1. Principles of Antimicrobial use and Drug Resistance Omilabu S.A, Ph.D Department of Medical Microbiology and Parasitology, CMUL. 16 th January 2015

2. Introduction Antibiotics are unique among therapeutic agents Directed at treating or preventing microbial disease However, antimicrobial use differs from other medications by its potential for collateral damage: Patient Wider population Efficacy is continuously threatened by drug resistance

3. The antibiotic creed M microbiology guides therapy wherever possible Iindications should be evidence-based Nnarrowest spectrum required D dosage appropriate to the site and type of infection Mminimise duration of therapy Eensure monotherapy in most situations

4. Identification of the Infective Organisms History taking Physical examination Laboratory

5. 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

6. Physical Examination

7. Laboratory Investigation in the Diagnosis of Infectious Agents Mandell, Douglas, and Bennett’s Principle and Practice of Infectious Diseases

8. Gram Stain

10. AFB Stain

11. FBC Increase in neutrophils indicates either Bacterial or fungi infection Lymppcyte elevation indicates aViral infection Monocyte elevation can indicate Infection with Listeria monocytogenes or M. tuberulosis Eosinophil elevation can indicateAllergic reaction, or parasitic infection Basophil elevation can indicate anAllergic response Malaria Microscopy, RDT, PCR etc Other parasites testing Other significant screening for infection

12. Factors affecting antimicrobial use and drug resistance Microbial Factors Host factors Antimicrobial factors

13. Microbial Factors: Antimicrobial susceptibility – Appropriate specimen collection and transport – Disk diffusion susceptibility testing – Minimal inhibitory concentration (MIC)

14. Microbial Factors: Antimicrobial Resistance Susceptible Bacteria New Resistant Bacteria Chromosomal mutations XX Resistant Bacteria Resistance Gene Transfer http://www.cdc.gov

15. Resistant Strains Rare x x Resistant Strains Dominant x x x x x x x x x x Antimicrobial Exposure Selection for Antimicrobial-resistant Strains http://www.cdc.gov

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

17. Underlying diseases Drug allergy Pregnancy/Breast feeding Age Genetic or Metabolic abnormalities Sites of infection Immune status Hepatic and renal function Host Factors

18. Antimicrobial Factors Spectrum Mechanisms of action Pharmacokinet ic Pharmacodyna mic Drug interaction Side effect Drug monitoring

19. Mechanisms of Action Bactericidal agents Bacteriostatic agents Bactericidal agents

20. 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

21. 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: T 1/2

22. 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

23. Indications for Antimicrobial Combinations Therapy Prevention of the emergence of resistant organisms Polymicrobial infections Empirical therapy Synergistic/Additive activity

24. Disadvantages of Inappropriate Use of Antimicrobial Combinations Antagonism Superinfection Cost Adverse effects

25. 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

26. 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

27. Other host factors Collection requiring drainage Necrotic tissue Foreign body Impaired immune defenses Development of drug resistance Superinfection

28. A major cause of antimicrobial overuse is “treatment” of contaminated cultures or colonization. Use Antimicrobials Wisely Treat infection, NOT contamination or colonization Use local data Know your local antibiogram Know your patient population Not all infections need antimicrobial therapy http://www.cdc.gov

29. When infection is cured When cultures are negative and infection is unlikely When infection is not diagnosed Use Antimicrobials Wisely Use Antimicrobials Wisely Stop antimicrobial treatment http://www.cdc.gov