• Information
  1. Epidemiology
  2. Characteristics
  3. Pneumococcal Pneumonia
  4. Otitis Media
  5. Pneumococcal Bacteremia
  6. Antibiotic Resistance
  7. Treatment
  8. Vaccination

A. Epidemiology

1. Streptococcus pneumoniae (S. pneumoniae, pneumococcus)
2. Over 90 serotypes have been identified thusfar
3. Incidence of invasive infections ~23 per 100,000 per year
   1. Highest in children <2 years (~169 per 100,000)
   2. Very high in adults >65 years (~60 per 100,000)
   3. Invasive pneumococcal disesase in >50 year olds reduced 28% between 1999 and 2003 [27]
   4. This reduction corresponded to a large increase in use of pediatric conjugate vaccine [27]
4. Incidence in blacks is ~2.6X as high as in whites
5. Mortality is elevated in high risk groups (see below)
6. Disease Entities
   1. Most common cause of pneumonia in all hosts - nearly 500,000 cases per year
   2. Bronchitis
   3. Otitis Media - nearly 7 million cases per year
   4. Sinusitis
   5. Meningitis - 3,000 cases annually, poor prognostic feature [1]
   6. Bacteremia - about 50,000 cases per year
   7. Uncommon - endocarditis, skin infections, pharyngitis, conjunctivitis [2]

B. Characteristics

1. Highly virulent, lancet shaped, Gram positive diplococcus
2. Virulence Factors
   1. Polysaccharide capsule confers resistance to phagocytosis
   2. Teichoic acids on surface are highly inflammatory
   3. Opsonization of pneumococcus by antibody is critical to host defence
   4. Without immunization, host production of antibodies is often suboptimal
   5. Mutations in mannose binding lectin (MBL) gene present in ~5% of Northern Europeans associated with increased risk of invasive disease [3]
3. Factors predisoposing to Pneumococcal infections
   1. Splenectomy (patients should be on Penicillin prophylaxis)
   2. Hypogammaglobulinemia
   3. Nephrotic syndrome
   4. HIV (5-40X increased risk)
   5. Narcotics (?)
   6. Smoking increases risk of invasive pneumococcal disease [4]
4. Recurrent pneumococcal infections suggest immunodeficiency

C. Pneumococcal Pneumonia

1. Symptoms
   1. Fevers usually with rigors, up to 102-103°F
   2. Patients are often toxic appearing, with severe malaise, diaphoresis
   3. Cough common with copious sputum production - thick, yellow, sputum
   4. Egophany and rales (crackles) are very common on examination
   5. Symptoms may be blunted in elderly and immunocompromised persons
   6. Rapidly progressive in most patients if untreated
   7. Accounts for up to 60% of community acquired pneumonias
2. Diagnosis
   1. Gram stain of sputum is often diagnostic
   2. Culture of organism and antibiotic sensitivity should be done in ALL cases
   3. Blood Cultures should be obtained: bacteremia is common, ~10% of cases
   4. Chest radiograph shows consolidation, usually unilobar; may progress to multilobar
   5. Air bronchograms are often present on radiograph as well
   6. Leukocytosis with marked left shift
3. Course
   1. Aggressive therapy is generally warranted
   2. Immunosuppressed patients, including diabetics, should usually be hospitalized
   3. Antibiotic monotherapy is suboptimal for severe bactermic pneumococcal pneumonia [5]
   4. Quinolones and macrolides and/or vancomycin are generally part of the regimen
   5. Third generation cephalosporins are probably less clinically effective [5]
   6. Progression to ARDS and/or shock may occur
   7. Mortality is 10-30%; higher in elderly and immunocompromised
   8. Multidrug resistant pneumonia outbreak in nursing home in unvaccinated persons [6]

D. Otitis Media

1. S. pneumoniae is most common cause
2. Serotypes 3, 6B, 9V, 14, 19F, and 23F
3. Acute ear pain, redness, often with fever
4. Typically occurs in children
5. Increasing penicillin-resistant strains
6. Heptavalent pneumococcal vaccine prevents acute otitis media [7]

E. Pneumococcal Bacteremia

1. Relatively frequent complication of pneumococcal pneumonia (~10%) and meningitis
2. Associated with high fevers, often >102°F, usually with rigors
3. Hypotension is not uncommon, and full-blown sepsis may ensue
4. Increasing levels of antibiotic resistance
   1. ~25% PCN resistant strains
   2. Increasing macrolide resistance (high of ~13/100,000 population)
   3. However, the incidence of resistance varies greatly by geography
   4. Heptavalent pneumococcal vaccine associated with reduced macrolide resistance [8]
5. Recurrence of pneumococcal bacteremia strongly suggests immunodeficiency [9]

F. Antibiotic Resistance

1. Increasing global problem
2. About 25% of all isolates are PCN resistant (1994 in USA), not related to ß-lactamase
3. Spain, Israel, South Africa and Hungary have very high (~40%) resistance rates
4. Mechanisms of Resistance [10]
   1. Mutations in one or more penicillin binding proteins which:
   2. Decrease affinity of cell wall synthesis enzymes for ß-lactam antibiotics
   3. These mutations appear to be more common in serotypes which affect children
   4. ß-lactamases are not usually involved in pneumococcal resistance to penicillin
   5. MefE and erm mutations mediate macrolide resistance [8]
5. Long term, low dose ß-lactams increase risk of ß-lactam-resistant pneumococcus [11]
6. Resistance to PCN is usually accompanied by resistance to:
   1. First and second generation cephalosporins including cephazolin, cefuroxime, cephalexin
   2. Erythromycin - variable
   3. Trimethoprim (TMP/SMX, Bactrim®, Septra®)
   4. Extended range penicillins (such as ticarcillin, mezlocillin)
   5. ß-Lactamase inhibitors (including clavulonic acid, sulbactam)
   6. Resistance to vancomycin, linezolid, imipenam or chloramphenicol is exceedingly rare

