Micro 4.2 Antibiotics

What is chemotherapy?

Any chemical(s) used to treat a medical condition

What is an antimicrobial?

A compound that inhibits the growth of microbes

What are examples of antimicrobials?

Heavy metals, quaternary ammonia (Lysol), Sodium Hypochlorite (Bleach/Chlorine), salt, sugar, honey

What does static mean?

Inhibits growth

What does cidal mean?

Kills microbes

What is selective toxicity?

The ability for a chemical to be only toxic to certain cells

What is ideal selective toxicity?

High ST for pathogens and little/no ST for host and non-pathogens

What does 'antibiotic' mean?

Anti = against, Bio = life

What do antibiotics treat?

Bacterial infections

Do antibiotics work against parasites?

Some have antiparasitic functions

Where do true antibiotics occur?

In nature

What are antibiotics derived from?

Typically derived from molds or bacteria

Why are some antibiotics semi-synthetic?

To increase function, lower host cell toxicity, and/or make them easier to administer/store

What factors influence antibiotic choice?

Location of infection, level of illness, immune status, drug penetration, liver/kidney function, drug interactions, side effects, pregnancy, resistance

What are characteristics of the 'ideal' antibiotic?

Easy/cheap to produce, easy to deliver, effective in small doses, long-lasting in host, high selective toxicity, no interference with other drugs, broad or narrow spectrum

What is broad spectrum?

Targets many microbes

What is narrow spectrum?

Targets few microbes

What was Salvarsan used for?

To treat syphilis

What are sulfonamides?

Synthetic 'antibiotics' developed in 1906

Who discovered penicillin?

Alexander Fleming

What did Fleming discover in 1922?

Lysozyme in tears

How does lysozyme work?

Breaks bacterial cell walls

What was penicillin first called?

'Mold Juice'

When was penicillin first used medically?

1942

Where was modern penicillin derived from?

A strain found on a cantaloupe at a farmer's market in Illinois

What is the 'Golden Age of Antibiotics'?

1950s - 1970s

Have new major antibiotics been discovered recently?

No new major antibiotics since the 1980s

What are the 5 main targets of antibiotic action?

Cell wall, cell membrane, ribosome, nucleic acid, folic acid metabolism

Why is the bacterial cell wall a good antibiotic target?

It is not found in animal cells

What is unique to bacterial cell walls?

Peptidoglycan

What do cell wall antibiotics target?

Cell wall synthesis mechanisms in newly formed cells

What is the result of disrupting the bacterial cell wall?

Cell lysis

Are cell wall antibiotics bactericidal or bacteriostatic?

Bactericidal

What do beta-lactam antibiotics do?

Insert into peptidoglycan chains and destabilize the cell wall

What are common beta-lactams?

Penicillins, Cephalosporins, Carbapenems, Clavulanic Acid

What are examples of penicillins?

Penicillin G, Amoxicillin, Ampicillin, Methicillin

What is clavulanic acid used for?

Combined with Amoxicillin to counter antibiotic resistance

What spectrum are glycopeptides?

Narrow spectrum for Gram Positive only

Why can't glycopeptides treat Gram Negative bacteria?

They cannot pass through the pores in the outer membrane

What are side effects of glycopeptides?

Nephrotoxicity, Neutropenia, Hearing Loss

What is vancomycin used for?

To treat MRSA and antibiotic-resistant Gram Positive Cocci

What does bacitracin target?

Cell walls

How is bacitracin used?

Topically only due to high nephrotoxicity

Where is bacitracin commonly found?

OTC creams, acne medications, conjunctivitis treatments

Why is the cell membrane a poor antibiotic target?

It is found in all cells

How do cell membrane antibiotics act?

Like a detergent, making lipids water soluble

What are the toxicities of cell membrane antibiotics?

Neurotoxic, Dermatoxic, Nephrotoxic

What type of bacteria do cell membrane antibiotics target most?

Gram Negative

Where is polymyxin B found?

Topical creams

What is polymyxin E also called?

Colistin

What is Colistin used for?

Antibiotic of last resort

When was Colistin resistance found in the US?

2015

What do ribosome-targeting antibiotics inhibit?

Translation

What ribosome subunits do prokaryotes have?

30S and 50S

What ribosome subunits do eukaryotes have?

40S and 60S

Why must ribosome-targeting antibiotics be used carefully?

They may affect mitochondria

Are ribosome-targeting antibiotics bactericidal or bacteriostatic?

Bacteriostatic

What are the 6 classes of ribosome antibiotics?

Aminoglycosides, Tetracyclines, Macrolides, Lincosamides, Chloramphenicol, Oxazolidones

What do aminoglycosides treat?

Aerobic Gram Negatives and some Gram Positives

What are examples of aminoglycosides?

Streptomycin, Gentamycin, Neomycin (topical only)

What is the spectrum of tetracyclines?

Most broad spectrum group

What are side effects of tetracyclines?

Photosensitivity, deposits in bone and teeth

What are common tetracyclines?

Doxycycline, Minocycline

Are tetracyclines safe during pregnancy?

No, not recommended

What are toxicities of macrolides?

Neurotoxic, Aplastic Anemia

What infections are macrolides used for?

Sepsis and meningitis

What are examples of macrolides?

Erythromycin, Azithromycin, Clarithromycin

What spectrum are lincosamides?

Gram Positive only

What is a risk of using lincosamides?

C. diff infection

What is an example of a lincosamide?

Clindamycin

What is unique about chloramphenicol?

Synthetic, not a true antibiotic

What is the newest major class of antibiotics?

Oxazolidones

What do oxazolidones treat?

Only effective against Gram Positive

What is an example of an oxazolidone?

Linezolid

What is the function of folic acid in cells?

Used in DNA synthesis

Where must bacteria get folic acid from?

They make their own

Why is folic acid synthesis a good antibiotic target?

Humans get folic acid from diet

What antibiotics target the folic acid pathway?

Sulfonamides and Trimethoprim

How do sulfonamides and trimethoprim work?

They target enzymes in folic acid synthesis

Are folic acid pathway antibiotics bacteriostatic or bactericidal?

Bacteriostatic

Why is targeting DNA/RNA risky in antibiotics?

Can easily harm host cells

What does DNA gyrase do?

Helps supercoil DNA

What is the function of RNA polymerase?

Transcribes RNA from DNA

What antibiotic targets DNA gyrase?

Fluoroquinolones

What are examples of fluoroquinolones?

Ciprofloxacin, Levofloxacin, Ofloxacin

What antibiotic targets RNA polymerase?

Rifampin

What is rifampin used to treat?

Mycobacterium tuberculosis, Neisseria meningitidis, Haemophilus influenzae

Why is rifampin not used alone?

Resistance can develop quickly

What is a unique side effect of rifampin?

Turns secretions orange

What causes a superinfection?

Antibiotic kills normal flora, allowing pathogen to overgrow

What are examples of superinfections?

Yeast infections, C. difficile (pseudomembranous colitis)

What is antibiotic resistance?

The ability of bacteria to survive and grow despite antibiotics

What are types of antibiotic resistance?

Natural and acquired

How can bacteria resist antibiotics?

Efflux pumps, degrading the drug, mutating the target

What causes acquired resistance?

Mutation or horizontal gene transfer

What is vertical transmission?

Passing mutations to daughter cells

What is horizontal transmission?

Transferring resistance between bacteria

What are the methods of horizontal gene transfer?

Conjugation, Transformation, Transduction

What is conjugation?

Plasmid transfer through pilus

What is transformation?

Uptake of naked DNA from environment