Bacterial Diseases Lecture Review

General Characteristics of the Staphylococci

• Common inhabitants of the skin and mucous membranes.
• Morphology: Spherical cells typically arranged in irregular clusters.
• Gram Stain: Gram-positive.
• Physiological Traits: Lack spores and flagella; may possess capsules.
• Classification: There are $47$ known species.
• Common Pathogenic Species:
  • Staphylococcus aureus
  • Staphylococcus epidermidis
  • Staphylococcus capitis
  • Staphylococcus hominis

Staphylococcus aureus

• Growth Characteristics:
  • Grows in large, round, opaque colonies.
  • Pigmentation: Often yellow (gold) in color.
  • Optimum Temperature: $37\,^{\circ}\text{C}$.
  • Microbial Metabolism: Facultative anaerobe.
  • Environmental Resistance: Capable of withstanding high salt concentrations, extremes in pH, and high temperatures.
• Virulence Factors: Produces several enzymes and toxins to aid pathogenesis:
  • Coagulase
  • Hyaluronidase
  • Exfoliative toxin
  • DNase

Epidemiology and Pathogenesis of Staphylococcus aureus

• Distribution: Present in most environments frequented by humans; readily isolated from fomites.
• Human Carriage:
  • Carriage rate for healthy adults ranges from $20\text{-}60\%$.
  • Primary colonization sites include the anterior nares (nostrils), skin, nasopharynx, and intestine.
• Predisposition to Infection:
  • Factors include poor hygiene, poor nutrition, tissue injury, preexisting primary infection, diabetes, and immunodeficiency.
• Community Factors:
  • Increasing incidence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA).
  • MRSA is resistant to almost all penicillins.

Staphylococcal Disease: Clinical Manifestations

• Staphylococcal diseases range from localized cutaneous infections to severe systemic diseases.
• Localized Cutaneous Infections: Bacteria invade the skin through wounds, follicles, or glands.
  • Folliculitis: Superficial inflammation of the hair follicle; usually resolves without complications but can progress.
  • Furuncle: Also known as a boil; occurs when inflammation of a hair follicle or sebaceous gland progresses into an abscess or pustule.
  • Carbuncle: A larger and deeper lesion created by the aggregation and interconnection of a cluster of furuncles.
  • Impetigo: Bubble-like swellings that can break and peel away; most common in newborns.
• Systemic Infections:
  • Osteomyelitis: Infection established in the metaphysis; results in abscess formation, tenderness, and potentially necrosis or bone breakage.
  • Bacteremia: Bacteria in the blood, primarily originating from another infected site or medical devices; can lead to endocarditis and may be fatal within a few days.
  • Pneumonia: Rare, occurring most often in children with cystic fibrosis (CF) or measles; carries a fatality rate of $50\%$.
• Toxigenic Disease:
  • Food intoxication: Caused by the ingestion of heat-stable enterotoxins; resulting in gastrointestinal distress.
  • Staphylococcal scalded skin syndrome (SSSS): A toxin-induced bright red flush and blisters followed by desquamation of the epidermis.
  • Toxic shock syndrome (TSS): Toxemia leading to shock and multi-organ failure.

Classification of Disease: Infection vs. Intoxication

• Infection: Implies that a pathogen is actively parasitizing a host (living on or within the host).
• Intoxication: Occurs when a person is exposed to a toxin; the toxin does not necessarily come from an active infection (e.g., toxin consumed from contaminated food).

Laboratory Identification and Clinical Concerns for Staphylococcus

• Specimen Sources: Frequently isolated from pus, tissue exudates, sputum, urine, and blood.
• Diagnostic Tests: Growth in differentiating medium, catalase tests, biochemical testing, and coagulase tests.
• Antibiotic Resistance:
  • $95\%$ of strains possess penicillinase, making them resistant to penicillin and ampicillin.
  • MRSA (Methicillin-resistant S. aureus): Carries multiple resistances to almost all penicillins.
  • Some strains are resistant to all major drug groups except vancomycin (“the drug of last resort”).
  • Some strains have now developed vancomycin resistance.
  • Hospital-acquired MRSA (HA-MRSA) accounts for $80\%$ of Staphylococcus infections.

