Background
Bloodstream infections can lead to prolonged hospital stays and high mortality.
Staphylococcus aureus is one of the main pathogenic bacteria causing bloodstream infections [
1‐
3]. The incidence of methicillin-resistant
Staphylococcus aureus (MRSA) infections in children in China is increasing (from 18.0% in 2005 to 30.4% in 2020 ), as in other countries worldwide, and is becoming a major public health problem [
3‐
5].
Previous studies have shown that several risk factors contribute to
Staphylococcus aureus bloodstream infection-associated deaths in children, including prematurity, low birthweight, congenital heart disease, infective endocarditis, pneumonia, and sepsis [
6,
7]. Sepsis is defined as life threatening organ dysfunction due to a dysregulated host response to infection,Which is a strong independent risk factor for mortality from
Staphylococcus aureus bloodstream infections. Early recognition and treatment of sepsis may substantially improve the prognosis [
8‐
11]. However, the risk factors for sepsis as a complication of
Staphylococcus aureus bloodstream infections remain unclear.
In this study, we aimed to investigate the clinical features of pediatric sepsis associated with Staphylococcus aureus bloodstream infections, and to identify risk factors for sepsis in children with Staphylococcus aureus bloodstream infections, to provide a basis for sepsis treatment.
Discussion
This study explored the clinical characteristics of children with
Staphylococcus aureus bloodstream infections at a large tertiary care children’s hospital, particularly the risk factors they had for developing sepsis. Sepsis occurred in approximately a third of the pediatric patients with
Staphylococcus aureus bloodstream infections.The pSOFA scores varied among the six children who died of sepsis. The number of organ failures and SOFA scores were closely related to mortality. Interestingly, unlike some previous studies [
2,
6,
16], we found that hospital-acquired infections, underlying diseases, implanted catheters, and elevated PCT levels were associated with sepsis among children with
Staphylococcus aureus bloodstream infections, and MRSA was not identified as a risk factor.
Bacterial bloodstream infections is one of the most common infectious diseases in children. The outcome of
Staphylococcus aureus bloodstream infections or staphylococcal sepsis is influenced by the characteristics of the patient (e.g., age, immunologic status, and comorbidities) and those of the infection (e.g., pathogen type, virulence, site of infection, and inoculum) [
16]. In our study, the proportion of sepsis complicated by
Staphylococcus aureus bloodstream infections was relatively high (37.2%). Liu et al. [
17] found that Group B
Streptococcus was the most common bloodstream infection bacterial pathogen among neonates in the neonatal intensive care unit with early-onset sepsis, accounting for 14.6% of bloodstream infections. The mortality of pediatric sepsis ranges from 4.0 to 50.0%, depending on the severity of the illness, risk factors, and geographic location [
18]. The mortality of sepsis in children with bloodstream infections differs according to the pathogen type. Li et al. [
19] found a 22.6% mortality among young children with
Klebsiella pneumoniae bloodstream infections. A prospective multicenter study has found that the mortality rates of sepsis or septic shock in adult patients with
Staphylococcus aureus bloodstream infections was 38.0–86.0%, and that sepsis was strongly associated with poor outcomes [
20]. In our study the mortality rate among children with staphylococcal sepsis was much higher than that reported for children with sepsis in a children’s hospital in the United States (6.7%) [
21]. In adult patients with suspected infections, the Sepsis-3 Task Force validated the SOFA score, and they discovered that it was either on par with or better than other scoring systems at differentiating in-hospital mortality [
11]. The SOFA score has a number of significant drawbacks, including the fact that it was created for adult patients and that the measurements it uses have a wide range of age-appropriateness. The best SOFA thresholds for children are currently the subject of much research [
9]. The pSOFA scores of the six children who died of sepsis in this study were different. The outcomes can be more biased in a big sample. The majority of children who died from sepsis had multiple-organ dysfunction syndrome [
18]. Each organ injury contributes to the patient’s risk of death, with complex interrelationships between systems [
22]. In this study a higher number of organ failures was associated with a higher mortality rate, similar to the findings of a retrospective study [
21].
The emergence of MRSA makes clinical antibiotic treatment a great challenge [
23].
Staphylococcus aureus is one of the pathogens that have a high resistance rate and are most likely to fail prophylactic antibiotic therapy [
24]. MRSA can prolong the duration of bloodstream infections and increase the likelihood of sepsis [
2,
16]. MRSA can cause various infections that are primarily attributed to the presence of extracellular and surface virulence factors, such as Panton–Valentine leucocidin (PVL) [
25], which is associated with an increased risk of sepsis. However, MRSA was not a risk factor for sepsis in in this study. Further interpretation of these results may require molecular typing and strain virulence identification. Moreover, our results suggest that prophylactic antibiotic use has little effect on sepsis in children with
Staphylococcus aureus bloodstream infections.
Sepsis is more common in children with underlying medical conditions, especially those with congenital heart disease, cancer, and gastrointestinal malformations. Children with underlying diseases often have concomitant immune deficiency and are frequently exposed to invasive surgery that may increase risk of sepsis [
26‐
28]. The mortality rate of sepsis in patients with underlying diseases is significantly higher than in previously healthy children [
29]. Children with intestinal malformations are prone to gastrointestinal dysfunction, such as paralytic ileus. Intestinal obstruction induces a shift in gastrointestinal bacteria, thereby increasing the risk of sepsis. Congenital gastrointestinal malformation is a risk factor for death in children with sepsis [
30]. The presence of a long-term intravascular catheter is associated with serious hematogenous complications in patients with
Staphylococcus aureus bloodstream infections [
31], consistent with our results. The present study showed that in children with
Staphylococcus aureus bloodstream infections, hospital-acquired infections were more likely than community-acquired infections to result in sepsis (
p = 0.01). In our study, children were primarily admitted to the intensive care unit and had intravenous catheters and long hospital stays, which increased the risk of hospital-acquired infections and sepsis [
32].
Compared with several other bloodstream biomarkers, PCT is the current standard for the identification of bacterial infections because of its wide biological range, short induction time after bacterial stimulus, and long half-life [
33‐
36]. A meta-analysis has suggested a cutoff of between 1.0 and 2.0 ng/mL PCT to distinguish patients with sepsis from those with other inflammatory conditions [
36]. In this study, logistic regression analysis showed that elevated PCT was a risk factor for sepsis in children with
Staphylococcus aureus bloodstream infections. The risk of sepsis was higher in children with a PCT level ≥ 1.7 ng/mL.
This study has several limitations. First, as a single-center retrospective cohort study, it was not possible to analyze the long-term trends associated with the study variables. Nevertheless, although the patient population may not be representative of all children with Staphylococcus aureus bloodstream infections, some assistance was provided to children in hospitals, particularly those with underlying illnesses, while they were being diagnosed and treated. Second, Due to the retrospective design, it was not possible to detect the virulence and resistance characteristics of Staphylococcus aureus, such as PVL virulence genes. Ultimately, the tiny sample size prevented us from validating the model. These findings, however, have offered some direction for additional study and should be confirmed by subsequent research using larger sample sizes.
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