Streptococcus pneumoniae (Pneumococcus)
Kacy A. Ramirez, Timothy R. Peters
Streptococcus pneumoniae (pneumococcus) is an important pathogen that kills more than 1 million children each year. Childhood pneumococcal disease is prevalent and typically severe, causes numerous clinical syndromes, and is a major cause of life-threatening pneumonia, bacteremia, and meningitis. Antimicrobial resistance in pneumococcus is a major public health problem, with 15–30% of isolates worldwide classified as multidrug resistant (MDR ; resistant to ≥3 classes of antibiotics). Pneumococcal polysaccharide-protein conjugate vaccines (PCVs ) developed for infants have been highly successful in the control of disease caused by virulent vaccine-specific serotypes. Epidemiologic surveillance reveals a dynamic pneumococcal ecology with emergence of highly virulent, MDR serotypes. Ongoing vaccine development and distribution efforts remain the best approach to control this threat to childhood health.
Etiology
Streptococcus pneumoniae is a gram-positive, lancet-shaped, polysaccharide encapsulated diplococcus, occurring occasionally as individual cocci or in chains; >90 serotypes have been identified by type-specific capsular polysaccharides. Antisera to some pneumococcal polysaccharides cross-react with other pneumococcal types, defining serogroups (e.g., 6A and 6B). Encapsulated strains cause most serious disease in humans. Capsular polysaccharides impede phagocytosis. Virulence is related in part to capsular size, but pneumococcal types with capsules of the same size can vary widely in virulence.
On solid media, S. pneumoniae forms unpigmented, umbilicated colonies surrounded by a zone of incomplete (α) hemolysis. S. pneumoniae is bile soluble (i.e., 10% deoxycholate) and optochin sensitive. S. pneumoniae is closely related to the viridans groups of Streptococcus mitis , which typically overlap phenotypically with pneumococci. The conventional laboratory definition of pneumococci continues to rely on bile and optochin sensitivity, although considerable confusion occurs in distinguishing pneumococci and other α-hemolytic streptococci. Pneumococcal capsules can be microscopically visualized and typed by exposing organisms to type-specific antisera that combine with their unique capsular polysaccharide, rendering the capsule refractile (Quellung reaction). Specific antibodies to capsular polysaccharides confer protection on the host, promoting opsonization and phagocytosis. Additionally, CD4+ T cells have a direct role in antibody-independent immunity to pneumococcal nasopharyngeal colonization. Conjugated PCVs promote T-cell immunity and protect against pneumococcal colonization, in contrast to the pneumococcal polysaccharide vaccine (PPSV23) that is used in adults and certain high-risk pediatric populations and that does not affect nasopharyngeal colonization.
Epidemiology
Most healthy individuals carry various S. pneumoniae serotypes in their upper respiratory tract; >90% of children between 6 mo and 5 yr of age harbor S. pneumoniae in the nasopharynx at some time. A single serotype usually is carried by a given individual for an extended period (45 days to 6 mo). Carriage does not consistently induce local or systemic immunity sufficient to prevent later reacquisition of the same serotype. Rates of pneumococcal carriage peak during the 1st and 2nd yr of life and decline gradually thereafter. Carriage rates are highest in institutional setting and during the winter, and rates are lowest in summer. Nasopharyngeal carriage of pneumococci is common among young children attending out-of-home care, with rates of 21–59% in point prevalence studies.
Before the introduction of heptavalent pneumococcal conjugate vaccine (PCV7 ) in 2000, serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F caused most invasive childhood pneumococcal infections in the United States. The introduction of PCVs resulted in a marked decrease in invasive pneumococcal infections (IPIs) in children. By 2005, however, IPIs began to increase slightly because of an increase in non-PCV7 serotypes, particularly serotype 19A. Serotype replacement can result from expansion of existing nonvaccine serotypes, as well as from vaccine-type pneumococci acquiring the polysaccharide capsule of a nonvaccine serotype (serotype switching ). Since the introduction of PCV13 in 2010 in the United States, there has been a decline in IPIs caused by new vaccine serotypes, including 19A. Nonetheless, 19A remains an important cause of meningitis. Indirect protection of unvaccinated persons has occurred since PCV introduction, and this herd protection is likely a result of decreases in nasopharyngeal carriage of virulent pneumococcal vaccine serotypes.