G. Treatment [12]

1. Up to 25% of current isolates are now penicillin (PCN) resistant [13]
   1. Therefore, PCN should not be the empiric therapy for serious pneumococcal infections
   2. If PCN sensitivity has been demonstrated, then dosing as follows:
   3. Mild to moderate PCN sensitive infections with PCN 600,000 Units q4-6 hours
   4. Penicillin sensitive severe infections are treated with 2-3 million (M) U q4-6 hrs
   5. For mild otitis or sinusitus, amoxicillin is recommended
   6. PCNs require dosing adjustments for renal failure
2. Penicillin Allergic Patients
   1. Generally treated with a macrolide, cephalosporin, or newer fluoroquinolone
   2. Mild and moderate infections: azithromycin 250-500mg po qd or newer fluoroquinolone
   3. Severe infections: ceftriaxone 2gm IV q24 hours in sensitive isolates
   4. Alternative is vancomycin 1gm q12 hr (resistant isolates)
   5. For meningitis, add rifampin 600mg po qd
3. Treatment of PCN resistant Pneumococcus [10,14]
   1. ~90% of resistant S. pneumoniae will be sensitive to cefotaxime and ceftriaxone
   2. Rifampin may be added in severe infections (based only on animal data)
   3. Newer fluoroquinolones are very effective and can be given IV or PO
   4. Newer fluoroquinolones include gatifloxacin, levofloxacin, moxifloxacin (PO only)
   5. Very high dose vancomycin should be used for resistant pneumococcal meningitis
   6. Severe infections including pneumonia (not meningitis): ceftriaxone or fluoroquinolone
   7. Meningitis is treated with combination vancomycin + cefotaxime or ceftriaxone
   8. Linezolid, an oxazolidinone is active against penicillin resistant pneumococci [15]
4. Mild to Moderate Infections (outpatient): fluoroquinolone is reasonable
5. Macrolide resistance has been increasing, but pneumococcal vaccine use has lead to reduced rates of resistance as well as overall invasive disease [8]

H. Vaccination [16,17,18]

1. Highly effective and underprescribed, as well as cost effective
2. Nonconjugated
   1. Based on 23 serotypes which cover >95% of all infections
   2. Requires intact T-lymphocyte independent immunity (direct B-cell activation)
   3. Poor or no responses in infants and young (age <2) children
   4. Relatively poor responses in patients with immunocomprise and/or chronic disease
   5. 23-vaccine is clearly effective, including multidrug resistant pneumococcus [6]
   6. In pneumococcal bacteremia patients, nearly all strains were represented in vaccine [19]
   7. 23-vaccine most beneficial in reducing pneumococcal bacteremia in age >65 years [20]
   8. No effect on incidence of pneumococcal pneumonia in age >65 years [20]
3. Heptavalent Conjugate Vaccine [16]
   1. Conjugated 7-valent vaccine is FDA approved available for anyone <5 years old
   2. Uses T-lymphocyte dependent immune responses with high vaccination rates
   3. Recommended for ALL infants <2 years old
   4. Also recommended for children 2-5 years old at increased risk for pneumococcus
   5. Strongly consider in any patient with poor immune function
   6. Covers ~80% of invasive childhood pneumococcal infections in USA
   7. Dosage: 3 total for 7-11 months, 2 total for 12-23 months, 1-2 for >23 months
   8. Conjugated vaccine covers nearly all pencillin-resistant pneumococcal strains [17,28]
   9. Reduced rates of invasive pneumococcal disease in children by 30-70% [21,28,29]
   10. Reduced rates of antibiotic resistant pneumococcal disease in children by ~80% [28]
   11. Efficacy ~80% in very high risk populations of young children [22]
   12. Very safe in postmarketing studies similar to other vaccines [23]
   13. Use associated with reduced incidence of macrolide resistant pneumococcus [8]
   14. Use in children strongly associated with reduction in invasive pneumococcal disease in adults >50 years old [27]
   15. One ore more doses, even given on non-approved schedules, associated with strong benefits in both healthy and chronically ill children [30]
4. Nonavalent Pneumococcal Vaccine [24,26]
   1. Diphtheria (CRM197) conjugate 9-valent pneumococcal vaccine
   2. In HIV negative children, reduced incidence of first invasive pneumococcal disease 83%
   3. In HIV+ children, reduced incidence of first invasive pneumococcal disease 65%
   4. Reduced incidence of penicillin and sulfa drug resistant pneumococcal disease 56-67%
   5. In rural African setting, reduced first pneumonia by 37% and mortality by 16% [26]
5. Increasing use will reduce morbidity from infections
6. Increasing use could reduce the spread of antibiotic resistant strains
7. All persons with chronic medical conditions, and those over 60-65 yrs, should get vaccine
8. Clearly cost effective in patients 50-64 years old [25]
9. Vaccination of all nursing home residents and personnel is strongly recommended

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