Epidemiology and clinical characteristics of pathogens responsible for the hospitalization of children with segmental/lobar pattern pneumonia

The occurrence of segmental/lobar pattern pneumonia (S/L-PP) in children increases with years. The pathogens of the disease may change for the abuse of antibiotics and the application of vaccines. Therefore, pathogens of S/L-PP in hospitalized children and their association with clinical characteristics may have changed. Objective: To analyze the pathogens of S/L-PP in hospitalized children and their association with clinical characteristics. Methods: The current study analyzed the epidemiological and clinical characteristics of pathogens in children with S/L-PP at a single hospital between 1st Jan 2014 and 31st Dec 2018 retrospectively. The pathogens and their associations with clinical characteristics were statistically analyzed. Results: A total of 593 children with S/L-PP received treatment at a single hospital during the study period by inclusion criteria. 451 patients were single positive for one pathogen and 83 patients had multiple infections. Mycoplasma pneumoniae (M.pneumoniae) (72.34%) was the most commonly detected pathogen, followed by streptococcus pneumoniae (S.pneumoniae) (8.77%). The infection of M.pneumoniae in children with S/L-PP increased with years (p<0.05). The positive rate of M.pneumoniae increased with ages of patients (p<0.05). M.pneumoniae was statistically associated to the extrapulmonary manifestations while S.pneumoniae was statistically associated with abnormal white blood cells (WBCs) and C reactive proteins (CRPs) (p<0.05). Conclusion: M.pneumoniae was the most positive pathogen in children with S/L-PP. The positive rate of M.pneumoniae in children with S/L-PP increased with years and the ages of children. M.pneumoniae was associated with extrapulmonary manifestations while S.pneumoniae was associated with abnormal WBCs and CRPs.


Introduction
Community-acquired pneumonia (CAP) is one of the most common respiratory disorders in children, which often needs hospitalization [1]. S/L-PP in children is one of the common CAPs based on chest radiological findings of consolidation. Patients with S/L-PP often suffer from cough, fever, and even serious complications such as pulmonary atelectasis, pulmonary consolidation, pulmonary necrosis and respiratory failure, increasing the rate of morbidity, mortality as well as the cost of health care. 3 However, the pathogen profile of S/L-PP in children has not been ever reported and they may vary The pneumonia pattern was characterized according to the World Health Organization Standardization of Interpretation of Chest Radiographs for the diagnosis of CAP in children [2]. Patients were included by the inclusion criteria: 1) Patients had a chest radiograph performed during hospitalization; 2) Patients had a serological test of pathogens detected ≥7 days following the onset of the disease.
Patients were excluded according the exclusion criteria: 1) Patients >14 years of age; 2) Patients suffering from known coexisting chronic, progressive or oncological illnesses; 3) Patients had a chest radiograph of pulmonary perihilar linear opacities or reticulonodular infiltrates.
During the study period, a total of 9342 patients visited the hospital and 593 patients with S/L-PP were included in this study. Data including gender, age, clinical signs and symptoms, complication, laboratory and radiological findings, and duration of hospitalization were collected. Microbial 4 cultivation was carried out by culturing and processing with blood or sputum specimens in accordance with standard microbiological procedures. Indirect immunofluorescence was used to detect M. But no significant differences in the positive rate for other pathogens with years between the groups were found.
Age distribution of pathogens Table.2 summarized the distribution of pathogens with age group and showed that the positive rate of M.pneumoniae increased with ages. Significant differences were observed in the positive rate of M.pneumoniae between the age groups. However, no significant differences were found in the positive rate of other pathogens between the age groups.
Sex distribution of pathogens  [4].In our research, the duration of fever and hospitalization of the patients with S/L-PP were 4.6±2.1 days and 15.5±3.1 days , which were similar to the previous report [4] . However, the pathogens distribution of the disease and their association with clinical characteristics in children has not been ever found to be reported. The microbes are difficult to isolate in children with S/L-PP for the difficulties in sputum expectoration and low positive rate of blood culture [5]. Some detection may be positive about a week after the onset of the disease. Therefore, the treatment of the disease based on knowledge and experience is very important. This research described the pathogens and their association with clinical characteristics in the patients with S/L-PP, which can add knowledge and experience of the disease for clinical doctors to treat it.
The positive rate of the pathogens in patients with S/L-PP was highly diverse in this research. M. 7 pneumoniae was the most commonly detected pathogen. The total positive rate of M. pneumoniae was 72.34 %(429/593) . It increased with years, which suggested M. pneumoniae has become the main pathogen of the disease. This was different from the previous report [6][7]. In fact, it is estimated that M. pneumoniae infection is accountable for up to 30-40% of CAP [8][9][10][11]. The classical radiological manifestions of M. pneumoniae pneumonia include segmental/lobar air-space consolidation, diffuse tiny centrilobular nodules and bronchovascular thickening [12][13][14][15]. The S/L-PP is considered to account for 17-76.5% of pediatric M. pneumoniae pneumonia cases. The incidence of S/L-PP shown an increasing trend [16][17][18][19]. So M. pneumoniae has drawn the great attention of clinical doctors and patients. However, there has been no any type of vaccines approved for use against M. pneumoniae now [20]. The positive rate of M. pneumoniae in patients with S/L-PP increased with ages of children.
It was postulated with 2 explanations. First, old patients prefer social activity in herd and chances for them to be infected were high. Second, the progression of the immune system in the patients was different between old patients and young ones. A report suggested that M. pneumoniae pneumonia was closely correlated with the immune system of the patients [20]. The different progression state of The second positive rate of pathogen in patients with S/L-PP was S.pneumoniae and it was 8% in the research. The positive rate of S.pneumoniae was much lower than that of M. pneumoniae, which was different from the previous understanding [6][7]. It was associated with the wide application of S.pneumoniae vaccines in China, which can prohibit the prevalence of S.pneumoniae infection [21][22][23][24]. The abuse of antibiotics was common in the nation, which can also bring down the infection of 8 S.pneumoniae. The microbial cultivation can bring false negative results in some samples. And samples were usually taken after the patients had taken oral or intravenous antibiotics. It was another reason for the low positive rate of S.pneumoniae in the study. Compared with other pathogens, S.pneumoniae was significantly associated with abnormal WBCs and CRP, which may be used for the determination of S/L-PP pathogens in clinical practice. However, M.pneumoniae and S.pneumoniae in children with lobar pneumonia counted for 81.1% of the pathogens in total, which was much higher than that reported by Saraya T [25]. Other pathogens had low positive rate in this research, which was not discussed here. Some patients were infected by two or more pathogens in the research. Two pathogens co-infection type was the most common one. The common co-infection type of two pathogens was M. pneumoniae and S.pneumoniae. The co-infection of 3 pathogens or more was less. The association between coinfection of pathogens and their clinical characteristics were not further discussed here for small cases.
The study is also associated with some limitations. First, clinical data were collected from medical records retrospectively, and therefore there may have been some selection bias. Second, the sample size of some samples was not large enough to obtain significance in some statistical analyses. Third, some pathogens may not be found due to the limitation of the detection method.  Availability of data and material The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.

Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' contributions
Li yuyun and Wang yanxia conceptualized the study. Li yuyun and Wang yanxia were responsible for data curation, formal analysis and wrote the original draft. Ma liji, Li ying, Zheng yanfei and Zhang xiaoyue were responsible for resources, supervision, validation and visualization. All authors read and approved the final manuscript.