Treatment and Prevention of Staphylococcal Infections

• Treatment Protocols:
  • Abscesses require surgical perforation and clearance of pus and foreign bodies.
  • Systemic infections require intensive, lengthy therapy, often via intravenous antibiotic treatment.
• Prevention Measures:
  • Use of universal precautions by healthcare providers to prevent nosocomial (hospital-acquired) infections.
  • Diligent hygiene and cleansing, especially of injuries.

Streptococcal Diseases: Characteristics and Classification

• General Features: Non-spore forming, non-motile; form capsules and slime layers.
• Morphology: Arranged in chains or as diplococci.
• Classification by Hemolysis Reactions:
  • $\beta$-hemolysis: Complete lysis of red blood cells. Examples include Streptococcus pyogenes and Streptococcus agalactiae.
  • $\alpha$-hemolysis: Partial lysis of red blood cells. Examples include Streptococcus pneumoniae and the group collectively called the Viridans.
• Specific Pathogens and Hemolytic Patterns:
  • $\beta$-hemolytic: S. pyogenes, S. agalactiae.
  • $\alpha$-hemolytic: Viridans streptococci, S. pneumoniae, Enterococcus faecalis.

Streptococcus pyogenes (Group A)

• General: The most serious streptococcal pathogen; a strict parasite.
• Habitat: Inhabits the throat, nasopharynx, and occasionally the skin.
• Virulence Factors:
  • Hemolysins
  • C-carbohydrates
  • C5a protease
  • M-protein
  • Hyaluronic acid
  • Erythrogenic toxin (in some instances)

Epidemiology and Pathogenesis of S. pyogenes

• Reservoir: Humans are the only reservoir ($5\text{-}15\%$ of the population are inapparent carriers).
• Transmission: Contact, droplets, food, and fomites.
• Portals of Entry: Skin or pharynx.
• Demographics: Children are the predominant group affected for cutaneous and throat infections.
• Seasonality: Skin infections are more common in summer; throat infections are more common in winter.
• Risks: Systemic infections and progressive sequelae are possible if left untreated.

Clinical Scope of S. pyogenes Disease

• Throat Infections:
  • Streptococcal pharyngitis (Strep throat): Can inflame the tonsils (tonsillitis), often associated with purulent exudate (pus-like coating).
• Skin Infections:
  • Impetigo (pyoderma): Superficial lesions that break and form a highly contagious crust.
  • Erysipelas: Entry through a break in the skin; spreads to the dermis and subcutaneous tissues. Can be superficial or systemic.
• Necrotizing Fasciitis (Flesh-eating disease):
  • Rare cases where skin infections lead to the release of exotoxins that poison epidermal and dermal tissues.
  • Flesh dies and sloughs off, allowing bacteria to invade deeper tissues.
  • High danger if mixed with anaerobic bacteria or involving septicemia.
• Systemic Infections:
  • Scarlet fever: Characterized by high fever and a rash over many body parts; can be a sequel to strep throat.
  • Septicemia.
  • Pneumonia: Rare ($5\%$ of bacterial pneumonias).

Long-Term Complications of S. pyogenes

• These complications are not active infections but immune reactions to the primary infection.
• Rheumatic Fever:
  • Follows pharyngitis or scarlet fever in children.
  • Symptoms: Arthritis, chorea, fever, and nodules under the skin.
  • Duration: Lasts $3\text{-}6$ months.
  • Outcome: Can lead to carditis with extensive valve damage, often not apparent until middle age.
  • Mechanism: Type II Hypersensitivity.
• Acute Glomerulonephritis:
  • Symptoms: Nephritis, increased blood pressure, occasionally heart failure.
  • Outcome: Can become chronic, leading to kidney failure.
  • Mechanism: Type III Hypersensitivity.

Treatment and Prevention of S. pyogenes

• Medication: Treated with penicillin or penicillin derivatives.
• Sequelae Management: No treatment for rheumatic fever or acute glomerulonephritis once developed; preceding infections must be treated early.
• Prophylaxis: Long-term penicillin prophylaxis recommended for those with a history of rheumatic fever or recurrent strep throat.
• Note: Tonsillectomy for chronic strep throat is questioned regarding its effectiveness.

