OBJECTIVE: To determine current rates of and trends in hospitalizations for community-acquired pneumonia (CAP) and CAP-associated complications among children.
METHODS: We performed a cross-sectional, retrospective, cohort study by using the 1997, 2000, 2003, and 2006 Kids' Inpatient Database. National estimates for CAP and CAP-associated local and systemic complication rates were calculated for children ≤18 years of age. Patients with comorbid conditions or in-hospital birth status were excluded. Percentage changes were calculated by using 1997 (before heptavalent pneumococcal conjugate vaccine [PCV7]) and 2006 (after PCV7) data.
RESULTS: There were a total of 619 102 CAP discharges for 1997, 2000, 2003, and 2006, after application of inclusion and exclusion criteria. Overall rates of CAP discharges did not change substantially between 1997 and 2006, but stratification according to age revealed a 22% decrease for children <1 year of age, minimal change for children 1 to 5 years of age, and increases for children 6 to 12 years (22%) and ≥13 years (41%) of age. Systemic complication rates were highest among children <1 year of age but decreased by 36%. In all other age groups, systemic complication rates remained stable. Local complication rates increased 78% overall. Children 1 to 5 years of age had the highest local complication rates.
CONCLUSIONS: After the introduction of PCV7 in 2000, rates of CAP-associated systemic complications decreased only for children <1 year of age. Rates of pediatric CAP-associated local complications are increasing in all age groups.
WHAT'S KNOWN ON THIS SUBJECT:
The incidence of IPD has decreased since widespread use of PCV7. Postlicensure epidemiological studies revealed conflicting data about changes in CAP and CAP-associated complications. Previous studies focused on empyema and typically did not include school-aged children or adolescents.
WHAT THIS STUDY ADDS:
With nationally representative data, we found that rates of CAP discharges remained relatively unchanged overall. Systemic complication rates were greatest for infants. Local complication rates increased in all age groups and were highest among 1- to 5-year-old children.
Streptococcus pneumoniae is the most-commonly identified bacterial cause of community-acquired pneumonia (CAP) in children. A heptavalent pneumococcal conjugate vaccine (PCV7) was licensed in the United States in February 2000 and subsequently was added to the routine childhood vaccination schedule. Since then, overall rates of invasive pneumococcal disease (IPD) (ie, bacteremia and meningitis) have decreased for both children1,–,7 and adults,8,–,10 largely because of significant reductions in the burden of disease caused by vaccine serotype isolates. However, reductions in the incidence of pediatric CAP seem to be less dramatic and have been limited to young children. In prelicensure, randomized, controlled trials, the risk of radiographically confirmed pneumonia was ∼20% lower for PCV7 recipients <2 years of age, compared with nonrecipients.11 Postlicensure epidemiological studies revealed decreases in all-cause pneumonia incidence rates of 39% to 52% among children <2 years of age12,13 but no changes for older children.13,14
The impact of PCV7 vaccination on the severity of pediatric CAP is less clear. Although vaccination with PCV7 has reduced the incidence of IPD in children, several authors reported regional increases in rates of pediatric empyema, a CAP-associated complication, after widespread PCV7 uptake.15,–,17 Studies examining national trends in pneumonia-associated complications also focused solely on empyema18,19 and were limited to infants and preschool-aged children.18 Among adults hospitalized with CAP, previous recipients of a 23-valent polysaccharide pneumococcal vaccine (PPV23) had lower all-cause mortality rates and risks of respiratory failure, sepsis syndrome, and cardiac arrest, compared with vaccine nonrecipients.20 To our knowledge, there have been no studies evaluating the impact of PCV7 introduction on the severity of illness in children hospitalized with CAP. We conducted a retrospective cross-sectional study by using a national database to determine the rates of hospitalizations with CAP and CAP-associated complications in otherwise healthy children in the United States and to describe changes in rates, if any, after the introduction of PCV7.
