Infectious Diseases Intro - Pharm.

• Study notes for Introduction to Infectious Diseases (Integrated Pharmacotherapy 4, Spring 2025).

Key Definitions

• Infectious disease: Caused by an agent invading a host, harming tissues, and being transmissible.
• Pathogen: An agent that causes infectious disease.
• True pathogens: Cause disease in virtually any susceptible host.
• Opportunistic pathogens: Rarely cause disease in individuals with healthy immune systems.
• Infection: Pathogen invades and begins to grow within a host (colonizes).
• Disease: Tissue function is impaired by pathogen invasion and growth.

Pathogen Categories

• Seven categories of human pathogens exist.
• Bacteria: Unicellular, prokaryotic organisms dividing by fission.
• Viruses: Non-living entities with a nucleic acid genome surrounded by a capsid, and possibly a lipid membrane.
• Fungi: Eukaryotic organisms with rigid cellulose or chitin-based cell walls.
• Prions: Abnormal host proteins resistant to proteases, promoting conversion of more proteins.
• Protozoa: Unicellular, flexible eukaryotes lacking cell walls.
• Helminths: Multicellular invertebrate animals (worms) with differentiated tissues.
• Ectoparasites: Insects (lice, fleas, bedbugs) or arachnids (mites, ticks, spiders).

Viral Characteristics

• Viruses: Non-living, consist of genetic material (DNA or RNA) surrounded by proteins (nucleocapsid).
• Viruses classified as either "active" or "inactive".
• Viral genetic material: Single or double-stranded DNA or RNA, with varying genome sizes.
• Number of viral genes: Does not influence virulence.
• Enveloped viruses: Have a membrane obtained from the host cell during budding.

Viral Replication

• Surface proteins mediate cell entry.
• Viral genetic material uses host cell enzymes to replicate and produce viral proteins.
• The process is different depending on viral characteristics.

Viral Transmission

• Direct transmission: Aerosols, sexual contact, hand to mouth, hand to eye, mouth to mouth, exchange of contaminated blood.
• Indirect transmission: Fecal-oral route, fomites.
• Incidental: Animal to human (bites, rodent contamination).
• Arthropod vector.

Bacterial Infectious Diseases

• A primary TBL unit goal: To describe the microbiological classification of microorganisms, and identify organisms based on Gram's stain and other tests
• Clinicians need to be able to recommend appropriate therapy based on initial laboratory results

Gram's Stain

• Gram's stain: Developed in 1884 and provides rapid, presumptive bacterial identification.
• Used by clinicians to select appropriate empiric antimicrobial therapy.
• Acronym for steps of the Gram’s stain: VIAS: Violet, Iodine, Alcohol, Safranin.

Response to Oxygen

• Strict aerobe: Requires oxygen for ATP generation.
• Strict anaerobe: Uses fermentation reactions; oxygen is toxic.
• Facultative anaerobe: Can grow with or without oxygen.

Other Lab tests

• Includes a rapid testing method used to test multiple pathogens at the same time, PCR, genetic level

Colonization vs. Infection

• Determine if a microorganism detected means antibiotic is needed, need to determine infection and severity
• Epithelial body surfaces colonized with microbial flora – normal in healthy people.
• Carrier state: Potentially pathogenic organisms found as colonizers.
• Resident flora: Keep out harmful microorganisms, compete for nutrients, produce suppressive byproducts.

Positive Effects of Colonization

• Normal gastrointestinal flora: Keeps Clostridioides difficile in check, preventing C. difficile infection (CDI).

Negative Effects of Colonization

• "Normal flora": May cause infection if introduced into a different body location in large numbers (e.g., viridans streptococci causing endocarditis).
• Antibiotic prophylaxis: May be given before dental work to patients at risk.

Keypoints about colonizers

• Normal to find in by body site.
• Antibiotics may eliminate, allowing growth of other organisms.
• They cause infection in other body sites.
• Blood, body fluids, bladder, and upper urinary tract are normally sterile.

Signs of infection

• Include fever and leukocytosis.
• Non-specific findings: Elevated ESR or biomarkers, loss of glucose control.
• The diagnosis depends on additional clinical data for the situation.

