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Case Discussion. Objective: Antibiotic usages in ambulatory medicine Topics General Principles of Antibiotic Usages Case Discussion Conclusion. Antibiotic Usages in Ambulatory Cares. Infecting Organism and Antimicrobial Susceptibility Host Factors: Hx of adverse drug reaction Age

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Case Discussion

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    1. Case Discussion Objective: Antibiotic usages in ambulatory medicine Topics • General Principles of Antibiotic Usages • Case Discussion • Conclusion

    2. Antibiotic Usages in Ambulatory Cares • Infecting Organism and Antimicrobial Susceptibility • Host Factors: • Hx of adverse drug reaction • Age • Genetic or metabolic abnormalities • Pregnancy • Renal and hepatic function • Site of infection

    3. Antibiotic Usages in Ambulatory Cares Antimicrobial Combinations • Indication for the Clinical Use of Antimicrobial Combinations • Prevention of the emergence of resistant organisms • Polymicrobial infections • Initial therapy • Decrease toxicity • Synergism

    4. In Vitro Results of Antimicrobial Combinations

    5. Antibiotic Usages in Ambulatory Cares Antimicrobial Combinations • Disadvantages of the Inappropriate Use of Antimicrobial Combinations • Antagonism • Cost • Adverse effects

    6. Antibiotic Usages in Ambulatory Cares Choice of Appropriate Route of Administration and Evaluation of Efficacy • Route of Administration • Monitoring the Response of the Patient to Antimicrobial Therapy • SIT, SBT, blood level • Clinical assessment and vital signs

    7. Pharmacokinetics And Pharmacodynamics Of Anti-infective Agents

    8. Overview of Interaction of Pharmacokinetics and Pharmacodynamics

    9. Serum Concentration Versus Time Profile of Two-Phase

    10. Pharmacokinetics Definitions and Abbreviations • Absorptions: F (bioavailability), Ka (absorption rate constant) • Distribution: Vd (volume of distribution), Vss (volume of distribution at steady state) • Metabolism: Vm (maximum metabolic capacity, Michaelis-Menten metabolism), Km (drug concentration at which the rate the an enzyme system can metabolize the drug is one half of Vm, CYP (Cytochrome P-450 enzyme systems)

    11. Pharmacokinetics Definitions and Abbreviations • Elimination: CLr (renal clearance), CLnr (non-renal clearance), T1/2 (half-life)

    12. Pharmacodynamics Definitions and Abbreviations • MIC90 (minimal inhibitory concentration for 90% of isolates) • EC50 (effective concentration for 50% of all isolates) • IC50 (Inhibitory concentration for 50% of isolates)

    13. Pharmacodynamics Definitions and Abbreviations • Cmax/MIC (Ratio of peak antimicrobial serum concentration to MIC, concentration-dependent killers)

    14. Pharmacokinetic and MIC Pharmacodynamic Relationship

    15. Time Kill Curves of P. aeruginosa

    16. Probability Graph of Cmax/MIC Ratio for Temperature Normalization by Aminoglycoside in Gram-Negative Pneumonia

    17. Pharmacodynamics Definitions and Abbreviations • AUC/MIC (Ratio of 24-hour area under the blood antimicrobial concentration versus time curve to (above) MIC ratio

    18. Relationship of AUC/MIC and Clinical (A) or Microbiologic (B) Cure in Gram Negative Pneumonia Treated by Ciprofloxacin

    19. Pharmacodynamics Definitions and Abbreviations • T > MIC (Time that the blood antimicrobial concentration is higher than the organism’s MIC, time-dependent killers) • SBT (Serum bactericidal titer, concentration) • PAE (Post-antibiotic effect)

    20. The Relationship of Time Above MIC and the Reduction in Bacterial Count in a Neutropenic Mouse Model of K. pneumoniae for Cefotaxime

    21. Post Antibiotic Effects • PAE: a delay before microorganisms recover and reenter a log-growth period. • PAE exists against gram-negative organisms for aminoglycosides, fluoroquinolones, erythromycin, clindamycin, and tetracycline. • Beta-lactam agents do produce abbreviated PAEs against gram-positive organisms.

    22. CASE 1 • This 22 year-old woman developed an abscess in a cervical lymph node following severe pharyngitis. What does the Gram stain of the fluid from this abscess show?

    23. Gram stain of aspirated fluid from lymph node

    24. Culture of the Aspirated Fluid from the Lymph Node

    25. Test for Production of Catalase

    26. Approach to Acute Pharyngitis in Adults • Lacks of unique clinical features for any causative agents • The objective in evaluating a patient with pharyngitis is to identify those with GAS pharyngitis. • Algorithms to approach this problem rely either upon • a clinical prognostic score, • rapid antigen testing or both.

