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Infectious Diseases
Pneumococcal infections and prevention in children
Clinical Overview and When to Suspect Pneumococcal Infection
Streptococcus pneumoniae (pneumococcus) is a Gram-positive lancet-shaped diplococcus that remains a leading cause of serious bacterial infection in children despite widespread vaccination.
— Well-appearing febrile child 6–36 months with WBC ≥15,000 and no clear source (occult bacteremia, now rare post-PCV)
— Lobar consolidation on CXR in a school-age child
— Purulent meningitis with CSF Gram stain showing Gram-positive diplococci
— AOM that fails initial observation or amoxicillin therapy
Major clinical syndromes: acute otitis media (AOM), sinusitis, community-acquired pneumonia (CAP), bacteremia, bacterial meningitis
Highest risk ages: 6 months–5 years (immature anti-polysaccharide antibody responses)
Suspect pneumococcus when:
Board pearl: Despite ↓ incidence from PCV13/PCV15/PCV20, S. pneumoniae is still the #1 bacterial cause of AOM, community-acquired bacterial pneumonia, and the most common identifiable cause of bacterial meningitis in children >1 month outside the neonatal period
Polysaccharide capsule is the principal virulence factor → >100 serotypes; vaccines target the most invasive serotypes
History — Presentation Patterns by Syndrome
AOM: Ear pain/tugging, fever, irritability, decreased feeding in infants; often follows viral URI by 3–5 days
Sinusitis: Nasal congestion + purulent discharge persisting ≥10 days without improvement, OR severe onset (fever ≥39°C + purulent discharge × ≥3 days), OR biphasic worsening after initial improvement
Pneumonia: Abrupt onset fever, cough, tachypnea, pleuritic chest pain; may have preceding URI; rigors suggest bacteremia
Bacteremia: High fever in a 6–36 month old who appears non-toxic; historically 'occult bacteremia' — now markedly reduced by PCV
Meningitis: Fever, irritability/lethargy, vomiting, poor feeding (infants), headache + neck stiffness + photophobia (older children); seizures at presentation in ~25%
Key history points: vaccination status (under-immunized children at higher risk for vaccine-type disease), daycare attendance (↑ colonization/transmission), recent antibiotic use (↑ risk of resistant strains), sickle cell disease or asplenia (functional or anatomic), cochlear implants, immunodeficiency
Clinical tip: A child with sickle cell disease presenting with fever ≥38.5°C must have blood cultures drawn and receive empiric parenteral antibiotics covering pneumococcus immediately — overwhelming sepsis risk is life-threatening
Physical Exam — Findings by Site of Infection
AOM: Bulging, erythematous, opacified tympanic membrane (TM) with ↓ mobility on pneumatic otoscopy; purulent middle ear effusion; TM perforation with otorrhea
Sinusitis: Purulent nasal drainage, facial tenderness (older children), periorbital edema may signal orbital complication
Pneumonia: Tachypnea (most sensitive sign by age: >60 in <2 months, >50 in 2–12 months, >40 in 1–5 years, >20 in >5 years), crackles, decreased breath sounds (effusion/empyema), dullness to percussion, grunting/nasal flaring/retractions in younger children
Meningitis: Nuchal rigidity, positive Brudzinski/Kernig signs (unreliable in infants <12–18 months), bulging fontanelle, altered mental status
Board pearl: In infants, meningeal signs are often absent — a bulging fontanelle, irritability paradoxical to being held, and poor feeding may be the only clues
Examine for petechiae/purpura → although classically associated with meningococcus, pneumococcal sepsis can also present with purpura fulminans
Empyema complicating pneumonia: Persistent fever despite appropriate antibiotics for 48–72 hr, ↓ breath sounds, dullness to percussion → obtain chest ultrasound or CT
Diagnostic Workup — Laboratory Studies
Blood cultures: Obtain before antibiotics in suspected bacteremia, meningitis, severe pneumonia, and all febrile patients with asplenia/sickle cell disease
CBC: WBC ≥15,000 historically used to risk-stratify occult bacteremia in pre-PCV era; now less useful given ↓ prevalence, but still obtained in toxic-appearing febrile children