Study Design and Data Source
We performed a cross-sectional analysis of pediatric hospitalizations in the United States by using the 1997, 2000, 2003, and 2006 Kids' Inpatient Database (KID). The KID is part of the Healthcare Cost and Utilization Project sponsored by the Agency for Healthcare Research and Quality. It is the only data set on hospital use and outcomes that was designed specifically to study children's use of hospital services in the United States The KID samples pediatric discharges from all community nonrehabilitation hospitals (including academic medical centers) in states participating in the Healthcare Cost and Utilization Project, across pediatric discharge type and hospital characteristics, by using a complex stratification system. Discharge-level weights assigned to discharges within the stratum permit calculations of national estimates. Each data set contains ∼3 million discharges (unweighted), and data sets have been released every 3 years, beginning in 1997. The 2006 KID is the most-recent data set available and contains hospital administrative data from 38 states, representing 88.8% of the estimated US population.21
Patients ≤18 years of age were eligible for inclusion if they required hospitalization because of CAP in 1997, 2000, 2003, or 2006.
Definition of Pneumonia
By using a previously validated algorithm, patients were considered to have CAP if they met 1 of 2 criteria, that is, (1) an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), primary diagnosis code indicating pneumonia (codes 480–483 and 485–486), empyema (code 510), or pleurisy (codes 511.0, 511.1, and 511.9) or (2) a primary diagnosis of a pneumonia-related symptom (eg, cough, fever, or tachypnea) (see Appendix 1 for ICD-9-CM codes) and a secondary diagnosis of pneumonia, empyema, or pleurisy.22
Patients with the following comorbid conditions were excluded, because these comorbidities are characterized by risk factors not reflective of the general pediatric population: acquired or congenital immunologic disorders, malignancies, collagen vascular disease, sickle cell disease, cystic fibrosis, organ transplant, congenital heart defects, and heart failure (Appendix 1). Cases identified as in-hospital births were excluded, to minimize the inclusion of perinatally acquired and neonatal nosocomial infections. Patients with a secondary diagnosis code indicating trauma also were excluded, because a diagnosis of pneumonia in this population likely reflects a nosocomial cause (Appendix 1). CAP-associated complications were identified by using ICD-9-CM diagnosis and procedure codes (Appendix 2). Complications were classified as local (empyema, lung abscess, necrotizing pneumonia, or bronchopleural fistula), systemic (acute respiratory failure, sepsis, extracorporeal membrane oxygenation, or hemolytic uremic syndrome), or metastatic (meningitis, central nervous system abscess, mastoiditis, pericarditis, endocarditis, osteomyelitis, or septic arthritis).
Cases were characterized on the basis of age, race, gender, presence and type of complication, and discharge status (in-hospital death). Analyses were subsequently stratified according to age and race. Age groups were defined as <1 year (infant), 1 to 5 years (preschool age), 6 to 12 years (school age), or ≥13 years (adolescent), to capture differences in CAP and CAP-associated complication rates related to age-influenced factors such as PCV7 vaccination status, CAP microbiologic cause, and age-based sociological factors.
Race was recorded as a single variable (white, black, other, or missing data). Rate estimates for each race category were calculated; cases with missing race data were included as a separate variable, to preserve the integrity of our estimates. Ratios of CAP discharge and CAP-associated complication rates for black and white study participants were calculated by using same-year data.
Categorical variable results were summarized as frequencies and proportions. Rate calculations were performed by using weighted observations as numerators and annual, age-specific population estimates obtained from the US Census Bureau as denominators.23 Point estimates with 95% confidence intervals (CIs) were calculated by using Taylor series estimates. Percentage changes for CAP and CAP-associated complications were calculated by using 1997 (pre-PCV7 period) and 2006 (post-PCV7 period) rates. Calculations were performed by using Stata 10 (Stata Corp, College Station, TX). This study was considered exempt from the need for review by the institutional review board of the Children's Hospital of Philadelphia.
The 1997, 2000, 2003, and 2006 KID contained a total of 28916332 weighted pediatric discharges. Of those, 619102 cases (2.1%) remained after inclusion and exclusion criteria for CAP were applied.
Table 1 presents subject characteristics according to year. Age category proportions remained stable over time, with children 1 to 5 years of age representing the largest age group. There was a slight predominance of male participants in all years. White children composed the largest represented racial group (35%–44%) in all years; race data were missing for 18% to 32% of discharges. Mortality rates were low at ≤ 0.25% for all pediatric CAP discharges in each sample year.
