L20, 21 Introduction to Antibiotics Flashcards
Appropriate antibiotic therapy depends on what factors?
- Knowledge/suspicion of the site of infection and subsequent infecting pathogen (where/what)
- Spectrum of activity of the antibiotic
- Host characteristics
True or false - it does not matter when you obtain a culture from a patient.
False - obtain cultures from the suspected site before antibiotics are initiated.
True or false - isolation of an organism from a clinical specimen does not always indicate the presence of infection.
True
What are the four possibilities when an organism is detected in culture?
- Normal flora
- Contamination
- Colonization
- Infection
What happens to a patient’s flora within 48 hours of admission?
They are colonized with “new flora” (usually gram-negative aerobes)
Why do normal flora suppress the growth of pathogenic bacteria?
They colonize sites that might be otherwise colonized by pathogenic bacteria.
What are the 7 sterile body sites and the fluids found in each?
- Bloodstream (blood)
- Subarachnoid space (CSF)
- Pleural space (pleural fluid)
- Peritoneum (peritoneal fluid)
- Pericardiam (pericardial fluid)
- Synovium (synovial fluid)
- Urinary tract (urine - directly from bladder)
What is contamination and a common example?
Organism inadvertently introduced into the specimen during collection or processing; coagulase negative staph in the blood of the patient
What is colonization and a common example?
Organism is present at a body site but is not invading host tissue or invading signs and symptoms of infection; pseudomonas aeruginosa in the sputum of a patient without signs of pneumonia
What is infection and a common example?
Pathogenic organism is damaging host tissue and eliciting signs and symptoms of infection; S. pneumoniae in the sputum of a patient with fever, productive cough, and shortness of breath
Certain bacteria have a propensity to commonly cause infection in particular ___. Give 2 examples.
Body sites or fluid; E. coli in the urine and S. aureus in skin abscesses
What information can help choose an antibiotic before the results of a culture are available?
- Site of infection
- Likely causative organism
- Gram-stain result
Why are antibiotics initiated when an infection is suspected but not confirmed?
Undue delay may lead to significant morbidity or mortality
What is the difference between empiric and direct/targeted therapy?
Empiric is chosen based on activity against likely pathogens; direct/targeted is modified once culture and susceptibility results are available
What is the antimicrobial spectrum of activity?
General list of bacteria that are killed or inhibited by an antibiotic; established during early clinical trials
What type of antibiotic has activity against a limited group of bacteria?
Narrow spectrum
What type of antibiotic has activity against a wide variety of bacteria?
Broad spectrum
___ testing is performed on individual bacterial isolates once grown and identified in culture.
Antibiotic susceptibility
What is the MIC (minimum inhibitory concentration)?
Lowest concentration of an antibiotic that inhibits visible bacterial growth
What is the MBC (minimum bactericidal concentration)?
Lowest concentration of an antibiotic that kills bacteria (decreases inoculum by 99.9%)
What are interpretive guidelines established by the CLSI that categorize specific antibiotic MIC values for a given bacteria?
Susceptibility breakpoints
What are the 3 susceptibility breakpoints and what do they mean?
- Susceptible: organism will most likely be eradicated with normal doses of the antibiotic
- Intermediate: treatment may be successful using maximal doses of the antibiotic
- Resistant: MIC exceeds usual serum concentrations of the antibiotic, so less than optimal results are expected
Why do S, I, and R vary for each antibiotic and each bacteria?
They are based on the PK of the drug, general activity of the antibiotic, site of infection, and data from clinical efficacy trials.
In general, can MIC values be compared between different antibiotics?
No
What are the two major methods for MIC determination and how do they work, generally?
- Macrodilution
- Microdilution
Two-fold serial dilutions of the antibiotic in broth are incubated with a standard inoculum of the infecting bacteria
In a broth dilution, what is the MIC?
The lowest concentration of antibiotic that prevents visible growth of the bacteria (first tube without visible growth)
How does a macrodilution differ from a microdilution?
A macrodilution involves test tubes with dilutions of one antibiotic; a microdilution involves microtiter plates or cassettes with serial dilutions of several antibiotics
Which type of dilution yields the exact MIC of the antibiotic?
