Prin of ID

Introduction to Infectious Diseases: 

Introduction to Infectious Diseases 1 Brooke Y. Patterson, PharmD, BCPS NU 7080: Advanced Pharmacology Research College of Nursing

Infectious Diseases Are Everywhere!: 

Infectious Diseases Are Everywhere! Influenza: 3-5 million infected annually HIV/AIDS: 45 million infected Hepatitis C: 170 million infected annually Malaria: 300 million new infections annually Hepatitis B: 2 billion infected Tuberculosis: 2-3 billion infected 2

Biology of Infectious Diseases: 

Biology of Infectious Diseases Microbial invasion Virulence factors Microbial adherence Microbial resistance Host defense mechanisms Natural barriers Non-specific immune responses Specific immune response 3

Microbial Invasion: 

Microbial Invasion Virulence factors Encapsulation Enzymatic activity Exotoxins Impairment of antibody production Phagocytosis resistance 4

Microbial Invasion: 

Microbial Invasion Microbial adherence Adhesins Biofilm Antimicrobial resistance Selection of resistant strains Drug 'pressure' 5

Host Defense Mechanisms: 

Host Defense Mechanisms Natural Barriers Skin Mucous membrane secretions Airway filters GI tract pH Non-specific Immune Responses Fever Increased production of neutrophils Inflammatory response 6

Host Defense Mechanisms: 

Host Defense Mechanisms Specific Immune Responses Antibodies Complement system 7

Principles of Treatment: 

Principles of Treatment How We Treat An Infection 8

Principles of Treatment: 

Principles of Treatment 9

Recognize Patient’s Illness: 

Recognize Patient’s Illness Fever Oral temp >99.5-100.5°F (37.5-38°C) Hallmark of infection Non-infectious causes Malignancy Drug fever Blood transfusions Absence in presence of suspected infection Antipyretics Corticosteroids Antimicrobial therapy Overwhelming infection (sepsis) 10

Recognize Patient’s Illness: 

Recognize Patient’s Illness White blood cell (WBC) count Increased (leukocytosis) Normal range: 4000-10,000 cells/mm3 11

Recognize Patient’s Illness: 

Recognize Patient’s Illness WBC Differential Mature neutrophils 50-70% Immature neutrophils ('bands') 3-5% Lymphocytes 20-40% Monocytes 0-7% Eosinophils 0-5% Bacterial infections Increased neutrophils ('left shift') Viral infections Increased lymphocytes (lymphocytosis) Allergic reactions and/or protozoal infection Increased eosinophils (eosinophilia) 12

Recognize Patient’s Illness: 

Recognize Patient’s Illness Pain and inflammation Symptoms referable to specific organ system 13

Recognizing Patient’s Illness: 

Recognizing Patient’s Illness Factors predisposing to illness Alterations in normal flora of host Disruption of natural barriers Skin/mucous membrane Cilia of respiratory tract pH and motility of bowel Age Immunosuppression 14

Principles of Treatment: 

Principles of Treatment 15

Identify Causative Organism: 

Identify Causative Organism Aerobic microorganisms Gram-positive cocci Gram-positive bacilli Gram-negative cocci Gram-negative bacilli Enterobacteriaceae family Anaerobic microorganisms Gram-positive cocci Gram-positive bacilli Gram-negative bacilli 16

Identify Causative Organism: 

Identify Causative Organism Our bodies are covered in bacteria! Normal flora Skin Staphylococci sp. Streptococci sp. Upper Respiratory Tract Haemophilus sp Streptococci (viridans group) Oral anaerobes 17

Identify Causative Organism: 

Identify Causative Organism Gastrointestinal Tract Bacteriodes sp. Enterobacteriaceae Enterococci Fusobacterium sp. Peptostreptococci Genital Tract Enterobacteriaceae Corynebacterium sp. Lactobacillus sp. Mycoplasma sp. Staphylococci Streptococci 18

Identify Causative Organism: 

Identify Causative Organism Collect infected material Aspiration of infected fluids Direct examination of fluids Gram stain AFB stain India ink Immunologic examination of fluids ELISA DNA probes Cultures 19

Identify Causative Organism: 

Identify Causative Organism Collect fluids Blood Sputum Urine LP Multiple specimens taken Error possiblecontamination 20

Principles of Treatment: 

Principles of Treatment 21

Choose Antimicrobial Therapy: 

Choose Antimicrobial Therapy Empiric vs. directed antimicrobial therapy Microorganisms most likely to cause infection Antimicrobial susceptibility pattern Selecting antibiotic Efficacy Microbiologic efficacy Susceptibility tests Resistance trends Pharmacokinetics 22

