L1 Pharm: Intro to Abx & Gen. Principles of Antimicrobial Therapy Flashcards
Antibiotic Therapy depends on 3 things:
- Knowledge/suspicion of the ______ of infection and infecting pathogen
- Spectrum of ________ of the antibiotic
- ______________________
- Knowledge/suspicion of the site of the infection (different flora found in different parts of the body and you can suspect different pathogenic organisms based on the site of infection)
- Spectrum of activity of the antibiotic
- Host characteristics
APPROPRIATE DIAGNOSIS IS CRUCIAL.
T/F: Antibiotic therapy should be started before cultures are obtained from a suspected site of infection.
False. Obtain cultures from the suspected site of infection before antibiotics are initiated. This helps with proper diagnosis.
This is important because isolation of an organism from a clinical specimen does not always indicate the presence of infection (normal flora vs. contamination vs. infection)
Normal flora can be found on the skin, respiratory tract, GU tract and GI tract.
How does normal flora affect pathogenic bacteria?
Suppress growth, compete with pathogenic organisms for nutrients, and stimulate cross-protective antibodies.
What happens to the flora of patient’s who are hospitalized within 48 hours of admission?
Patients become colonized with “new flora,” usually gram-negative aerobes.
What specimens are found in the following sterile body sites?
- Bloodstream
- Subarachnoid Space
- Pleural Space
- Peritoneum
- Pericardium
- Synovium
- Urinary Tract
- Bloodstream- Blood
- Subarachnoid Space-CSF
- Pleural Space- Pleural Fluid
- Peritoneum - Peritoneal Fluid
- Pericardium- Pericardial Fluid
- Synovium- Synovial Fluid
- Urinary Tract - Urine (directly from the bladder)
T/F: You take a specimen from a patient and isolate bacteria from it. This is indicative of infection.
False:Isolation of a bacteria from a clinical specimen is not always an indication of infection
Differentiate between contamination, colonization, and infection.
Contamination
Organisms inadvertently introduced during ________ _____________ or processing.
Organism inadvertently introduced during specimen collection or processing
An example is isolation of coagulase negative staphylococci (normally found on skin) in the blood of a patient where the blood is drawn via a peripheral stick and the patient does not have signs of infection. Normal skin flora bacteria contaminated blood culture.
Colonization
Organism is present at body site but is not _______ host tissue or _______ signs and symptoms of infection.
Organism is present at body site but is not invading host tissue or inducing signs and symptoms of infection.
Ex: isolation of pseudomonas aeruginosa from a sputum culture in a patient without fever, cough, or infiltrate on chest X-ray. Pathogenic bacteria is in the patient without clinical/radiological signs of pneumonia.
Infection
_______ organism is damaging host tissue and eliciting signs and symptoms of infection.
Pathogenic organism.
An example of infection is streptococcus pneumonia in the CSF of a patient with headache, fever, and neck stiffness.
Antibiotics may be chosen before the results of the cultures are available based on some preliminary information. Name two:
1.
2.
- Site of infection and likely causative organism- certain bacteria have a propensity to commonly cause infection in particular sites of the body (E.Coli in urine for example)
- Gram stain results (does result correlate with most likely suspected organism?)
Interpretation of lab culture requires knowledge of:
- Sites with normal flora vs. ___________ _________
- Contamination (lab), colonization (no infection) and infection
Sterile Sites
Antibiotics are usually initiated when an infection is __________ because delaying treatment may lead to significant morbidity or mortality.
Infection is suspected.
Antibiotic are chosen that have activity against likely pathogens (empiric therapy)
The regimen is modified once culture and susceptibility results are available (targeted therapy)
An antibiotic’s spectrum of activity tells you what?
Spectrum of activity is a general list of bacteria that are killed or inhibited by an antibiotic.
It is established during clinical trials, and because of resistance, susceptibility patterns of each bacteria should be continuously evaluated.
Narrow Spectrum = antibiotic has activity against a ______ _____ of bacteria
Broad Spectrum = antibiotic has activity against a _____ variety of bacteria
Narrow spectrum: works against a limited group
Broad spectrum: kills a wide variety of bacteria
What do the MIC and MBC tell you? Which one is a greater concentration?
