Etiological profile and clinical characteristics of segmental/lobar pattern pneumonia in hospitalized children

The occurrence of segmental/lobar pattern pneumonia in children increases with years recently. The pathogens of the disease may change for the abuse of antibiotics and the application of pneumococal vaccines. The pathogens of segmental/lobar pattern pneumonia in hospitalized children and their association with clinical characteristics are poorly understood nowadays. The current study retrospectively analyzed the pathogens and clinical characteristics of segmental/lobar pattern pneumonia in children at a single hospital between 1 st Jan 2014 and 31 st Dec 2018. The pathogens and their associations with clinical characteristics were statistically analyzed. A total of 593 children with segmental/lobar pattern pneumonia received treatment at a single hospital during the study period. 451 patients were positive for one pathogen and 83 patients were positive for two pathogens or more. 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 segmental/lobar pattern pneumonia 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 WBCs and CRPs (p<0.05). In a summary, M.pneumoniae was the most positive pathogen of segmental/lobar pattern pneumonia in hospitalized children. The positive rate of M.pneumoniae in children with segmental/lobar pattern pneumonia 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 . Segmental/lobar pattern pneumonia is one of the common CAPs based on chest radiological findings of consolidation. Patients with segmental/lobar pattern pneumonia often suffer from cough, fever, and even serious complications such as pulmonary necrosis, pulmonary atelectasis, pulmonary consolidation and respiratory failure, increasing the rate of morbidity, mortality as well as the cost of health care in our society. However, the epidemiology of pathogens of segmental/lobar pattern pneumonia in hospitalized children has not been ever reported and it may vary with regions, times, antibiotics use, vaccines and so on. The detection of pathogens often needs several hours or even days. Then doctors have to treat patients with antibiotics on experiences usually, which may cause improper use of antibiotics, prolong the suffering of patients and cause more sequelae. Therefore it was important to find the pathogens profile of segmental/lobar pattern pneumonia in hospitalized children and their associations with clinical characteristics.
The occurrence of segmental/lobar pattern pneumonia in hospitalized children has increased recently, which has drawn the great attention of patients and doctors. In this research, the pathogens of segmental/lobar pattern pneumonia and their clinical characteristics were retrospectively analyzed in children who were hospitalized in Zibo Central Hospital during 1 st Jan 2014 and 31 st Dec 2018 as follows.

Including and excluding criteria
Zibo city is located in the central of Shandong Province in China. Zibo Central hospital serves as a primary source of healthcare for about six million people in the area, which has moderate economic development and stable infrastructure. In the study, a retrospective review of the medical records from children with pneumonia (as defined by 4 the specifications in the International Classification of Diseases, 10 th edition, ICD-10 code) who were admitted to Zibo Central Hospital between 1 st Jan 2014 and 31 st Dec 2018 was conducted.
Patients who presented with clinical signs and symptoms of pneumonia underwent a chest radiograph during hospitalization. The pneumonia pattern was characterized based on the World Health Organization Standardization of Interpretation of Chest Radiographs for the diagnosis of CAP in children 2 . Two experienced pediatric radiologists evaluated chest Radiographs independently and agreed on the conclusion. Patients diagnosed with pneumonia were included in this study if the serological test of pathogens were detected ≥7 days following the onset of the disease and the chest radiographs showed segmental/lobar pattern pneumonia. Patients with pulmonary perihilar linear opacities or infiltrates or reticulonodular infiltrates by chest radiography were excluded. Patients >14 years old or suffering from known coexisting chronic, progressive or oncological illnesses were also excluded from the analysis.
A total of 9342 patients with pneumonia were admitted during the study period, of which 593 patients with segmental/lobar pattern pneumonia were included in this study. Data were collected regarding age, gender, clinical signs and symptoms, laboratory and radiological findings, complications and duration of hospitalization. Microflora was also detected using blood or sputum specimens by culturing and processing in accordance with standard microbiological procedures.

Statistical analysis.
Statistical analyses were performed using the Statistical package for the Social Science for Windows version 11.5 (SPSS, Inc., Chicago, IL, USA). Continuous variables were reported as the mean ±standard deviation. The levels of certain laboratory indices 5 including white blood cell counts (WBCs), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) may have an association with ages of patients, so these quantitative data were transformed into categorical data (normal or abnormal). Statistical significance was assessed using the Chi-square test for categorical variables and the ttest for continuous variables. P<0.05 was considered to indicate a statistically significant difference.  respectively. There were significant differences in the positive rate of M.pneumoniae between the groups divided by years of patients (p<0.05). But no significant differences were found in the positive rate for other pathogens between the groups. 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 (p<0.05). However, no significant differences were found in the positive rate of other pathogens between the age groups.

Sex distribution of pathogens
Significant differences were not observed for M. pneumoniae and S.pneumoniae between male patients and female patients. 18 patients were positive for IFB including 6 male patients and 12 female patients. Female patients displayed significantly higher positive rate for IFB than male ones. No significant difference was observed for the other pathogens between sex groups.

Seasonal distribution of pathogens
In general, the seasonality profile of each individual pathogen was diverse. However, we did not observe distinct patterns for the pathogens.

Mixed infection types of pathogens
Co-infections with multiple pathogens were common. There were 91 patients in whom 2 or more pathogens were positive, representing 15.34% of the patients, and the types of co-7 infection were complex. These data indicated that 27.40% of the children with M.pneumoniae infections were co-infected with other pathogens. A total of 15 patients showed infection with 3 pathogens or more. (Table.3)  The second positive rate of pathogen in patients with segmental/lobar pattern pneumonia 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 may be 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 misuse of antibiotics was common in the nationwide, which can also cut down the infection of S.pneumoniae. The germ culture was a low positive method. And samples used for germ culture were usually taken after the patients had taken oral or intravenous antibiotics, which was another reason for the low positive rate of S.pneumoniae in the study. Compared with other pathogens, S.pneumoniae was significantly associated with higher WBCs and CRP, which may be used for the determination of segmental/lobar pattern pneumonia pathogens in clinical practice. But it should be studied further.

Association between pathogens and patients' demographic and clinical characteristics
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. The study is also associated with some limitations. First, clinical data were retrospectively collected based on medical records, and therefore there may have been some selection bias. Second, the sample size was not sufficiently large to obtain significance in some statistical analyses. Third, some pathogens may not be found due to the limitation of the detection method.

Declarations
We thank the hospital pediatricians and clinical teams on all the pediatric wards who provide care to the children.

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.

Ethical statement.and consent to participate
This study was approved by the Institutional Ethical Review Board of Zibo Central Hospital.
Written informed consent was obtained from the guardians of the patients.

Patients consent for publication
Written informed consent for the publication was obtained from the guardians of the patients.

Availability of data and materials
The datasets used and/or analyzed during the current study are available fronm the corresponding author on reasonable request.

Conflicts of interest
The authors declare no conflict of interest.