Microbial Control, Immunity, and Human Infections

Posted on Nov 24, 2025 in Microbiology

Sterilization, Disinfection, and Antimicrobial Therapy

This chapter covers the methods used to control microbial growth and the principles governing antibiotic use and resistance.

Key Definitions in Microbial Control

Sterilization

Destroys all microbial life, including spores and viruses.

Disinfection

Removes pathogens from inanimate surfaces (not sterilizing).

Antisepsis

Removes pathogens from living tissues (e.g., skin, mucosa).

Sanitation

Reduces microbe numbers to “safe” levels; not sterilizing.

Cidal Agents

Kill microbes (e.g., bactericidal, fungicidal, virucidal).

Static Agents

Inhibit microbial growth (e.g., bacteriostatic).

D-value

Time needed to kill 90% of microorganisms under specific conditions.

Physical Methods of Microbial Control

• Autoclaving: Standard sterilization method. Uses 121°C at 15 psi for 20 minutes.
• Pasteurization: Invented by Louis Pasteur (1864). Uses moderate heat to kill Coxiella burnetii.
• Refrigeration: 4–8°C to slow microbial growth (Listeria is an exception).
• Freezing: Long-term storage at -70°C, often with glycerol.
• Lyophilization: Freeze-drying under vacuum; preserves cultures.
• Filtration: 0.2 µm filters remove bacteria; filters <20 nm are required to remove viruses.
• Irradiation:
  • UV light: Surface sterilization.
  • Gamma rays, electron beams, X-rays: Deeper penetration. Measured in grays (Gy); approved for various foods.

Chemical Methods of Microbial Control

Factors Influencing Chemical Efficacy:

• Presence of organic matter (e.g., blood).
• Type of microbe.
• Agent stability, corrosiveness, and odor.

Disinfectant Levels:

• High-level: Kill all microbes, including spores. Examples: Ethylene oxide, glutaraldehyde.
• Intermediate-level: Kill bacteria, fungi, most viruses. Examples: Phenolics, halogens.
• Low-level: Kill some bacteria, fungi, some viruses. Examples: Alcohols, quaternary ammonium compounds (Quats).

Testing Efficacy:

• Phenol coefficient test (historical).
• Use-dilution test (current standard for surface disinfection).

Gas Sterilization: Used for plasticware, catheters, etc. Uses ethylene oxide (EtO) or gamma irradiation.

Antimicrobial Principles

Selective Toxicity

Drugs harm microbes but not host cells.

Spectrum of Activity

• Narrow-spectrum: Targets specific microbes.
• Broad-spectrum: Targets a wide range (both Gram-positive and Gram-negative).

Minimum Inhibitory Concentration (MIC)

Lowest concentration that prevents visible growth.

Minimum Bactericidal Concentration (MBC)

Concentration that kills 99.9% of bacteria (confirmed by plating).

Chemotherapeutic Index

Ratio of toxic dose to therapeutic dose. A higher index indicates a safer drug.

Synergism

Combined drug effect is greater than the sum of the parts. Example: Aminoglycoside + vancomycin.

Antagonism

Drugs interfere with each other. Example: Penicillin + macrolides.

Antibiotic Mechanisms of Action

• Cell Wall Synthesis Inhibitors: Penicillins, cephalosporins, vancomycin.
• Cell Membrane Disruptors: Polymyxins.
• DNA Synthesis Inhibitors: Quinolones (e.g., ciprofloxacin).
• RNA Synthesis Inhibitors: Rifampin.
• Protein Synthesis Inhibitors:
  • 30S subunit: Tetracyclines, aminoglycosides.
  • 50S subunit: Macrolides, chloramphenicol.
• Antimetabolites: Sulfonamides, trimethoprim (block folic acid pathway).

Antimicrobial Resistance

• Intrinsic Resistance: Natural (e.g., Mycoplasma lacks a cell wall).
• Acquired Resistance: Genetic mutation or horizontal gene transfer.
• Persister Cells: Survive antibiotics by being dormant or embedded in biofilms.

