Elsevier

Vaccine

Volume 34, Issue 50, 7 December 2016, Pages 6243-6249
Vaccine

Changes in empyema among U.S. children in the pneumococcal conjugate vaccine era

https://doi.org/10.1016/j.vaccine.2016.10.062Get rights and content

Highlights

  • Parapneumonic empyema started increasing among U.S. children before PCV7 introduction in 2000, and continued afterwards.

  • PCV13 introduction was associated with a reduction in parapneumonic empyema among U.S. children.

  • The empyema rate reached a historical low among children <2 years after PCV13 introduction.

Abstract

Background

Parapneumonic empyema, a serious complication of pneumonia, started increasing among U.S. children before the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000, and continued afterwards. This increase was due in part to pneumococcal serotypes not included in PCV7 that were included in the new 13-valent (PCV13) vaccine introduced in 2010. We assessed changes in the incidence of empyema hospitalizations among U.S. children after PCV13 introduction.

Methods

We calculated annualized empyema hospitalization rates among U.S. children <18 years using Nationwide Inpatient Sample and Census data (1997–2013) for four periods based on PCV7 and PCV13 introductions. Relative rates (RR) and 95% confidence intervals (CI) were calculated by age group and sex, comparing PCV7 [early-PCV7 (2001–2005) and late-PCV7 (2006–2009)] and PCV13 (2011–2013) periods with the pre-PCV7 period (1997–1999). Secondary analyses examined changes in pneumococcal, streptococcal, staphylococcal and unspecified empyema.

Results

Among children <18 years of age, annualized empyema hospitalization rates peaked at 3.6 per 100,000 in the late-PCV7 period compared with 2.1 per 100,000 in the pre-PCV7 period [RR: 1.70 (95% CI: 1.11–2.60)]. However, annualized rates in the post-PCV13 period declined to 2.0 per 100,000, similar to rates in the pre-PCV7 period. Empyema rates among children <2 years were lower in the post-PCV13 period compared to the pre-PCV7 period [RR: 0.77 (95% CI: 0.61–0.96)], but rates in the two periods among children 2–4 and 5–17 years were similar. Most empyema were of unspecified etiology. Pneumococcal and unspecified empyema declined after PCV13 introduction.

Conclusions

Although empyema hospitalization rates among U.S. children peaked after PCV7 introduction, rates decreased substantially following the introduction of PCV13.

Introduction

Parapneumonic empyema, a rare but serious complication of pneumonia, is associated with increased morbidity, mortality and length of hospital stay among patients with pneumonia [1], [2], [3], [4], [5], [6]. Parapneumonic empyema among children <18 years of age in the United States (U.S.) started increasing before the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000, and continued afterwards [2], [7], [8], [9]. Greater awareness of empyema, improved diagnostics, and more complete coding may have contributed to an apparent increase in empyema [7], [8]. However, the changing ecology of Streptococcus pneumoniae after PCV7 introduction likely contributed to a real increase as well [5], [10].

The serotypes most commonly associated with parapneumonic empyema among children (1, 3, 7F and 19A) were not included in PCV7 [3], [10], [11], [12], [13], [14], [15]. The incidence of pneumococcal pneumonia involving PCV7 serotypes decreased after PCV7 introduction, but with an increasing proportion of pneumococcal pneumonia attributed to non-PCV7 serotypes (such as 1, 7F and 19A) [3], [16], [17], [18]. This increased representation of serotypes historically associated with parapneumonic empyema likely contributed to the increasing incidence of parapneumonic empyema observed after PCV7 introduction [3], [10].

The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in 2010 to reduce further the incidence of invasive pneumococcal disease (IPD) due to non-PCV7 serotypes, and included serotypes 1, 3, 7F and 19A, among others. Vaccination coverage has been high and widespread among young U.S. children as coverage with ⩾3 doses of PCV7 was >90% in 2007–2008 and has been >92% for ⩾3 doses of PCV13 since 2010 [19], [20]. However, little information is available regarding national parapneumonic empyema rates in the U.S. after PCV13 introduction. Therefore, we assessed changes in hospitalizations for parapneumonic empyema among U.S. children after PCV13 introduction.

Section snippets

Data sources

We used the Nationwide Inpatient Sample (NIS) to obtain national hospitalization data from 1997 to 2013 for all U.S. children <18 years of age. The NIS is the largest publicly available database for all-payer inpatient healthcare in the U.S., representing over 35 million hospitalizations annually from all states that participate in the Healthcare Cost and Utilization Project (HCUP) [21]. Information on each hospitalization includes hospital characteristics, patient demographics, primary and

Results

During the study period, parapneumonic empyema was rare, and accounted for 1.3% of pneumonia hospitalizations among U.S. children <18 years of age. Among all children, the annualized rate of hospitalizations for parapneumonic empyema per 100,000 persons was 2.1 (95% CI: 1.7–2.4) in the pre-PCV7 period, and progressively rose to 3.6 per 100,000 in the late-PCV7 period [RR: 1.70 (95% CI: 1.11–2.60)]. Rates in the post-PCV13 period declined and were similar to rates in the pre-PCV7 period [RR:

Discussion

Rates of hospitalizations for parapneumonic empyema among U.S. children continued increasing and peaked after PCV7 introduction into the U.S. childhood immunization schedule, but decreased to historical low levels after PCV13 introduction. Importantly, rates of hospitalizations for parapneumonic empyema were significantly lower in the post-PCV13 period compared to the pre-PCV7 period among children <2 years, the target population for the pneumococcal conjugate vaccination program. In addition, a

Conclusion

In contrast to the increased incidence of hospitalizations for parapneumonic empyema observed after PCV7 introduction, PCV13 introduction into the U.S. childhood immunization schedule was associated with a substantial reduction of hospitalizations for parapneumonic empyema among U.S. children. The expanded serotype coverage of PCV13 likely contributed to the return of hospitalization rates for parapneumonic empyema closer to historical rates observed prior to PCV7 introduction.

Conflict of interest

Dr. Grijalva has served as consultant for Pfizer Inc. (New York, NY). Dr. Griffin received grant support from MedImmune (Gaithersburg, MD). The other authors have no conflicts of interest relevant to this article to disclose.

Acknowledgements

This work was supported by the Agency for Healthcare Research and Quality – United States (R03HS022342).

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