Intro to antibiotics (2 lectures) Flashcards
Sites and their fluids that are considered sterile
Bloodstream Blood Subarachnoid space CSF Pleural space Pleural fluid Peritoneum Peritoneal fluid Pericardium Pericardial fluid Synovium Synovial fluid Urinary tract Urine (directly from bladder)
anything that grows in these sites is a pathogen/infection
Contamination
organism inadvertently introduced during specimen collection or processing
ex. Coag-neg staph in blood of patient
Colonization
organism is present at body site but is not invading host tissue or inducing signs and symptoms of infection
ex. Pseudomonas aeruginosa in the sputum of a patient who is not displaying signs of pneumonia
Infection
Infection
pathogenic organism is damaging host tissue and eliciting signs and symptoms of infection
ex. Streptococcus pneumoniae in sputum of patient with fever, productive cough, and shortness of breath
Antibiotics may be chosen before results of the cultures are available based on what information
Site of infection and likely causative organism
Gram-stain result (does result correlate with most likely suspected organism?) (in the CSF gram stain may give an exact diagnosis)
empiric therapy vs. directed or targeted therapy
empiric therapy - Antibiotics are chosen that have activity against likely pathogens
direct therapy - Antibiotic regimen is modified once culture and susceptibility results are available
Spectrum of Activity
Spectrum of activity is the general list of bacteria that are killed or inhibited by an antibiotic
- Established during early clinical trials of the antibiotic
- Recent local, regional and national susceptibility patterns of each bacteria should be continuously evaluated because antibiotic activity may change over time due to emergence of resistance
narrow vs broad spectrums of activity
Narrow Spectrum = antibiotic has activity against a limited group of bacteria
Broad Spectrum = antibiotic has activity against a wide variety of bacteria
Appropriate antimicrobial therapy depends on
knowledge of: the potential site of infection; the infecting pathogen(s); the expected activity of the antibiotic(s) against the infecting pathogen(s); and host characteristics.
Therefore, appropriate diagnosis is crucial.
Minimum Inhibitory Concentration or MIC
lowest concentration of an antibiotic that inhibits visible bacterial growth (unaided eye) of a bacteria after 18
to 24 hours of incubation
Minimum Bactericidal Concentration or MBC
the lowest concentration of an antibiotic that results in a decrease of > 99.9% of the bacterial inoculum
(MIC
Susceptibility Breakpoints
based on the MIC of an antibiotic for a specific bacteria
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
Susceptibility Breakpoints are based on
- Pharmacokinetics of the drug - achievable serum and tissue concentrations
- General activity of the antibiotic
- Site of infection
- Data from clinical efficacy trials
In general, MIC values should not be compared between different antibiotics
Interpretive guidelines for S, I and R for each antibiotic and each bacteria are different
how is the MIC determined
Macrodilution, microdilution, Disk Diffusion – Kirby Bauer, E-Test®, and PCR
Macrodilution
Macrodilution - two-fold serial dilutions of an antibiotic are incubated with a standard inoculum of the infecting bacteria in test tubes
• MIC = first tube without visible growth
• Results yield the EXACT MIC of the antibiotic against the infecting organism
• Not routinely performed because it is labor and resource intensive
MBC from macrodilution
(not routine) – extension of macrodilution test; MBC represents the antibiotic concentration that kills bacteria (no colonies are present on agar plates)
Microdilution
microtiter plates or cassettes with (already prepared) serial dilutions of several antibiotics tested at the same time
• Automated; most common method
•Due to size restraints of cassettes, not all concentrations of an antibiotic can be tested for susceptibility
• Result may be reported as an MIC range, such as ≤ 8 µg/ml Susceptible
• Vitek,Microscan
Disk Diffusion – Kirby Bauer
QUALITATIVE test of the in vitro activity of an antibiotic; MIC is not determined
• Filter paper disks impregnated with a fixed concentration of an antibiotic are placed on agar plates inoculated with a standard concentration of the infecting bacteria
• Clear zone of inhibition is observed around the disk - bacteria only grows where concentrations of the antibiotic are below those required to inhibit bacterial growth
• Zone diameters (in mm) correlate with S, I, R
E-Test®
Combines quantitative benefits of broth dilution with the ease of disk diffusion; yields an MIC
• Plastic strip impregnated with known, predefined concentration gradient of antibiotic is placed on agar plates • inoculated with standard concentration of infecting bacteria
• Clear elliptical zone of inhibition is observed around strip - bacteria only grow where concentrations are below those required to inhibit bacterial growth
• MIC = where ellipse crosses the strip
Hospital Antibiograms
- Susceptibility data for most common bacteria isolated in hospital annually
- Helps guide choice for empiric antibiotic therapy before bacteria has been identified
Empiric therapy
Antibiotics are administered that have activity against the predicted or most likely pathogens causing a patient’s infection based on the signs and symptoms of infection. The site of infection may or may not be known, and the culture results are pending, negative, or unobtainable.
- Therapy chosen based on DOC for most likely organism and regional susceptibility patterns
- Given until culture and susceptibility results for infecting bacteria are available
Directed or targeted therapy
antibiotics are selected to treat documented/established infections
• Antibiotic selected based on results of susceptibility studies → change to a more narrow spectrum agent
• Given for predefined duration of therapy
Prophylactic therapy
antibiotics given to prevent the development of infection
• Therapy chosen based on DOC for most likely organism and regional susceptibility patterns
• Administered for as long as patient is at risk
examples: antibiotics given during surgery or dental procedures,
Combination therapy
Broaden bacterial coverage to cover all organisms causing infection
Decrease the emergence of resistance
Take advantage of synergy when antibiotics are used together