CRP/ESR: Nonspecific; CRP useful for monitoring treatment response in invasive disease (e.g., empyema)
Lumbar puncture for meningitis: CSF findings → ↑ WBC (often >1000 with neutrophil predominance), ↑ protein, ↓ glucose (<40 or CSF:serum glucose ratio <0.4), Gram stain shows Gram-positive lancet-shaped diplococci in ~80%
CSF culture: Gold standard; latex agglutination or PCR can assist when Gram stain is negative or antibiotics were given pre-LP
Board pearl: Partially treated meningitis (antibiotics given before LP) may show negative cultures and modified CSF parameters, but CSF PCR and protein/glucose abnormalities often persist
Urinary antigen: NOT reliable in children — high false-positive rate due to nasopharyngeal colonization; do NOT use for diagnosis in pediatrics
Procalcitonin: emerging role in distinguishing bacterial from viral infection; ↑ values support bacterial etiology in pneumonia
Diagnostic Workup — Imaging and Special Considerations
Chest radiograph: Not routinely needed for uncomplicated outpatient pneumonia in well-appearing children; obtain when: hospitalization required, suspected complication (effusion, empyema, abscess), failure to improve on empiric therapy
Typical pneumococcal pneumonia → lobar consolidation (often single lobe), round pneumonia (pseudo-mass, especially in children <8 years — classic board image)
Board pearl: Round pneumonia is essentially pathognomonic for S. pneumoniae in a febrile child <8 years — do NOT obtain CT or biopsy; treat with antibiotics and repeat imaging in 4–6 weeks
Chest ultrasound: Increasingly first-line for detecting parapneumonic effusion/empyema; superior to CXR for quantifying fluid
CT chest with contrast: Reserved for complicated pneumonia (necrotizing pneumonia, lung abscess, empyema not responding to chest tube drainage)
Sinus imaging: NOT recommended for uncomplicated acute bacterial sinusitis; CT reserved for suspected orbital or intracranial complications
AOM: Diagnosis is clinical with pneumatic otoscopy — no imaging or labs needed
Tympanocentesis: not routine; indicated for AOM failing second-line therapy, AOM in immunocompromised host, or neonatal AOM to guide targeted therapy
Management — AOM and Sinusitis
AOM first-line: High-dose amoxicillin 80–90 mg/kg/day divided BID × 10 days (children <2 yr or severe), 5–7 days (≥2 yr, mild)
Observation option (no antibiotics): ≥2 years with unilateral non-severe AOM OR ≥6 months with bilateral non-severe AOM and reliable follow-up
AOM treatment failure (48–72 hr): Switch to high-dose amoxicillin-clavulanate (90 mg/kg/day amoxicillin component) to cover β-lactamase-producing H. influenzae/M. catarrhalis
Second-line alternatives: IM ceftriaxone × 3 days, clindamycin (for confirmed resistant pneumococcus), or tympanocentesis
Acute bacterial sinusitis first-line: Same as AOM → high-dose amoxicillin 80–90 mg/kg/day; amoxicillin-clavulanate if daycare attendance, recent antibiotics, or failure to improve
Duration for sinusitis: treat until symptom-free + 7 additional days (typically 10–14 day total course)
Board pearl: High-dose amoxicillin overcomes intermediate penicillin resistance in pneumococcus by achieving high middle-ear and sinus fluid concentrations — this is the reasoning behind 80–90 mg/kg/day dosing
PCN-allergic (non-anaphylactic): cefdinir, cefuroxime, cefpodoxime; anaphylactic allergy: azithromycin (though ↑ resistance) or clindamycin
Management — Pneumonia
— First-line: high-dose amoxicillin 90 mg/kg/day divided BID
— Rationale: pneumococcus is the most common bacterial cause; amoxicillin achieves excellent pulmonary concentrations
— Add azithromycin if atypical pathogen suspected (school-age child with gradual onset, prominent cough, bilateral infiltrates)
— Ampicillin IV 150–200 mg/kg/day divided q6h — preferred over broader agents in fully immunized children per IDSA/PIDS guidelines
— Narrower spectrum = better stewardship; covers pneumococcus effectively
— Add azithromycin if atypical coverage needed
Outpatient CAP (≥3 months, not toxic):
Inpatient CAP (fully immunized, non-ICU):
Inpatient CAP (ICU-level): Ceftriaxone 50–100 mg/kg/day ± vancomycin if concern for resistant pneumococcus ± azithromycin