S. pneumoniae is the most frequent cause of bacteremia, bacterial pneumonia, otitis media, and bacterial meningitis in children. The decreased ability in children <2 yr old to produce antibody against the T-cell–independent polysaccharide antigens and the high prevalence of colonization may explain an increased susceptibility to pneumococcal infection and the decreased effectiveness of polysaccharide vaccines. Children at increased risk of pneumococcal infections include those with sickle cell disease, asplenia, deficiencies in humoral (B-cell) and complement-mediated immunity, HIV infection, certain malignancies (e.g., leukemia, lymphoma), chronic heart, lung, or renal disease (particularly nephrotic syndrome), cerebrospinal fluid (CSF) leak, and cochlear implants. Table 209.1 lists other high-risk groups. Some American Indian, Alaska Native, and African American children may also be at increased risk. Children <5 yr old in out-of-home daycare are at increased risk (approximately 2-fold higher) of experiencing IPIs than other children. Males are more frequently affected than females. Because immunocompetent vaccinated children have had fever episodes of IPI, the proportion of infected children with immunologic risk factors has increased (estimated at 20%).
Table 209.1
Children at Increased Risk of Invasive Pneumococcal Infection
| RISK GROUP | CONDITION |
|---|---|
| Immunocompetent children | Chronic heart disease* |
| Chronic lung disease † | |
| Diabetes mellitus | |
| Cerebrospinal fluid leaks | |
| Cochlear implant | |
| Children with functional or anatomic asplenia | Sickle cell disease and other hemoglobinopathies |
| Congenital or acquired asplenia, or splenic dysfunction | |
| Children with immunocompromising conditions | HIV infection |
| Chronic renal failure and nephrotic syndrome | |
| Diseases associated with treatment with immunosuppressive drugs or radiation therapy, including malignant neoplasm, leukemia, lymphoma, and Hodgkin disease; or stem cell and solid-organ transplantation | |
|
Congenital immunodeficiency ‡ Toll-like receptor signaling defects (IRAK-4, IKBKG, MyD88) NEMO gene defects |
* Particularly cyanotic congenital heart disease and cardiac failure.
† Including asthma if treated with high-dose oral corticosteroid therapy.
‡ Includes B-(humoral) or T-lymphocyte deficiency; complement deficiencies, particularly C1,C2,C3, and C4 deficiency; and phagocytic disorders, excluding chronic granulomatous disease.
Adapted from Centers for Disease Control and Prevention: Licensure of a 13-valent pneumococcal conjugate vaccine (PCV13) and recommendations for use among children: Advisory Committee on Immunization Practices, MMWR 59(RR-11):1–18, 2010 (Table 2).
Pneumococcal disease usually occurs sporadically but can be spread from person to person by respiratory droplet transmission. S. pneumoniae is an important cause of secondary bacterial pneumonia in patients with influenza. During influenza epidemics and pandemics, most deaths result from bacterial pneumonia, and pneumococcus is the predominant bacterial pathogen isolated in this setting. Pneumococcal copathogenicity may be important in disease caused by other respiratory viruses as well.
Pathogenesis
Invasion of the host is affected by a number of factors. Nonspecific defense mechanisms, including the presence of other bacteria in the nasopharynx, may limit multiplication of pneumococci. Aspiration of secretions containing pneumococci is hindered by the epiglottic reflex and by respiratory epithelial cell cilia, which move infected mucus toward the pharynx. Similarly, normal ciliary flow of fluid from the middle ear through the eustachian tube and sinuses to the nasopharynx usually prevents infection with nasopharyngeal flora, including pneumococci. Interference with these normal clearance mechanisms by allergy, viral infection, or irritants (e.g., smoke) may allow colonization and subsequent infection with these organisms in otherwise normally sterile sites.
