Discussion
As bacterial pneumonia in patients with respiratory viral infection is associated with a poor prognosis and increased mortality, we tried to know whether bacterial pneumonia-causing pathogens varied according to the type of the preceding respiratory virus. On the basis of our results, we found that the cause of bacterial pneumonia in adults with respiratory viral infection varies with the preceding virus type. Specifically, influenza type A/B virus, rhinovirus, and hMPV infections primarily led to pneumonia caused by S. aureus, while coronavirus, parainfluenza virus, and RSV infections primarily led to pneumonia caused by gram-negative rods. In children, M. pneumonia was the most frequent pneumonia-causing bacterium, regardless of the type of preceding virus. Additionally, we found that the incidences of post-viral pneumonia and post-viral bacterial pneumonia varied according to the virus type; hMPV was associated with the highest incidence of post-viral pneumonia, while type B influenza virus was associated with the highest rate of post-viral bacterial pneumonia.
A previous study reported that there were no significant differences in symptoms, demographic characteristics, and hospital visit frequency between respiratory viral infection patients with and without post-viral bacterial pneumonia
8. Nevertheless, it is important to distinguish between the two groups, because patients with respiratory viral infection and post-viral bacterial pneumonia exhibit a worse prognosis compared with patients with respiratory viral infection only
9. The prognosis of the former patients could be improved by the selection of appropriate empirical antibiotics according to the bacterial pathogen that is significantly associated with the culprit respiratory virus type
7.
In patients aged ≥16 years in the present study, type A/B influenza virus infections preceded bacterial pneumonia caused by
S. aureus,
Klebsiella spp.,
S. pneumoniae, and
Acinetobacter spp. Unlike in previous studies,
Haemophilus influenzae and
S. pyogenes were not identified
5,6,7. Instead, gramnegative bacteria such as
Klebsiella spp. and
Acinetobacter spp. were identified. Bacterial pathogens in patients with human rhinovirus infection included
S. aureus,
Pseudomonas spp.,
Klebsiella spp., and
C. pneumoniae. In another study, post-rhinovirus bacterial pathogens included
H. influenzae,
S. pneumoniae, and
M. catarrhalis15. hMPV infection preceded pneumonia caused by
S. aureus,
Klebsiella spp., and
Acinetobacter spp. In a previous study, six patients with community-acquired pneumonia had hMPV infection and complicating bacterial pneumonia with
S. pneumoniae,
M. pneumoniae, or
C. pneumoniae16. The other virus-bacteria associations (in our study) were as follows: coronavirus—
Acinetobacter spp.,
Klebsiella spp., and
Pseudomonas spp.; parainfluenza virus—
Acinetobacter spp.,
Klebsiella spp., and
M. pneumoniae; and RSV—
E. coli,
Acinetobacter spp., and
Enterococcus spp. In summary, pneumonia in patients with influenza virus (type A/B), rhinovirus, and hMPV infections was caused by similar bacteria, and the findings indicated that
S. aureus pneumonia was very common in these patients. In contrast, coronavirus, parainfluenza virus, and RSV infections were associated with pneumonia caused by gram-negative bacteria.
In the <16 year age group in the present study, the most common pathogen causing bacterial pneumonia secondary to viral infection was
M. pneumoniae. In a previous study determining pathogens in children,
S. pneumoniae,
M. pneumoniae, and
C. pneumoniae were the commonly detected bacteria causing post-viral bacterial pneumonia
13. Despite the retrospective study design and the difficulty of sampling in children, the detection rate of
M. pneumonia was very high in the present study.
In our study, hMPV was found to be the most common virus complicating pneumonia, followed by type A influenza. This is an interesting finding that has been reported in previous studies as well. One study compared viruses in 450 asymptomatic adults and 183 adult patients with pneumonia
17 and reported significantly higher detection rates for influenza virus, RSV, and hMPV in patients with pneumonia. In another study, RSV and hMPV in children, and rhinovirus and hMPV in adults, were strongly associated with community-acquired pneumonia
18. Yet another study suggested that hMPV frequently induces pneumonia complicating acute respiratory distress syndrome (ARDS) in patients without significant comorbidities or immunosuppression
19. Taken together, hMPV can cause more serious diseases, such as pneumonia and ARDS, compared with influenza virus. Therefore, research on hMPV, including the development of therapeutic agents, is urgently required. In addition, we found that secondary bacterial pneumonia were relatively common in patients with pneumonia secondary to influenza, coronavirus, rhinovirus, adenovirus, and hMPV infections, a finding that has not been reported previously. Our results suggest that in patients with pneumonia and confirmed infection with the above mentioned viruses, it is necessary to pay more attention to the occurrence of bacterial pneumonia.
This study has some limitations because of its retrospective design. First, for patients aged <16 years, sufficient sputum culture tests were not performed in comparison with blood culture and serological tests. Therefore, except mycoplasma and chlamydia, which can be determined by serology and PCR, other bacterial pathogens are likely to have been underestimated. Second, since we used single titer IgM detection EIA, the prevalence of C. pneumoniae and M. pneumoniae could be overestimated. Third, we did not evaluate the underlying disease (malnutrition, steroid use) and lung condition (bronchiectasis, chronic obstructive pulmonary disease) that could affect bacterial colonization. To consolidate our findings, additional prospective studies are necessary. Forth, the study sample was small, which may affect the generalizability of our results.
In conclusion, the present study demonstrated that postviral bacterial pneumonia-causing pathogens differ according to the type of the culprit respiratory virus. Despite the study limitations, the findings are significant because of the lack of previous research on the etiology of secondary bacterial pneumonia in patients with respiratory virus infections other than influenza, and they will aid in the appropriate selection of empirical antibiotics for patients with (proven) respiratory viral infection and (radiological) pneumonia. For the treatment of post-viral pneumonia in infants and children, antibiotics with activity against M. pneumoniae (e.g., macrolides) should be considered. In adults, antistaphylococcal antibiotics should be considered when pneumonia occurs in patients with influenza virus (type A/B), rhinovirus, and hMPV infections, while antibiotics against a wide range of gram-negative bacteria should be considered when pneumonia occurs after coronavirus and parainfluenza virus infections. To confirm our retrospective results, further replicative prospective studies are needed.