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The Rational Use of Antibiotics

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

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The Rational Use of Antibiotics

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  1. The Rational Use of Antibiotics Victor Lim International Medical University Kuala Lumpur, Malaysia

  2. 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

  3. 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

  4. 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

  5. Prescribing an antibiotic • Is an antibiotic necessary ? • What is the most appropriate antibiotic ? • What dose, frequency, route and duration ? • Is the treatment effective ?

  6. 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

  7. 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.

  8. Is an antibiotic necessary ? • Not all bacterial infections require antibiotics • Consider other options : • antiseptics • surgery

  9. Choice of an antibiotic • Aetiological agent • Patient factors • Antibiotic factors

  10. The aetiological agent • Clinical diagnosis • clinical acumen • the most likely site/source of infection • the most likely pathogens • empirical therapy • universal data • local data

  11. 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

  12. 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

  13. Patient factors • Age • Physiological functions • Genetic factors • Pregnancy • Site and severity of infection • Allergy

  14. 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

  15. 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

  16. Important PK/PD Parameters Important PK/PD Parameters Time above MIC :Proportion of the dosing interval when the drug concentration exceeds the MIC 8 6 Drug A Drug A Drug B 4 Drug B Antibiotic concentration (ug/ml) 2 B B 0 Time A Time above MIC

  17. Important PK/PD Parameters Area under the curve over MIC AUC/MICis the ratio of the AUC to MIC Peak/MICis the ratio of the peak concentration to MIC PEAK Antibiotic concentration MIC Time

  18. 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

  19. Goal of therapy based on PK/PD

  20. 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

  21. 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

  22. 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

  23. 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

  24. Recommended minimum durations of treatment

  25. 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

  26. Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Antimicrobial-ResistantPathogen Prevent Infection PreventTransmission Infection Antimicrobial Resistance Effective Diagnosis & Treatment Optimize Use Antimicrobial Use Antimicrobial Resistance:Key Prevention Strategies Susceptible Pathogen Pathogen

  27. Campaign to Prevent Antimicrobial Resistance in Healthcare Settings 12 Break the chain 11 Isolate the pathogen 10 Stop treatment when cured 9 Know when to say “no” to vanco 8 Treat infection, not colonization 7 Treat infection, not contamination 6 Use local data 5 Practice antimicrobial control 4 Access the experts 3 Target the pathogen 2 Get the catheters out 1 Vaccinate Prevent Transmission Use Antimicrobials Wisely Diagnose & Treat Effectively Prevent Infections 12 Steps to Prevent Antimicrobial Resistance

  28. 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

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