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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. Duration of fever

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Principles of antimicrobial use

Principles of Antimicrobial Use

Siriluck Anunnatsiri, MD, MCTM, MPH

Infectious Diseases & Tropical Medicine

Department of Medicine

Khon Kaen University


Identification of the infective organisms
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

History Taking




Laboratory investigation in the diagnosis of infectious agents
Laboratory Investigation in the Diagnosis of Infectious Agents

Mandell, Douglas, and Bennett’s Principle and Practice of Infectious Diseases


Gram stain
Gram Stain Agents


Gram stain1
Gram Stain Agents


Afb stain
AFB Stain Agents



Wright stain
Wright Stain Agents




Microbial factors antimicrobial susceptibility
Microbial Factors: AgentsAntimicrobial susceptibility

  • Appropriate specimen collection and transport

  • Disk diffusion susceptibility testing

  • Minimal inhibitory concentration (MIC)


Microbial factors antimicrobial resistance

Resistant Bacteria Agents

Chromosomal mutations

XX

Resistance Gene Transfer

New Resistant Bacteria

Microbial Factors:Antimicrobial Resistance

Susceptible Bacteria

http://www.cdc.gov


Mechanism of r gene transfer
Mechanism of R-gene Transfer Agents

Levy, SB. The challenge of antibiotic resistance. Sci Am 1998:46-53.


Selection for antimicrobial resistant strains

x Agents

x

Resistant StrainsRare

Antimicrobial

Exposure

Resistant Strains

Dominant

x

x

x

x

x

x

x

x

x

x

Selection for Antimicrobial-resistant Strains

http://www.cdc.gov


Mechanisms of antimicrobial resistance
Mechanisms of Antimicrobial Resistance Agents

Levy, SB. The challenge of antibiotic resistance. Sci Am 1998:46-53.


Host factors
Host Factors Agents

  • Underlying diseases

  • Drug allergy

  • Pregnancy/Breast feeding

  • Age

  • Genetic or Metabolic abnormalities

  • Sites of infection

  • Immune status

  • Hepatic and renal function


Antimicrobial factors

Spectrum Agents

Mechanisms of action

Pharmacokinetic

Pharmacodynamic

Drug interaction

Side effect

Drug monitoring

Antimicrobial Factors


Mechanisms of action
Mechanisms of Action Agents

Bactericidal agents

Bacteriostatic agents

Bactericidal agents


Pharmacokinetics of antimicrobial agents
Pharmacokinetics of Antimicrobial Agents 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 agents1
Pharmacokinetics of Antimicrobial Agents 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
Pharmacodynamics of Antimicrobial Agents 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
PD Parameters affecting Antibiotic Potency Agents

AUC/MIC

>125 for GNB

>25-50 for GPC

Cmax/MIC >10

> 40-50% of dosing interval

Postantibiotic effect


Inoculum effect
Inoculum Effect Agents

  • 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



Indications for antimicrobial combinations therapy
Indications for Antimicrobial AgentsCombinations 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
Disadvantages of Inappropriate Use of Antimicrobial Combinations

  • Antagonism

  • Superinfection

  • Cost

  • Adverse effects


Reasons for treatment failure
Reasons for Treatment Failure Combinations

  • 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 failure1
Reasons for Treatment Failure Combinations

  • 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 failure2
Reasons for Treatment Failure Combinations

  • 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
Summary: Combinations 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 therapy1
Summary: Combinations 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 Combinations

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
Use Antimicrobials Wisely CombinationsStop antimicrobial treatment

  • When infection is cured

  • When cultures are negative and infection is unlikely

  • When infection is not diagnosed

http://www.cdc.gov


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