Virulent pneumococci are intrinsically resistant to phagocytosis by alveolar macrophages. Pneumococcal disease frequently is facilitated by viral respiratory tract infection, which may produce mucosal injury, diminish epithelial cell ciliary activity, and depress the function of alveolar macrophages and neutrophils. Phagocytosis may be impeded by respiratory secretions and alveolar exudate. In the lungs and other tissues, the spread of infection is facilitated by the antiphagocytic properties of the pneumococcal capsule. Surface fluids of the respiratory tract contain only small amounts of immunoglobulin G and are deficient in complement. During inflammation, there is limited influx of IgG, complement, and neutrophils. Phagocytosis of bacteria by neutrophils may occur, but normal human serum may not opsonize pneumococci and facilitate phagocytosis by alveolar macrophages. In tissues, pneumococci multiply and spread through the lymphatics or bloodstream or, less often, by direct extension from a local site of infection (e.g., sinuses). In bacteremia the severity of disease is related to the number of organisms in the bloodstream and to the integrity of specific host defenses. A poor prognosis correlates with very large numbers of pneumococci and high concentrations of capsular polysaccharide in the blood and CSF.
Invasive pneumococcal disease is 30- to 100-fold more prevalent in children with sickle cell disease and other hemoglobinopathies and in children with congenital or surgical asplenia than in the general population. This risk is greatest in infants <2 yr old, the age when antibody production to most serotypes is poor. The increased frequency of pneumococcal disease in asplenic persons is related to both deficient opsonization of pneumococci and absence of clearance by the spleen of circulating bacteria. Children with sickle cell disease also have deficits in the antibody-independent properdin (alternative) pathway of complement activation, in addition to functional asplenia. Both complement pathways contribute to antibody-independent and antibody-dependent opsonophagocytosis of pneumococci. With advancing age (e.g., >5 yr), children with sickle cell disease produce anticapsular antibody, augmenting antibody-dependent opsonophagocytosis and greatly reducing, but not eliminating, the risk of severe pneumococcal disease. Deficiency of many of the complement components (e.g., C2 and C3) is associated with recurrent pyogenic infection, including S. pneumoniae infection. The efficacy of phagocytosis also is diminished in patients with B- and T-cell immunodeficiency syndromes (e.g., agammaglobulinemia, severe combined immunodeficiency) or loss of immunoglobulin (e.g., nephrotic syndrome) and is largely caused by a deficiency of opsonic anticapsular antibody. These observations suggest that opsonization of pneumococci depends on the alternative complement pathway in antibody-deficient persons, and that recovery from pneumococcal disease depends on the development of anticapsular antibodies that act as opsonins, enhancing phagocytosis and killing of pneumococci. Children with HIV infection also have high rates of IPI similar to or greater than rates in children with sickle cell disease, although rates of invasive pneumococcal disease decreased after the introduction of highly active antiretroviral therapy (HAART).
Clinical Manifestations
The signs and symptoms of pneumococcal infection are related to the anatomic site of disease. Common clinical syndromes include otitis media (Chapter 658 ), sinusitis (see Chapter 408 ), pneumonia (Fig. 209.1 ) (Chapter 428 ), and sepsis (Chapter 88 ). Before routine use of PCVs, pneumococci caused >80% of bacteremia episodes in infants 3-36 mo old with fever without an identifiable source (i.e., occult bacteremia). Bacteremia may be followed by meningitis (Chapter 621 ), osteomyelitis (Chapter 704 ), suppurative (septic) arthritis (Chapter 705 ), endocarditis (Chapter 464 ), and rarely, brain abscess (Chapter 622 ). Primary peritonitis (Chapter 398.1 ) may occur in children with peritoneal effusions caused by nephrotic syndrome and other ascites-producing conditions. Local complications of infection may occur, causing empyema, pericarditis, mastoiditis, epidural abscess, periorbital cellulitis, or meningitis. Hemolytic-uremic syndrome (Chapter 511.04 ) and disseminated intravascular coagulation also occur as rare complications of pneumococcal infections. Epidemic conjunctivitis caused by nonencapsulated or encapsulated pneumococci occurs as well.