Six Major Resistance Mechanisms:

1. Destroy antibiotic (e.g., β-lactamase).
2. Pump antibiotic out (efflux pumps).
3. Reduce permeability (e.g., porin changes).
4. Alter drug target (e.g., ribosomal changes).
5. Modify the antibiotic (chemical modification).
6. Protect the target (e.g., ribosomal shielding).

Antiviral Agents

• Uncoating Inhibitors: Amantadine (influenza).
• Release Inhibitors: Oseltamivir (Tamiflu), Zanamivir (Relenza).
• Nucleic Acid Synthesis Inhibitors: Acyclovir (HSV, VZV), AZT (HIV), Ribavirin (RSV, HCV).
• HIV-Specific Agents:
  • Protease inhibitors: Lopinavir, Nelfinavir.
  • Entry inhibitors: Maraviroc (blocks CCR5).
  • HAART/ART: Combination therapy to reduce resistance.

Antifungal Agents

• Polyenes: Disrupt membranes by binding ergosterol. Examples: Amphotericin B, Nystatin.
• Azoles: Inhibit ergosterol synthesis. Examples: Fluconazole, Ketoconazole.
• Allylamines: Block ergosterol synthesis. Example: Terbinafine (Lamisil).
• Echinocandins: Inhibit fungal cell wall synthesis. Example: Caspofungin.
• Other Agents: Griseofulvin (inhibits mitosis); Flucytosine (inhibits fungal DNA synthesis).

Antiprotozoal Agents

• Folic Acid Inhibitors: Pyrimethamine, Sulfamethoxazole.
• Aminoquinolines: Chloroquine (disrupts parasite use of hemoglobin).
• Protein Synthesis Inhibitors: Paromomycin, Azithromycin.
• Free Radical Generators: Metronidazole, Benznidazole (effective against anaerobic protozoa).

High-Yield Clinical Case Pearls

• MRSA Cross-Contamination: Lapses in glove hygiene caused patient death.
• Meningitis Case: Ampicillin used empirically; H. influenzae confirmed.
• Drug-Resistant Pneumonia: Previous doxycycline use led to resistance to multiple drugs; resolved with vancomycin.
• HIV During Pregnancy: AZT used to prevent vertical transmission.
• Blastomycosis: Treated initially with IV Amphotericin B, then oral fluconazole.

The Normal Human Microbiota

The human body hosts trillions of microbes (bacteria, archaea, viruses, fungi). The microbiota refers to the microbial communities living symbiotically in and on the human body. These communities differ by location (skin, gut, oral cavity, etc.).

Microbiota Composition by Body Site

• Skin: 2 m² surface area; ~10¹² microbes. Conditions: dry, moist, salty, or acidic. Dominant species: Staphylococcus epidermidis, Cutibacterium acnes.
• Eye: Lysozyme in tears prevents overgrowth. Colonized by Corynebacterium, Staphylococcus, and others.
• Oral/Nasal Cavities: Colonization begins hours after birth. Initial microbes: Neisseria, Streptococcus, Lactobacillus, Actinomyces. Streptococcus mutans causes dental plaques (glycocalyx biofilm). Risk: Dental procedures can cause bacteria to enter the bloodstream, leading to subacute bacterial endocarditis.
• Respiratory Tract: Mucociliary escalator clears pathogens. Unclear if healthy lungs are truly sterile or have a “low-biomass microbiota.”
• Stomach: Acidic (pH ~1–2), hostile to most microbes. Helicobacter pylori survives in mucosa and can cause ulcers.
• Intestine: ~10¹¹–10¹³ microbes per gram of feces. Mostly anaerobes (Bacteroides, Firmicutes). Jejunum is alkaline; ileum/colon are acidic. Functions: ferment undigested carbohydrates, synthesize vitamins, and develop the immune system.
• Genitourinary Tract: Lower urethra and vagina have microbiota. Lactobacilli in the vagina protect via lactic acid production.

