Week 3 - Intro to Antibiotics Flashcards
Antimicrobial encompasses
Antibacterial, antifungal, antiparasitic, antiviral
Selective Toxicity
Antibiotics need to injure the invading organism while causing minimal adverse effects to the host
What is major target of antibiotics?
Cell wall - There is no cell wall in humans so it wont affect us! Antibiotics can damage cell wall and render bacteria damaged, killing them
Toxicity of antibiotics
- Extension of mechanism of action.
ex. Trimethoprim can inhibit folate metabolism in humans resulting in bone-marrow suppression… - Unintended consequences
ex. Vancomycin can stimulate histamine release resulting in red man syndrome
Therapudic index
High therapeutic index means fewer adverse reactions (cell wall inhibitors)
What does trimethoprim inhibit? (extension of mechanism action)
Folate metabolism in humans resulting in bone-marrow suppression
What does vancomycin stimulate? (Unintended consequence)
Release of histamines resulting in red man syndrome..
Spectrum of Activity
Spectrum of antibiotics
Narrow - Gram negative cocci
Extended - Gram negative rods and cocci
Broad - Many gram positive and gram negative organisms
Narrow spectrum antibiotics target?
Gram negative cocci
Extended spectrum antibiotics target?
Gram negative rods and cocci
Broad spectrum antibiotics target?
Many gram positive and gram negative organisms
Prophylaxis Therapy
Treating infections that has not yet developed but is at a high risk of developing an infection
Pre-emptive Therapy
Lab test that shows infection but no symptoms are showing yet. The advantage is that it decreases amount of antibiotics used
Empiric Therapy
Take culture, patient has infection with serious potential consequences but the organism has not been identified (broad spectrum). Example meningitis
Definitive Therapy
Pathogen identified (mono therapy, narrow spectrum)
Suppressive Therapy
After initial disease is controlled, therapy is continued at a lower dose
Which of the following situations describes empiric antibiotic therapy?
A. Beginning nitrofurantoin for a patient with a history of repeated urinary tract infections to prevent another infection
B. Beginning nitrofurantoin for a patient with signs and symptoms of a urinary tract infection with a positive urinalysis
C. Beginning nitrofurantoin for a patient with signs and symptoms of a urinary tract infection with E. coli growing in the urine that are susceptible to nitrofurantoin
D. Beginning nitrofurantoin for a patient with signs and symptoms of a urinary tract infection with E. coli growing in the urine that are resistant to nitrofurantoin
B
Pharmacokinetics
Body’s effect on a drug - must treat the individual with the right drug, right dose, right route, and right duration to kill ENOUGH bacteria to elimiate the infection (Rely on immune system to kill remaining)
What are the 4 R’s of a drug?
Must treat the individual with right drug, right dose, right route, and right duration to kill enough bacteria to eliminate the infection
Absorption of drug
movement of drug into vascular system
Distribution of a drug
transfer of drug from intravascular to extravasular blood brain barrier presents a challenge
Metabolism of a drug
irreversible transformation of parent compound into daughter metabolites often in the liver
Excretion of drug
elimination of the drug from the body through urine or feces
Drug-drug interaction
drug interactions often occur when one drug inhibits or induces the uptake or
clearance of another drug
Types of drug administration
Oral, IV, IM, SQ, Inhalant, SL, Intrathecal (into CSF fluid - to brain), rectal, or topical
6-year old patient presents to you in clinic with a high fever and inflamed throat. The mother is asking for antibiotics. What will you do?
Check to see if it is bacterial!
Responsible writing of prescriptions is important since:
1. Need to minimize the development of antibiotic resistant microorganisms
- Minimize harm to the patient caused by toxicity due to the use of an
unnecessary or inappropriate drug. - Provide cost effective treatment. Hospital purchases of antibiotics usually
represent 25-30% of the drug budget.
Rapid strep test is…
A positive rapid antigen detection test is diagnostic specific (>95%) available in minutes but sensitivity is (80-90%)
Serologic test- characteristic proteins or polysaccharides are detected with antibodies
May have a false negative or infection could be due to another bacterial organism
Lateral Flow Assay Architecture
draw it. Going to see how fast the material moves through the strip.. the test line will get stuck to RED carbohydrates and you can see a positive strip..
Gram Stain and Morphologic Analysis
Used if rapid strep test is negative… takes 24-48 hours then do gram stain and morphologic analysis. Look for structure (chain vs cluster) (cocci vs bacilli)
Biochemical Tests
Catalase, coagulase test, hemolysis, glucose/lactose fermentation
Catalase Test
monitors degradation of H2O2; differentiates between staphylococci (present) and streptococci (absent)
Coagulase Test
differentiates Staphylococcus strains
Hemolysis Test
clearing around colonies on a blood agar plate differentiates between streptococci
α-hemolytic form green ring
β-hemolytic clearing around colonies on agar plates
γ-hemolysis no hemolysis
Glucose/lactose fermentation test
Can distinguish bacteria by their metabolic properties
Throat Culture Q
From your patient’s throat culture, you get back the following images for the Gram stain and growth on blood agar.You identify the bacteria as …
Streptococcus pyogenes
Streptococcus pneumoniae
Staphlococcus aereus
Staphlococcus epidermis
Neisserria meningitidis
Need a consult
Gram positive. Streptoccoccus (long chain)
B is a diplococci..
