The Rational Use of Antibiotics

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					The Rational Use of
    Antibiotics
            Victor Lim
 International Medical University
     Kuala Lumpur, Malaysia
             Antibiotics
   One of the most commonly used
    group of drugs
   In USA 23 million kg used annually;
    50% for medical reasons
   May account for up to 50% of a
    hospital’s drug expenditure
   Studies worldwide has shown a high
    incidence of inappropriate use
Reasons for appropriate use
   Avoid adverse effects on the patient
   Avoid emergence of antibiotic
    resistance - ecological or societal
    aspect of antibiotics
   Avoid unnecessary increases in the
    cost of health care
     Ecological/Societal Aspect
   Antibiotics differ from other classes of
    drugs
   The way in which a physician and other
    professionals use an antibiotic can affect
    the response of future patients
   Responsibility to society
   Antibiotic resistance can spread from
       bacteria to bacteria
       patient to patient
       animals to patients
    Prescribing an antibiotic
   Is an antibiotic necessary ?
   What is the most appropriate
    antibiotic ?
   What dose, frequency, route and
    duration ?
   Is the treatment effective ?
Is an antibiotic necessary ?
 Useful only for the treatment of
  bacterial infections
 Not all fevers are due to infection
 Not all infections are due to bacteria
   There is no evidence that antibiotics will
    prevent secondary bacterial infection in
    patients with viral infection
Arroll and Kenealy, Antibiotics for the common
cold. Cochrane Database of Systematic Reviews.
Issue 4, 2003



Meta-analysis of 9 randomised placebo
  controlled trials involving 2249 patients

Conclusions: There is not enough evidence of
  important benefits from the treatment of upper
  respiratory tract infections with antibiotics and
  there is a significant increase in adverse
  effects associated with antibiotic use.
Is an antibiotic necessary ?
 Not all bacterial infections require
  antibiotics
    Consider other options :
    antiseptics
    surgery
     Choice of an antibiotic

   Aetiological agent
   Patient factors
   Antibiotic factors
    The aetiological agent
 Clinical diagnosis
   clinical acumen
     the most likely site/source of
      infection
     the most likely pathogens
   empirical therapy
     universal data
     local data
 Importance of local antibiotic
       resistance data
 Resistance patterns vary
   From country to country
   From hospital to hospital in the same
    country
   From unit to unit in the same hospital
 Regional/Country data useful only for
  looking at trends NOT guide empirical
  therapy
    The aetiological agent
 Laboratory diagnosis
   interpretation of the report
   what is isolated is not necessarily
    the pathogen
   was the specimen properly
    collected ?
   is it a contaminant or coloniser ?
   sensitivity reports are at best a
    guide
            Patient factors
   Age
   Physiological functions
   Genetic factors
   Pregnancy
   Site and severity of infection
   Allergy
          Antibiotic factors
 Pharmacokinetic/pharmacodynamic
  (PK/PD) profile
     absorption
     excretion
     tissue levels
     peak levels, AUC, Time above MIC
 Toxicity and other adverse effects
 Drug-drug interactions
 Cost
         PK/PD Parameters
   Increasing knowledge on the
    association between PK/PD parameters
    on clinical efficacy and preventing
    emergence of resistance
   Enabled doctors to optimise dosage
    regimens
   Led to redefinition of interpretative
    breakpoints in sensitivity testing
   Important PK/PD Parameters
   Important PK/PD Parameters
Time above MIC :   8




                   Antibiotic concentration (ug/ml)
  Proportion of
                   6                                             Drug A
  the dosing                                                     Drug A
  interval when    4                                  Drug B
                                                      Drug B
  the drug
  concentration    2
  exceeds the                                            B
                                                         B
  MIC
                   0
                                                             A            Time