Benefits of the Microbiota

• Digest food (ferment polysaccharides).
• Synthesize vitamins (e.g., B12, K).
• Prevent pathogen colonization: Outcompete for attachment and nutrients.
• Produce antimicrobial substances.
• Train the immune system: Modulate cytokine secretion.
• Enterotoxins may have protective anti-cancer effects (e.g., stimulate calcium influx, leading to antiproliferative effects).

Microbiome and Health

• Dysbiosis: Microbial imbalance leading to disease (e.g., C. difficile infection). Causes include antibiotics, diet, infection, and stress.
• IBS (Irritable Bowel Syndrome): Caused by altered microbiota composition. May respond to probiotics or a FODMAP diet.
• SIBO (Small Intestine Bacterial Overgrowth): Excessive growth of microbes like E. coli and Bacteroides. Causes bloating, diarrhea, and malabsorption (e.g., low B12). Treated with antibiotics.

Microbiome Communication and Risk

• Microbiota ↔ Host Communication: Via metabolites (e.g., indole from E. coli), which strengthens the gut barrier and reduces inflammation.
• Gut-Brain Axis: Microbial signals affect the Central Nervous System (CNS). Emerging links to mood, cognition, and disease.
• Risk Factors:
  • Opportunistic Infections: Immunocompromised hosts are at risk. Microbes may escape niches (e.g., bloodstream infections).
  • Antibiotic Resistance: Resistance can develop within the microbiota and be transmitted to pathogens.

Therapies and Control

• Probiotics: Live microbes (e.g., Bifidobacterium, Lactobacillus) ingested to restore balance.
• Fecal Microbiota Transplant (FMT): Transfer of healthy donor stool to treat diseases like C. difficile colitis.
• Phage Therapy: Use of bacteriophages to target specific pathogens.
• Disappearing Microbiota Hypothesis: Modern hygiene, antibiotics, and C-sections reduce microbiome diversity, potentially leading to more chronic diseases.

The Hygiene Hypothesis

Suggests that a lack of early childhood exposure to microbes increases the risk of:

• Allergies
• Asthma
• Autoimmune diseases

High-Yield Case Studies

• Jason (IBS): Symptoms included mucus stools, cramping, and bloating. Treatment with a FODMAP diet and probiotics resolved symptoms.
• Renita (SIBO): Symptoms included greasy stool, low B12, and bloating. Diagnosis confirmed bacterial overgrowth in the jejunum. Treatment involved antibiotics.

Vaccines and Immunization

Vaccines stimulate the immune system to develop protection. Immunization can be active (body produces its own response) or passive (pre-formed antibodies given).

Types of Immunization

• Active Immunization: Injected antigen stimulates the adaptive immune system. Results in long-term memory (B cells + T cells). Example: MMR vaccine.
• Passive Immunization: Direct transfer of protective antibodies. Provides temporary protection. Examples: IV immunoglobulin, antitoxins, maternal antibodies via breast milk.

Characteristics of Effective Vaccines

• Safe and does not cause illness.
• Stimulates both B-cell (antibody) and T-cell (cell-mediated) immunity.
• Induces long-term memory.
• Requires minimal boosters.
• Targets relevant antigens of the natural pathogen.

Vaccine Types and Platforms

Killed/Inactivated Vaccines:

• Pathogen is chemically or physically killed. Antigenic structures remain intact.
• Examples: Cholera, Hepatitis A, inactivated influenza, rabies.
• Pros: No reversion risk, stable.
• Cons: Weaker immune response, requires boosters.

Live Attenuated Vaccines:

• Weakened form of the pathogen. Grown in different hosts or under suboptimal conditions.
• Examples: MMR, BCG (TB), Sabin (oral polio), varicella.
• Pros: Strong immunity, often one dose.
• Cons: Risk of reversion to virulence in rare cases, limited shelf life.

