lecture 5/6 - antibiotics

Question 1

antiviral

Answer 1

treat viral infections

Question 2

antifungal

Answer 2

treat fungal infections

Question 3

antibiotics treat …

Answer 3

treat bacterial infection

Question 4

antimicrobials

Answer 4

treat any microbial infection (virus, bacteria, protists, fungal)

Question 5

what are the two forms of antimicrobial resistance?

Answer 5

1. natural resistance
   - natural feature of any microbe; encoded in microbe’s chromosome
   - Existed before antibiotic use
2. Acquired resistance
   - arises in some strains of species; mutations occur on chromosome, plasmid, or transposon.
   - increased with antibiotic use

Question 6

where do antibiotics come from?

Answer 6

metabolic products from aerobic bacteria and fungi.

-new drugs arise from altering the natural structure

Question 7

what is minimum inhibitory concentration (MIC)

Answer 7

LOWEST concentration of antibiotic in which a species CANT GROW

Question 8

what are the consequences of treating microbes with lower doses than MIC

Answer 8

-adds pressure but allows for microbial survival and potential for evolution of resistance.

Question 9

In vitro kinetics

Answer 9

Done in broth or plate cultures to find the concentration of the antibiotic that inhibits growth.

Question 10

In vivo kinetics

Answer 10

Diffusion in tissues, host protein interaction, drug interactions, immune system, multiple simultaneous infections, virulence of organism, site and severity of infection, dosage maintenance*

Question 11

what are the goals of antimicrobials

Answer 11

Disrupt the cell processes or structures of bacteria, fungi, and protozoa
-inhibit viral replication

Question 12

how do antimicrobial drugs work?

Answer 12

• interfere with the function of enzymes required to synthesize and assemble macromolecules
• or, destroy structures already formed in the cell

Question 13

selectively toxic

Answer 13

drugs kill or inhibit microbial cells without damaging host tissues

Question 14

name the 5 targets of antimicrobials

Answer 14

1. protein synthesis inhibitors acting on ribosomes
2. folic acid synthesis in the cytoplasm
3. cell wall inhibitors
4. cell membrane
5. DNA/RNA

Question 15

why isn’t the cell membrane the best target?

Answer 15

-poor selective toxicity d/t all organisms having cell membranes

Question 16

what do organisms use to supercoil DNA?

Answer 16

gyrase —- critical for growth

** in all organisms

Question 17

what type of antimicrobials inhibit DNA gyrase?

Answer 17

broad spectrum

Quinolone

ex) Nalidixic acid
ex) Ciprofloxacin

Question 18

antimicrobials that act on RNA synthesis inhibit which replication action?

Answer 18

Transcription - copying of DNA into RNA

**works well because it is essential for all bacteria

Question 19

what type of agents inhibit RNA synthesis?

Answer 19

Rifampin

• binds to RNA polymerase (enzyme) tp prevent elongation of transcription
• only bacteria
• usful for TB

Pyronins

Question 20

antimicrobials that act on Protein synthesis inhibit which replication action?

Answer 20

Translation - coding of RNA into proteins

**works well as it is a part of all bacterial replication

Question 21

how do agents that block enzyme functioning work?

Answer 21

“competitive inhibition”

-antibiotic mimics normal substrate to block enzyme binding

Question 22

what is a sulpha drug?

Answer 22

sulfanilamide inhibits folic acid synthesis in bacteria and protozoans by blocking enzyme receptors.

-folic acid is an essential nutrient made by PABA (we get from diet)

Question 23

Even pathogens with few virulence factors can infect through this portal of entry:

Answer 23

Intravenous
- HIV is able to get through the skin barrier via a needle and can infect us due to the lack of body defenses once in the blood stream

Question 24

Why are culture independent techniques important in the lab for identifying pathogens?

Answer 24

Many pathogens and most microorganisms don’t grow in the lab. Need alternate techniques that don’t need us to culture them- ex: virus so need culture independent to study and identify them. DNA sequencing, antibody-based techniques, PCR- aren’t strictly culture independent (refers to pathogen itself)

Question 25

Briefly describe the difference between an infection and a disease.

Answer 25

Infection: body colonized by infection can spread, may not be sick (many people can be carriers, but they don’t recognize they are sick ex: HIV (infectious agent), AIDS (disease) Disease is when you’re actually showing symptoms

Question 26

what makes antibiotics effective?

Answer 26

harm the microbe and not the host

Question 27

what action is taken when a micro becomes resistant to antibiotics? what is the consequence of this?

Answer 27

Pathogens become resistance to first line so we move to second and third line defences -increases the risk of them harming us while they are hurting the disease (less selective toxicity)

Question 28

what are the two main issues related to antibiotic use?

Answer 28

1. Antibiotic-resistant bacteria | 2. Complications from the use of antibiotics, such as Clostridium difficile colitis.

Question 29

CRE

Answer 29

carbapenem-resistent enterobacteriaceae * *resistant to nearly all antibiotics - only old drugs c/ significant toxicities and side effects work - kills 1/2 people who go septic c/ CRE

Question 30

MRSA

Answer 30

methicillin resistant Staphylococcus aureus * popular . 80000/year --> >11000 deaths * sask accounts for 8% of cases * **nosocomial infection - normal flora of skin, rose, respiratory tract, GI tract. ** commonly causes skin/ bone tissue infections, pneumonia, sepsis

Question 31

what does MRSA resistance mean?

Answer 31

first line treatments will FAIL. second line drugs are LESS EFFECTIVE and have more SIDE EFFECTS infections that might be treated with pills, now need IV medication

Question 32

VRE

Answer 32

vancomycin-resistant Enterococcus - few to no treatment options d/t natural resistance - emerged in 1988 - 20000 cases per year, 1300 deaths * normal flora of bowels

Question 33

how is VRE transferred and why is VRE a fear?

