Principles of Antimicrobial Use
Siriluck Anunnatsiri, MD, MCTM, MPH
Infectious Diseases & Tropical Medicine
Department of Medicine
Khon Kaen University
Identification of the Infective Organisms
History taking
Physical examination
Laboratory
History Taking
• Duration of fever
• Associated symptoms:
Systematic review
• History of treatment
• Underlying diseases and
Medication
• Occupation
• Living place
• Traveling
• Pets
• Vaccination and drug
prophylaxis
• Illness in family
• Diseases outbreak
• Food consumption
Physical Examination
Physical Examination
Laboratory Investigation in the Diagnosis of Infectious Agents
Mandell, Douglas, and Bennett’s Principle and Practice of Infectious Diseases
Gram Stain
Gram Stain
AFB Stain
Modified AFB Stain
Wright Stain
India Ink Preparation
Fresh Smear / KOH Preparation
Microbial Factors:
Antimicrobial susceptibility
• Appropriate specimen collection and transport
• Disk diffusion susceptibility testing
• Minimal inhibitory
concentration (MIC)
Microbial Factors:
Antimicrobial Resistance
Susceptible Bacteria
Resistant Bacteria
Resistance Gene Transfer
New Resistant Bacteria
http://www.cdc.gov
Mechanism of R-gene Transfer
Levy, SB. The challenge of antibiotic resistance. Sci Am 1998:46-53.
Selection for Antimicrobial-resistant
Strains
Resistant Strains
Rare
Antimicrobial
Exposure
Resistant Strains
Dominant
http://www.cdc.gov
Mechanisms of Antimicrobial Resistance
Levy, SB. The challenge of antibiotic resistance. Sci Am 1998:46-53.
Host Factors
Underlying diseases
Drug allergy
Pregnancy/Breast feeding
Age
Genetic or Metabolic abnormalities
Sites of infection
Immune status
Hepatic and renal function
Antimicrobial Factors
Spectrum
Mechanisms of action
Pharmacokinetic
Pharmacodynamic
Drug interaction
Side effect
Drug monitoring
Mechanisms of Action
Bactericidal agents
Bacteriostatic agents
Bactericidal agents
Pharmacokinetics of Antimicrobial Agents
• Absorption
• Consider extent and rate of absorption via route of
administration
• Consider drug interaction and food effect
• Distribution to the site of infection
• Volume of distribution (Vd)
• Water soluble drug, small Vd  high serum conc.
• Lipophilic drug, large Vd  extensively distributed
in body fluid and tissue
• Vascular supply
Pharmacokinetics of Antimicrobial Agents
• Distribution to the site of infection (cont.)
• Protein binding
• Local factor at site of infection: pH, dense population
of organism, foreign body
• Metabolism
• Mainly in liver
• Active vs. Inactive metabolites
• Route of metabolism esp. CYP P450 system
• Elimination
• Route of elimination: mainly by kidney, liver
• Rate of elimination: T1/2
Pharmacodynamics of Antimicrobial Agents
• Pharmacodynamic characteristics
• Time-dependent bactericidal action
• Concentration-dependent bactericidal actions
• Bacteriostatic action
• Postantibiotic effect
• Inoculum effect
• In vitro action of antibiotic combination
PD Parameters affecting Antibiotic Potency
AUC/MIC
>125 for GNB
>25-50 for GPC
Cmax/MIC >10
> 40-50% of dosing interval
Postantibiotic effect
Inoculum Effect
• The effect of inoculum size on antimicrobial
activity
• Dense population can be less susceptible to lactams
• Failure to express receptor (PBP)
• High concentration of -lactamases
• Trend to presence of resistant subpopulation
In Vitro Testing of Antibiotic Combination
Indications for Antimicrobial
Combinations Therapy
Prevention of the emergence of resistant organisms
Polymicrobial infections
Empirical therapy
As narrow as possible, as broad as necessary
Synergistic/Additive activity
Disadvantages of Inappropriate Use of
Antimicrobial Combinations
Antagonism
Superinfection
Cost
Adverse effects
Reasons for Treatment Failure
Delay in diagnosis or therapy
Wrong or incomplete diagnosis
No infection
Nonbacterial infection
Polymicrobial infection
Errors in susceptibility testing
Decreased activity at site of infection
Chemical factor (pH and others)
Antibiotic antagonism
Reasons for Treatment Failure
Inadequate concentration of antibiotic at the site
of infection
Improper dose
Decreased absorption from food or drug interaction
Increased elimination of agent
High protein binding
Poor delivery (eg. shock, vascular diseases)
Reasons for Treatment Failure
Other host factors
Collection requiring drainage
Necrotic tissue
Foreign body
Impaired immune defenses
Development of drug resistance
Superinfection
Summary: Step in Approaching Patients
When Considering Antibiotic Therapy
• Make a tentative diagnosis based on the history
and physical examination including bed-side lab.
• Determine if antibiotic therapy is necessary for the
given infection
• Choose the individual agent for the infection
based on the following:
In vitro activity of the antibiotic against the most likely
pathogens in the disease
Summary: Step in Approaching Patients
When Considering Antibiotic Therapy
Evidence-based results demonstrate efficacy, safety,
and cost-effectiveness of the antibiotic in the
disease and in patient populations similar to that of
the presenting patient
Side effect profile of the drug:
Allergic reaction
Direct adverse effects of drug
Drug-drug and drug-food interaction
Use least expensive and narrowest-spectrum drug
possible (Optimal drug, dose, and duration)
Use Antimicrobials Wisely
Treat infection, NOT contamination or
colonization
A major cause of antimicrobial overuse is “treatment”
of contaminated cultures or colonization.
Use local data
Know your local antibiogram
Know your patient population
Not all infections need antimicrobial therapy
http://www.cdc.gov
Use Antimicrobials Wisely
Stop antimicrobial treatment
•
•
•
When infection is cured
When cultures are negative and
infection is unlikely
When infection is not diagnosed
http://www.cdc.gov