Rates of CAP
The rates of CAP discharges according to year are shown in Table 2. Overall rates of pediatric CAP discharges peaked in 2000 and then returned to pre-PCV7 levels.
According to Age
The rates of CAP discharges varied inversely with age, with the highest rates occurring for children <1 year of age. The rates of CAP discharges for children <1 year of age decreased by 21.9% between 1997 and 2006, with 90% of the decrease occurring by 2003. There were minimal interval changes in rates of CAP discharges for children 1 to 5 years of age, whereas rates increased by 21.9% for children 6 to 12 years of age and by 40.5% for children ≥13 years of age (Table 3).
According to Race
Rates of CAP discharges for black children were greater than those for white children in all years studied (Table 4). However, this difference decreased over time, from a rate ratio of 1.98 in 1997 to a rate ratio of 1.59 in 2006.
Rates of CAP-Associated Complications
Between 1997 and 2006, the rate of discharges with any CAP-associated complication increased by 28% (11.8 and 15.1 cases per 100 000 population, respectively), whereas the rate of local complications increased by 77.8% (5.4 and 9.6 cases per 100 000 population, respectively). Empyema accounted for >97% of all local complications. The systemic complication rate decreased by 8.8% (6.8 and 6.2 cases per 100 000, respectively) (Table 2). The proportion of discharges with any associated complication increased from 5.9% to 7.5%, whereas the proportion with local complications increased from 2.7% to 4.8%. The proportion with systemic complications remained relatively stable at 3.1% to 3.7%. In 1997, 2000, 2003, and 2006, there were an estimated 75, 100, 72, and 98 discharges, respectively, with CAP-associated metastatic complications. There were so few metastatic complications as to preclude us from presenting meaningful rates or subset analyses.
According to Age
Between 1997 and 2006, rates of any CAP-associated complication among children <1 year of age decreased (Fig 1A), whereas rates in all other age groups increased (Fig 1 B–D). The rate of any CAP-associated complication was highest at each time point for children <1 year of age; however, this group experienced a 25.5% decrease between 1997 and 2006 (from 54.9 to 40.9 cases per 100 000). Among children 1 to 5 years of age, the rate of any complication increased 31.5%, from 19.7 to 25.9 cases per 100 000. Among children 6 to 12 years of age, the rate of any complication increased 44.4%, from 5.4 to 7.8 cases per 100 000. Children ≥13 years of age had the largest percentage rate increase, with a 67.2% increase between 1997 and 2006 (from 6.1 to 10.2 cases per 100 000).
Rates of CAP-associated systemic complications were highest among children <1 year of age in all years studied, whereas the lowest rates occurred among children 6 to 12 years of age. Between 1997 and 2006, rates of systemic complications in children <1 year of age decreased from 49.0 to 31.6 cases per 100 000, representing a 35.5% decrease. Rates remained stable among the other age groups.
Rates of CAP-associated local complications increased in all age groups. Although rates of local complications were highest among children 1 to 5 years of age for all years studied, children ≥13 years of age had the largest percentage increase in rates over time. Among children <1 year of age, rates increased 67.2%, from 6.7 to 11.2 cases per 100 000 (Fig 1A). Among children 1 to 5 years of age, rates increased 79.3%, from 9.2 to 16.5 cases per 100 000 (Fig 1B). Among children 6 to 12 years of age, rates increased 71.4%, from 3.5 to 6.0 cases per 100 000 (Fig 1C). Children ≥13 years of age experienced an 88.1% increase in rates between 1997 and 2006 (from 4.2 to 7.9 cases per 100 000) (Fig 1D).
According to Race
Rates of any, systemic, and local CAP-associated complications were higher for black children than for white children for all years studied (Table 4). Ratios of rates for black and white children for any, systemic, and local complications showed a downward trend between 1997 and 2003, with a slight increase from 2003 to 2006. Between 1997 and 2006, rates of any CAP-associated complication increased 24.6% for white children and 16.3% for black children. Systemic complication rates decreased 18.5% for black children and 9.4% for white children. The groups experienced similar increases in rates of local complications (64.5% and 65.9% for white and black children, respectively).