MIC: Minimum Inhibitory Concentration- lowest concentration of an antibiotic that inhibits visible bacterial growth
MBC: Minimum Bactericidal Concentration- lowest concentration of an antibiotic that kills bacteria; decreases innoculum by 99.9%.
MIC is less than or equal to the MBC
Susceptibility Breakpoints categorize specific antibiotic _____ values for a given bacteria as:
S- susceptible
I- intermediate
R- resistant
Should these values be compared amongst antibiotics?
MIC values
Susceptible: organism will most likely be eradicated with normal doses of the abx
Intermediate: treatment may be successful using maximum dose of the abx
Resistant: MIC exceeds usual serum concentrations of the antibiotic, so less than optimal results are expected.
MIC values should not be compared between different antibiotics! They depend on pharmacokinetics, activity of abx, site of infection, and data from clinical efficacy trials.
MIC Determination- Are broth dilutions (micro/macrodilutions/serial dilutions) quantitative or qualitative?
Quantitative tests of the in vitro activity of an antibiotic- yields an MIC or MIC RANGE**.
MIC is the lowest concentration of antibiotic that prevents visible growth of the bacteria.
Macrodilution- results yield the _________ MIC of the antibiotic against the infecting organism. How can you tell what the MIC is? Can you tell the MBC from this test?
Gives EXACT MIC.
The MIC is the first tube without visible growth.
You can determine MBC from macrodilution. MBC is an extension of the test- test tubes without visible growth are cultured on agar plates. After incubation colonies are counted- MBC is the concentration that reduced the original inoculum by 99.9% after 24 hrs of incubation.
Macro dilution is a 2 fold serial dilution of an antibiotic thats incubated with a standard inoculum of the infecting bacteria in test tubes.
Microdilution
Microtiter plates or cassettes with serial dilutions of ________ antibiotics at the same time.
What test is more common, macrodilution or microdilution? Why?
Is it Qualitative or Quantitative?
Tests several antibiotics at the same time. Due to size restraints of cassettes, not all concentrations of an antibiotic can be tested for susceptibility.
Microdilution is automated and is the MOST COMMON METHOD for quantitatively determining MIC! Macrodilution is labor and resource intensive.
- QUANTITAVE (but often only gives a RANGE of the MIC)
Kirby Bauer Disk Diffusion Test
Qualitative or Quantitative?
What does a clear zone represent? What do their diameters correlate to?
Qualitative test of the in vitro activity of an antibiotic- MIC is NOT determined!
Clear zones represent antibiotic inhibition. No growth occurred here. Bacteria only grow where concentrations of the antibiotic are below those required to inhibit bacterial growth.
Zone diameters mm size correlate with S, I, R.
E-Test
Plastic strip impregnated with known, predefined _______ __________ of antibiotic is placed on agar plates inoculated with standard concentration of infecting bacteria
How can you tell the MIC from this test?
Is it EXACT or a RANGE?
Quantitative or Qualitative?
Concentration Gradient.
Clear elliptical zone of inhibition is observed- bacteria only grow where concentrations are less than MIC.
You can tell an EXACT MIC from an E-Test- where ellipse crosses the strip.
QUANTITATIVE!
Are susceptibility reports used in direct therapy or empiric therapy?
Used for antibiotic selection (directed therapy)
Susceptibility Reports will list the antibiotics tested for susceptibility including MIC values and CLSI interpretation (S, I, R) for an individual bacteria.
Caution – only an Indication of the antibiotic’s activity in the test tube (in vitro studies)
Are hospital antibiograms used for direct therapy or empiric therapy?
Antibiograms help guide choices for empiric antibiotic therapy before the bacteria has been identified.
An antibiogram is susceptibility data for most common bacteria isolated in a hospital annually.
Example Susceptibility Report
Specimen: Urine Culture Result: > 105 Escherichia coli Susceptibilities: Drug MIC | (ug/ml) |CLSI (S,I,R) Ampicillin| > 32 |(Resistant) Cefazolin |
S, I, R are based on 1. 2. 3. 4.
