In our study, we observed several differences between HASS and CASS, with both internal and external factors. Several studies have been conducted on this aspect. However, research on differences between HASS and CASS in children and in China is limited.
Internal factors, including the patients’ underlying diseases, determine their susceptibilities. Significant differences have been observed between HASS and CASS patients[13, 14]. Studies state that patients with HASS were mainly older children with underlying diseases (76.9%); whereas, 65.9% patients had hematologic/oncologic diseases. Research also suggests that most of the blood malignancies in HASS patients can lead to immune deficiency, which is a risk factor for infection and death[15–17]. Compared with CASS, children with HASS had significantly lower WBCs and thrombocytopenia. At the same time, neutropenia was also one of the factors that increased the risk of infection. In comparison, 67.7% of the CASS patients were infants without underlying diseases.
In our study, the major differences were seen in external factors between the two groups. (1) Differences in infection sites: HASS patients mostly had bloodstream and digestive tract infections, which is similar to the findings of study by Westphal et al. and Baker. According to the study by Baker, the chemotherapy damages the gastrointestinal mucosa; therefore, enterogenic sepsis and bacteremia mainly occurs in hospitals. In our study, the infection sites of CASS were primarily the respiratory tract, central nervous system, and digestive tract. The infection sites of CASS varied widely among studies; however, the main site was the respiratory tract, which is in line with the findings of our study. (2) Differences in chief complaint symptoms: Fever was the principal symptom in both groups. Interestingly, we discovered that patients in the HASS group had significantly fewer chief complaints than those in the CASS group. Similar findings were noted in the study by Heinz et al. He found that in patients with neoplasm of neutropenia, the signs and symptoms of infection usually atypical or not obvious. He also stated that fever may be the sole clinical symptom. Therefore, early attention should be paid to fever in HASS patients. (3) Differences in inflammatory indicators: CRP in the HASS group was higher than that in the CASS group; whereas PCT was lesser than that in the CASS group. Study by Matta stated that CRP in nosocomial infection was higher than that in the community-acquired infections. However, opinions vary on PCT between the groups. The research by Johansson suggested that the PCT level of patients infected by Streptococcus pneumoniae is higher than that of other bacteria. Some studies found that Gram-negative bacteria results in higher PCT levels than Gram-positive bacteria in patients with neutropenia[23–25]. Another study suggested that PCT levels in patients with surgical enterogenic sepsis were higher than that in patients with medical sepsis. Charles believed that PCT value depends on many factors, such as type and degree of infection, systemic inflammation, pathogens, immune status, sample duration, and even previous infection events. However, Jensen et al  pointed out that anti-infection treatment would cause PCT levels to stop or reduce the synthesis rate, resulting in the rapid decrease of its plasma concentration. (4) Differences in pathogen distribution: No difference was observed in pathogen detection rate between the two groups. The HASS group had higher positive rate of blood culture and was dominated by Gram-negative bacteria. A review indicated that Gram-negative bacteria, especially K. pneumoniae and P. aeruginosa, were still common in tumor patients, which is consistent with findings of our study. However, the review also found that Gram-positive bacteria had an increasing trend in recent years. The reason for this difference was related to the underlying diseases of the patients. Under the influence of gastrointestinal mucositis caused by chemotherapy and long-term neutropenia, children with nosocomial infection, mostly with hematologic neoplasms, are at high risk for Gram-negative bacteremia. However, it seems to be generally accepted that the predominant type of pathogen in CASS is Gram-positive bacteria. However, there are still reports of community-acquired infections with Gram-negative bacteria, such as P. aeruginosa; however, these patients often had underlying diseases. At the same time, our study found that the 28-day mortality rate of children in the HASS group was 3.661 times higher than that of children in the CASS group. Therefore, more attention should be paid to patients with HASS once the blood culture is positive.
There are some difference in treatment and complications between the two groups. Patients with HASS received two or more antimicrobial therapies (54.9%); however, 86.8% patients had MODS; 33.3% was the in-hospital mortality rate and 62.6% was the 28-day mortality rate, which were significantly higher than those with CASS. Similar studies have been reported in literature, which suggested that the number of antimicrobial agents is not related to death due to septic shock[14, 31]. The different mortality rates between the two groups were similar to those of another multi-center cohort study, in which the mortality from nosocomial infection was 64.6% and community infection was 37.5%.
Furthermore, because of the abovementioned differences, the predictors of 28-day mortality in the two groups varied remarkably. In the multivariate logistic regression analysis, we found that MODS was the risk factor for death in 28 days during treatment in the HASS group. For the HASS children who had MODS, the mortality was 10.524 times higher than that without MODS. Several studies also found MODS was an independent predictor of sepsis mortality[33, 34]. In our research, we found that MODS was a predictor of mortality only in HASS patients and not in CASS patients. We analyzed the clinical data again and found that 69.6% patients with MODS in the HASS group showed irreversible organ damage during the treatment. However, in CASS patients with MODS, 60.9% of them recovered their organ function after treatment. Therefore, although there was no statistical difference in the number of patients diagnosed with MODS between the two groups, these patients’ prognoses differed. Mortality rate in the CASS group was predicted on mechanical ventilation, similar to those of several studies[35, 36]. The need for invasive mechanical ventilation was considered as a risk factor for mortality due to the following reasons: (1) The patients treated with invasive ventilator had more severe condition: PIM2 at the ICU admission of CASS patients requiring mechanical ventilation was 11 (6.3, 25.9). In comparison, PIM2 during the ICU admission of CASS patients without mechanical ventilation was 5.5 (2.6, 9.4). (2) Adverse effects of invasive ventilation on hemodynamics: An international consensus stated that invasive mechanical ventilation can aggravate the condition of septic shock patients, and the reason for the aggravation of the condition is the deterioration of hemodynamics.
We also found that infection sites, bacterial species, and MDR bacteria were not related to outcome, which was consistent with an earlier report in another literature. Simultaneously, the inflammation indexes (CRP and PCT) were not correlated with the outcome in sepsis patients[39, 40].
Our study had some limitations. First, this study is of single-center retrospective cohort nature that relies on routine clinical data, with lost cases and a small amount of missing data in the data variables. Second, although the total number of cases was nearly 300, data of multifactor regression analysis after grouping were relatively small. The number of included parameters needed to be 0.1 of the data number, while only 34 patients in the nosocomial infection group survived; therefore, three parameters were provided for regression. Although we got the expected results, we could have acquired more data, resulting in a much better conclusion.