Diagnosis
The diagnosis of pneumococcal infection is established by recovery of S. pneumoniae from the site of infection or the blood/sterile body fluid. Although pneumococci may be found in the nose or throat of patients with otitis media, pneumonia, septicemia, or meningitis, cultures of these locations are generally not helpful for diagnosis, since they are not indicative of causation. Blood cultures should be obtained in children with pneumonia, meningitis, arthritis, osteomyelitis, peritonitis, pericarditis, or gangrenous skin lesions. Because of the implementation of universal vaccination with PCVs, there has been a substantial decrease in the incidence of occult bacteremia, but blood cultures should still be considered in febrile patients with clinical toxicity or significant leukocytosis. Leukocytosis often is pronounced, with total white blood cell counts frequently >15,000/µL. In severe cases of pneumococcal disease, WBC count may be low.
Pneumococci can be identified in body fluids as gram-positive, lancet-shaped diplococci. Early in the course of pneumococcal meningitis, many bacteria may be seen in relatively acellular CSF. With current methods of continuously monitored blood culture systems, the average time to isolation of pneumococcal organisms is 14-15 hr. Pneumococcal latex agglutination tests for urine or other body fluids suffer from poor sensitivity and add little to gram-stained fluids and standard cultures. Multiplex real-time polymerase chain reaction (PCR) assays are specific and more sensitive than culture of pleural fluid, CSF, and blood, particularly in patients who have recently received antimicrobial therapy. Additional investigational assays, including serotype-specific urinary antigen detection, have not been validated.
Treatment
Antimicrobial resistance among S. pneumoniae continues to be a serious healthcare concern, especially for the widely used β-lactams, macrolides, and fluoroquinolones. Serotypes 6A, 6B, 9V, 14, 19A, 19F, and 23F are the most common serotypes associated with resistance to penicillin. Consequently, the introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13 ) has altered antimicrobial resistance patterns.
Resistance in pneumococcal organisms to penicillin and the extended-spectrum cephalosporins cefotaxime and ceftriaxone is defined by the minimum inhibitory concentration (MIC), as well as clinical syndrome. Pneumococci are considered susceptible, intermediate, or resistant to various antibacterial agents based on specific MIC breakpoints. For patients with pneumococcal meningitis, penicillin-susceptible strains have MIC ≤0.06 µg/mL, and penicillin-resistant strains have MIC ≥0.12 µg/mL. For patients with nonmeningeal pneumococcal infections, breakpoints are higher; in particular, penicillin-susceptible strains have MIC ≤2 µg/mL, and penicillin resistant strains have MIC ≥8 µg/mL. For patients with meningitis, cefotaxime- and ceftriaxone-susceptible strains have MIC ≤0.5 µg/mL, and resistant strains have MIC ≥2.0 µg/mL. For patients with nonmeningeal pneumococcal disease, breakpoints are higher, and cefotaxime- and ceftriaxone-susceptible strains have MIC ≤1 µg/mL, and resistant strains have MIC ≥4 µg/mL. In cases when the pneumococcus is resistant to erythromycin but sensitive to clindamycin, a D-test should be performed to determine whether clindamycin resistance can be induced; if the D-test is positive, clindamycin should not be used to complete treatment of the patient. More than 30% of pneumococcal isolates are resistant to trimethoprim-sulfamethoxazole (TMP-SMX); levofloxacin resistance is low but has also been reported. All isolates from children with severe infections should be tested for antibiotic susceptibility, given widespread pneumococcal MDR strains. Resistance to vancomycin has not been seen at this time, but vancomycin-tolerant pneumococci that are killed at a slower rate have been reported, and these tolerant pneumococci may be associated with a worse clinical outcome. Linezolid is an oxazolidinone antibacterial with activity against MDR gram-positive organisms, including pneumococcus, and has been used in the treatment of MDR pneumococcal pneumonia, meningitis, and severe otitis. Despite early favorable studies, use of this drug is limited by myelosuppression and high cost, and linezolid resistance in pneumococcus is reported.
