Antimicrobial Treatment

Where do the greatest number of antibiotic drugs come from? List some examples.

Fungi & bacteria

• Streptomyces, Bacillus, Penicillium, Cephalosporium

Broad spectrum drugs

effective against multiple groups of bacteria

• tetracyclines

Narrow spectrum drugs

only target a specific group

• polymyxin

Metabolism of actively dividing cell: (4)

• Production of new cell wall components

• DNA, RNA

• Proteins

• Cell membrane

What are the metabolic targets of chemotherapeutic agents? (5)

• inhibition of cell wall synthesis

• inhibition of protein synthesis

• inhibition of nucleic acid (DNA/RNA) structure & function

• interference w cell membrane structure or function

• inhibition of folic acid synthesis

Describe the idea of selective toxicity

antimicrobial drugs should kill or inhibit microbial cells without simultaneously damaging host tissues

What is an important aspect of the best drugs (currently)? Give examples.

The best drugs in current use block the actions or synthesis of molecules in microbes but not vertebrate cells

• Penicillins

• Cillin

• Targetting cell walls

Protein synthesis inhibitors acting on ribosomes:

50S subunit, 30S subunit

Chemotherapeutic drug

any chemical used in the treatment, relief, or prophylaxis of a disease

Prophylaxis

use of a drug to prevent imminent infection of a person at risk

antimicrobial chemotherapy

the use of chemotherapeutic drugs to control infection

antimicrobials

all-inclusive term for any antimicrobial drug

antibiotics

substances produced by the natural metabolic processes of some microbes (or man-made) that can inhibit or destroy microbes

Semisynthetic drugs

drugs that are chemically modified in the laboratory after being isolated from natural resources

synthetic drugs

drugs produced entirely by chemical reactions within a laboratory setting

List some characteristics of the ideal antimicrobial drug

• selectively toxic to microbe, nontoxic to host

• microbicidal

• relatively soluble

• doesn’t cause antimicrobial resistance

• reasonably priced

• readily delivered to the site of infection

• does not disrupt host’s health thru allergies or leading to other infections

• remains active in tissues & body fluids

• complements/assists activities of the host’s defenses

Why is Penicillin so important? Who discovered it?

Bactericidal - good at killing

• major role in World War

• discovered by Alexander Fleming

What structure is naturally occurring in Penicillium?

Beta-lactam ring

How did bacteria acquire resistance to Penicillins?

Certain bacteria can break the beta-lactam ring with beta-lactamase

Features of 1st generation penicillins

• not resistant to beta-lactamase

• Primarily used for treatment of susceptible gram-positive bacterial infections

• narrower spectrum

• Penicillin G, Penicillin V

Features of 2nd generation penicillins

• resistant to beta-lactamase

• treatment of staphylococcal infections, including those resistant to 1st-gen penicillins

• broader spectrum

• Nafcillin, Oxacillin, Dicloxacillin

Cephalosporins

• bactericidal

• similar to penicillins

• less susceptible to beta-lactamase

Tetracyclines

• bacteriostatic

• frequently lead to secondary infection

  • can kill good bacteria, making you immunocompromised (Candida albicans)

Tetracyclines: Short acting, intermediate, & long acting

• short acting (6-12h) —> tetracyclines

• intermediate (12-13h) —> demeclocycline

• long acting (18-20h) —> Doxycycline

What is the Kirby-Baeur technique used for?

Testing drug susceptibility

Describe the Kirby-Bauer technique

• surface of a plate of special medium is spread w test bacterium

• small disks containing antibiotics are dispensed onto bacterial “lawn”

• a zone of inhibition (no growth) is formed during incubation & is measured & compared w a standard for each drug

  • antibiogram

antibiogram

a profile of antimicrobial sensitivity

Minimum inhibitory concentration

the smallest concentraton (highest dilution) of drug that visibly inhibits growth

What is minimum inhibitory concentration useful for?

determining smallest effective dosage (how much)

• provides a comparative index against other antimicrobials

What performs tests for minimum inhibitory concentration?

automated machinery

What three things need to be identified before starting treatment?

1. ID microbe

2. ID susceptibility of microbe

3. ID overall medical condition of the patient

Is it easy to choose a drug? Briefly identify are the 2 case studies regarding this question.

No

• Elderly patient w pneumonia complicated by liver & kidney damage

• Cancer patient w systemic Candida infection

What are the 2 ways microbes gain antimicrobial resistance?

• spontaneous mutation

  • chromosomal genes

• acquisition of new genes or sets of genes

  • horizontal transfer from another species (plasmids)

List the mechanisms of drug resistance (5)

• new enzymes made

• drug efflux (pump drug out of cell)

• inactivation of drug (chemical modification)

• modification of target enzyme/organelle

• use of alternate pathway or increased production of target metabolite

MRSA

Methicillin-Resistant Staphylococcus aureus

What is HA-MRSA, CA-MRSA, & VRSA?

• HA-MRSA = hospital acquired MRSA

  • 1/3 people carry Staph in nose w/o any illness

• CA-MRSA = community acquired

• VRSA = vancomycin-resistant

Vancomycin-resistant Enterocuccus (VRE)

• enterococci bacteria are normally commensal

  • normally spread in hospitals

• Tericoplanin, docycycline, chloramphenicol, rifampin used in an “antibiotic cocktail”

• Even w best treatments mortality rates range from 60-70%

How are threats categorized?

based on levels of concern: urgent, serious, & concerning

Carbapenem-resistant enterobacteriaceae (CRE)

• untreatable & difficult to treat infections from CRE are rising in patients in medical facilities

• CRE resistant to all/most antibiotics

• 50% of patients w bloodstream infections from CRE bacteria die from the infection

• Patients w devices (catheters) & patients taking long courses of antibiotics most at risk for CRE

Clostridium difficile

• cause life-threatening diarrhea

• common in people w recent medical care & antibiotics & hospitalized/recently hospitalized patients

What does Neisseria gonorrhoeae cause? What does it do to the body?

• causes Gonorrhea (STD)

  • can result in discharge & inflammation at the urethra, cervix, pharynx, or rectum

Candida auris

• can cause outbreaks in healthcare facilities

• can be carried on skin w/o casing infection, spreading to others

• became resistant to antifungals

What did the golden age of antibiotics lead to?

drastic reduction in infectious disease & mortality in the 20th century

What is happening to mortality rates today?

It is rising

What else could be causing the rise in mortality rates? Could it all be due to drug resistance?

• Pathogens could be evolving virulence factors

• Microbes are very intertwined in food & daily life, it could be easier to be more resistant

What is an issue with development & research of antimicrobial drugs?

not a lot of money is put towards making more antibiotics