Board pearl: Ampicillin (NOT ceftriaxone) is the recommended empiric IV antibiotic for uncomplicated pneumococcal pneumonia in hospitalized, fully immunized children — a favorite board question testing antibiotic stewardship principles
Duration: typically 7–10 days; complicated cases (empyema) may need 2–4 weeks
Parapneumonic effusion/empyema → chest tube drainage (VATS or fibrinolysis if loculated) + IV antibiotics
Management — Meningitis and Invasive Disease
— Penicillin-susceptible (MIC ≤0.06 µg/mL): narrow to penicillin G or ampicillin
— Cephalosporin-susceptible (MIC ≤0.5 µg/mL): ceftriaxone alone → discontinue vancomycin
— Cephalosporin-resistant: continue vancomycin + ceftriaxone ± rifampin
Empiric meningitis therapy (>1 month): Vancomycin (60 mg/kg/day divided q6h) + ceftriaxone (100 mg/kg/day divided q12h)
Rationale for dual therapy: covers possible cephalosporin-resistant pneumococcus until sensitivities return
Once susceptibilities confirmed:
Board pearl: MIC breakpoints for pneumococcal meningitis are LOWER than for non-meningeal infections — an isolate 'susceptible' for pneumonia may be 'resistant' for meningitis; always check meningitis-specific breakpoints
Dexamethasone: 0.15 mg/kg q6h × 2–4 days, given BEFORE or WITH first antibiotic dose; strongest evidence in H. influenzae type b meningitis, but often administered empirically before organism identified; may ↓ hearing loss in pneumococcal meningitis
Duration: pneumococcal meningitis → 10–14 days IV antibiotics
Audiologic evaluation before discharge or within 1 month — sensorineural hearing loss is the most common long-term sequela of pneumococcal meningitis
Age-Specific Considerations — Neonates and Young Infants
Neonates (<1 month): pneumococcus is an uncommon but recognized cause of late-onset neonatal sepsis/meningitis; NOT covered by standard empiric regimen of ampicillin + gentamicin unless a third-generation cephalosporin is added
Febrile infants 29–60 days: pneumococcal bacteremia enters the differential; protocols (e.g., Philadelphia, Rochester, step-by-step) incorporate inflammatory markers to risk-stratify; low-risk infants may be managed as outpatients, but LP is recommended for infants <2 months if fever source unclear
3–36 months (historically highest risk): occult bacteremia peaked in this age group in the pre-PCV era; PCV13 has dramatically ↓ invasive pneumococcal disease (IPD); however, under-immunized or unvaccinated children remain at risk
Board pearl: PCV introduction reduced occult bacteremia rates to the point where routine CBC/blood cultures in well-appearing febrile toddlers without a source are no longer standard practice — this is a major shift in the approach to fever without source
Infants <6 months with IPD should be evaluated for immunodeficiency (particularly complement, antibody, and splenic function) given their young age
Age-Specific Considerations — School-Age and Adolescents
School-age children (5–18 years): S. pneumoniae remains the top bacterial cause of CAP; lobar consolidation and round pneumonia are classic presentations
Distinguish from atypical pneumonia (Mycoplasma, Chlamydia pneumoniae) — gradual onset, prominent cough, bilateral interstitial infiltrates → these are more common in children >5 years but pneumococcus still occurs and should be covered
Approach to school-age CAP: Many guidelines recommend amoxicillin as first-line PLUS azithromycin if clinical features suggest atypical etiology; if presentation is clearly lobar/toxic → amoxicillin alone covers pneumococcus
Adolescents with meningitis: differential includes N. meningitidis prominently; empiric therapy (vancomycin + ceftriaxone) covers both
CSF Gram stain is crucial: Gram-positive diplococci → pneumococcus; Gram-negative diplococci → meningococcus
Adolescents with recurrent sinusitis → consider anatomic issues, allergic rhinitis, CF, immunodeficiency (check immunoglobulin levels and vaccine-specific antibody titers to assess polysaccharide response)
Board pearl: Inability to mount antibody responses to pneumococcal polysaccharide antigens (checked with PPSV23 post-vaccination titers) is a classic finding in specific antibody deficiency — suspect when a child has recurrent sinopulmonary infections despite normal total immunoglobulin levels