Children ≥1 mo old with suspected pneumococcal meningitis should be treated with combination therapy using vancomycin (60 mg/kg/24 hr divided every 6 hr IV), and high-dose cefotaxime (300 mg/kg/24 hr divided every 8 hr IV) or ceftriaxone (100 mg/kg/24 hr divided every 12 hr IV). Proven pneumococcal meningitis can be treated with penicillin alone, or cefotaxime or ceftriaxone alone, if the isolate is penicillin susceptible. If the organism is nonsusceptible (i.e., intermediate or full resistance) to penicillin but susceptible to cefotaxime and ceftriaxone, pneumococcal meningitis can be treated with cefotaxime or ceftriaxone alone. However, if the organism is nonsusceptible to penicillin and to cefotaxime or ceftriaxone, pneumococcal meningitis should be treated with combination vancomycin plus cefotaxime or ceftriaxone, not with vancomycin alone, and consideration should be given to the addition of rifampin . Some experts recommend use of corticosteroids in pneumococcal meningitis early in the course of disease, but data demonstrating clear benefit in children are lacking.
The 2011 Infectious Diseases Society of America guidelines recommend amoxicillin as first-line therapy for previously healthy, appropriately immunized infants and preschool children with mild to moderate, uncomplicated community-acquired pneumonia. Ampicillin or penicillin G may be administered to the fully immunized infant or school-age child admitted to a hospital ward with uncomplicated community-acquired pneumonia, when local epidemiologic data document lack of substantial high-level penicillin resistance for invasive S. pneumoniae . Empirical therapy with a parenteral third-generation cephalosporin (ceftriaxone or cefotaxime) should be prescribed for hospitalized infants and children who are not fully immunized, in regions where local epidemiology of invasive pneumococcal strains documents widespread penicillin resistance, or for infants and children with life-threatening infection, including those with empyema. Non–β-lactam agents, such as vancomycin, have not been shown to be more effective than third-generation cephalosporins in the treatment of pneumococcal pneumonia, given the degree of drug resistance currently seen in the United States.
Higher doses of amoxicillin (80-100 mg/kg/24 hr) have been successful in the treatment of otitis media caused by penicillin-nonsusceptible strains. If the patient has failed initial antibiotic therapy, alternative agents should be active against penicillin-nonsusceptible pneumococcus as well as β-lactamase–producing Haemophilus influenzae and Moraxella catarrhalis . These include high-dose oral amoxicillin-clavulanate (in the 14 : 1 formulation to reduce risk of diarrhea), oral cefdinir, cefpodoxime, or cefuroxime; or a 3-day course of intramuscular (IM) ceftriaxone if patients fail oral therapy. Empirical treatment of pneumococcal disease should be based on knowledge of susceptibility patterns in specific communities.
For individuals with a non–type I allergic reaction to penicillin, cephalosporins (standard dosing) can be used. For type I allergic reactions (immediate, anaphylactic) to β-lactam antibiotics, clindamycin and levofloxacin are preferred alternatives depending on the site of infection (e.g., clindamycin may be effective for pneumococcal infections other than meningitis). TMP-SMX may also be considered for susceptible strains, but erythromycin (or related macrolides; e.g., azithromycin, clarithromycin) should be avoided given high rates of resistance.
Prognosis
Prognosis depends on the integrity of host defenses, virulence and numbers of the infecting organism, age of the host, site and extent of the infection, and adequacy of treatment. The mortality rate for pneumococcal meningitis is approximately 10% in most studies. Pneumococcal meningitis results in sensorineural hearing loss in 20–30% of patients and can cause other serious neurologic sequelae, including paralysis, epilepsy, blindness, and intellectual deficits.
