Liam - GPC Strep, GPC Staph, Clostridium,Bacilli,Non-ES forming GPR
Chapter 19: Pathogenic Gram Positive Bacteria
General Information on Genus Streptococcus
Characteristics:
Gram-positive cocci found in pairs or chains.
Catalase negative (do not produce the enzyme catalase).
Categorized by hemolysis type and Lancefield classification.
Some strains require CO2 for enhanced growth.
Typically require blood for cultivation.
Hemolysis Types in Streptococci
Beta (β) Hemolysis:
Complete lysis of red blood cells (RBCs).
Exhibits a clear zone around colonies (e.g., Group A Streptococcus).
Alpha (α) Hemolysis:
Partial lysis of RBCs.
Exhibits a green zone around colonies (e.g., Streptococcus pneumoniae).
Gamma (γ) Hemolysis:
No lysis of RBCs.
No hemolytic activity (e.g., Enterococcus sp.).
Lancefield Classification
Developed by Rebecca Lancefield based on bacterial cell wall antigens.
Major Groups:
Group A: Streptococcus pyogenes (S. pyogenes)
Group B: Streptococcus agalactiae (S. agalactiae)
Group D: S. bovis
Groups C, F, G: Other less common species.
Diseases Associated with Streptococcus pyogenes
Pharyngitis (Strep Throat):
Can progress to Scarlet Fever characterized by red cheeks and rash due to erythrogenic toxin.
Impetigo/Pyoderma:
Highly infectious skin condition.
Necrotizing Fasciitis:
Known as "flesh-eating strep"; extremely severe with up to 50% fatality rate.
Consequences of Untreated Infections:
Autoimmune response leading to Rheumatic Heart Fever (RHF) or Glomerulonephritis.
Diagnostic Tests for Streptococcus
Rapid Strep Test: Up to 30% false negatives.
Bacitracin Test: Reference for identifying Group A Strep.
Latex Agglutination Test: For laboratory identification of Streptococcus species.
Treatment of Beta-Hemolytic Group A Infections
Remain sensitive to Penicillin.
Alternatives for penicillin-allergic patients include cephalosporin or erythromycin.
Bacitracin is effective topically.
Necrotizing fasciitis requires surgery.
Streptococcus agalactiae (Group B)
Primarily affects newborns.
Colonizes in GI, urinary, and genital tracts.
Disease risk is higher if maternal antibodies are absent:
Early-onset: Infects newborns during birth.
Late-onset: Infection from caretakers after the first week of life.
Can cause severe conditions like sepsis, meningitis, and pneumonia.
Prevention of Group B Streptococcus Disease
Expectant mothers are cultured for BSGB before birth.
If positive, IV antibiotics (such as Penicillin G) are administered during labor.
This practice has reduced early-onset infections by 70%.
A BSGB vaccine is in development.
Identifying Group B Streptococcus
Characterized by beta hemolysis.
CAMP Test: Enhances the beta hemolysis of Staphylococcus aureus.
Antigen detection tests from culture samples.
Non-Beta-Hemolytic Streptococci
Streptococcus pneumoniae:
Diplococci appearance (lancet-shaped).
Major cause of pneumonia and other infections.
Viridans Streptococci (e.g., S. mutans):
Associated with dental caries and endocarditis.
Streptococcus bovis:
Found in the GI tract and associated with colon cancer.
Enterococcus:
Thrives in the intestinal tract, resistant to various conditions, indicator of fecal contamination.
Treatment of Enterococcal Diseases
Commonly found in UTIs, lungs, and causing septicemia.
Accounts for 10% of nosocomial infections.
Increased resistance, such as Vancomycin-resistant Enterococcus (VRE).
Overview of Acid-Fast Bacteria
Definition: Acid-fast bacteria are those that retain the primary stain even when treated with a strong acid alcohol, indicating the presence of mycolic acid in their cell walls.
Key Staining Characteristics:
Special Stain: Requires an acid-fast stain to rinse primary stain off, which is different from the Gram stain process.
Result: If a bacterium is acid-fast, it will not wash out the primary stain.