Complications and When to Escalate Care
— Persistent/worsening fever after 48–72 hr of appropriate antibiotics → obtain chest ultrasound
— Empyema management: chest tube + fibrinolysis (tPA/DNase) or VATS; prolonged IV antibiotics
— Necrotizing pneumonia (pneumatoceles, cavitation): often caused by PVL+ S. aureus but pneumococcus serotype 3 and 19A can also cause it
— Acute: cerebral edema, subdural empyema, hydrocephalus, seizures, DIC
— Long-term: sensorineural hearing loss (most common — up to 30%), cognitive deficits, motor deficits, epilepsy
Complicated pneumonia: Parapneumonic effusion → empyema → necrotizing pneumonia → lung abscess
Meningitis complications:
Bacteremia → secondary foci: Meningitis, osteomyelitis, septic arthritis, peritonitis (especially in nephrotic syndrome patients with ascites)
Board pearl: Children with nephrotic syndrome are at markedly ↑ risk of pneumococcal spontaneous bacterial peritonitis due to urinary loss of immunoglobulins and complement factors — ensure vaccination is up to date and maintain a low threshold for paracentesis in febrile nephrotic patients with ascites
Mastoiditis: AOM complication → post-auricular swelling, protrusion of pinna → CT temporal bone → IV antibiotics ± mastoidectomy
High-Risk Populations and Special Circumstances
— Daily penicillin V prophylaxis: begin by 2 months of age in SCD; continue at least until age 5 (many experts continue lifelong)
— Enhanced vaccination schedule (PCV + PPSV23, see prevention chunks)
Functional/anatomic asplenia (sickle cell disease, post-splenectomy): Overwhelming post-splenectomy infection (OPSI) risk; pneumococcus is the #1 cause
HIV/immunodeficiency: ↑ risk of IPD; ensure complete PCV series; consider PPSV23 at ≥2 years
Cochlear implant recipients: ↑ risk of pneumococcal meningitis; complete age-appropriate PCV series + PPSV23 at ≥2 years
CSF leak (traumatic or congenital): Recurrent pneumococcal meningitis → repair leak + ensure vaccination
Complement deficiency (especially C3): ↑ susceptibility to encapsulated organisms including pneumococcus
Board pearl: Any child with a SECOND episode of pneumococcal meningitis should be evaluated for CSF leak, complement deficiency, and antibody deficiency
Children receiving eculizumab (terminal complement inhibitor): ↑ risk of encapsulated organisms; vaccination alone is insufficient — consider prophylactic penicillin
Key Differentials — Pneumonia
Viral pneumonia (RSV, influenza, parainfluenza, adenovirus, SARS-CoV-2): More common than bacterial in young children; diffuse bilateral infiltrates, wheezing, gradual onset; supportive care unless bacterial superinfection suspected
Mycoplasma pneumoniae: School-age/adolescent; gradual onset, prominent cough, headache, bilateral interstitial infiltrates; may have associated rash (erythema multiforme), cold agglutinins; treat with azithromycin
Staphylococcal pneumonia: Rapidly progressive; pneumatoceles, empyema; consider post-influenza; treat empirically for MRSA
Group A Streptococcus pneumonia: Less common; can cause empyema; associated with varicella or preceding viral illness
Key distinction: Lobar consolidation + acute onset + high fever + rigors in a child → think pneumococcus first. Bilateral interstitial pattern + gradual onset + prominent cough in school-age → think atypical
Round pneumonia: Mimics pulmonary mass on CXR → in a febrile child <8 years, treat as pneumonia; repeat imaging in 4–6 weeks to confirm resolution before pursuing further workup
Foreign body aspiration: Unilateral hyperinflation, persistent cough/wheeze, history of choking episode → inspiratory/expiratory films or decubitus views
Key Differentials — Meningitis and Bacteremia
— Neonates: GBS, E. coli, Listeria → ampicillin + gentamicin (± cefotaxime)
— 1–3 months: GBS, E. coli, Listeria, S. pneumoniae → ampicillin + ceftriaxone (≥2 months) or cefotaxime
— >3 months: S. pneumoniae, N. meningitidis → vancomycin + ceftriaxone
Bacterial meningitis by age:
Board pearl: After the neonatal period, S. pneumoniae is the MOST COMMON cause of bacterial meningitis in children in the U.S.