We describe national changes in discharge rates for pediatric CAP and CAP-associated complications in the pre-PCV7 and post-PCV7 periods. Since the introduction of PCV7 in 2000, uptake has been rapid, with 68% of 19- to 35-month-old children having received ≥3 doses in 2003 and 87% in 2006.24 We report that, although overall rates of CAP discharges remained relatively unchanged, rates decreased for children <1 year of age and increased for children ≥6 years of age. Overall rates of systemic complications were dramatically higher for infants than for any other age group, but infants were the only age group to experience decreases over time in this area. In contrast, local complication rates were found to be increasing in all pediatric age groups and were highest among children 1 to 5 years of age. Race seemed to play a role, because black children had consistently higher discharge rates of CAP and CAP-associated complications than did white children in all years studied.
Although CAP-related hospitalization rates for the entire cohort were stable overall, there were differences according to age group. Infants were the only age group to experience a decrease in CAP discharge rates, a finding consistent with other studies that showed post-PCV7 reductions in all-cause pneumonia rates for children <2 years of age.11,–,13,25 Although previous postlicensure studies did not show CAP rate changes for children >2 years of age,13,14 we report that CAP discharge rates increased for children >5 years of age. We might have been able to find a difference in rates for the older age groups because of the larger size of our cohort, compared with previous studies.13,14 However, the reason for the increase in CAP discharges is unclear. Pneumococcal serotype replacement has been occurring since the introduction of PCV71,5,–,7,15 and may contribute to the increase in CAP discharge rates for older children, although data suggest that serotype replacement is more commonly seen among young children and older adults.5,6,15 It also is possible that changes in the epidemiological features of other pathogens, such as methicillin-resistant Staphylococcus aureus26,27 or atypical organisms, rather than changes in rates of IPD, are responsible for this trend.
This is the first national study to examine rates of systemic CAP-associated complications in the pre-PCV7 and post-PCV7 eras. Rates of systemic complications varied inversely with age, with infants having the highest rates and children ≥6 years of age having the lowest rates. The decrease in systemic complication rates for the entire cohort was largely attributable to the decrease in rates for infants and might be explained in part by the fact that infants have been the primary recipients of PCV7.28 Adult data suggest that pneumococcal vaccination can modify the severity of illness for patients hospitalized with CAP and may reduce the occurrence of CAP-associated complications.20 A plausible mechanism may be the reduction of concomitant pneumococcal bacteremia among PPV23 recipients.29 Experimental model studies showed that cell wall components of killed pneumococci are capable of triggering an inflammatory cascade response in the host, resulting in death.30 The reduction of pneumococcal bacteremia may prevent the initiation of these inflammatory processes, reducing the severity of illness among patients requiring hospitalization for CAP. Large decreases in rates of IPD, including bacteremia, occurred among children <2 years of age after PCV7 licensure,6,7,15,31,–,35 which possibly explains why, similar to findings for adult recipients of PPV23, PCV7 may reduce the frequency of CAP-associated systemic complications.
In contrast to trends in CAP-associated systemic complication rates, rates of local complications increased for all age groups, with the highest rates occurring among preschool-aged children. In addition, the presence of any CAP-associated complication among children 1 to 18 years of age was largely attributable to local complications. It is unclear, however, whether this trend can be attributed fully to the changing epidemiological features of IPD after the introduction of PCV7. Two studies reported increasing regional rates of empyema in children before PCV7 licensure,27,36 which raises the possibility that the current increase in local complication rates is a continuation of a previous trend. Rates of local complications also may be influenced by the increasing prevalence of community-acquired methicillin-resistant S aureus, which has become the pathogen most commonly isolated from empyema in several centers.26,27 The limitations of standard microbiologic isolation techniques have made etiologic and incidence studies of empyema problematic. Bacteria are isolated infrequently from blood or pleural fluid cultures for children with empyema17,26,27 and, at one center, culture-negative empyema accounted for most of the increase in empyema frequency.17 Small studies using polymerase chain reaction-based assays identified S pneumoniae in 75% to 87.5% of culture-negative empyema cases.37,–,40 Empyema may be an overlooked major category of IPD in the post-PCV7 era.
