lecture 5/6 - antibiotics Flashcards
antiviral
treat viral infections
antifungal
treat fungal infections
antibiotics treat …
treat bacterial infection
antimicrobials
treat any microbial infection (virus, bacteria, protists, fungal)
what are the two forms of antimicrobial resistance?
- natural resistance
- natural feature of any microbe; encoded in microbe’s chromosome
- Existed before antibiotic use - Acquired resistance
- arises in some strains of species; mutations occur on chromosome, plasmid, or transposon.
- increased with antibiotic use
where do antibiotics come from?
metabolic products from aerobic bacteria and fungi.
-new drugs arise from altering the natural structure
what is minimum inhibitory concentration (MIC)
LOWEST concentration of antibiotic in which a species CANT GROW
what are the consequences of treating microbes with lower doses than MIC
-adds pressure but allows for microbial survival and potential for evolution of resistance.
In vitro kinetics
Done in broth or plate cultures to find the concentration of the antibiotic that inhibits growth.
In vivo kinetics
Diffusion in tissues, host protein interaction, drug interactions, immune system, multiple simultaneous infections, virulence of organism, site and severity of infection, dosage maintenance*
what are the goals of antimicrobials
Disrupt the cell processes or structures of bacteria, fungi, and protozoa
-inhibit viral replication
how do antimicrobial drugs work?
- interfere with the function of enzymes required to synthesize and assemble macromolecules
- or, destroy structures already formed in the cell
selectively toxic
drugs kill or inhibit microbial cells without damaging host tissues
name the 5 targets of antimicrobials
- protein synthesis inhibitors acting on ribosomes
- folic acid synthesis in the cytoplasm
- cell wall inhibitors
- cell membrane
- DNA/RNA
why isn’t the cell membrane the best target?
-poor selective toxicity d/t all organisms having cell membranes
what do organisms use to supercoil DNA?
gyrase —- critical for growth
** in all organisms
what type of antimicrobials inhibit DNA gyrase?
broad spectrum
Quinolone
ex) Nalidixic acid
ex) Ciprofloxacin
antimicrobials that act on RNA synthesis inhibit which replication action?
Transcription - copying of DNA into RNA
**works well because it is essential for all bacteria
what type of agents inhibit RNA synthesis?
Rifampin
- binds to RNA polymerase (enzyme) tp prevent elongation of transcription
- only bacteria
- usful for TB
Pyronins
antimicrobials that act on Protein synthesis inhibit which replication action?
Translation - coding of RNA into proteins
**works well as it is a part of all bacterial replication
how do agents that block enzyme functioning work?
“competitive inhibition”
-antibiotic mimics normal substrate to block enzyme binding
what is a sulpha drug?
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)
Even pathogens with few virulence factors can infect through this portal of entry:
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
Why are culture independent techniques important in the lab for identifying pathogens?
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)
Briefly describe the difference between an infection and a disease.
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
what makes antibiotics effective?
harm the microbe and not the host
what action is taken when a micro becomes resistant to antibiotics? what is the consequence of this?
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)
what are the two main issues related to antibiotic use?
- Antibiotic-resistant bacteria
2. Complications from the use of antibiotics, such as Clostridium difficile colitis.
CRE
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
MRSA
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
what does MRSA resistance mean?
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
VRE
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
how is VRE transferred and why is VRE a fear?
-fecal contamination from not washing hands; occurs easily esp. in immunocompromised
fear that it could be transferred to other microbes such as MRSA
Resistant N. gonorrhoeae
- *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)
clostridium difficile
- 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
what is the importance of hand washing?
80% of common infections are spread through hand contact
-hand washing can prevent this
Carbapenems
- beta-lactam antibiotics, broad spectrum
- LAST RESORT - esp c/ E.coli
- resistance rising since 2001
**outbreak in is real (2006) killed 50-70%
virus
DNA inside a protein shell (capsid)
-hijacks host cell machines to reproduce
bacteriophage
-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
Mycobacterium tuberculosis
Cause of TB
- has been around since 4000 BCE
- in america since 100 CE
Yersinia pestis
cause of the 14th century black plague
-killed 75-200 million (30-60% Europe population)
how did bacteria affect human health prior to antibiotics?
- -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
who discovered penicillin?
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
how does antibiotic resistance occur?
natural selection
-lots of opportunity for gene mutations as bacteria replicate in 20 mins (some)
-caused by over use and improper use of antibiotics
why is antibiotic resistance bad for health care workers and the human population?
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.
what are three examples of situations in which antibiotics would be administered as a protective measure
- 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
antimicrobial stewartship
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
S&S of bacterial infections
- Temperature (> 37°C)
- White Blood Cell Count (WBC > 10)
- Vital Signs (respiration, heart rate)
- Radiology Data
- Laboratory Data
Empiric Therapy
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)
Targeted therapy
Treatment of an infection based on available test results:
Radiology Tests
Microbiology Results
How is the right dose of antibiotic determined?
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)
how is the right duration of antibiotics determined?
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)
how is the right rough determined?
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
How is antimicrobial stewartship enforced?
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