Viral (aseptic) meningitis: Enteroviruses most common; CSF: lymphocytic pleocytosis, normal glucose, mildly ↑ protein; often summer/fall
HSV encephalitis: Altered mental status, temporal lobe seizures; CSF may show RBCs; PCR is diagnostic → acyclovir empirically
Bacteremia differentials in febrile young children: UTI (most common bacterial infection in febrile infants), Salmonella (infants <3 months), Kingella kingae (6 months–4 years, osteoarticular infections)
Key distinction: Toxic-appearing child with petechiae/purpura + meningitis → N. meningitidis vs S. pneumoniae; Gram stain differentiates (Gram-negative diplococci vs Gram-positive diplococci)
Partially treated meningitis: may show mixed/atypical CSF → use CSF PCR, bacterial antigen testing, clinical judgment
Prevention — Pneumococcal Conjugate Vaccines (PCV)
— PCV15 or PCV20 can be used for any dose in the series
— If PCV15 is used, PPSV23 is recommended at ≥2 years for high-risk children; if PCV20 is used, no additional PPSV23 is needed
PCV conjugates polysaccharide capsule antigens to a carrier protein → elicits T-cell-dependent immune response → effective in infants (who cannot respond to pure polysaccharide antigens)
PCV13 (Prevnar 13): Covered serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F
PCV15 (Vaxneuvance) and PCV20 (Prevnar 20): Newer vaccines with expanded serotype coverage; PCV15 adds 22F, 33F; PCV20 adds 8, 10A, 11A, 12F, 15B, 22F, 33F
Routine schedule (healthy children): 4-dose series at 2, 4, 6, and 12–15 months
Catch-up: Healthy children 24–59 months with no prior PCV → 1 dose of PCV20 (or PCV15 followed by PPSV23 ≥8 weeks later)
Board pearl: PCV transformed pediatric infectious disease — IPD rates ↓ >90% for vaccine serotypes; herd immunity reduced disease in adults as well
Non-vaccine serotypes (serotype replacement) now account for most remaining IPD — an important concept for the boards
Prevention — PPSV23 and Special Populations
— Functional/anatomic asplenia (SCD, post-splenectomy)
— Immunocompromising conditions (HIV, malignancy, transplant, chronic immunosuppressive therapy)
— Chronic heart, lung, liver, or kidney disease; diabetes mellitus
— CSF leak, cochlear implant
— Complement deficiency, patients on eculizumab
PPSV23 (Pneumovax): 23-valent pure polysaccharide vaccine → T-cell-independent response → NOT effective in children <2 years (immature immune response to polysaccharides)
Indicated at ≥2 years for HIGH-RISK children:
Timing: PPSV23 given ≥8 weeks after completing PCV series; a second dose of PPSV23 is recommended 5 years later for certain groups (asplenia, immunocompromised)
If PCV20 is used for the primary series, PPSV23 is generally NOT additionally needed (PCV20 covers more serotypes with a conjugate response)
Board pearl: PCV must ALWAYS be given BEFORE PPSV23 in PCV-naïve children — conjugate vaccine primes the immune system for a better response to subsequent polysaccharide exposure (hyporesponsiveness can occur if PPSV23 is given first)
Penicillin prophylaxis in SCD: Complements vaccination; start penicillin V 125 mg BID at 2 months → 250 mg BID at age 3 years → continue at least to age 5
Family Counseling, Education, and Psychosocial Considerations
— PCV is inactivated (cannot cause infection)
— Common side effects: injection site soreness, mild fever; serious adverse events are exceedingly rare
— Frame in terms of risk reduction: 'Before this vaccine, hundreds of children died from pneumococcal meningitis annually in the U.S.'
