Risk factors of 90-day rehospitalization following discharge of pediatric patients hospitalized with mycoplasma Pneumoniae pneumonia

Readmission of patients initially hospitalized for community acquired pneumonia (CAP) is relatively common [1, 2, 3]. Both of preventable and non-preventable risk factors have been explored, but the main participants in these studies were the elderly and patients with multiple comorbidities, not children [4, 5, 6, 7].

The previous three studies described 14 days [8], 30 days [9] readmission rates (range of 1.5–8%) for children with pneumonia or lower respiratory infections (LRIs) [10]. In these studies, one of the consistent identified risk factors was chronic medical conditions. But in fact, a large number of children who are rehospitalized are caused by acute diseases [11]. If patients with chronic conditions are excluded, the difficulty is to detect readmission risk factors associated with the current acute infection. In addition, children with LRIs, a relatively broad diagnosis, or pneumonia with an underlying chronic illness may bring compounding factors conferring susceptibility for readmission. A promising approach to resolve this problem is to narrow down study sample according to the pathogenic or clinical features, such as Mycoplasma pneumoniae pneumonia (MPP), which accounts for up to 40% pediatric CAP [12], and its diagnosis is based on etiology and clinical evidence, thereby elevating the power to detect readmission risk factors associated with the current acute infections. We hypothesized that MPP children may have different characteristic during the first hospital stay between patients with and without readmission. This study was therefore conducted to enroll pediatric MPP patients without other underlying chronic diseases.

Our aims were to (1) describe the incidence and type of readmission after MPP discharge, (2) investigate the differences between patients with and without readmission at the initial hospital stay, (3) examine the risk factors for 90-day pneumonia-related rehospitalization.

Generally, readmissions after pneumonia are common. In terms of safety and cost, it is important to assess the relationship between initial hospital stay and readmission outcomes [9, 20]. Although the investigation of risk factors is challenging, significant progress has been made on the elderly, that the readmission was found to be largely depends on the comorbidities and factors external to the patient [1, 2, 4, 21]. This has also been observed in children, and one of the identified risk factors is chronic medical conditions such as underlying pulmonary or cardiovascular disease [9, 10, 11]. To date, research on potential risk factors for readmission has hardly focused on current acute infections or specific pathogens. Because pneumonia is a complex heterogenous disease that can be caused by a variety of pathogens, 1) studying pneumonia patients with the same infectious pathogen can reduce heterogeneity, 2) exclusion of patients with underlying diseases can improve the ability to detect readmission risk factors associated with the current acute infections. Therefore, we investigated the rate of 90-day pneumonia-related readmission in hospitalized children with MPP who had no basal or chronic disease. After comparing the clinical information of the first hospitalization between patients who were readmitted and not readmitted to the hospital, we obtained the following findings: 1) 48 (11.3%) children were readmitted within 90 days of the first MPP discharge; 2) at the index hospital stay, readmission patients manifested different characteristics; 3) co-infection with influenza A increased the risk of 90-day readmission.

In this study, the readmission rate after MPP discharge was 11.6%. Pneumonia and bronchial pneumonia were the majority diagnoses on readmission. Nakamura et al. identified that 5.5% cases readmitted after LRI hospitalization, and the most common readmission diagnose was LRI (48.2%) [10]. Similar to the pattern observed by Neuman and colleagues, nearly half of the 8% of patients who were discharged from initial pneumonia hospitalization were also associated with pneumonia [9]. Previous work has shown that 30% pediatric readmissions are potentially preventable, especially the index admission and readmission are causally related [22]. This is one of the reasons we focus on pneumonia-related readmission. Meanwhile, we observed a trend in patients with relatively mild radiological symptoms and lower levels of acute inflammatory markers that are more likely to be rehospitalized. The cause of this phenomenon may be related to two points, including different host immunity and treatment strategies. First, clinical presentation depends on the host’s immune response, rather than direct microbial destruction during the progression of M. pneumoniae infection [23]. Patient with a reduced immune system, such as younger ones who have had less time to develop immunity, may be characterized by mild clinical symptoms but with a prolonged recovery period. Second, pediatricians will adopt different treatment strategies for patients with severe or mild symptoms. Patients at risk of readmission may receive different medication times due to M. pneumoniae virulence or host immune response.

In this present study, we found that influenza coinfection increased the risk of readmission, which is consistent with previous investigations of children with complicated pneumonia. William et al. found that although there was a trend to increase mortality, patients with flu coinfection were less likely to readmitted in 2 weeks readmission, [24]. Brogan et al. observed that children who were infected with influenza during the initial hospital stay had a higher rate of readmission than children who were not infected with influenza [25]. Regarding the elderly, researches show that influenza vaccination is associated with a lower likelihood of readmission [5, 26, 27]. In view of these findings, influenza vaccination should be promoted not only in pediatric hospitals at CAP discharge, but also for all people, particularly in high risk groups including children under 5 years old, and those with asthma. In addition, we observed that younger children are liable to readmit, which is consistent with previous findings, demonstrating a higher rate of readmission for children under 1 year of age [9, 28]. As explained by Gay JC et al., pneumonia in young patients usually has protracted and waning course, leading to structural lung damage or immune paresis and further pneumonia episodes [28]. Second, younger patients may be more prone to new infections due to higher exposure during nursery attendance and the previous lack of immunity to respiratory pathogens, which will be resulting in rehospitalization. Furthermore, Studies of children with asthma have found that the rate of readmission of children under 1 year of age in higher, further highlighting the need to improve inpatient decision-making for young patients.

To our knowledge, this is the first study to explore the factors of readmission for pediatric MPP patients. Further research in larger cohorts is needed to validate the data. Meanwhile, some questions remain to be answered: first, it has been reported that pneumonia attributed to potentially antibiotic-resistant bacteria is associated with an increased risk of readmission [21], we strongly felt that macrolide resistance has a role on the risk of readmission, but what is the role? Second, coinfection with influenza A will increase the risk of readmission, what is the underlying mechanism?

This study has several limitations. First, the sample size may be small because only 48 patients were rehospitalized within 90 days. Second, if the child is readmitted to another institution, we may underestimate the rate of readmission. Third, in the absence of the information after first discharge, the interference factor related to age may be introduced into this research, as the rehospitalization may be caused by a new infection during nursery attendance. Fourth, other clinical information to document severity is not included in the study, such as oxygen requirement, antibiotic or corticoid duration. Fifth, a potential limitation would be that the serological assays have a high false positive detection rate and it is difficult to obtain the second serum. In our report, only 6 children provided paired sera, and the other 123 patients (123/424, 29%) had positive serological results with only a single high titer, but the PCR results were negative. Last, although there were significant differences in CRP, LDH levels or patient characteristics between rehospitalized and non-rehospitalized patients, these factors cannot be controlled and of low value in clinical practice.

In conclusion, rehospitalization after MPP is relatively common and is related to patients’ age and co-infected pathogens. Careful attention to clinical variables may reduce the frequency of rehospitalization of pediatric patients after discharge on MPP.