Principles of Infectious Disease and Antimicrobial Therapy Flashcards
Systematic approach for Selecting Antimicrobial Agents
- Confirm the presence of infection
- Determine the site of infection
- Identify the pathogen
- Select presumptive therapy
- Refine therapy
- Monitor therapeutic response
Factors to help confirm the presence of infection
H&P
Predisposing factors
Signs and Sxs
- Fever
- WBC count with differential
- Normal 4500-10,000
- Inc WBC with left shift (more neutrophils= bacterial)
- Other: ESR, CRP, procalcitonin
- Pain and inflammation
- Disease specific signs and sxs
Normal temperature
98.6F or 37C
Febrile temperatures
100.4F 38C
102F 39C
104F 40C
Drugs that can cause a false positive and false negative fever
False +
- Drug induced
False -
- ASA, APAP, NSAIDS
- Corticosteroids
WBC Differential
With bacterial infection, WBC may be as high as 30,000-40,000
Presence of immature bands (neutrophils), that are >10%, is indicative of bone marrow response to bacterial infection
Other tests of inflammation
ESR
CRP
Procalcitonin (PCT)–appears to reflect severity of infection
Identification and Classification of Pathogen
- Stains–Gram stain, acid fast, India ink
- Serologies
- Culture and activity
Common Uses of Gram Stain
Empiric antimicrobial treatment
Routinely performed on:
- CSF for meningitis
- Urethral smears for UTI
- Abscesses or effusions
Selection of Presumptive Therapy is Based On….
Host factors
Drug factors
Host factors
Drug allergies
Age
Pregnancy
Renal and hepatic function
Site of infection
Concomitant drug therapy
Underlying disease states
Drug factors
Antimicrobial activity
Spectrum of activity
Pharmacokinetics
Pharmacodynamics
Tissue penetration
Adverse effect profile
Cost and convenience
Antimicrobial activity
Bactericidal
- Kills sensitive organisms so that the number of viable organisms falls rapidly after drug exposure
Bacteriostatic
- Inhibits the growth of the bacteria but does not kill them; immunologic mechanisms are required to eliminate organisms
Most common mechanism of action of antibiotics
Blocks cell wall synthesis and protein synthesis
Antimicrobial Spectrum of Activity
Narrow
Extended
Broad
Minimum Inhibitory Concentration
The lowest antimicrobial concentration that prevents visible growth of an organism after 24hrs of incubation
Susceptibility Testing Methods
Macrodilution method
Microdilution method–Multiple Abx
Kirby-Bauer disk diffusion method
E-test – strip
Automated methods
Bacteria can be classified as
(Sensitivity and Resistance)
Susceptible
Intermediate
Resistant
Based on the relationship between MIC adn peak serum concentration of typical doses
Peak should be 2-4X MIC to be susceptible
Factors that increase antibiotic resistance
Overuse of antibiotics
Low dose and inadequate levels
Prlonged exposure
Inappropriate antibiotics
Day Care
Resistance also varies with region, and increases with careless antibiotic use
Requirements for antibiotic activity
Penetrate Cell
Reach Intracellular Target
Kill Organism
Mechanism of Resistance
Decreased permeability
Drug efflux
Drug inactivation
Altered target
Pharmacokinetic and Pharmacodynamic factors to consider when choosing presumptive therapy
Concentration and time dependent effects
- MIC
- CDKR: Concentration-Dependent Killing Rate
- PAE: Postantibiotic effect
CDKR
Concentration-Dependent Killing Rate
More bacteria are killed at higher concentrations of antibiotics
i.e.aminoglycosides and fluoroquinolones
Not beta lactams
PAE
Postantibiotic Effect
Persistent effect of an antibiotic on bacterial growth after the antibiotic is removed
Most bactericidal antibiotics exhibit PAE
Less frequent dosing allowed
