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 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 • Genetic or metabolic abnormalities • Pregnancy • Renal and hepatic function • Site of infection
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
Antibiotic Usages in Ambulatory Cares Antimicrobial Combinations • Disadvantages of the Inappropriate Use of Antimicrobial Combinations • Antagonism • Cost • Adverse effects
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
Pharmacokinetics And Pharmacodynamics Of Anti-infective Agents
Overview of Interaction of Pharmacokinetics and Pharmacodynamics
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)
Pharmacokinetics Definitions and Abbreviations • Elimination: CLr (renal clearance), CLnr (non-renal clearance), T1/2 (half-life)
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)
Pharmacodynamics Definitions and Abbreviations • Cmax/MIC (Ratio of peak antimicrobial serum concentration to MIC, concentration-dependent killers)
Probability Graph of Cmax/MIC Ratio for Temperature Normalization by Aminoglycoside in Gram-Negative Pneumonia
Pharmacodynamics Definitions and Abbreviations • AUC/MIC (Ratio of 24-hour area under the blood antimicrobial concentration versus time curve to (above) MIC ratio
Relationship of AUC/MIC and Clinical (A) or Microbiologic (B) Cure in Gram Negative Pneumonia Treated by Ciprofloxacin
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)
The Relationship of Time Above MIC and the Reduction in Bacterial Count in a Neutropenic Mouse Model of K. pneumoniae for Cefotaxime
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.
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?
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.
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
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.
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.
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.
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
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
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
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.
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.
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.
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
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
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.
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.