Week 2: Bacterial Infections (Dr. Tsuji) Flashcards
Relationships based on that one figure in the slides ( You know the one)
- Drug —-> Host=?
- Host —–>Drug=?
- Drug —–> Bacteria=?
- Bacteria-> Drug=?
- Bacteria-> Host=?
- Host——> bacteria=?
- Toxicodynamics
- Pharmacokinetics
- Pharmacodynamics
- Resistance
- Infection
- Host defenses
Bacteria at site of infection usually already live there asymptomatically.
What makes the bacteria cause infection?
Breakage and compromise of barrier
Non Specific Indicators of Infection
- Fever
- daily variations in
temperature occur
-Increased temperature (caused by pyrogen such as interleukins (IL-1, TNF), other causes: autoimmune disease, drug induced, antibiotics)
-Leukocytosis
(Differential White Blood Cell (WBC): 5-10,000/mm3
& Increased in immature neutrophils (bands) “Shift to the left” Normal 40-60% SEGS, 0-5% bands.)
- Elevated immunoglobulins (non-specific antibodies)
- Physical Evidence: Pain, swelling, inflammation, erythema, tenderness, purulent drainage.
- Radiological evidence
Host defenses: Mechanical and Non Specific Factors
a) Skin and mucous membranes:
- effective barriers against microbes bc very few organisms can penetrate skin.
- Desquamation: epithelial cell turnover at body services remove large numbers of adhering microbes. Skin conditions not ideal: dry, acidic, salt, temperature < 370C
b) Elimination: tearing, peristalsis, defecation, urination etc.
c) Acidity: gastrointestinal tract pH, urine etc. decreases pathogen ability to invade.
d) Cytokines: hormone like polypeptides produced in response to invading microorganisms trigger immune system
e) Fever: Temperature > 100.50F, 38.10C
Infecting microorganisms: Endogenous vs exogenous
Endogenous:
natural flora, commensal organisms.
-Benefit the host.
- May become pathogenic if translocated.
Exogenous: acquired from external sources. -Carriers: Humans Animals Insects Objects
Infecting Microorganisms: Attributes
a) Adherence: microbial adherence to epithelial cell surfaces
- Filamentous structures: fimbriae
- Lipoteico acid projections
- Adhesion molecules
b) Toxin Production
- Endotoxins: Lipid A (lipoidal acylated glucosamine disaccharide)
- Exotoxins: Can suppress IgM activity: Toxic Shock Staphylococcal Toxin
c) Enzyme Production
- aids in organism invasion
- antibiotic destruction
d) Non-toxin Factors
- slow growth (eg. tuberculosis)
- Glycocalyx production (eg. Staphylococcus epidermidis)
- IgA1 protease (eg. H. influenzae)
- incorporates human transferin, produces IgA1 protease (N. gonorrhea)
- binding to human transferin, lactoferin, coating with soluble fibrin ( Treponema pallidum)
Infectious Diseases: Diagnosis
- Clinical Signs and Symptoms
- Patient history
- Physical exam
- Radiologic evidence
- Gram’s stain
- Culture
Infectious diseases: Specific Indicators
- Gram-stain of pathogenic organism
- blood or wound cultures of pathogenic organisms
- Immunodiagnosis of infection
Antimicrobial Susceptibility Testing:
-Minimum Inhibitory Concentration [What is it?]
&
-Minimum Bacterial Concentration [What it is, method]
- What is tolerance?
- Clinical Utility of MIC/MBC
- Minimum Inhibitory Concentration (MIC): Lowest concentration of given antimicrobial that will inhibit (visual) the patient’s organism from growing after 18- 24 h incubation.
- Minimum Bactericidal Concentration (MBC): Lowest concentration of a given antimicrobial that will kill (99.9%) of the patient’s organism after 18-24 h incubation.
Determined following the performance of the broth dilution MICs.
Method: dilutions of the antimicrobial agents MIC are subcultured onto antibiotic-free agar. Plates are incubated. Lowest conc. of antibiotics able to kill > 99.9% of original inoculum is the MBC.
Determination of MBC is not a routinely performed procedure.
The test is not standardized between laboratories. May be determined for serious infections or to help characterize investigational agents.
-Tolerance: defined as a wide disparity between MIC and MBC (MIC/MBC ratio >32). Clinical significance is unknown.
-Clinical use:
~MIC: utilized to determine selection of definitive antibiotic therapy.
~MBC: determined when bactericidal activity required for successful outcome (e.g., meningitis, endocarditis etc.) MBC>MIC > 32 the organism is considered “tolerant “to the antibiotic.
Disk Diffusion (Kirby-Bauer Test)
- Qualitative test applicable to organisms that grow rapidly on artificial media.
- Creates zone of inhibiton
- Size of zone correlates with susceptibility.
- Results are expressed as S (sensitive), I intermediate) or R (resistant).
- Advantages: speed, low cost and minimum labor. Disadvantage: no MBC
Broth Dilution: What is it? Process
Macrotube vs. microtube
-Macrotube: serial two fold dilutions of antimicrobial agents are made into Mueller- Hinton broth followed be the addition of bacteria. The MIC is defined as the tube containing the highest dilution of antimicrobial inhibiting visual growth.
Microtube: same as macrotube, only performed in smaller volumes in plastic microtiter plates.
-Employed by many hospitals due to adaptability to automation (Microscan, Viotek etc.).
Advantages: ability to determine MBC and automated.
Disadvantage: macrotube procedure is labor intensive.
E- test: Process, advantages, disadvantages
- antibiotics diffuse from plastic strips into agar to interact with bacteria that have been streaked onto the agar plate.
- Each plastic strip is impregnated with the antibiotic in a gradient fashion. The strip is placed directly onto the surface of the agar plate with standardized inoculum
- Plate is incubated for 18-24 h at 370C.
- A tear shaped zone of inhibition is formed and the MIC is read as the lowest point of intersection on the E-strip.
Advantages:
- Quantify MIC
- Easy to perform with high reproducibility.
- Multiple antibiotics can be tested per plate.
Disadvantages:
- E-strips are very expensive.
- MBC cannot be determined by this method.