Common Acid-Fast Bacteria: Includes species from Mycobacterium, Nocardia, and Actinomycetes.
Structure of Acid-Fast Bacterial Cell Walls
Cell Wall Composition:
Thick layer of Mycolic Acid above peptidoglycan.
Presence of Arabinogalactan linking mycolic acids and peptidoglycan.
Permeability:
Small hydrophilic molecules require porins to pass through the outer membrane (10 nm) adjacent to a cell membrane (7 nm).
Mycobacterium Species Overview (True Acid-Fast Bact)
Characteristics:
Waxy, water-resistant cell walls due to lipid mycolic acids-
Mycolic acivd keeps bact from drying out, increases resistance to AB’s and Chem DI’s but also slows down growth, nutrients dont enter as easily.
Grows intracellularly
Prevents dehydration.
Increases resistance to antibiotics and disinfectants.
Slows nutrient uptake, thus inhibiting rapid growth.
Can evade destruction after phagocytosis due to unique cell wall properties.
Cultivation:
Growth rate is slow; it can take weeks to form visible colonies in laboratory settings.
Not susceptible to Gram staining due to cell wall structure.
Major Species Causing Human Diseases
Mycobacterium tuberculosis
Responsible for tuberculosis (TB).
Mycobacterium leprae
Causes leprosy.
Mycobacterium avium-intracellulare
Affects immunocompromised individuals, particularly those with AIDS.
Mycobacterium tuberculosis Details
Historical Context:
A longstanding human pathogen evident in ancient remains (e.g., Egyptian and Native American mummies).
Disease Mechanism:
When the immune system is weakened, bacteria can escape containment, leading to active disease characterized by granuloma formation in the lungs.
Common in conditions of poverty, stress, malnutrition, and existing illnesses.
Public Health Concern:
Previously known as the "White Plague," tuberculosis can remain latent in 90-95% of infected individuals without causing illness for years.
Symptoms and Treatment:
Historical treatments included rest in sanitariums and exposure to fresh air to support the immune system against TB.
Conclusion
Understanding the characteristics and challenges posed by acid-fast bacteria such as Mycobacterium species is crucial for recognizing their roles in human diseases, particularly TB and leprosy.
Diagnosis of TB
PPD, Mantoux or Tuberculin Skin Test
A purified protein derivative of TB is injected under the skin.
If the person is infected, sensitized T cells cause a delayed hypersensitivity reaction.
Resulting area becomes red, hard, and swollen.
Limitations of PPD Test
Does not indicate whether TB is active or latent.
Requires an X-ray of the lungs to look for walled-off tubercles or active cavities.
Determination of Disease State
If tubercles are seen, next step is to determine if the disease is active or latent.
Check for Acid-Fast Bacilli (AFB) in sputum: presence of AFB indicates active TB.
Laboratory Diagnosis
Culture Growth
Example shown: Mycobacterium tuberculosis on Lowenstein Jensen Agar.
Colonies resemble cauliflower.
AFB Tests
Special acid-fast staining techniques used to visualize Mycobacterium species in clinical samples (lungs, lymph nodes, etc.).
Antibiotic Resistance and Treatment
Multidrug-Resistant TB (MDR TB)
Defined as TB resistant to the two most effective first-line drugs: isoniazid and rifampin.
Extensively Drug-Resistant TB (XDR TB)
MDR TB that is also resistant to effective second-line drugs commonly used for treatment.
Totally Drug Resistant TB
An extreme form of resistance with significant treatment challenges.
Directly Observed Therapy (DOT)
Involves a health worker visiting daily to ensure medication adherence, a strategy used to combat drug resistance.
Vaccination Against TB
BCG Vaccine
Bacillus of Calmette & Guerin, a vaccine derived from M. bovis, a cattle pathogen.
Promotes immunity to TB and has been in use since the 1920s.
Commonly administered outside the U.S., but rarely used in the U.S. due to complications in testing (positive PPD from vaccination interferes with screening).
