harm to microbes

• Therapeutic index: ratio of the lowest dose toxic to host to dose required to kill microorganism

What distinguishes a broad spectrum antibiotic from narrow spectrum?

Broad: affect different types of bacteria

Narrow: affect only few related types of bacteria

What are some adverse effects of antibiotics?

• Allergic reactions: common with penicillin and amoxicillin

• Toxic effects: affects teeth, hearing, blood forming systems

• Inhibition of mitochondrial processes

What are some classifications of antibiotics?

• Antibacterial

• Antifungal

• Antiprotozoan/parasitic

• Antiviral

How is antibiotic sensitivity measured? What is MIC vs. MLC?

• We can use zone of inhibition and dilution assay to measure antibiotic sensitivity.

• MIC: minimum inhibitory concentration

• MLC: minimum lethal concentration

What bacterial processes and structures do antibacterial drugs target?

• Cell wall, protein, nucleic acid, and cell membranes

• Metabolic pathways

How do penicillins works?

It prevents the synthesis of the cell wall by blocking cross-linking of peptidoglycan.

What is a beta-lactam?

A type of antibiotic that interfere with peptidoglycan synthesis (inhibits enzymes like penicillin-binding proteins which crosslink peptidoglycan).

What is a beta-lactamase?

They are enzymes that break down beta-lactam.

What are cephalosporins?

They are beta-lactam antibiotics that are resistant to penicillinases and can have cephalosporinases.

What is augmentin and what are its benefits over amoxicillin?

It is a beta-lactamase inhibitor (amoxicillin + clavulanic acid).

What are some advantages to using cephalosprins?

They are a type of beta-lactam antibiotics that are resistant to penicillinases. (But they can have cephalosporinases.)

What are carbapenems? What activities do they possess?

They are antibiotics that affect cell wall synthesis like penicillins and cephalosporins.

• Possess activity against gram neg. and pos.

• Has both anti-peptidoglycan synthesis activity and beta-lactamase inhibitor

What are some examples of inhibitors of DNA replication?

• Fluoroquinolones (e.g. ciprofloxacin)

• Novobiocin

• Nalidixic acid

• Metronidazole

What is polymyxin B?

A type of polypeptide antibiotic that disrupt bacterial membranes.

What is bacitracin?

A type of polypeptide antibioticc that affect membrane and blocks the secretion of peptidoglycan precursors.

What is rifampin?

It is an antibiotic that inhibits mRNA synthesis by binding to RNA polymerase.

What is metronidizole? What must activate it?

A type of antibiotic that disrupt electron transport and leads to DNA damage. It also must be activated by anaerobic organisms.

What are some inhibitors of protein synthesis?

• tetracyclines (e.g. doxycycline)

• chloramphenicol

• macrolide (e.g. erythromycin)

• lincosamide (e.g. clindamycin)

• aminoglycosides (e.g. streptomycin, gentamycin)

Which antibiotics inhibit folic acid synthesis?

Trimethoprim

How can bacteria become antibiotic resistant?

• Impermeability: Change permeability

• Binding-site altered: change target site

• Alternative pathway: bypass inhibited reaction with developed alternative pathway

• Inactivation of antibiotic: new enzyme that inactivates (beta-lactamase) and chemical modification

• Increase in amount of sensitive site in cell

• Production of a system to excrete the antibiotic

What are the modes of action of antibacterial medications?

• Inhibition of cell wall synthesis

• Inhibition of protein synthesis

• Disruption of cytoplasmic membranes

• Inhibit of nucleic acid synthesis

• Competitive inhibition

What are some antibiotics used to treat “pink eye”?

• Antibiotic eye drops (e.g. erythromycin, gentamicin, tobramycin, or ciprofloxacin)

• Antibiotic ointment (e.g. erythromycin ointment)

What are some limitations of antimicrobial agents?

• Selection of antibiotic-resistant bacteria: have spontaneous resistance (mutation) and role of gene transfer in spread of resistance

• Antibiotics for farm animals

• Use of antimicrobial hand soaps

What are some antibiotic resistance mechanisms?

• Impermeability

• Binding-site altered

• Alternative pathway

• Inactivation of antibiotic (enzyme that inactives antibiotic, e.g. beta-lactamase)

• Increase in amount of sensitive site in cell

• Production of a system to excrete the antibiotic