Educate families that pneumococcal vaccines are among the most impactful childhood immunizations — preventing meningitis, bacteremia, and severe pneumonia
Address vaccine hesitancy:
For children with sickle cell disease: emphasize dual protection (vaccine + daily penicillin prophylaxis); educate about fever as an emergency → present to ED immediately if temperature ≥38.5°C
Discuss signs of pneumonia warranting medical evaluation: tachypnea, difficulty breathing, chest pain, persistent high fever
Recurrent ear infections: discuss role of tympanostomy tubes after ≥3 AOM episodes in 6 months or ≥4 in 12 months; pneumococcal vaccination reduces but does not eliminate AOM
Board pearl: Parents often ask if pneumococcal vaccine prevents ear infections — PCV modestly ↓ AOM incidence (~6–7%) and ↓ recurrent AOM/tube placement, but AOM is multifactorial (H. influenzae, Moraxella, viral) so the effect is not dramatic compared to the ↓ in invasive disease
High-Yield Associations and Rapid-Fire Facts
Gram-positive lancet-shaped diplococci + α-hemolytic (green) on blood agar + optochin-SENSITIVE + bile-SOLUBLE = S. pneumoniae
α-hemolytic + optochin-RESISTANT = Viridans group streptococci (key distinction)
Most common bacterial cause of AOM, sinusitis, CAP, and meningitis (>1 month) in children
Polysaccharide capsule → principal virulence factor; quellung reaction = capsular swelling with type-specific antisera
IgA protease → colonization advantage in respiratory mucosa
Sickle cell disease: pneumococcus is #1 cause of overwhelming sepsis → penicillin prophylaxis + PCV + PPSV23
Nephrotic syndrome → spontaneous bacterial peritonitis → pneumococcus
Cochlear implant → ↑ meningitis risk → ensure PCV + PPSV23
Recurrent pneumococcal meningitis → evaluate for CSF leak, complement deficiency, antibody deficiency
Round pneumonia in child <8 years = pneumococcus until proven otherwise
Board pearl: Penicillin resistance in pneumococcus is due to altered penicillin-binding proteins (PBPs) — NOT β-lactamase production. Therefore, β-lactamase inhibitors (e.g., clavulanate) do NOT help overcome pneumococcal resistance; instead, higher doses of amoxicillin/penicillin achieve concentrations above the MIC
One-Line Recap
Streptococcus pneumoniae — a Gram-positive lancet-shaped diplococcus whose polysaccharide capsule drives virulence and vaccine design — remains the #1 bacterial cause of AOM, sinusitis, CAP, and post-neonatal meningitis in children; treat AOM/sinusitis with high-dose amoxicillin (80–90 mg/kg/day to overcome PBP-mediated resistance, NOT β-lactamase), uncomplicated inpatient pneumonia with IV ampicillin (stewardship-focused), and meningitis with vancomycin + ceftriaxone (± dexamethasone before/with first dose) narrowed by meningitis-specific MIC breakpoints; prevent with PCV (PCV13/15/20) given at 2, 4, 6, 12–15 months — which revolutionized pediatric infectious disease by ↓ IPD >90% for vaccine serotypes — supplemented by PPSV23 at ≥2 years for high-risk groups (asplenia/SCD, immunodeficiency, cochlear implant, CSF leak), always giving PCV BEFORE PPSV23; high-risk children with SCD also require daily penicillin prophylaxis starting at 2 months; and recurrent pneumococcal meningitis mandates evaluation for CSF leak, complement deficiency, and antibody deficiency.
Board Question Stem Patterns
4-year-old, fever, cough, CXR shows round opacity in right lower lobe → round pneumonia → treat with high-dose amoxicillin; NO biopsy or CT
2-year-old, bilateral AOM, fever 39.5°C → treat (not observe) → high-dose amoxicillin 80–90 mg/kg/day
Same child fails amoxicillin after 72 hr → switch to high-dose amoxicillin-clavulanate
3-year-old with sickle cell disease, fever 39°C → blood cultures + empiric ceftriaxone IMMEDIATELY regardless of appearance
18-month-old, fever, irritability, bulging fontanelle, CSF: WBC 2500 (90% PMNs), glucose 15, protein 250, Gram-positive diplococci → pneumococcal meningitis → vancomycin + ceftriaxone + dexamethasone
Child with meningitis, CSF culture: S. pneumoniae, ceftriaxone MIC 0.5 µg/mL → susceptible for non-meningeal but intermediate for meningitis → continue vancomycin + ceftriaxone
6-year-old with second episode of pneumococcal meningitis → evaluate for CSF leak, complement deficiency, antibody deficiency
2-year-old with SCD, parents ask about stopping penicillin → continue at least until age 5; ensure PCV + PPSV23 given
High-risk child received PCV15 series → next step: give PPSV23 at ≥2 years (≥8 weeks after last PCV dose)
Previously healthy 4-year-old, IPD with non-vaccine serotype → PCV does not cover all serotypes; serotype replacement phenomenon
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