Alpha-Hemolytic Streptococci: The Viridans Group

• Includes: Streptococcus mutans, S. oralis, S. salivarius, S. sanguis, S. milleri, and S. mitis.
• Habitat: Residents of gums, teeth, and oral cavity; also found in the nasopharynx, genital tract, and skin.
• Entry: Not very invasive; entrance facilitated by chewing hard candy, dental, or surgical procedures.
• Diseases:
  • Bacteremia, meningitis, abdominal infection, and tooth abscesses.
  • Dental caries: S. mutans produces slime layers that adhere to teeth, forming the basis for plaque.
• Subacute Endocarditis:
  • Blood-borne bacteria settle on heart lining or valves, particularly in those with preexisting heart disease.
  • Formation of thick biofilms called “vegetations.”
  • Batches of bacteria can break off from vegetations and spread.
  • Diagnosis: Blood culture.
  • Treatment: Long-term Penicillin-G to kill vegetation bacteria.
• Prevention: Prophylactic antibiotics before oral surgery for persons with heart conditions.

Streptococcus pneumoniae: The Pneumococcus

• Disease Association: Causes $60\text{-}70\%$ of bacterial pneumonias; also causes meningitis and otitis media (ear infections).
• Characteristics:
  • Small, lancet-shaped cells in pairs or short chains.
  • Cultivation: Requires blood or chocolate agar; growth improved by $5\text{-}10\%$ $CO_2$.
  • Physiological Limit: Lacks catalase and peroxidases; cultures die in $O_2$.
• Virulence Factors:
  • Large capsules to evade phagocytosis.
  • Specific Soluble Substance (SSS): A sugar antigen in the capsule; $90$ different types identified.
• Epidemiology:
  • $5\text{-}50\%$ of people carry it as normal flora in the nasopharynx.
  • Delicate organism; does not survive long outside the habitat.
  • Predisposed groups: Children, elderly, immunocompromised, those with lung disease/viral infection, and those in close quarters.

Pathology and Diagnosis of S. pneumoniae

• Otitis Media: Cells enter middle ear via the eustachian tube.
• Meningitis: Most common cause of adult meningitis; common in children.
• Pneumonia: Cells aspirated into the lungs induce an overwhelming inflammatory response.
• Diagnosis: Cultivation of sputum or spinal fluid (for meningitis); Gram stain for presumptive identification.
• Treatment and Prevention:
  • Traditionally Penicillin G or V; however, resistance is increasing.
  • Prevention: Capsular antigen vaccine (for high-risk/older adults, effective for $5$ years) and Conjugate vaccine (for children $2\text{-}23$ months, associated with diphtheria antigens).

Neisserial Diseases

• Genus Characteristics: Gram-negative, bean-shaped diplococci; residents of mucous membranes of warm-blooded animals.
• Neisseria gonorrhoeae (The Gonococcus):
  • Causes Gonorrhea (an STI in the top $5$ list).
  • Virulence Factors: Fimbriae (attachment), IgA protease (cleaves secretory IgA).
  • Epidemiology: Strictly human infection; infectious dose (ID) $100\text{-}1,000$; survives only $1\text{-}2$ hours on fomites.
  • Symptoms in Males: $10\%$ asymptomatic; urethritis, yellowish discharge, scarring, infertility.
  • Symptoms in Females: $50\%$ asymptomatic; vaginitis, urethritis, salpingitis (Pelvic Inflammatory Disease/PID), sterility, and ectopic pregnancies.
  • Extragenital Infections: Anal, pharyngeal, conjunctivitis, septicemia, arthritis.
  • Neonatal Infection: Passed through the birth canal; causes eye inflammation and blindness. Prevented by prophylaxis at birth.
  • Diagnosis/Treatment: Gram stain for Gram-negative intracellular diplococci in neutrophils. Many cases are penicillinase-producing (PPNG) or tetracycline-resistant (TRNG). Treatment: Cephalosporin.
• Neisseria meningitidis (The Meningococcus):
  • Virulence Factors: Capsule, adhesive fimbriae, IgA protease, Endotoxin (LPS).
  • Epidemiology: Nasopharynx reservoir ($3\text{-}30\%$ of adults); high risk in close quarters (dorms, institutions).
  • Pathogenesis: Enters bloodstream, crosses blood-brain barrier, grows in CSF.
  • Meningococcemia: Stays in circulation; causes cytokine-mediated vessel destruction, petechiae, decreased $O_2$ in limbs, and potential ecchymoses.
  • Meningitis: Rapid onset; fever, stiff neck, convulsions. Neurological symptoms caused by endotoxin release during the immune response.
  • Treatment: Intravenous Penicillin G or cephalosporin.