    27. Approaches to Acute Pharyngitis in Adults Clinical predictors • The Centor criteria have been the most widely used and accepted. These criteria including • exudates • tender anterior cervical adenopathy • fever and sore throat by history • absence of cough and no significant rhinorrhea

    28. Approaches to Acute Pharyngitis in Adults Predictive Value, Sensitivity and Specificity of Centor Criteria • If three or four of these criteria are met, the positive predictive value are 40 to 60 percent. • The absence of three or four of the criteria has a fairly high negative predictive value of 80 percent. • Both the sensitivity and specificity of this prediction rule are 75 percent compared to throat cultures. • These authorities prefer to restrict treatment to those with positive rapid antigen testing (RAT) or culture.

    29. Acute Pharyngitis • accounted for 2 percent of all ambulatory. • The major treatable pathogen is group A streptococcus (GAS), being the cause of pharyngitis in only approximately 10 percent. • 73 percent of adults got antibiotics. • 68 percent of these were more expensive, broader spectrum agents than those recommended in practice guidelines. • Represent the major causes of antibiotic abuse.

    30. Causes of Pharyngitis • Major causes of pharyngitis is viral agents including • influenza, parainfluenza, coronavirus, rhinovirus, adenovirus, enterovirus, herpes simplex virus (HSV), EBV, and the human immunodeficiency virus (HIV). • The most important treatable agent is GAS, accounting for 10 percent of cases. • Other bacterial agents that may cause pharyngitis include: • Mycoplasma pneumoniae, Chlamydia pneumoniae, Neisseria gonorrhoeae, and Corynebacterium diphtheriae.

    31. An Estimated Distributions of Organisms in All Age Groups • Rhinoviruses — 20 percent • Group A streptococci — 15-30 percent • Coronaviruses — 5 percent • Adenoviruses — 5 percent • Group C streptococci — 5 percent • HSV — 4 percent • Parainfluenza virus — 2 percent

    32. An Estimated Distributions of Organisms in All Age Groups • Influenza virus — 2 percent • EBV — <1 percent • HIV — <1 percent • Neisseria gonorrhoeae — <1 percent • Corynebacterium diphtheriae — <1 percent • Mycoplasma pneumoniae — <1 percent • Chlamydia pneumoniae — unknown

    33. Distribution of Organisms of 106 Sore Throat Cases from Finland • Viruses — 25.5 percent • Non group A beta-hemolytic streptococci — 17.9 percent • Mycoplasma pneumoniae — 9.4 percent • Chlamydia pneumoniae — 8.4 percent • Group A streptococci — 4.7 percent • No microbe identified — 31 percent • Simultaneous identification of two microbes — 2.8 percent

    34. Approaches to Acute Pharyngitis in Adults Diagnostic tests • Throat cultures, the "gold standard" for diagnosing GAS pharyngitis, can be used to isolate another pathogen, such as N. gonorrhoeae. • Rapid Antigen Test (RAT) have a sensitivity of 80 to 90 percent and specificity of 90 to 100 percent.

    35. Approaches to Acute Pharyngitis in Adults Throat culture • Relatively insensitive, presumably due to the methods of specimen collection and laboratory processing as routinely performed in clinical practice. • False positive results due to a one to five percent carrier rate for the organism. • With proper techniques in adults, the sensitivity should be approximately 90 percent and specificity should be 95 to 99 percent.

    36. Approaches to Acute Pharyngitis in Adults Serology • a fourfold rising within 2-3 weeks of pair serums in antistreptolysin (ASO), anti-deoxyribonuclease B or other streptococcal antibody titer, such as dehydrogenase • Most cases of streptococcal pharyngitis show a rapid rise in titers suggesting an amnestic response with ASO levels >300 U/ml during acute infection followed by a peak within two to three weeks.

    37. Approaches to Acute Pharyngitis in Adults Management strategies: There are four reasons to treat a streptococcal pharyngitis • To prevent rheumatic fever • To prevent peritonsillar abscess • To reduce symptoms • To prevent transmission

    38. Approaches to Acute Pharyngitis in Adults Recommendations • Using the Centor criteria and the RAT • Empirically treat patients who have all four clinical criteria (fever, tonsillar exudate, tender anterior cervical adenopathy, and absence of cough). • Do not treat with antibiotics or perform diagnostic tests on patients with zero or one criterion. • Perform RAT on those with two or three criteria and use antibiotic treatment only for patients with positive RAT results

    39. Approaches to Acute Pharyngitis in Adults • Empiric treatment of all patients with three or four Centor criteria results in unnecessary antibiotic exposure to at least 50 percent. • The Infectious Diseases Society of America recommend antibiotics only if there is a positive RAT or culture. • This criterion will result in undertreatment of 10 to 20 percent, but the consequences of undertreatment in adults are nil.

    40. Approach to the patient with a negative evaluation for GAS • Acute pharyngitis will resolve in most adults without sequelae. • Symptomatic treatment, including antipyretics, fluids, and gargles, can be helpful. • In the vast majority of patients, no further diagnostic measures are required.