What are the clinically important encapsulated bacteria, associated risk factors, and recommended prevention and treatment strategies?

Encapsulated Bacteria: Clinical Overview

Major Pathogenic Species

The clinically important encapsulated bacteria are Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, and Streptococcus agalactiae (Group B Streptococcus), which have historically caused the majority of severe invasive infections including bacteremia and meningitis in children and adults. 1

Additional encapsulated pathogens include:

• Salmonella typhi 2
• Klebsiella pneumoniae 3

Virulence Mechanisms

The polysaccharide capsule functions as the primary virulence factor through multiple mechanisms:

• Blocks phagocytosis by preventing host immune cell recognition and binding to bacterial surface proteins 3
• Impairs complement opsonization by inhibiting C3b/iC3b deposition on the bacterial surface through both alternative and classical pathways 4
• Masks subcapsular antigens from antibody recognition, reducing IgG and C-reactive protein binding 4
• Inhibits conversion of C3b to iC3b on the bacterial surface, further reducing opsonization 4
• Prevents phagocytosis mediated by Fcγ receptors, complement receptors, and non-opsonic receptors 4

High-Risk Populations

Immunocompromised States

Patients with asplenia (anatomic or functional) face substantially increased risk of fulminant sepsis from encapsulated bacteria, with mortality rates of 40-70% for meningococcal infections. 5

Specific high-risk groups include:

• Asplenic patients: Both surgical splenectomy and functional asplenia (sickle cell disease, hemoglobinopathies) 5
• Complement deficiency: Particularly increases meningococcal disease risk 5
• Chronic GVHD patients: Requiring ongoing immunosuppressive therapy 5
• HIV-infected individuals: At risk at all CD4 counts 5
• Patients on prolonged corticosteroids: Creates relative immunocompromise 6
• Hypogammaglobulinemia: IgG levels <400-500 mg/dL 5
• Malignancy, diabetes, alcohol dependency: Cause relative immunocompromise 5

Age-Related Risk

• Children under 4 years: High risk for rapid TB meningitis progression and invasive H. influenzae disease (prior to Hib vaccine) 6, 5
• Adults over 50 years: Increased pneumococcal disease incidence 5
• Adults over 60 years: Higher Listeria risk (though Listeria is not encapsulated) 5
• Young adults (late teens/early 20s): Second peak of meningococcal disease 5

Anatomic and Clinical Risk Factors

• Skull fracture or CSF leak: Predisposes to recurrent pneumococcal meningitis 5
• Upper respiratory tract infections (otitis media, sinusitis): Often precede pneumococcal meningitis 5

Prevention Strategies

Vaccination Protocols for Asplenic Patients

Asplenic patients must receive sequential pneumococcal vaccination with PCV13 first, followed by PPSV23 6-12 weeks later, with PPSV23 revaccination every 6 years. 5

Complete vaccination schedule for asplenia:

• Pneumococcal: PCV13 → PPSV23 (6-12 weeks later) → PPSV23 revaccination every 6 years 5
• H. influenzae type b: Conjugated Hib vaccine (if not previously immunized per childhood schedule) 5
• Meningococcal: Tetravalent conjugated MenACWY vaccine with appropriate revaccination 5

Vaccination timing is critical: perform 2 weeks before planned splenectomy, or if not possible, 14 days after surgery—no additional benefit from longer delays. 5

Post-HSCT Vaccination

For hematopoietic stem cell transplant recipients 5:

• Pneumococcal vaccine: Administer 23-valent polysaccharide vaccine at 12 and 24 months post-HSCT 5
• Timing consideration: Limited immunogenicity in this population, but potential benefit justifies administration 5

Antibiotic Prophylaxis

Allogeneic HSCT recipients with chronic GVHD require antibiotic prophylaxis against encapsulated organisms (S. pneumoniae, H. influenzae, N. meningitidis) for the entire duration of active GVHD treatment. 5

Key prophylaxis considerations:

• TMP-SMZ for PCP prophylaxis also provides pneumococcal protection, though resistance exists 5
• Antibiotic selection should be guided by local resistance patterns 5
• Not recommended: Routine monthly IVIG >90 days post-HSCT without severe hypogammaglobulinemia (IgG <400 mg/dL) 5

Special Considerations for Eculizumab Therapy

For patients receiving eculizumab (complement inhibitor therapy) 7:

• Meningococcal vaccines required immediately: Both quadrivalent A, C, W, Y conjugate vaccine AND meningococcal B vaccine 7
• Antimicrobial prophylaxis mandatory: Penicillin or macrolides throughout eculizumab treatment 7
• Monitor continuously for fever, headache, neck stiffness indicating meningococcal infection 7

Clinical Presentations

Typical Infection Patterns

Encapsulated bacteria characteristically cause invasive infections including bacteremia, meningitis, pneumonia, and septic arthritis, with S. pneumoniae accounting for 82-92% of occult bacteremia cases in febrile children. 5

Specific presentations by organism:

• S. pneumoniae: Sinopulmonary infections, bacteremia, meningitis; often associated with concurrent upper respiratory infection 5
• N. meningitidis: Meningitis, meningococcemia with characteristic rash 5
• H. influenzae: Dramatically reduced invasive disease post-Hib vaccine; remaining disease primarily from non-typeable strains causing mucosal infections 5

Occult Bacteremia in Children

In children aged 3-36 months with fever without source 5:

• Incidence: 1.5-2% develop occult bacteremia 5
• Sequelae risk: 5-20% of bacteremic patients develop significant complications (pneumonia, cellulitis, septic arthritis, osteomyelitis, meningitis, sepsis) 5
• Overall serious sequelae: 0.3% of all febrile children; 0.03% develop sepsis or meningitis 5

Treatment Principles

Empiric Antibiotic Selection

Antibiotic selection must be guided by local resistance patterns, as TMP-SMZ and penicillin resistance exists in pneumococcal strains. 5

Infection Control

• Appropriate isolation precautions for hospitalized patients with S. pneumoniae infections to prevent HSCT recipient exposure 5

Immune Support

Maintain trough serum IgG concentrations >400-500 mg/dL in hypogammaglobulinemic HSCT recipients through individualized IVIG dosing, monitored approximately every 2 weeks. 5

Common Pitfalls

• Delaying vaccination in asplenic patients: Must vaccinate 2 weeks pre-splenectomy or exactly 14 days post-splenectomy—not earlier, not later 5
• Using polysaccharide vaccines in children <2 years: Ineffective in this age group; conjugate vaccines required 5
• Discontinuing prophylaxis prematurely: Continue antibiotics throughout entire duration of active chronic GVHD treatment 5
• Forgetting meningococcal prophylaxis with eculizumab: Both vaccination AND antibiotic prophylaxis are mandatory 7
• Assuming Hib vaccine eliminated all H. influenzae disease: Non-typeable strains still cause mucosal infections 5