Fever

• IDSA definition: A single oral temperature > 101°F or a sustained temperature of > 100.4°F for ≥ 1 hour.
• The hypothalamus controls body temperature, with circadian rhythm variations.
• Core body temperature: Measured via tympanic membrane (ear) or rectal route, usually 1 degree F > oral.
• Axillary temperature: Usually 1 degree F < oral.

Body's febrile response

• Complex physiologic reaction: Cytokine-mediated rise in core temperature, generation of acute phase reactants, and immune system activation.
• Treatment: Decisions specific to the individual patient, with consideration of the risks and interference with daily activities
• Fever beneficial: Enhancing resistance to viral and bacterial infections (studies have found).
• Fever harmful: Associations in children (seizures) and underlying cardiovascular/pulmonary disorders (increased metabolic demands).
• Management: Short courses of approved doses are used as a standard.

Drug Fever

• Often goes unrecognized due to its occurrence and association with illness
• Occurs in 10% of hospitalized patients
• The fever is accompanied by a normal, or below normal pulse rate given the temperature

Leukocytosis

• Elevated white blood cell (WBC) count (normal range: 4,500 – 11,000 / mm³).
• Complete blood cell count branch diagram values must be multiplied by 1,000
• The WBC count comes with a "Normal Differential of WBCs" that will give specific types of WBCs in a range
• The percentage of each cell type equals 100%

Use of clinical practice terms include the frequently used

• Left-shift refers to the % of cells shifting higher.

Neutropenia Definition

• ANC < 1,000 cells/mm³
• Severe neutropenia: ANC < 500 cells/mm³.
• Risk of infection increases as ANC decreases.
• Calculate ANC: Total WBC x (% segs + % bands)

Treatment Success

• Signs of treatment success include an improvement in the patient's clinical symptoms
• A normalization of WBC, temperature, and radiologic findings
• A normalization means The patient does not need to remain in the hospital for the entire course of therapy even if IV medications are required.
• PICC line is placed in patients to continue IV medications while at home

Sepsis/Shock Definitions

• See table 8 for definitions

Antimicrobial Stewardship

• 4 D's
  • Right drug
  • Right dose
  • De-escalation to pathogen directed therapy
  • Right duration

How to know what Antimicrobial agent(s) to use?

• Definitions to know:
  • Spectrum of activity
    • Has broad and narrow definitions
    • Use appropriate spectrums agents to minimize collateral damage
  • Emperic therapy
    • Chosen before determination and antimicrobial therapy
    • Initial therapy is chosen based on an educated "guess"
  • Directed therapy
    • Agent chosen after determination and antimicrobial therapy

Antimicrobial use

• Judicious use of antimicrobial agents is included in discussion
• Included in the cost is the antimicrobial agent and the fiscal cost

Use of a high or low grade of oral Bioavalability

• May be switched from an IV to oral dosage
• Must be able to absorb oral meds

Treatment Failure reasonings

• The clinician needs to determine potential reasons with these criteria
  • Must use
  • The wright diagnosis
  • The targeted pathogen
  • Has the immune system activated
  • The drug interactions

Culture and Susceptibility Testing Methods

• The description of these methods is FYI, but is included for completeness See table 7-11

Lecture Goals

• The goal of the lecture is to describe the microbiological classification of organisms.
• Identify microorganisms based on Gram’s stain and laboratory results.
• Recognize the clinical presentation of a patient with an infection.
• Select an antimicrobial agent based on patient-specific and drug-specific factors.

Introduction to Microorganisms

• Scientific naming is done using genus and species names, written in italics, such as Chlamydia trachomatis.

Gram Stain Key Points

• The Gram’s stain does not detect all microorganisms.
• When assessing a Gram stain, check for color, morphology, arrangement of cells, epithelial cells, and white blood cells.
• Morphology includes bacilli (rod-shaped cells), cocci (spherical cells), and spiral or curved forms.
• Arrangement of cells may be in clusters, chains, or diplococci.
• Presence of epithelial cells on a Gram stain indicates contamination.
• White blood cells on sample indicates infection.
• Preliminary micro results will assist with proper antimicrobial selection.