                                                      Time above MIC
    Important PK/PD Parameters

                                      Area under the curve
AUC/MIC is the                              over MIC




                      concentration
                        Antibiotic
  ratio of the AUC
                                                              PEAK
  to MIC
Peak/MIC is the
  ratio of the peak   MIC

  concentration to
  MIC
                                                       Time
 PK/PD and Antimicrobial Efficacy
 2 main patterns of bacterial killing
   Concentration dependent
      Aminoglycosides, quinolones, macrolides, azalides,
       clindamycin, tetracyclines, glycopeptides,
       oxazolidinones
      Correlated with AUC/MIC , Peak/MIC

   Time dependent with no persistent effect
      Betalactams
      Correlated with Time above MIC (T>MIC)




                                        Craig, 4th ISAAR, Seoul 2003
   Goal of therapy based on PK/PD
 Pattern of Activity       Antimicrobials          Goal of therapy
                                                    and relevant
                                                  PK/PD Parameter

Concentration          AMGs, Quinolones,          Maximise
dependent killing      Daptomycin, ketolides,     concentrations;
                       Macrolides, azithro-       AUC/MIC, peak/MIC
                       mycin, clindamycin,        Use high doses;
                       streptogramines,tetracyc   daily dosing for
                       lines, glycopeptides,      some agents
                       oxazolidinones
Time dependent killing Betalactams                Maximise duration
with no persistent                                of exposure; T>MIC
effects                                           Use more frequent
                                                  dosing; longer
                                                  infusion times
                                                  including continuous
                                                  infusion
          Cost of antibiotic
   Not just the unit cost of the antibiotic
   Materials for administration of drug
   Labour costs
   Expected duration of stay in hospital
   Cost of monitoring levels
   Expected compliance
       Choice of regimen
 Oral vs parenteral
 Traditional view
   “serious = parenteral”
   previous lack of broad spectrum oral
    antibiotics with reliable bioavailability
 Improved oral agents
   higher and more persistent serum and
    tissue levels
   for certain infections as good as
    parenteral
    Advantages of oral treatment
   Eliminates risks of complications
    associated with intravascular lines
   Shorter duration of hospital stay
   Savings in nursing time
   Savings in overall costs
      Duration of treatment
   In most instances the optimum
    duration is unknown
   Duration varies from a single dose to
    many months depending on the
    infection
   Shorter durations, higher doses
   For certain infections a minimum
    duration is recommended
Recommended minimum
 durations of treatment
      Monitoring efficacy
 Early review of response
   Routine early review
 Increasing or decreasing the level of
  treatment depending on response
   change route
   change dose
   change spectrum of antibacterial
    activity
   stopping antibiotic
    Campaign to Prevent Antimicrobial Resistance in Healthcare Settings



                 Antimicrobial Resistance:
            Key Prevention Strategies
                Susceptible Pathogen
            Antimicrobial-Resistant Pathogen
                        Pathogen
     Prevent                                                                 Prevent
Transmission                                                                 Infection

                                                                          Infection
  Antimicrobial
   Resistance
                                                                             Effective
 Optimize                                                                    Diagnosis
                                                                             & Treatment
     Use

                              Antimicrobial Use
      Campaign to Prevent Antimicrobial Resistance in Healthcare Settings




 12 Steps to Prevent
 Antimicrobial Resistance

                          12 Break the chain
                       11 Isolate the pathogen      Prevent Transmission
                    10 Stop treatment when cured
                  9 Know when to say “no” to vanco
                8 Treat infection, not colonization Use Antimicrobials Wisely
             7 Treat infection, not contamination
           6 Use local data
         5 Practice antimicrobial control
      4 Access the experts                          Diagnose & Treat Effectively
    3 Target the pathogen
  2 Get the catheters out
1 Vaccinate                                         Prevent Infections
             Conclusions
   Antibiotic resistance is a major
    problem world-wide
   Resistance is inevitable with use
   No new class of antibiotic introduced
    over the last two decades
   Appropriate use is the only way of
    prolonging the useful life of an
    antibiotic