Gram Negative Cocci

  • Gram-Negative Cocci

     

     

     

     

     

     

     

     

     

     

     

    Gram negatives have a thin peptidoglycan wall

     

    LIPID A - Endotoxin

    • Neisseria gonorrhea - Cervicitis, Urethritis

    • Neisseria meningitis - Meningitis esp. college

    • Gonorrhea is a leading cause of infertility in women

     

    Gram-Negative Cell Wall Structure

     

    • Gram negatives take up and do not retain crystal violet stain when (decolorized with alcohol)

    • Thinner peptidoglycan wall that is sandwiched between an inner cell membrane and bacterial outer cell membrane.

    • Alcohol destroys the outer membrane

    • Outer membrane has lipopolysaccharide (LPS) endotoxin, crucial for protecting the bacteria from host defenses.

    • Endotoxin: Lipid A, the component of LPS found in the outer membrane, is recognized by toll-like receptor 4 (TLR-4) in host cells, triggering potent inflammatory responses, which can be especially disastrous if the bacteria gain access to the bloodstream or central nervous system through breaches in normal barriers.

     

     

    Neisseria Species

    • Gram-negative "coffee bean" diplococci

    • Aerobic to facultative anaerobe (organism that can grow in both the presence and absence of oxygen. It prefers to use oxygen for respiration when available but can switch to anaerobic metabolism when oxygen is not present).

    • Oxidase positive (A positive oxidase test indicates that the organism can utilize oxygen for energy production)

    • Outer membrane has LIPOPOLYSACCHARIDE (LPS) or sometimes LIPO-OLIGO-SACCHARIDE

    • Lipid A portion activates macrophages, complement and tissue factor (clotting), this is why it is called an ENDOTOXIN.

    • It hyperactivates innate defense (like a cytokine storm sort of.)

     

    1. Neisseria gonorrhoeae

    • Disease: Responsible for gonorrhea, a prevalent sexually transmitted infection (STI).

    • The bacteria can get into the bloodstream (gonococcemia) or liver (Fitz Hugh Curtis Syndrome)

    • Only oxidize glucose

    • Four types: T1, T2, T3, and T4

    • Fimbriae (pili) are very important for attachment. If N. gonorrhoeae doesn't have fimbriae, that means it is avirulent)

    • Cytotoxic substances (LPS ENDOTOXIN) - damage ciliated epithelial cells in fallopian tubes.

    • Extracellular protease - cleaves a proline-threonine bond in immunoglobulin IgA

    • PATHOGENESIS:

      • "Inoculation" is when you first get the disease.

      • It has to adhere to cells using a pilus or fimbria. It can’t stick to squamous but can stick to tranisitional (urothelial) or cervical glandular epithelium.

      • It makes IgA protease, and once it multiplies it is called colonization.

      • Once the bacteria breakdown, they start to release LOS (it's version of LPS)

      • The LOS activates macrophages, complement, clotting (Lipid A part of LOS)

      • Now the macrophages and complement call in neutrophils to eat the bugs

    • Symptoms:

      • Men: Experience urethritis characterized by dysuria (painful urination) and a burning sensation.

      • Women: Often present with cervicitis and can be asymptomatic, leading to the risk of pelvic inflammatory disease (PID), which can result in long-term complications including infertility and ectopic pregnancies.

      • Pharyngeal and Anorectal infections

      • Occasionally causes sepsis (with C5-C9 deficiencies); C meaning complement

      • Causes conjunctivitis in neonates (ophthalmia neonatorum), gonorrhea in the eye

    • Resistance: Increasing emergence of resistant strains exacerbates public health concerns, making gonorrhea a complex STI to manage. Lipid A plays a role in inflammation during infection.

    • Dx: urethral exudate containing gram (-) negative intracellular diplococci,  (Thayer-Martin VCN lysed RBC media), CNTG test (Neisseria, gonorrhea and chlamydia)

    • Treatment:

      • Ceftriaxone + azithromycin

      • Doxycycline

     

    1. Neisseria meningitidis (Meningococcus)

    • Oxidize glucose and maltose

    • Virulence associated with antiphagocytic capsule (also used for antigenic grouping), you can immunize for the capsule

    • Starts in the lungs (as a respiratory disease) then disease goes into nasopharynx

    • Pili allow attachment

    • Endotoxin, LPS is toxic (hemorrhage/petechiae and sepsis)

    • IgA1 protease found in pathogenic Neisseria can cleave IgA.

    • Dx: Gram stain and culture of CSF on Thayer-Martin VCN media and PCR

    • Rx: third generation cephalosporin (or other beta-lactam or quinolone such as ciprofloxacin)

    • Clinical Significance: Although less common than other causes, it can lead to severe bacterial meningitis with potential for lethal outbreaks, notably in crowded settings (e.g., college dormitories).

    • Outbreak Response: Rapid vaccination campaigns and close monitoring of contacts are essential during outbreaks. Early recognition is vital due to the swift progression of symptoms, which may include fever, headache, and purulent meningitis signs.

    • Meningococcemia: hemorrhagic skin lesions that don't blanch when you press.