Subunit, Acellular, or Toxoid Vaccines:

• Use purified components (capsule, toxoids).
• Examples:
  • Toxoids: Diphtheria, tetanus.
  • Acellular: Pertussis (DTaP).
  • Capsular: H. influenzae B, pneumococcus, meningococcus.

New Vaccine Platforms:

• DNA Vaccines: Viral genes injected to express antigens (not yet widely used).
• RNA Vaccines: mRNA encoding spike proteins (e.g., COVID-19 vaccines).
• Viral Vector Vaccines: Modified viruses deliver antigen genes (e.g., Johnson & Johnson COVID vaccine).

Examples of Approved Vaccines

• BCG (TB): Live attenuated, intradermal.
• Polio (Salk): Inactivated, IM.
• Polio (Sabin): Live attenuated, oral.
• MMRV: Combo vaccine for measles, mumps, rubella, varicella.
• DTaP: Diphtheria, tetanus, acellular pertussis.
• Gardasil (HPV): Subunit vaccine (capsid proteins types 6, 11, 16, 18).
• Influenza: Killed (IM) or live (intranasal) forms.
• Hepatitis A & B: Inactivated and subunit vaccines.

Herd Immunity

When enough of the population is immunized, disease transmission is reduced. This protects individuals who cannot be vaccinated. The threshold varies by disease, often requiring ≥75% coverage.

Clinical Case Pearl

Maureen: An immunocompromised kindergarten teacher on rituximab (targets B cells). She contracted measles pneumonia despite prior vaccination. Measles PCR was positive, but no detectable IgG or IgM due to suppressed B-cell function. Treated with ribavirin + IV immunoglobulins. Source: An unvaccinated child.

Key Definitions in Immunization

Toxoid

Inactivated bacterial toxin used in vaccines.

Attenuation

Weakening a pathogen to reduce virulence.

Subunit Vaccine

Uses only key antigens, not the whole organism.

Adjuvant

Substance added to a vaccine to enhance the immune response.

Microbial Pathogenesis

Fundamental Concepts

Pathogenesis

The process by which microbes cause disease.

Virulence Factors

Molecules produced by pathogens that contribute to disease (e.g., toxins, enzymes, pili).

Pathogenicity Island

A distinct region in microbial DNA (different GC content) containing virulence genes; acquired by horizontal gene transfer.

Genomic Island

DNA region with foreign sequence signatures, often from plasmids or phages.

Stages of Microbial Infection

1. Entry into host.
2. Attachment & colonization.
3. Avoidance of host immunity.
4. Host damage.
5. Exit and transmission.

Attachment and Colonization

• Adhesins: Microbial molecules that promote attachment.
• Pili (Fimbriae): Appendages that bind host receptors.
  • Type I pili: Static; used only for attachment.
  • Type IV pili: Dynamic; enable twitching motility.
• Non-pilus Adhesins: Surface proteins (e.g., fibronectin-binding proteins).
• Biofilms: Enable microbial adhesion to surfaces. They protect against host defenses and antibiotics and contribute to chronic infection (e.g., dental plaque, UTIs).

Immune Evasion Strategies

Extracellular Pathogens:

• Capsules: Prevent phagocytosis.
• Surface Proteins: E.g., Protein A in Staphylococcus aureus binds the antibody Fc region.
• Antigenic Variation: Change surface proteins.
• Quorum Sensing: Use autoinducers to coordinate group behavior.

Intracellular Pathogens:

• Facultative: Can live inside or outside cells (e.g., Salmonella, Shigella, Listeria).
• Obligate: Must live inside cells (e.g., Rickettsia, Coxiella).

Survival Strategies within Host Cells:

• Escape phagosome (Listeria).
• Survive in phagosome (Coxiella).
• Prevent phagosome-lysosome fusion (Salmonella).

Bacterial Toxins

• Exotoxins: Proteins secreted by bacteria (mostly Gram-positive). Often AB-type (A = active, B = binding).