Choose Antimicrobial Therapy: 

Choose Antimicrobial Therapy Susceptibility testing Based on MIC Broth dilution, agar dilution, E-test Lowest concentration resulting in >99% decrease in organism Reported in 3 different categories Susceptible Intermediate Resistant 23

Choose Antimicrobial Therapy: 

Choose Antimicrobial Therapy 24

Choose Antimicrobial Therapy: 

Choose Antimicrobial Therapy 'The tissue is the issue' Distribution Serum concentrations Host factors to consider when choosing an agent Allergy or h/o ADRs Age and weight Pregnancy Genetic or metabolic abnormalities (pharmacodynamics) Renal and hepatic function Concomitant drug therapy Underlying disease states 25

Principles of Treatment: 

Principles of Treatment 26

Monitor For Improvement: 

Monitor For Improvement Clinical assessment Physical exam Radiographic evidence Laboratory tests Cultures Therapeutic drug monitoring 27

Monitor For Improvement: 

Monitor For Improvement Assessment of Clinical Failures Antimicrobial selection Host factors Microorganism factors Laboratory errors 28

Antimicrobial Resistance: 

Antimicrobial Resistance Why Some Bacteria Are Hard To Treat 29

Antimicrobial Resistance: 

Antimicrobial Resistance Intrinsic resistance Acquired resistance Mutation Genetic exchange Acquisition of new DNA 30

Susceptibility Testing: 

Susceptibility Testing Determine if microorganism is susceptible to drug Guides therapy 31

Susceptibility Testing: 

Susceptibility Testing Minimum Inhibitory Concentration (MIC) Lowest concentration that prevents visible growth Broth dilution NCCLS 'breakpoints' used to categorize MIC Susceptible Intermediate Resistant 32

Susceptibility Testing: 

Susceptibility Testing Disc Diffusion (Kirby-Bauer) Antibiotic-impregnated disk is placed on agar plate of growing organism Zone created by antibiotic leaching from the disk into the agar is compared to NCCLS ranges 33

Pathogenic Bacteria: 

Pathogenic Bacteria What Makes Us Sick 34

Gram-Positive Bacteria: 

Gram-Positive Bacteria Marked increase in antibiotic resistance Serious and difficult-to-treat infections 35

Staphylococci: 

Staphylococci Staphylococcus aureus Remarkable amount of disease manifestations MRSA Bacteremia and TSS possible Staphylococcus epidermidis Coagulase-negative staph Staphylococcus saprophyticus 36

Staphyloccocus aureus: 

Staphyloccocus aureus 37

Staphylococcus Epidermidis: 

Staphylococcus Epidermidis 38

Staphylococcus Saprophyticus: 

Staphylococcus Saprophyticus 39

Pneumoccoci: 

Pneumoccoci Streptococcus pneumoniae Forcefully attack human body Cause significant amounts of tissue damage Associated with extensive inflammatory response 40

Streptococcus pneumoniae: 

Streptococcus pneumoniae 41

Enterococci: 

Enterococci 'Fickle' residents of the human GI tract Enterococcus faecalis Enterococcus faecium 42

Enterococci: 

Enterococci 43

Gram-Negative Bacteria: 

Gram-Negative Bacteria Most common cause of infection in humans Enterobacteriaceae Large family of bacteria responsible for GI, urinary and opportunistic infections Enteric gram-negative rods 44

Enterobacteriaceae: 

Enterobacteriaceae Escherichia coli Klebsiella spp Proteus spp Enterobacter spp Serratia spp Citrobacter spp Providenicia spp Morganella spp Salmonella enterica Shigella spp Yersinia spp 45

Enterobacteriaceae: 

Enterobacteriaceae 46

Pseudomonas: 

Pseudomonas Pseudomonas aeruginosa Frequent cause of hospital-acquired infections Harbors an array of resistance mechanisms 47

Pseudomonas Aeruginosa: 

Pseudomonas Aeruginosa 48

Neisseria: 

Neisseria Neisseria meningitidis Meningitis Bacteremia possible Neisseria gonorrhoeae Genital gonorrhea 49

Anaerobic Bacteria: 

Anaerobic Bacteria Bacteria unable to grow in the presence of physiologic concentrations of oxygen Mucosal surfaces 50

Clostridia: 

Clostridia Gram-positive spore-forming anaerobic bacteria Clostridium difficile Clostridium tetani 51

Clostridia spp: 

Clostridia spp 52

Questions???: 

Questions??? 53

Clostridia spp: 

Clostridia spp 52

Questions???: 

Questions??? 53