Genus Clostridium

• General: Spore formers; diseases caused by potent exotoxins.
• Groups:
  • Wound and tissue infections: Clostridium tetani.
  • Food intoxication: Clostridium botulinum.

Tetanus (Lockjaw)

• Pathogen: Clostridium tetani.
• Habitat: Soil and GI tracts of animals.
• Epidemiology: Common in geriatric patients, IV drug users, and neonates in developing countries.
• Pathology:
  • Spores enter through punctures, burns, or umbilical stumps.
  • Requires an anaerobic environment for germination.
  • Tetanospasmin: Neurotoxin that blocks the release of neurotransmitters for muscular contraction inhibition.
• Symptoms: Jaw muscle contractions (risus sardonicus), extreme arching of back, leg extension; death by respiratory paralysis.
• Management: Antitoxin therapy (Human Tetanus Immune Globulin/TIG), penicillin/tetracycline, and muscle relaxants. Vaccine: DTaP ($10\text{-}year$ booster).

Botulism

• Pathogen: Clostridium botulinum, an anaerobic spore-former in soil and water.
• Botulinum Food Poisoning: Inadequate food preservation (home-canned). Spores germinate in anaerobic conditions.
• Pathogenesis: Releases “botulin” toxin, which blocks acetylcholine release at neuromuscular junctions.
• Symptoms: Double vision, difficulty swallowing, flaccid paralysis, respiratory compromise.
• Specific Types:
  • Infant Botulism: Ingested spores (raw honey/baby food) germinate in the immature immune system. Causes “floppy baby syndrome.”
  • Wound Botulism: Spores enter wounds (increasing in IV drug users).
• Treatment: Antitoxin; cardiac/respiratory support; penicillin for infectious cases.
• Prevention: Proper canning (boil home-bottled food for $10$ minutes), salt/vinegar preservatives, avoid bulging cans.
• Botox: Medical form of botulin used to relax muscles (medical/facelift); lasts $4\text{-}6$ months.

Mycobacterium tuberculosis (The Tubercle Bacillus)

• Characteristics: Acid-fast bacilli, gram-positive irregular bacilli; strict aerobes.
• Cell Wall: Possess mycolic acids and unique peptidoglycan; resistant to drying, acids, and germicides.
• Virulence Factors: Waxes and “cord factor” prevent destruction by lysosomes/macrophages; long thin rods growing in strands called cords.
• Epidemiology:
  • Transmission: Airborne respiratory droplets; can survive $8$ months in aerosol.
  • Risk factors: Poor nutrition, AIDS, lung damage.
  • Infectious Dose (ID): $10$ bacteria.
• Phases of TB:
  • Primary TB: Phagocytosed by alveolar macrophages; formation of tubercles (granulomas). Necrotic caseous lesions may heal by calcification.
  • Secondary TB (Latent/Recurrent): Reactivation of bacilli; tubercles expand and drain. Symptoms: Coughing, bloody sputum, fever, weight loss. Mortality rate of $60\%$ if untreated.
  • Extrapulmonary TB: Dissemination to kidneys, bones, genital tract, brain.
• Diagnosis: Mantoux test (intradermal PPD, look for induration in $48\text{-}72$ hours); X-rays; acid-fast staining; PCR.
• Management: Long-term multi-antibiotic treatment (e.g., Rifater: isoniazid, rifampin, pyrazinamide). Vaccine: BCG (attenuated M. bovis), used outside the U.S.

Pseudomonas aeruginosa

• General: Small gram-negative rods with polar flagellum; aerobic respiration; produce water-soluble pigments.
• Characteristics: Resistant to soaps, dyes, disinfectants, and drying. Found in soil, water, and as a contaminant in ventilators/IV solutions.
• Clinical: Opportunistic pathogen. Causes nosocomial infections in burns, cystic fibrosis, and premature infants. Symptoms: “Blue pus” (pyocyanin) and a grapelike odor.
• Management: Multidrug resistant; treated with third-generation antibiotics.