Prevention
The highly successful PCVs have resulted in a marked decrease in IPIs in children. PCVs provoke protective antibody responses in 90% of infants given these vaccines at 2, 4, and 6 mo of age, and greatly enhanced responses (e.g., immunologic memory) are apparent after vaccine doses given at 12-15 mo of age (Table 209.2 ). In a large clinical trial, PCV7 was shown to reduce invasive disease caused by vaccine serotypes by up to 97% and to reduce invasive disease caused by all serotypes, including serotypes not in the vaccine, by 89%. Children who received PCV7 had 7% fewer episodes of acute otitis media and underwent 20% fewer tympanostomy tube placements than unvaccinated children. Following PCV13, a 64% reduction in IPIs caused by vaccine serotypes has been seen, particularly in children <5 yr old. The number of pneumococcal isolates and percentage of isolates with high-level penicillin resistance from cultures taken from children with otitis media or mastoiditis for clinical indications have decreased, largely related to decreases in serotype 19A. Rates of hospitalization for pneumococcal pneumonia among U.S. children decreased after PCV13 introduction. The number of cases of pneumococcal meningitis in children remain unchanged, but the proportion of PCV13 serotypes have decreased significantly. In addition, pneumococcal conjugate vaccines significantly reduce nasopharyngeal carriage of vaccine serotypes. PCVs have significantly decreased rates of invasive pneumococcal disease in children with sickle cell disease, and studies suggest substantial protection for HIV-infected children and splenectomized adults. Adverse events after the administration of PCV have included local swelling and redness and slightly increased rates of fever, when used in conjunction with other childhood vaccines.
Table 209.2
| CARRIER PROTEIN | PNEUMOCOCCAL CAPSULAR POLYSACCHARIDES | MANUFACTURER |
|---|---|---|
| Diphtheria CRM197 protein | 4, 6B, 9V, 14, 18C, 19F, 23F | Wyeth Lederle (PCV7, Prevnar) |
| Diphtheria CRM197 protein | 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F | Wyeth Lederle (PCV13, Prevnar 13) |
| None | 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F | Sanofi Pasteur MSD (PPSV23, Pneumovax II) |
* PCV7 serotypes in bold .
Immunologic responsiveness and efficacy after administration of pneumococcal polysaccharide vaccines (PPSV23) is unpredictable in children <2 yr old. PPSV23 contains purified polysaccharide of 23 pneumococcal serotypes responsible for >95% of invasive disease. The clinical efficacy of PPSV23 is controversial, and studies have yielded conflicting results.
Immunization with PCV13 is recommended for all infants on a schedule for primary immunization, in previously unvaccinated infants, and for transition for those partially vaccinated with PCV7 (Table 209.3 ). High-risk children ≥2 yr old, such as those with asplenia, sickle cell disease, some types of immune deficiency (e.g., antibody deficiencies), HIV infection, cochlear implant, CSF leak, diabetes mellitus, and chronic lung, heart, or kidney disease (including nephrotic syndrome), may benefit also from PPSV23 administered after 2 yr of age following priming with the scheduled doses of PCV13. Thus, it is recommended that children 2 yr of age and older with these underlying conditions receive supplemental vaccination with PPSV23. A 2nd dose of PPSV23 is recommended 5 yr after the 1st dose of PPSV23 for persons ≥2 yr old who are immunocompromised, have sickle cell disease, or functional or anatomic asplenia. Additional recommendations have been made for at-risk children 6-18 yr old (Table 209.4 ).
Table 209.3
| AGE AT 1ST DOSE (mo) | PRIMARY PCV13 SERIES* | PCV13 BOOSTER DOSE † |
|---|---|---|
| 2-6 | 3 doses | 1 dose at age 12-15 mo |
| 7-11 | 2 doses | 1 dose at age 12-15 mo |
| 12-23 | 2 doses | — |
| 24-59 (healthy children) | 1 dose | — |
| 24-71 (children with certain chronic diseases or immunocompromising conditions ‡ ) | 2 doses | — |
* Minimum interval between doses is 8 wk except for children vaccinated at age <12 mo, for whom minimum interval between doses is 4 wk. Minimum age for administration of 1st dose is 6 wk.
† Given at least 8 wk after the previous dose.
‡ See Table 209.1 .
From Centers for Disease Control and Prevention. Licensure of a 13-valent pneumococcal conjugate vaccine (PCV13) and recommendations for use among children: Advisory Committee on Immunization Practices, MMWR 59(RR-11):1–18 (Table 8); 59:258–261, 2010 (Table 3).