This is beta hydrolysis.. Then use dichotimous key to determine it is A.
Use John Hopkin’s guide to identify the appropriate antibiotic for treatment of Group A streptococcal infection and consider what factors will effect which antibiotic you choose
Pregnancy, cost, administration, patient (kid vs adult) etc
What classes of drugs have many allergies?
Beta-lactams (penicillin) and sulfonamides etc…
In some cases, allergy to a particular drug will predict allergies to other drugs in the class.
Must be careful about labeling a patient as allergic since this can result in treatment with inferior drugs
Can do a skin test to confirm and try penicillin desensitization.
What can be done to confirm a penicillin allergy?
Skin test
Age of pt important. Why?
In elderly pts, kidney function is reduced.. With decreases excretion…
Does pt have any other diseases?
ex. Chloramphenicol is inactivated by liver metabolism.
With impaired liver function, dose should be reduced.
Bacteriostatic
Limits growth and if removed the organism can grow again… Usually successful because it allows immune system to catch back up
Bactericidal
Kills 99.9% of bacterial reduction in bacterial inoculums within a 24 hour period. Attacks cell well, disfiguring it and altering osmotic barrier. Bacterial cells lyse.
What happens when antibiotics are administered to bacteria that are not actively dividing?
Wont work.
Some drugs can be baceriostatic against one organism and bactericidal against another
Plot of number of viable bacteria vs Time
If your patient was undergoing cancer chemotherapy and had a suppressed immune system, would you choose drug A or drug B to treat the infecting organism? Why?
draw it. Drug B is bactericidal, Use drug B for ppl who are immunocompramized*
Are there genetic factors that make pt susceptible to toxic side effects? (ex?)
Yes. Sufonamides - may cause hemolysis of RBCs in pts with G6P dehydrogenase deficiency
Is the pt pregnant?
Important. Look on Johns Hopkins guide of ABx to find risk. Look at table 1… B is really not a risk. 1st trimester is most critical usually.. some drugs may be safe in 3rd semester but not 1st..
Has the pt recently been on an antibiotic?
Confirm correct organism. Think drug resistance or super infection
Drug resistance
Increased elimination, Drug-interacting enzymes, decreased uptake, alteration in target molecule
Superinfection
Consequences of overly broad antibiotic treatment…
The balance of the normal residents of the bowel, skin, etc. is maintained by competition for nutrients and the production by bacteria of compounds that inhibit the growth of other bacteria. When an antibiotic kills an important resident bacterium, other harmful bacteria may be able to multiply and cause a secondary infection or superinfection.
The broader the spectrum of activity and the longer time period of antibiotic treatment, the more likely that treatment with the antibiotic will cause superinfection.
Symptoms of superinfection range from mild diarrhea to acute enteritis.
Intrinsic Resistance
Is an absence of inaccessibility of the target for the drug reaction. Ex mycoplasma lack cell walls so they are intrinsically resistant to cell wall inhibitors. No change in the genetics of the bacteria occurs..
Acquired Drug Resistance
What is very important to understand?
Bacteria change their DNA (mutation) OR acquire new DNA resulting in resistance to a drug
*VERY IMPORTANT to understand that the drug itself is not causing the resistance
What is very important about drug resistance?
The drug itself is NOT causing the resistance
DNA-mediated transformation
Look at picture. after replication. 1 daughter cell will be resistant, one won’t.. the one with the resistance then will start increaseing more rapidly. Transformation
Bacteriophage can introduce new DNA through transduction
look at picture. Transduction
Ways of drug resistance
Transformation, transduction, conjucation, transposition
Conjugation
transfer of R plasmid may contain several resistance determinant genes common amongst gram NEG. look at video of this..
Transposition
Can then cause the movement of genetic material within the genome
How is antibiotic resistance transferred from Enteroccoccus to Staphylococcus?
Look at pic…think MRSA
Few new antibiotics are being developed..
..more and more organisms are becoming resistant
Antibiotic Susceptibility Testing
Results can be at least as important as determining the etiologic agent… some organisms
Minimum Inhibitory Concentration (MIC)
Lowest concentration of antibiotic that prevents visible growth in culture, ug/ml
What is MIC Breakpoint?
lk
If MIC is lower than breakpoint…
er
What is advantage of agar testing vs broth testing?
Contamination and heterogenous populations are more obvious. Agar is preferred…
Phenotypic test
Looking at outcome of growth in presence of antibiotic
Genotypic test
Look at actual genes.. look this up. Can look up if gene is resistant..
12 Steps to prevent antimicrobial resistance
Look at picture
What happens if a pt does not take full course of antibiotics?
..the antibiotics dont work as well after they are stopped becasue the first few doses will kill the MOST susceptible bacteria.. the more resistant form will still be there to reproduce..not there are tougher bacteria to try and get rid of.
What ways can we form a mutualistic partnership with bacteria?
Use antibiotics in a way that limits harm to microbiome..
NBME Q
c diff.