Atypical Organisms Requiring Special Staining

• Mycoplasma spp.
• Chlamydia (Chlamydophilia) spp.
• Legionella spp.
• Mycobacterium spp.
• Nocardia spp.
• Bartonella spp.

Gram Positive and Negative Bacteria

• Gram-positive bacteria have peptidoglycan and teichoic acids.
• Gram-negative bacteria have periplasm, an outer membrane with porins, and lipopolysaccharide (LPS), an endotoxin.

Aerobic Gram Positive Bacteria

• Aerobic Gram-Positive Cocci are classified using catalase.
• Catalase-positive bacteria (Staphylococci) are differentiated using coagulase.
• Coagulase-positive = S. aureus.
• Coagulase-negative = S. epidermidis, S. saprophyticus.
• Catalase-negative Gram-Positive Cocci (Streptococci and Enterococci) occur in pairs/chains.
• MSSA: methicillin-sensitive Staphylococcus aureus.
• MRSA: methicillin-resistant Staphylococcus aureus.

Streptococci types

• Alpha-hemolytic include Viridans streptococci and S. pneumoniae.
• Beta-hemolytic include Group A strep (S. pyogenes) and Group B strep (S. agalactiae).
• Group now own includes Group D strep (S. bovis) and Enterococci.

Anaerobic Gram + Cocci

• Includes peptostreptococci

Gram + Rods

• Aerobic:
  • Listeria monocytogenes.
  • Corynebacterium spp. (including C. diphtheriae, C. jeikeium).
  • Lactobacillus spp.
  • Bacillus spp. (B. anthracis, B. cereus).
• Bacillus spp are spore-forming organisms.
• Anaerobic:
  • Propionibacterium acnes.
  • Clostridium spp. (C. botulinum, C. difficile, C. perfringens, C. tetani).
  • Clostridium spp are spore-forming organisms.

Gram Negative Cocci

• Aerobic include Neisseria spp. (N. gonorrhoeae, N. meningitidis) and Moraxella catarrhalis.
• Anaerobic include Veillonella spp.

Gram Negative Rods

• Anaerobic:
  • Bacteroides fragilis.
  • Also Fusobacterium spp., Prevotella spp.
• Aerobic: Several.

Aerobic Gram Negative Rods

• Haemophilus influenzae
• Campylobacter spp.
• Lactose-positive: Klebsiella spp., Enterobacter spp., E. Coli, Citrobacter spp., Serratia.
• Lactose-negative: Proteus spp., Morganella spp., Salmonella spp., Shigella spp., Providencia spp., Serratia marcescens, Acinetobacter spp., Stenotrophomonas maltophilia.
• Oxidase differentiates which ones are Lactose-negative and Lactose-positive.
• Glucose non-fermenters: Pseudomonas aeruginosa, Burkholderia cepacia.
• Enterobacteriaceae.

Encapsulated Organisms

• S. pneumoniae
• N. meningitidis
• H. influenzae

Common Organisms by Infection Site

• Acute Otitis Media/Sinusitis: S. pneumoniae, H. influenzae, M. catarrhalis.
• Meningitis (adults): S. pneumoniae, N. meningitidis, L. monocytogenes (in neonates, elderly, immunocompromised).
• Strep Throat: S. pyogenes (GAS).
• Endocarditis: S. aureus, S. epidermidis (prosthetic valves), Viridans streptococci, S. bovis, Enterococci.
• Community-acquired pneumonia: S. pneumoniae, H. influenzae, M. catarrhalis.
• Community-acquired pneumonia (atypical): Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila.
• Intra-abdominal: Enteric gram negatives (E. coli, Klebsiella), Enterococcus (E. faecalis, E. faecium), Anaerobes (Bacteroides fragilis).
• Urinary tract infection (cystitis): Enteric gram negatives (E. coli, Klebsiella, Proteus), Enterococcus (E. faecalis, E. faecium), S. saprophyticus.
• Skin (Cellulitis): S. aureus, S. pyogenes.
• Osteomyelitis: S. aureus.
• Diabetic Foot: Anaerobes, Enterococcus, Enteric gram negatives, Pseudomonas.