Table 209.4
Medical Conditions or Other Indications for Administration of PCV13,* and Indications for PPSV23 † Administration, and Revaccination for Children Age 6–18 Yr ‡
| RISK GROUP | UNDERLYING MEDICAL CONDITION | PCV13 RECOMMENDED | PPSV23 RECOMMENDED | REVACCINATION 5 YR AFTER 1ST DOSE |
|---|---|---|---|---|
| Immunocompetent persons | Chronic heart disease § | ✓ | ||
| Chronic lung disease || | ✓ | |||
| Diabetes mellitus | ✓ | |||
| Cerebrospinal fluid leaks | ✓ | ✓ | ||
| Cochlear implants | ✓ | ✓ | ||
| Alcoholism | ✓ | |||
| Chronic liver disease | ✓ | |||
| Cigarette smoking | ✓ | |||
| Persons with functional or anatomic asplenia | Sickle cell disease, other hemoglobinopathies | ✓ | ✓ | ✓ |
| Congenital or acquired asplenia | ✓ | ✓ | ✓ | |
| Immunocompromised persons | Congenital or acquired immunodeficiencies ¶ | ✓ | ✓ | ✓ |
| HIV infection | ✓ | ✓ | ✓ | |
| Chronic renal failure | ✓ | ✓ | ✓ | |
| Nephrotic syndrome | ✓ | ✓ | ✓ | |
| Leukemia | ✓ | ✓ | ✓ | |
| Lymphoma | ✓ | ✓ | ✓ | |
| Hodgkin disease | ✓ | ✓ | ✓ | |
| Generalized malignancy | ✓ | ✓ | ✓ | |
| Iatrogenic immunosuppression** | ✓ | ✓ | ✓ | |
| Solid-organ transplant | ✓ | ✓ | ✓ | |
| Multiple myeloma | ✓ | ✓ | ✓ |
* 13-valent pneumococcal conjugate vaccine.
† 23-valent pneumococcal polysaccharide vaccine.
‡ Children age 2-5 yr with chronic conditions (e.g., heart disease, diabetes), immunocompromising conditions (e.g., HIV), functional or anatomic asplenia (including sickle cell disease), cerebrospinal fluid leaks, or cochlear implants, and who have not previously received PCV13, have been recommended to receive PCV13 since 2010.
§ Including congestive heart failure and cardiomyopathies.
|| Including chronic obstructive pulmonary disease, emphysema, and asthma.
¶ Includes B- (humoral) or T-lymphocyte deficiency, complement deficiencies (particularly C1, C2, C3, and C4 deficiencies), and phagocytic disorders (excluding chronic granulomatous disease).
** Diseases requiring treatment with immunosuppressive drugs, including long-term systemic corticosteroids and radiation therapy.
From Centers for Disease Control and Prevention: Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among children aged 6-18 years with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices, MMWR 62:521–524, 2013.
Immunization with pneumococcal vaccines also may prevent pneumococcal disease caused by nonvaccine serotypes that are serotypically related to a vaccine strain. However, because current vaccines do not eliminate all pneumococcal invasive infections, penicillin prophylaxis is recommended for children at high risk of invasive pneumococcal disease, including children with asplenia or sickle cell disease. Oral penicillin V potassium (125 mg twice daily for children <3 yr old; 250 mg twice daily for children ≥3 yr old) decreases the incidence of pneumococcal sepsis in children with sickle cell disease. Once-monthly IM benzathine penicillin G (600,000 units every 3-4 wk for children weighing <60 lb; 1,200,000 units every 3-4 wk for children weighing ≥60 lb) may also provide prophylaxis. Erythromycin may be used in children with penicillin allergy, but its efficacy is unproved. Prophylaxis in sickle cell disease has been safely discontinued after the 5th birthday in children who have received all recommended pneumococcal vaccine doses and who had not experienced invasive pneumococcal disease. Prophylaxis is often administered for at least 2 yr after splenectomy or up to 5 yr of age. Efficacy in children >5 yr old and adolescents is unproved. If oral antibiotic prophylaxis is used, strict compliance must be encouraged.
Given the rapid emergence of penicillin-resistant pneumococci, especially in children receiving long-term, low-dose therapy, prophylaxis cannot be relied on to prevent disease. High-risk children with fever should be promptly evaluated and treated regardless of vaccination or penicillin prophylaxis history.