  Modes of Action:

  • Disrupt membranes (e.g., Staph alpha toxin, causing pore formation).
  • Block protein synthesis (e.g., diphtheria toxin).
  • Disrupt signal pathways (e.g., cholera toxin, increasing cAMP).
  • Modify immune response (e.g., anthrax toxin, causing edema and lethal factors).
• Endotoxins: Lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria. Released during cell death. Triggers fever, vasodilation, inflammation, shock, and death.

Toxin Secretion Systems

Bacteria use specialized systems to export virulence factors:

• Type I: Sec-dependent, single-effector secretion.
• Type II: “Piston” mechanism, related to pili.
• Type III: “Syringe” injectosome; derived from flagella (e.g., Salmonella, Yersinia).
• Type IV: “Tube,” related to conjugation (e.g., Helicobacter).
• Type V: Autotransporters.
• Type VI: Derived from phage tails.

Viral Pathogenesis Mechanisms

• Rhinovirus: Many serotypes (~100); immune evasion via antigenic variation. Antibodies to one strain do not protect against others.
• Influenza: Segmented RNA virus.
  • Antigenic Drift: Minor mutations in HA/NA genes (yearly changes).
  • Antigenic Shift: Major reassortment of genome segments during co-infection, leading to pandemics.

Case Studies in Pathogenesis

• Robert Stevens (Anthrax): Inhaled spores led to anthrax meningitis, caused by Bacillus anthracis. This was the first bioterrorism case (2001). Symptoms included high fever, CNS signs, and hypotension, leading to death.
• Will (Whooping Cough): Caused by Bordetella pertussis, resulting in a violent cough and “whoop.” Diagnosed via antibody test and slow culture. Treated with azithromycin (macrolide).

Infections of the Skin and Eye

Skin Structure and Function

• Epidermis: Outer layer; dead keratinocytes, 5 sublayers.
• Dermis: Connective tissue, blood vessels, follicles, nerves.
• Mucosa: Epithelial lining continuous with skin (mouth, eyes, genitals).
• Skin Functions: Microbial barrier, immune surveillance, temperature regulation.

Types of Rashes

• Exanthem: Widespread skin rash accompanied by systemic symptoms (fever, malaise).
• Enanthem: Rash on mucous membranes.

Morphologies:

• Macular: Flat, red.
• Papular: Raised.
• Pustular: Pus-filled.
• Maculopapular: Raised and red.
• Vesicular: Small blisters.

Viral Skin Infections

• Measles (Rubeola):
  • Virus: ssRNA, paramyxovirus.
  • Entry: Respiratory tract → viremia → skin/mucosa.
  • Signs: Koplik’s spots (buccal mucosa), maculopapular rash, high fever (104°F).
  • Complications: ADEM, SSPE (delayed CNS degeneration), death, blindness, myocarditis.
  • Prevention: MMR vaccine.
• Chickenpox / Shingles (Varicella-Zoster Virus):
  • Primary infection: Chickenpox (varicella). Itchy vesicular rash, trunk → face/limbs. Latency in dorsal root ganglia.
  • Reactivation: Shingles (herpes zoster). Dermatomal vesicular rash, painful.
  • Treatment: Acyclovir (shingles), oatmeal baths.
  • Prevention: Varicella vaccine (children); zoster vaccine (60+).
• HSV-1 & HSV-2 (Herpes Simplex):
  • HSV-1: Oral (cold sores), also genital.
  • HSV-2: Primarily genital.
  • Latency: In ganglia; reactivation triggers lesions.
  • Complications: Herpetic whitlow (fingers), gladiatorum (athletes), keratitis (cornea).
  • Treatment: Acyclovir, valacyclovir, famciclovir.
• Smallpox (Variola Virus):
  • Transmission: Inhalation or fomites.
  • Symptoms: Pustules (exanthem), oral spots (enanthem).
  • Status: Eradicated (1979); vaccine stockpiled.
  • Note: No current routine vaccination or FDA-approved treatment.