Kinetics, general activity, site of infection, clinical data
Empiric Therapy: antibiotics are given with activity against _____ _______ infecting bacteria.
You do empiric therapy until what?
Most likely infecting bacteria.
Empiric therapy is chosen based on Drug of Choice for most likely organism and regional susceptibility patterns.
Empiric therapy given until culture and susceptibility results for infecting bacteria are available.
Directed/targeted therapy: antibiotics dare selected to treat ________ infection.
Documented infection.
Antibiotic selected based on results of susceptibility studies; change to a more narrow spectrum agent
Given for predefined duration of therapy
Prophylactic Therapy- antibiotics are given to prevent what? What type of patients get prophylactic therapy?
List an example.
Antibiotics are given to prevent the development of infection during a procedure or immunocompromised state
Ex: pt with a prosthetic heart valve given amoxicillin to prevent endocarditis at the time of a bacteremia induced dental procedure
Treating infectious disease requires that therapy is given for a _________ duration of time.
Finite- a particular number of days is established based on previous clinical data for the infection type/infecting organism.
How long is prophylaxis therapy administered for?
As long as the patient is at risk- i.e. a single dose of antibiotics for a dental patient or pre-operative prophylaxis versus longer duration for antibiotic therapy during immunosuppressive states.
Combination Therapy is used to broaden bacterial coverage to cover all organisms causing infection. This decreases the emergence of what?
Resistance.
Combination (or multi-drug) therapy is the primary way to treat Tuberculosis!
Synergy
Is (A+B) greater than,less than , or equal to A+B?
(A+B)>A + B
The activity of the antimicrobial combination is greater than that expected from the additive activity of the individual antimicrobials.
Ampicillin + Gentamicin are administered together. Are their effects: additive, synergistic, or antatonistic?
Synergistic
Ampicillin & Gentamicin are administered together in the treatment of Enterococcal endocarditis in order to produce bactericidal activity and achieve successful eradication of the infection
-Alone each agent is bacteriostatic against Enterococcus
Additive & Antagonistic
What is the relationship of (A+B) to A + B?
Additive
(A+B)=A+B - activity of the antimicrobial combination is no greater than the sum of the effects of each individual component
Antagonism
(A+B)<a></a>
A patient with a community acquired pneumonia comes into the hospital. They are unable to expectorate a sputum sample. They are presenting with signs of bacterial meningitis and a lumbar puncture is performed. When would you administer antibiotics to this patients?
Antibiotics would be administered immediately after the lumbar puncture. EMPIRIC THERAPY. The location/symptoms are indicative of a meningitis infection. The exact site of infection may or may not be known, and the culture results may be pending.
A patient has bacteremia with methicillin-susceptible Staphylococcus aureus. You give them Nafcillin therapy to treat the infection. Is this:
a) Prophylactic therapy
b) Direct/targeted therapy
c) Empiric therapy
Direct/Targeted therapy
Culture is identified, there is an established infection, a causative pathogen, and antibiotic susceptibilities are known.
Bacteriostatic: antibiotic that _________ bacterial growth; _________ depends on host defense mechanisms.
What are disadvantages of using a bacteriostatic antibiotic?
Abx inhibits bacterial growth; killing depends on host defense mechanisms.
Disadvantages: in setting of inadequate host defenses, any partially inhibited organisms may survive, replicate, and produce recurrent infection when the antibiotic is discontinued (or serum concentrations fall below MIC)
Bactericidal: antibiotic _______ bacteria; less dependent on host defense mechanisms.
When is a bactericidal antibiotic required? When is it preferred?
Antibiotic kills bacteria.