Answer 33

-fecal contamination from not washing hands; occurs easily esp. in immunocompromised fear that it could be transferred to other microbes such as MRSA

Question 34

Resistant N. gonorrhoeae

Answer 34

* *urgent threat - 1/3 cases are resistant - almost 250000 cases of resistance -- mostly to tetracycline Resistance: - Control efforts begin to fail, leading to increasing rates of spread. - Increase in HIV (infection with Gonorrhoea makes spread of HIV easier) * increases susceptibility - Increase in Pelvic Inflammatory Disease (major cause of female infertility) - Increase in Epididymitis (cause of male infertility)

Question 35

clostridium difficile

Answer 35

- 1/4million infections per year c/ 14000 deaths | - infection occurs as a result of antibiotic use - wipes out good bacteria and allows c.diff to overgrow

Question 36

what is the importance of hand washing?

Answer 36

80% of common infections are spread through hand contact -hand washing can prevent this

Question 37

Carbapenems

Answer 37

- beta-lactam antibiotics, broad spectrum - LAST RESORT - esp c/ E.coli - resistance rising since 2001 **outbreak in is real (2006) killed 50-70%

Question 38

virus

Answer 38

DNA inside a protein shell (capsid) -hijacks host cell machines to reproduce

Question 39

bacteriophage

Answer 39

-specifically infects bacterial cells by poking through cell membranes c/ needle like structure. and injecting viral DNA inside to use machines and replicate its material, assemble viral particles and leave cell to infect more

Question 40

Mycobacterium tuberculosis

Answer 40

Cause of TB - has been around since 4000 BCE - in america since 100 CE

Question 41

Yersinia pestis

Answer 41

cause of the 14th century black plague | -killed 75-200 million (30-60% Europe population)

Question 42

how did bacteria affect human health prior to antibiotics?

Answer 42

- -90% of children with bacterial meningitis died - -Strep throat was potentially fatal - -ear infections could spread to the brain, causing severe problems - -1 in 200 women died from infections acquired during childbirth - -3 in 10 people died from pneumonia - -1 in 10 people with a skin infection (from a scrape, cut, or scratching a bite) lost a limb - 1910--> 46% of deaths were d/t infectious disease

Question 43

who discovered penicillin?

Answer 43

1928 by Alexander Fleming - Ring where bacteria were not growing; discovered that the fungus (Penicillin) produces an antibiotic that prevents growth of and kills bacteria - first used in 1941 on a police officer ( worked well while supplies lasted

Question 44

how does antibiotic resistance occur?

Answer 44

natural selection -lots of opportunity for gene mutations as bacteria replicate in 20 mins (some) -caused by over use and improper use of antibiotics

Question 45

why is antibiotic resistance bad for health care workers and the human population?

Answer 45

Increased rates of antibiotic resistant organisms and decreased rates of new antibiotic discovery are leading us to a point where we will no longer have antibiotics to treat or prevent infections.

Question 46

what are three examples of situations in which antibiotics would be administered as a protective measure

Answer 46

- Oncology -(cancer treatment) to prevent opportunistic infections that may kill patient - Surgery - hip and knee replacements in elderly pop especially - Obstetrics - c sections are safer with antibiotics to prevent infections during childbirth

Question 47

antimicrobial stewartship

Answer 47

promoting optimal pt outcomes c/ antibiotic use -IS IT NECESSARY? (right drug, dose, duration, route) -collaborative effort c/ all health care workers in ALL facilities/ places

Question 48

S&S of bacterial infections

Answer 48

- Temperature (> 37°C) - White Blood Cell Count (WBC > 10) - Vital Signs (respiration, heart rate) - Radiology Data - Laboratory Data

Question 49

Empiric Therapy

Answer 49

Initial treatment of an infection based on the best and most recent ‘evidence’: Guidelines (best treatment/ what works best) Medical Studies Local Algorithm (rules to follow c/ different infections ) Local Antibiogram (road map for what bugs in your local region are resistant to what drugs)

Question 50

Targeted therapy

Answer 50

Treatment of an infection based on available test results: Radiology Tests Microbiology Results

Question 51

How is the right dose of antibiotic determined?

Answer 51

1.The type or severity of infection -more severe > dose Example: Upper vs. Lower UTI 2. The site of infection -Hard to hit areas: CNS, bone, and heart valves have higher doses 3. Patient specific factors -Liver and Kidney function (alters metabolism)

Question 52

how is the right duration of antibiotics determined?

Answer 52

Depends on infection: Uncomplicated UTI = 3 days Cellulitis = 5-7 days (if diabetic foot infection = 14 days, if there is bone involvement = up to 3 months) Prosthetic joint infection = up to 6 weeks Endocarditis = 2-8 weeks (depends on type of bug/valve) Prolonged antibiotic use = resistance (BALANCING ACT)

Question 53

how is the right rough determined?

Answer 53

Parenteral (IV) versus oral (tablet/capsule/liquid) 1) Type of infection 2) Type of drug 3) Patient factors: - clinically stable? - other oral medications? - regular diet? - functioning GI tract? Less time with IV = less chance of picking another infection/another infection May need IV if low bioavailability as oral Oral antibiotic is generally better if they are eating/drinking/taking other oral meds

Question 54

How is antimicrobial stewartship enforced?

Answer 54

``` Prospective audit and feedback -Hospital units or community settings -Specific antimicrobials -Specific disease states Formulary restriction and preauthorization -Save the ‘big guns’ for when we need them Educate -health care workers -public Research ```