Bacterial Skin Infections

• Staphylococcus aureus:
  • Normal nasal flora; causes skin infections via: Coagulase (fibrin barrier, leading to abscesses) and Exotoxins (TSST for toxic shock, exfoliative for SSSS).
  • Diseases: Folliculitis → boils/furuncles → carbuncles.
  • Impetigo: Honey-colored crust; treated with topical antibiotics.
  • MRSA: Methicillin-resistant strain; treat with vancomycin.
• Streptococcus pyogenes (Group A Strep):
  • Reservoir: Nasopharynx, skin.
  • Diseases: Necrotizing fasciitis (rapid tissue destruction), Impetigo (nonbullous, bullous types).
  • Virulence: M protein, streptolysins, DNase, hyaluronidase, SPEs (superantigens leading to toxic shock).
  • Sequelae: Rheumatic fever (cross-reactivity with heart tissue), Glomerulonephritis.
  • Treatment: Clindamycin, metronidazole, gentamicin.
• Acne Vulgaris:
  • Caused by Propionibacterium acnes.
  • Triggers: Sebum, hormones, genetics.
  • Types: Comedonal (blackheads/whiteheads), Inflammatory (papules, pustules), Cystic (severe).
  • Mechanism: Inflammation via TLR-2 activation.

Fungal Skin Infections

• Dermatophytes: Infect keratinized tissue (Trichophyton, Microsporum, Epidermophyton).

  Tinea (Ringworm) Types:

  • Tinea capitis: Scalp (children).
  • Tinea corporis: Body.
  • Tinea cruris: Groin.
  • Tinea pedis: Feet.
  • Tinea unguium: Nails.
  • Diagnosis: KOH prep, culture on Sabouraud agar.
  • Treatment: Imidazoles (clotrimazole).
• Tinea versicolor (Malassezia yeast): Hypopigmented lesions, chronic in warm climates. Yeast-to-hyphal switch leads to stratum corneum invasion.
• Candida Infections: Candida albicans, normal flora. Causes candidal intertrigo in skin folds. Dimorphic yeast (yeast ↔ mycelial).

Eye Infections

• Conjunctivitis (Pink Eye):
  • Viral: Watery discharge, bilateral.
  • Bacterial: Purulent, painful. Caused by Staph, Strep, Chlamydia, Neisseria gonorrhoeae.
• Chlamydia trachomatis:
  • Inclusion conjunctivitis: Newborns (acquired during passage through the birth canal).
  • Trachoma: #1 cause of infectious blindness globally. Eyelashes scar the cornea (trichiasis).
  • Treatment: Erythromycin (topical), azithromycin.
• Herpes Eye Infections: HSV-1 causes keratitis and keratoconjunctivitis. Reactivation leads to scarring and potential blindness. HZO (shingles involving the eye) is treated with antivirals.
• Fungal Eye Infections: Fusarium, Aspergillus, Candida. Risk factors: trauma, contact lens use. Diagnosis: corneal scraping, PCR. Treatment: Natamycin, Amphotericin B.
• Parasitic Eye Infections: Acanthamoeba causes keratitis. Found in soil, water, HVAC systems. Symptoms: pain, photophobia, vision loss. Contact lens use is the main risk factor.

Infections of the Respiratory Tract

Anatomy and Defense Mechanisms

• Upper Tract: Nasal passages, oral cavity, pharynx, larynx.
• Lower Tract: Trachea, bronchi, lungs, alveoli.
• Mucociliary Escalator: Goblet cells produce mucus that traps microbes. Cilia sweep them away from the lungs.
• Eustachian Tube: In infants, the tube is shorter and more horizontal, increasing the risk of ear infections.