Required for treatment of meningitis, endocarditis, osteomyelitis, febrile neutropenia
Preferred bactericidal abx treatment when host immune system is compromised or does not function well (neturopenic or immunosuppressed)
Are the following bactericidal or bacteriostatic? Cell Wall Inhibitors Protein Synthesis Inhibitors Nucleic Acid Synthesis Inhibitors Metabolic Inhibitors
Cell Wall Inhibitors- bactericidal
Protein Synthesis Inhibitors- bacteriostatic besides aminoglycosides
Nucleic Acid Synthesis Inhibitors- bactericidal
Metabolic Inhibitors- bactericidal
Pharmacokinetics: Concentration/Time
Pharmacodynamics: Concentration/Effect
What is PK/PD?
Effect vs. Time
Define the following pharmacodynamic parameters:
- Cmax
- AUC/MIC
- Time above MIC
Cmax: maximum concentration of the antibiotic
AUC/MIC- area under the curve/minimum inhibitory concentration
Time above MIC- what is clinically relevant
Post-Antibiotic Effect (PAE)
Time it takes for a bacteria to regrow once serum concentrations of the antibiotic have dropped below the MIC
-Duration of PAE is ______ & _______ specific
-Agents with long PAE can be dosed to allow serum concentrations to fall below the _______
- Duration of PAE is drug and organism specific
- Agents with long PAEs can be dosed to allow serum concentrations to fall below the MIC
Describe the PAE for gram positive and gram negative bacteria.
- Gram-positive bacteria - all antibiotics have some PAE; 2 hours for beta-lactams
- Gram-negative bacteria - prolonged PAEs with protein or nucleic acid synthesis inhibitors such as aminoglycosides and fluoroquinolones
Concentration Dependent Killing
The _______ the serum concentrations, the more rapid and extensive killing
Prolonged persistent (post antibiotic) effects
The higher the serum concentration
Time Dependent Killing
Killing depends on __________ above the MIC not ________ serum concentrations
Killing depends on time of exposure above the MIC not higher serum concentrations
What are the 3 Infection-Specific Parameters to consider when choosing an antibiotic?
- ______ of infection
- ______ of infection
- __________ organism
- Severity of infection
- Site of infection
- Infecting organism
How do the following host factors influence what antibiotic to choose?
- Allergies
- Age
- Pregnancy
- Renal/Hepatic Function
- Concomitant Drug Therapy
- Underlying disease states
- Allergies- allergy history/verify allergic reaction. Patients in need of a specific abx that they are allergic to can start low dose IV monitored treatments of drug to induce tolerance.
- Age- influences PK (infants/elderly)
- Pregnancy- increased Volume of Distribution, greater renal clearance in pregnant women. Consider if abx can cross the placenta barrier.
- Renal/Hepatic Function- diminished function may lead to drug accumulation and undue toxicity
- Concomitant Drug Therapy- assess for potential drug interactions that may augment toxicity or alter PK
- Underlying disease states- may predispose a patient to a particular infection or pathogen
What drug factors should be considered when choosing an antibiotic?
- in vitro activity and current ____________
- established _______ __________
- _____ of _______ charts
- _____ and tissue penetration
- _____________
- ______ __________ Profiles
- $________$
*In vitro activity and current susceptibilities
*Established clinical efficacy - FDA-approved indications or other published clinical trials
*Drug of choice charts – treatment guidelines, books
*PK and tissue penetration - drug must get sufficient concentrations at the site of infection; route of administration needed
* PD - what type of bacterial activity is needed for organism and infection type
*Side effect profiles - potential adverse effects associated with each drug
*Cost
Cost of antibiotic itself
Number of administrations per day
Number of antibiotics required to treat the infection
Intravenous versus oral
Monitoring of serum concentrations and toxicity
What drugs cause concentration dependent bactericidal killing? (4)
- Lipopeptides - DAPTOMYCIN
- Aminoglycosides - Gent, tobra, Amikaicn
- Fluoroquinolones - Ciprofloxacin, Levo, Moxi
- Metronidazole
What drugs are bacterioSTATIC? (6)
- Macrolides ( erythro, azithro, clarithromycin)
- Tetracyclines: Doxycyline, tetra, tigecycline
- CHloramphenicol
- Lincosamides - Clindamycin
- Streptogramins (quinupristin/dalfopristin - Synercid)
- Oxazelidinones - Linezolid (only CIDAL for strep pneumoniae)