Macrodilution
What does MBC do?
Extends the macrodilution test and represents the antibiotic concentration that kills the bacteria
What is a qualitative test of the in vitro activity of an antibiotic (MIC not determined)?
Disk diffusion (Kirby Bauer)
What test combines the quantitative benefits of broth dilution with the ease of disk diffusion and yields an MIC? Where is the MIC?
E-test; where the ellipse crosses the strip
What is included in a hospital antibiogram?
Susceptibility data for the most common bacteria isolated in the hospital annually
What type of therapy decreases the emergence of resistance?
Combination therapy
What is it called when the activity of the antimicrobial combination is greater than expected from the additive activity of the individual antibiotics?
Synergy combination therapy
What is it called when the activity of the combination is no greater than the sum of the effects of each individual agent?
Additive combination therapy
What is it called when the activity of the combination is less than expected from the additive activity of the individual agents?
Antagonistic combination therapy
What type of antibiotic inhibits bacteria growth? What does killing depend on?
Bacteriostatic; the host defense mechanisms
What are the disadvantages of bacteriostatic antibiotic therapy?
In the 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)
What are 8 examples of bacteriostatic antibiotics?
- Macrolides
- Ketolides
- Tetracyclines
- Glycylcyclines
- Sulfonamides
- Clindamycin
- Synercid
- Linezolid
What type of antibiotic kills bacteria?
Bactericidal
What are bactericidal antibiotics preferred? When are they required?
Preferred: immunocompromised
Required: endocarditis, osteomyelitis, febrile neutropenia
What are 10 examples of bactericidal antibiotics?
- Penicillins
- Cephalosporins
- Carbapenems
- Aztreonam
- Fluoroquinolones
- Aminoglycosides
- Vancomycin
- Daptomycin
- Bactrim
- Metronidazole
Which categories of antibiotics are bactericidal? Which are bacteriostatic?
Bactericidal: cell wall synthesis inhibitors, nucleic acid synthesis inhibitors, metabolic inhibitors
Bacteriostatic: protein synthesis inhibitors
PK/PD looks at the ___ vs. ___.
Effect; time
What is the PAE (post-antibiotic effect)?
The time it takes for a bacteria to regrow once serum concentrations of the antibiotic have dropped below the MIC; it is specific to the drug and organism
Agents with ___ (long/short) PAEs can be dosed to allow serum concentrations to fall below the MIC.
Long
Describe the PAE of Gram-positive bacteria.
All antibiotics have some PAE; 2 hours for beta-lactams
Describe the PAE of Gram-negative bacteria.
Prolonged PAEs with protein or nucleic acid synthesis inhibitors such as aminoglycosides and fluoroquinolones
The higher the concentration, the ___ (greater/lesser) the killing. This is concentration-dependent killing.
Greater
Describe time dependent killing.
In time-dependent killing, the killing depends on the time of exposure above the MIC, not on the serum concentration.
Changing the ___ can extend the time of infusion to improve time dependent killing.
Rate of infusion
What are the 5 general steps to anti-microbial selection?
- Confirm presence of infection
- Select empiric therapy
- Identify pathogen
- Modify antibiotic therapy
- Monitor therapeutic response
What are the 3 infection-specific parameters to consider when choosing an antibiotic?
- Severity of infection (affects route of administration, dose, # of antibiotics)
- Site of infection
- Infecting organism
What are the 6 host factors to consider when choosing an antibiotic?
- Allergies
- Age
- Pregnancy or nursing
- Renal/hepatic function
- Concomitant drug therapy
- Underlying disease states
Which 7 antibiotics are primarily eliminated by the kidneys?
- Most beta-lactams
- Vancomycin
- Aminoglycosides
- Some FQs
- Bactrim
- Daptomycin
- Tetracyclin
Which 9 antibiotics are eliminated by the liver?
- Macrolides
- Synercid
- Linezolid
- Clindamycin
- Metronidazole
- Some FQs
- Bactrim
- Doxycycline
- Tigecycline
What drug factors should be considered when choosing an antibiotic?
- In vitro activity and current susceptibilities
- Established clinical efficacy
- Drug of choice charts
- PK and tissue penetration
- PD
- Side effects
- Cost