Black race is an independent risk factor for IPD,6,41 and racial disparities among children with IPD are greatest for children <2 years of age.42,43 Discharge rates of CAP and CAP-associated complications were higher for black children than for white children. Our findings suggest that the difference in rates of CAP discharges and systemic complications between black and white children has decreased over time. Postlicensure data demonstrated a similar reduction in the racial disparity in rates of IPD among children after the first 2 years of widespread PCV7 vaccination.42,–,44 Rates of CAP discharges and systemic complications among black children have seemed to plateau, with no additional decreases after 2003. The groups experienced similar increases in rates of local complications over time. Additional efforts will be required to ensure that reductions in racial disparity can be maintained as the epidemiological features of IPD change.
This study has several limitations. First, the KID is an administrative database of discharge-level data, without clinical information beyond that captured in ICD-9-CM codes. The identification of CAP discharges depends on the accuracy of ICD-9-CM coding, and miscoding of cases with CAP and CAP-associated complications is possible. We might have underestimated the rate of complications, because patients with CAP and a CAP-associated metastatic complication such as osteomyelitis might have received a primary discharge diagnosis of osteomyelitis rather than CAP, which would have resulted in the exclusion of such patients from our study. This might explain the extremely low incidence of metastatic complications found in our study. We expect that such misclassification would not occur disproportionately in one year versus the next, and the observed trend in CAP-associated complication rates likely reflects a true trend. Second, although ICD-9-CM discharge diagnosis codes identify CAP with high sensitivity, ICD-9-CM codes have poor sensitivity in identifying pneumonia caused by specific pathogens.45 Therefore, we could not identify whether changes in rates of CAP-associated complications were attributable to specific pathogens. Third, patients with hospital-acquired pneumonia might have been included, because there is no specific ICD-9-CM code for CAP. We minimized the likelihood of such misclassification by using a previously validated approach to identifying patients with CAP.22 In this approach, patients with pneumonia listed as a secondary diagnosis rather than a primary diagnosis must have a pneumonia-related symptom (eg, cough or tachypnea) listed as the primary diagnosis. For example, a patient hospitalized after traumatic injury who develops ventilator-associated pneumonia is likely to have trauma, rather than pneumonia or a pneumonia-related symptom, listed as the primary diagnosis. Fourth, we were unable to determine the vaccination status of our study population, to assess the efficacy of PCV7 in preventing CAP, and could only infer the impact of PCV7 introduction on the general pediatric population. Last, the inclusion of every third year in the KID might have affected our ability to interpret trends accurately, given year-to-year epidemiological fluctuations in incidence caused by factors unrelated to pneumococcal vaccination.
Since the introduction of PCV7 in 2000, rates of CAP hospitalizations have decreased for children <1 year of age but seem to be increasing for children >5 years of age. Rates of systemic complications have decreased for children <1 year of age, but rates of local complications are increasing in all pediatric age groups. Additional studies are needed to determine the underlying epidemiological factors associated with these changes.
Drs Lee and Kronman are recipients of a Young Investigator Award from the Academic Pediatric Association. Dr Shah received support from the National Institute of Allergy and Infectious Diseases (grant K01 AI73729) and the Robert Wood Johnson Foundation, through its Physician Faculty Scholar Program.
- Accepted May 11, 2010.
- Address correspondence to Samir S. Shah, MD, MSCE, Children's Hospital of Philadelphia, Division of Infectious Diseases, Room 1526, North Campus, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104. E-mail:
The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
Funded by the National Institutes of Health (NIH).
- CAP =
- community-acquired pneumonia •
- PCV7 =
- heptavalent pneumococcal conjugate vaccine •
- PPV23 =
- 23-valent polysaccharide pneumococcal vaccine •
- IPD =
- invasive pneumococcal disease •
- KID =
- Kids' Inpatient Database •
- ICD-9-CM =
- International Classification of Diseases, Ninth Revision, Clinical Modification •
- CI =
- confidence interval
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- Copyright © 2010 by the American Academy of Pediatrics