Common Viral Infections

• Common Cold:
  • Cause: Rhinovirus (main), coronavirus, influenza, RSV.
  • Signs: Runny nose, sore throat, nasal congestion, typically no fever.
• RSV (Respiratory Syncytial Virus):
  • Causes fusion, leading to syncytium formation.
  • Leading cause of bronchiolitis and pneumonia in infants (<1 year).
  • Spread: Contact, droplets.
• Influenza:
  • Type A: Pandemic potential; infects humans, pigs, birds.
  • Type B: Humans only; mild.
  • Type C: Rare/mild.
  • Key proteins: HA (hemagglutinin) binds respiratory cells; NA (neuraminidase) releases virus; M2 aids uncoating.
  • Antigenic drift = small mutations (yearly changes).
  • Antigenic shift = genome reassortment (pandemics).
• COVID-19: SARS-CoV-2, ssRNA, enveloped. Symptoms: fever, cough, dyspnea, cytokine storm. Many cases are asymptomatic.
• Croup (Laryngotracheobronchitis): Affects children 6 months–5 years. Characterized by a barking cough and inspiratory stridor. Caused by parainfluenza virus types 1 & 2.

Upper Respiratory Bacterial Infections

• Otitis Media: Common in children; caused by Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis. Related to the short, horizontal Eustachian tube in children.
• Bacterial Sinusitis: Often follows colds or otitis. Signs: facial pain, pressure, foul breath.
• Streptococcal Pharyngitis (Strep Throat):
  • Cause: Streptococcus pyogenes (GAS).
  • Signs: Sudden sore throat, high fever, enlarged cervical nodes, tonsillar exudate, no cough.
  • Complications: Scarlet fever (SPE toxin), strawberry tongue, Rheumatic fever (heart/joint inflammation), Glomerulonephritis.
• Diphtheria:
  • Caused by Corynebacterium diphtheriae.
  • Signs: Gray membrane on the throat, “bull neck.”
  • Toxin-mediated. Treated with penicillin + antitoxin. Prevented by DTaP vaccine.
• Whooping Cough (Pertussis):
  • Caused by Bordetella pertussis. Spread by droplets; 3 phases:
  • Catarrhal: Cold-like.
  • Paroxysmal: Whooping cough.
  • Convalescent: Gradual recovery.

Lower Respiratory Bacterial Infections

• Bronchitis: Inflammation of the bronchi. Viral or bacterial. Persistent productive cough lasting more than five days.
• Community-Acquired Pneumonia (CAP):
  • Typical: Streptococcus pneumoniae.
  • Atypical: Mycoplasma pneumoniae, Legionella, Chlamydophila.
• Streptococcus pneumoniae: Gram-positive diplococci with a capsule. Classic lobar pneumonia: fever, chest pain, productive cough. Vaccine: PPSV (covers 23 serotypes).
• Mycoplasma pneumoniae: Atypical pneumonia. Lacks a cell wall, so β-lactams are ineffective. Symptoms include headache, malaise, and a dry cough.
• Legionella pneumophila: Atypical pneumonia. Found in water systems (e.g., fountains). Intracellular pathogen; avoids lysosome fusion.
• Hospital-Acquired Pneumonia: Pseudomonas aeruginosa is a common cause. CF (Cystic Fibrosis) patients are high-risk.
• Tuberculosis (TB):
  • Caused by Mycobacterium tuberculosis, an acid-fast bacillus.
  • Latent TB: Non-infectious; Primary TB: Active.
  • Signs: Cough, weight loss, fever, night sweats.
  • Granulomas are known as Ghon complexes. MDR (Multi-Drug Resistant) strains are an increasing concern.
• Inhalation Anthrax: Caused by Bacillus anthracis, spore-forming. Symptoms include hemoptysis, chest pain, and dyspnea. Rapidly fatal, requiring urgent antibiotics.

Fungal and Parasitic Infections

These infections often involve occupational or environmental exposure and are generally not spread person-to-person. Risk increases in immunocompromised patients.

• Blastomycosis: Blastomyces dermatitidis. Found in Mississippi/Ohio River valleys; moist soil.
• Histoplasmosis: Histoplasma capsulatum. Associated with bat/bird droppings; Ohio/Mississippi valleys.
• Coccidioidomycosis: Coccidioides immitis (“Valley Fever”).
• Cryptococcosis: Cryptococcus neoformans. Can cause meningoencephalitis in AIDS patients.