      • It can kill your adrenal glands, which is called Waterhouse Friedrichsen syndrome(BOARD QUESTION)

      • It prevents you from making cortisol, so you cannot respond to the stress, hence fatal

      • It can spread to the brain and increase pressure in the brain

      • It can push your brain down the spinal cord and kill the person

      • Symptoms are: Headache, change in consciousness, fever

      • BOARD QUESTION: Splenectomy makes encapsulated infections worse

     

    1. Moraxella  & Kingella

    • Gram-negative diplococcus

    • Aerobic to facultative anaerobic

    • Oxidase positive

    • Dx: culture

    • Rx: many different antibiotics are effective, can be resistant to beta-lactams

    • Associated Diseases: Known to cause upper respiratory tract infections such as otitis media in children, sinusitis, bronchitis, and, in some cases, pneumonia.

    • Co-infection: Often found in conjunction with Haemophilus influenzae, which complicates treatment due to bacterial synergy.

    • Moraxella catarrhalis: colds, upper respiratory, occasionally worse

    • Kingella kingae

      • Causes pediatric septic arthritis & osteomyelitis

      • Adult and pediatric endocarditis, pneumonias and meningitis

     

    Gram-Negative Bacteria Characteristics

    • Membrane Structure: The double membrane structure contributes to the pathogenicity of gram-negative cocci. The outer membrane acts as a barrier to antibiotics and detergents, making infections caused by these bacteria harder to treat.

    • Adhesion and Mobility: Many gram-negative cocci possess appendages like pili, which enhance their adherence to host tissues. Flagella facilitate mobility, helping them to colonize and establish infections effectively.

     

    Gram Staining Technique

    • Process: The classic Gram staining technique differentiates bacteria into positive and negative based on their cell wall composition:

      • Apply crystal violet stain (purple), followed by iodine, which acts as a mordant to fix the color.

      • A wash with alcohol or acetone disrupts the outer membrane of gram-negative bacteria, causing them to lose the purple stain.

      • A counterstain with safranin (red) reveals that gram-negative bacteria will appear red under microscope examination.

      • Gram negative is Red, Gram positive is BLUE-BLACK

    • Clinical Relevance: The differential staining is a fundamental step in bacteriological diagnosis.

     

    Diagnosis and Culture

    • Gonorrhea Diagnosis: Confirmed by:

      • Culture on Thayer-Martin medium, which supports the growth of Neisseria species while inhibiting others.

      • Microscopic examination reveals gram-negative diplococci within purulent exudate from the urethra, indicative of infection.

    • Co-infection: Gonorrhea often co-occurs with Chlamydia trachomatis, necessitating dual treatment approaches to cover common pathogens.

    Complications of Gonorrhea

    • Gonococcemia: In severe cases, the bacteria can enter the bloodstream, potentially resulting in systemic complications, including septic arthritis or Fitz-Hugh-Curtis syndrome, characterized by inflammation of the liver capsule.

    • Ophthalmia Neonatorum: This eye infection can occur in newborns during birth and is treated with prophylactic antibiotics.

    Gender Differences in Infection Presentation

    • Men: Typically present with more overt symptoms, which leads to earlier diagnosis and treatment.

    • Women: Often asymptomatic and may remain undiagnosed until complications arise, highlighting the need for regular screenings in sexually active women.

    Neisseria meningitidis Details

    • Capsule: The polysaccharide capsule enhances virulence and is a key component of the meningococcal vaccine.

    • Transmission and Symptoms: The bacteria initially provoke respiratory symptoms, later disseminating to the bloodstream and meninges. Peak incidence is observed in young adults, particularly in community settings, including military recruits and college students. Risk factors like complement deficiencies significantly increase susceptibility to infection.

    Meningococcal Infection Symptoms and Risks

    • Clinical Presentation: Meningococcal sepsis may manifest through petechiae, purpura, and significant systemic illness.

    • Complicated Cases: Waterhouse-Friderichsen syndrome, where adrenal failure occurs, can precipitate rapid shock and multi-organ failure

    • Meningitis Risks: Elevated intracranial pressure and associated complications can occur, necessitating prompt intervention to avoid severe morbidity or mortality.

    Management of Meningococcal Disease

    • Treatment: Immediate initiation of intravenous antibiotics such as cephalosporins is crucial to improve survival outcomes.

    • Prevention: Vaccination is strongly recommended for at-risk groups. Special considerations need to be taken for individuals who have undergone splenectomy, as they face increased risk for encapsulated pathogens.

    Other Rare Infections

    • Moraxella catarrhalis: Besides upper respiratory infections, it could also contribute to acute exacerbations of chronic bronchitis in patients with underlying respiratory conditions.

    • Kingella: Can lead to serious complications such as septic arthritis and endocarditis primarily in the pediatric population.

    Conclusion

    • Importance of Ongoing Education: Regular review of the characteristics, diseases caused by gram-negative cocci, and their implications is crucial for healthcare professionals to ensure effective management and treatment strategies. Swift recognition and response to infections caused by these organisms are paramount in clinical settings.