Global TB Statistics
Incidence of TB
Annually, around 10 million people develop TB, with 1.5 million fatalities, making it the top infectious killer worldwide.
Vulnerability
Especially harmful to individuals with HIV.
Contributes significantly to antimicrobial resistance.
Geographical Distribution
Predominantly affects low- and middle-income countries, but TB exists globally.
Major burden concentrated in eight countries: Bangladesh, China, India, Indonesia, Nigeria, Pakistan, Philippines, and South Africa.
Gram Positive Rods
1. Bacillus anthracis
Causes Anthrax:
Common disease in wild & domestic animals (outside the US).
Endospores can survive for years in the soil, waiting for grazing animals to ingest them.
Highest risk for humans are those in close proximity to infected animals.
Most common cause of anthrax in the US arises from imported hides or souvenirs made with animal skin.
Gram Stain Identification:
Presence of spores located in the center of the rods.
2. Human Disease: Anthrax
Pulmonary Anthrax:
Most severe type of anthrax, occurs when endospores are inhaled.
Also known as "Woolsorters Disease" due to aerosolized spores from infected animal hides.
Initial symptoms similar to flu, progressive impairment of breathing.
Untreated case fatality rate: 90%.
Cutaneous Anthrax:
Occurs when broken skin contacts endospores, resulting in lesions.
Lesions can deepen, potentially leading to sepsis.
Most common form (95% of all cases).
Untreated case fatality rate: 20%.
Intestinal Anthrax:
Occurs if contaminated meat is ingested (rarest form).
Fatality rate ranges from 20-60% if untreated.
Mostly seen in predators consuming prey skin.
3. Treatment/Transmission of Anthrax
Treatment Options:
Doxycycline, Ciprofloxacin, and Penicillin are effective.
Tetracycline and Erythromycin also have effectiveness.
Transmission:
Anthrax is not transmissible from person to person.
Could be used as a biological warfare agent; endospores need to be aerosolized for maximum effect.
4. Bacillus cereus
Food Intoxication:
Produces two enterotoxins leading to two types of foodborne illness:
Heat-stable toxin: Rapid onset (1-6 hours), causing vomiting.
Heat-labile toxin: Onset (8-12 hours), causing diarrhea.
Associated with food like cooked rice or fried rice, which are held at room temperature too long before serving.
Mechanism:
Endospores survive boiling and germinate in favorable conditions, leading to multiplication at room temperature and toxin production.
Toxin remains viable, even if food is reheated.
Notes on Bacillus cereus
No antibiotics needed for treatment of Bacillus cereus infections.
Spores do not cause the swelling of the cell.
Clostridium botulinum
Causes: Botulism, a severe form of food poisoning; can also contaminate wounds.
Exotoxin: Produces a potent neurotoxin, regarded as the most powerful natural toxin known; as little as 1µg can be fatal for a normal adult.
Symptoms:
Initial: Blurred vision and double vision.
Progression: Muscle weakness, difficulty swallowing, leading to potential respiratory or cardiac failure (flaccid paralysis).
Botulism Types
Adult Botulism
Pathway: Occurs primarily due to ingestion of canned food containing spores of C. botulinum that survive the sterilization process.
Growth: Spores germinate in the anaerobic environment of can, producing a dangerous toxin.
Infant Botulism
Risk: Infants are more susceptible due to their immature intestinal flora compared to adults, which protects against the proliferation of C. botulinum.
"Floppy Baby Syndrome": Occurs when infants ingest honey or spores leading to botulism.
Precaution: Honey should never be given to babies since it may contain spores.
Botox
Definition: A diluted form of botulinum toxin.
Medical Uses:
Effective for treating migraines, muscle spasms, excessive sweating, misaligned eyes, and some motion disorders like tip-toe walking.
Also popular in cosmetic treatments to reduce wrinkles.
Clostridium perfringens
Role: Primary cause of gangrene, leading to tissue death from lack of blood supply.
Process: Gangrene initiates in anaerobic conditions of wounds where tissue necrosis assists bacterial growth, leading to rapid infection and gas production.