Systemic Viral and Bacterial Infections

Systemic Viral Infections

• Epstein-Barr Virus (EBV) – Mononucleosis:
  • Virus type: Human herpesvirus 4 (HHV-4).
  • Transmission: Saliva (“Kissing Disease”).
  • Target cells: Oropharyngeal epithelium, tonsils, salivary glands, B-cells (causing atypical appearance).
  • Symptoms: Fever, pharyngitis, swollen tonsils, cervical lymphadenopathy, fatigue.
  • Complications: Splenomegaly (risk of rupture with physical activity).
  • Associated with: Burkitt’s lymphoma (fast-growing jaw tumors in children; chemotherapy used).
  • Prevention: Avoid contact; no vaccine.
• Cytomegalovirus (CMV):
  • Virus type: HHV-5, dsDNA virus; latent in host genome.
  • Transmission: Saliva, urine; vertical (transplacental).
  • Symptoms: Often asymptomatic.
  • Immunocompromised: Reactivation leads to pneumonia, encephalitis, hepatitis.
  • Note: Reinfection is possible with a second strain. Diagnosis via serology, PCR.
• Dengue Hemorrhagic Fever:
  • Region: Tropical climates.
  • Vector: Mosquitoes.
  • Symptoms: Severe joint/muscle pain (“breakbone fever”), rash, bleeding.
• Ebola Virus:
  • Transmission: Contact with body fluids.
  • Symptoms: Sudden fever, muscle aches, multi-organ bleeding.
  • High mortality; no specific treatment.
• Chikungunya Virus:
  • Symptoms: Disabling joint/muscle pain.
  • Region: Indian Ocean, Europe, parts of the U.S.
  • Vector: Mosquitoes.

Systemic Bacterial Infections

Sepsis and Septic Shock:

• Bacteremia: Bacteria in the blood (may be transient).
• Sepsis: Systemic immune response to infection.
• SIRS (Systemic Inflammatory Response Syndrome): Increased heart/respiratory rate, abnormal WBC count.
• Septicemia: High replication of the pathogen in the blood.
• Septic Shock: Blood pressure drops dangerously.
• Cause: Superantigens or PAMPs (LPS, lipoteichoic acid).

Case Studies and Pathogens:

• Plague – Yersinia pestis:
  • Forms: Bubonic (buboes in lymph nodes, not transmissible); Septicemic (bacteria in blood, not transmissible); Pneumonic (lung infection, transmissible human-to-human).
  • Virulence Factors: F1 capsule (anti-phagocytic), Lipoproteins (block immune response), Type III secretion system (injects virulence proteins), Biofilm formation (transmission via fleas).
  • Treatment: Gentamicin + tetracycline.
• Lyme Disease – Borrelia burgdorferi:
  • Vector: Ixodid (deer) tick. Type: Spirochete, linear genome.
  • Stages: Stage 1 (3–30 days): Bull’s-eye rash (Erythema migrans), fever, joint pain. Stage 2 (weeks–months): Dissemination to organs, neuro/cardio symptoms. Stage 3 (months–years): Encephalopathy, neuropathy.
  • Treatment: Doxycycline (early treatment is best).
• Typhoid Fever – Salmonella enterica serovar Typhi:
  • Infects: Macrophages, spreading systemically.
  • Transmission: Fecal–oral route.
  • Symptoms: Fever, GI issues, multi-organ effects.
  • Carrier state: Shed in stool during/after infection.
• Rocky Mountain Spotted Fever (RMSF) – Rickettsia rickettsii:
  • Vector: Ticks and lice.
  • Symptoms: Rash starts at wrists/ankles and spreads centrally.

Special Clinical Concepts

• Staphylococcus epidermidis: Normal flora; contamination of IV site cultures often suggests contamination rather than true sepsis.
• Diagnosis of Sepsis: Requires positive blood cultures from multiple sites.