There are few data on the frequency and spectrum of secondary bacterial infections associated with the recent 2009 H1N1 infection.6,7,15
In this study, we observed an increase in hospitalization of children with pneumonia complicated by empyema during a severe outbreak of 2009 H1N1 during the spring and summer of 2009, compared with historical data over 4 seasons. All children reported an ILI before hospitalization for pneumonia with empyema. Among children hospitalized with empyema, one-third of those tested a median of 8 days after symptom onset ILI had influenza A detected by PCR, 4 of these were 2009 H1N1 influenza. S. pneumoniae
and S. pyogenes
were the most common cause of empyema during the 2009 H1N1 outbreak. Although a temporal association does not prove causality, the increase in empyema may represent bacterial pneumonia complicating 2009 H1N1 infection. Further supporting evidence comes from an increase in IPD among young adults in the Denver area coincident with an increase in influenza-associated hospitalizations in October of 2009 (CDC, unpublished data, available at: http://www.cdc.gov/h1n1flu/in_the_news/pneumococcal.htm
, accessed December 3, 2009).
The association between pandemic and seasonal influenza and pneumococcal infection has been appreciated for decades.5,16,17
Morens et al16
reviewed autopsy specimens from the victims of the 1918–1919 pandemic and the microbiologic literature of the time, and concluded that the majority of influenza deaths were due to secondary bacterial pneumonia. Outbreaks of severe pneumococcal disease after infection with seasonal influenza have been described and several studies have reported correlation between seasonal influenza and IPD.8,18–20
In vitro and animal and human studies suggest that there is synergy between respiratory viral infections and bacterial infections, but the mechanisms remain poorly understood.21,22
In previous pandemics, before the use of pneumococcal conjugate vaccine or the emergence of community-acquired methicillin-resistant S. aureus
(MRSA), S. pneumoniae
, S. pyogenes
, and less commonly S. aureus
pneumonia were the dominant causes of secondary bacterial infection.16
Bacteriologic data are extremely limited during the current pandemic. Using newer molecular methods, we could demonstrate a bacterial etiology in 80% of children with empyema complicating pneumonia during the peak of 2009 H1N1 activity. Each of these children had either S. pneumoniae
or S. pyogenes
infections. Despite the use of several molecular targets for detection of S. aureus
, we did not observe any staphylococcal empyema. Our findings are somewhat similar to a recent review of 77 postmortem lung specimens from adults and children with pneumonia during the 2009 H1N1 outbreak.7
Twenty-two (29%) specimens had histopathologic, immunohistochemical, and molecular evidence of coinfection with an identified bacterium. S. pneumoniae
or S. pyogenes
either alone or in combination with other bacteria were identified in 16 of 22 (72%) of positive specimens, whereas S. aureus
alone or in combination with other bacteria were identified in 7 of 22 (32%) lung specimens.6
In contrast, a recent review of 36 children who died with 2009 H1N1 infection, a bacterial infection was documented in 10 of 23 (43%) in whom pathology or microbiology results were available. Half were due to S. aureus
(including 3 MRSA), 3 were S. pneumoniae
, and one each were S. pyogenes
and Streptococcus constellatus
Infection with MRSA has increasingly been reported as a cause of severe and often fatal pneumonia after seasonal influenza.23
Because MRSA pneumonia was relatively uncommon in Utah before the arrival of 2009 H1N1,17
the absence of MRSA as an etiology of pneumonia among the cases described here may reflect preexisting regional differences and predominance of S. pneumoniae
as the etiology of bacterial pneumonia in Utah.
All of the S. pneumoniae
identified from children with empyema in our study were of non-PCV7 serotypes, consistent with the increasing role of these serotypes in IPD and parapneumonic empyema in the United States and Europe.24–27
These findings are also consistent with a recent review of the changing epidemiology of IPD among Utah children over a 13-year period. More than 95% of S. pneumoniae
isolated from 2005 to 2008 were non-PCV7 serotypes; serotypes 7F, 19A, 1, and 3 were the most common.28
Fortunately, each of these 4 serotypes is included in the 13-valent pneumococcal conjugate vaccine licensed in February 2010 by the Food and Drug Administration. Because receipt of pneumococcal conjugate vaccine has been associated with a 45% reduction in risk of influenza-associated hospitalization,29
the use of 13-valent conjugate vaccine represents an opportunity to reduce influenza-associated morbidity and mortality, either directly for children younger than 5 years or through indirect effects on older children and adults.
Cases similar to those described here are likely to continue until the pandemic is over and thus represent an opportunity for prevention. Children and adults with signs and symptoms of influenza infection should be promptly and empirically treated with antiviral agents according to current recommendations (available at: http://www.cdc.gov/H1N1flu/recommendations.htm
). Providers should ensure that children are up to date on pneumococcal conjugate vaccine and, for those with certain high-risk medical conditions who are 2 years of age or older, pneumococcal polysaccharide vaccine (http://www.cdc.gov/H1N1flu/guidance/ppsv_h1n1.htm
). Finally, persons with clinical findings consistent with pneumonia should be treated empirically with both antiviral medications and antibacterial agents until additional clinical and laboratory information can be used to guide therapy.
There are a number of limitations to the study. Virologic confirmation of prior 2009 H1N1 infection by PCR or by serology was not performed on all hospitalized children with empyema, and most specimens for molecular viral tests were obtained at least 1 week after the onset of ILI symptoms. However, the hospitalizations for IPD described in this report occurred during a period when other respiratory viruses associated with pneumonia and empyema, ie, RSV and hMPV were not in circulation. Second, although there may be variations in infection with bacterial pneumonia and empyema, from 2004 to 2008 the months of April to July have consistently been low periods for admissions with bacterial pneumonia and empyema. Third, the epidemiology of IPD in Utah is distinctive. A high proportion of circulating serotypes are ones that may have an increased propensity to cause complicated pneumonia, specifically serotype 1, 3, and 7F.24,30
Fourth, not all PCV7 vaccine records were available in children hospitalized with empyema. Finally, although we used strategies to minimize misclassification and performed manual review, ICD-9 coding is subject to error.