Complications
Can cause severe uterine infections post-abortion due to its presence in the genital tract, which can lead to life-threatening sepsis.
If it originates from normal intestinal flora, perforation of the bowel may result in gangrene in the peritoneum.
Treatments: Penicillin or hyperbaric oxygen therapy; advanced cases may necessitate limb amputation due to necrosis.
C. perfringens Food Poisoning
Prevalence: One of the most common causes of foodborne diarrhea in the U.S.
Mechanism: Bacteria thrive in the intestines and release enterotoxins, resulting in pain and diarrhea 8 to 12 hours post-consumption.
Association: Often linked to improperly refrigerated meat.
Clostridioides difficile (formerly C. difficile)
Occurrence: Chief cause of hospital-acquired diarrhea and pseudomembranous colitis.
Characteristics:
Notable foul odor reminiscent of horse stables.
Usually part of the gut flora but can overgrow when antibiotics eliminate other microbes, particularly after using antibiotics like ampicillin or clindamycin.
Fatality Rate: Between 27-44% if untreated, affecting roughly 3.5 million North Americans annually.
Treatment: Standard options include metronidazole (Flagyl) or vancomycin (Vancocin, costs $1128).
Visual: Pseudomembranous colitis shows significant intestinal abnormalities compared to the normal colon lining.
Gram Positive Rods Overview
Definition: Bacteria that retain the crystal violet stain used in the Gram staining procedure.
Endospore Forming Gram Positive Rods (GPR)
Characteristics:
Can survive extreme conditions such as:
Lack of food
Temperature extremes
Lack of moisture
Metabolically inactive when in spore form, making them resistant to destruction.
Examples:
Clostridium spp. (anaerobic)
Bacillus spp. (aerobic)
Non-Endospore Forming Gram Positive Rods
Characteristics:
Lack the ability to form endospores.
Examples:
Corynebacterium
Listeria
Gardnerella (variable Gram staining)
Lactobacillus
Propionibacterium acnes
Actinomycetes (weakly acid-fast)
Mycobacterium (acid-fast)
Clostridium Species
General Characteristics:
Anaerobic GPR that produce endospores and are associated with destructive toxins.
Specific Clostridium Species:
Clostridium tetani
Morphology: Round, terminal endospores resembling tennis rackets or lollipops.
Disease: Tetanus (caused by neurotoxin tetanospasmin)
Mechanism: Blocks muscle relaxation, leading to rigid contraction ("lockjaw") and muscle spasms.
Clostridium botulinum
Morphology: Oval, sub-terminal endospores.
Clostridium perfringens
Morphology: Oval, sub-terminal endospores, usually causing double zone hemolysis.
Clostridioides difficile
Morphology: Oval, sub-terminal endospores, has a characteristic odor similar to horse manure.
Tetanus (Clostridium tetani)
Pathology:
First Symptom: Stiffness of the jaw (lockjaw), progressing to severe muscle spasms.
Affected individuals may experience:
Rigid muscles in back and legs
Potentially fatal muscle spasms leading to respiratory failure.
Mechanism of Tetanus Toxin:
Toxin binds to inhibitory interneurons, reducing the release of neurotransmitters (glycine and GABA).
Inhibition leads to constant muscle contraction.
Transmission and Infection Risks
Common Sources of Infection:
Soil, particularly around animal feces.
Entry routes:
Deep tissue injections (e.g., through puncture wounds)
IV drug use with non-sterile equipment.
At-Risk Populations:
70% of cases in the U.S. are in individuals over age 50 whose vaccinations are not up to date.
Tetanus Prevention and Treatment
Vaccination:
DTP Vaccine: Inactivated toxin that stimulates antibody production for immunity against tetanus.
Booster Shots: Required every 10 years (Tdap) to maintain immunity; many in the U.S. are unvaccinated.
Post-exposure Treatment:
Unvaccinated individuals may receive tetanus immune globulin (TIG) for immediate protection.
Antibiotics (e.g., metronidazole) can eliminate the bacteria.
Note: Awareness of symptoms is crucial for diagnosis, as cultures are only positive in 30% of cases.