Tularemia and Pertussis

• Tularemia (Francisella tularensis):
  • Zoonotic disease (“rabbit fever”); ID $10\text{-}50$ bacteria.
  • Transmission: Contact with animals/vectors (ticks, fleas).
  • Symptoms: Fever, ulcerative skin lesions, swollen lymph nodes, pulmonary involvement.
  • Treatment: Gentamicin or tetracycline.
• Pertussis (Bordetella pertussis):
  • Communicable childhood affliction (“whooping cough”).
  • Pathogenesis: Receptors bind to ciliated respiratory epithelial cells; toxins destroy cilia, leading to mucus buildup.
  • Symptoms: Severe coughing fits followed by “whoops.”
  • Treatment: Erythromycin, azithromycin.
  • Vaccine: DTaP (acellular vaccine).

Enterobacteriaceae: E. coli and Salmonella

• Escherichia coli:
  • Most common aerobic gut bacterium.
  • Strains:
    • Enterotoxigenic (ETEC): Severe diarrhea, heat-labile/stable toxins.
    • Enterohemorrhagic (EHEC): Strain O157:H7; causes intestinal hemorrhage and kidney damage.
    • O157:H7: Features Shiga toxin; ID is $100$ cells. Identified via Rainbow Agar (colonies appear black).
  • Infections: Infantile diarrhea, $70\%$ of traveler’s diarrhea, $50\text{-}80\%$ of UTIs.
• Salmonella:
  • True pathogens; flagellated and resistant to bile/dyes.
  • Salmonella typhi: Causes Typhoid Fever. ID $1,000\text{-}10,000$ cells. Causes invasive diarrhea, ulceration, and septicemia. Chronic carriers may shed from the gallbladder.
  • Animal Salmonelloses (Enteric Fevers): Caused by Salmonella enterica serotypes (zoonotic: cattle, poultry, reptiles). Poultry is assumed contaminated.

Yersinia pestis (The Plague)

• Characteristics: Gram-negative rod, bipolar staining, capsule.
• Transmission: Flea vectors (coagulase blocks flea esophagus); reservoirs in $200$ mammal species.
• Manifestations (ID $3\text{-}50$ bacilli):
  • Bubonic: Bubo formation in groin or axilla.
  • Septicemic (“Black Plague”): Intravascular coagulation, subcutaneous hemorrhage, purpura.
  • Pneumonic: Localized to lungs; highly contagious and fatal without treatment.
• Management: Streptomycin, tetracycline; rodent/flea control.

Haemophilus influenzae

• Characteristics: Small, gram-negative, encapsulated rods; fastidious.
• Disease: Major cause of bacterial meningitis ($85\%$ share with S. pneumoniae and N. meningitidis). Also causes epiglottitis and otitis media.
• Fatality: $90\%$ if untreated; $33\%$ of treated children sustain residual disability.
• Prevention: Subunit vaccine (Hib), often delivered with DTaP.

Miscellaneous Bacterial Agents

• Syphilis (Treponema pallidum):
  • Spiral spirochete; human is sole host; ID is $57$.
  • Stages:
    • Primary: Hard chancre site; lasts $3\text{-}6$ weeks.
    • Secondary: Fever, core throat, red/brown rash on palms/soles.
    • Tertiary: Neural/cardiovascular symptoms; gummas. Can last $20$ years.
  • Congenital Syphilis: Transplacental; results in bone deformation and nasal discharge.
  • Treatment: Penicillin G.
• Lyme Disease (Borrelia burgdorferi):
  • Transmitted by Ixodes ticks (white-footed mouse reservoir).
  • Symptoms: “Bull’s eye rash,” fever, late-stage polyarthritis, and cardiac symptoms.
  • Treatment: Tetracycline, amoxicillin.
• Campylobacteriosis (Campylobacter jejuni):
  • S-shaped vibrio; cause of bacterial gastroenteritis worldwide.
  • Toxin: CJT (similar to cholera toxin).
  • Symptoms: Bloody or watery diarrhea.
• Rocky Mountain Spotted Fever (Rickettsia rickettsii):
  • Obligate intracellular parasite in endothelial cells; transmitted by dog ticks.
  • Symptoms: Spotted rash, vasculitis, gangrene; fatal in $20\%$ of untreated cases.
• Chlamydial Urethritis (Chlamydia trachomatis):
  • Alternate between two stages: Elementary body (infectious) and Reticulate body (dividing).
  • Trachoma: Eye infections and STD.
  • STD is the second most prevalent; causes PID and scarring. Up to $10\%$ of population are carriers.