PBSI is always associated with poor outcome, treating PBSI is still a significant challenge. In this prospective study, the prevalence rate of PBSI was 5.4% (218/4066) among inpatients with positive blood cultures. The rate was similar to that in a previous study, which reported a rate of 6% in the late 1980s (19). We identified that the 30-day mortality rate of PBSI was 40.8% (89/218) in our study. A previous study showed that the average mortality due to PBSI was 47% (11). However, its clinical presentation and the factor associated with prognosis were rarely reported. In our study, we observed that patients with poor prognosis showed more severe systemic inflammatory response, including elevated WBC and C-reactive protein, reduced platelet, and more frequency to be septic shock (2). Inappropriate initial empirical antimicrobial therapy, WBC > 11.2*109 and platelet ≤ 54*109 were exhibited to be independent risk factors for PBSI-related 30-day mortality (3). Gram-negative organisms accounted for most pathogens, and Klebsiella pneumoniae and Acinetobacter spp. ranked the first and second (4). It worth noting that patients co-infected with fungi was associated with worsen prognosis (5) SOFA scores was more accurate in predicting the prognosis of patients with PBSI.
To help direct our selection of treatment methods and improve patients’ early survival rate, we discussed the risk factors for 30-day mortality. Inappropriate initial empirical antimicrobial therapy was a main prognostic factor for early mortality in this study. Effective initial empirical treatment before receiving the blood culture results is necessary. The choice of empirical antibiotics is often a challenge for physicians. Some reports have demonstrated that appropriate antibiotic treatment can reduce mortality and improve clinical outcomes in patients with BSI(20). In our study, the rate of inappropriate initial empirical antibiotic therapy in the nonsurvival group was 30.3%, which was 16.3% (p < 0.05) higher than that in the survival group. In another report, the rate was 53.6% for PBSI patients in the emergency department. Among the patients who received inappropriate initial empirical antibiotic therapy, only 17.4% of the patients received no empirical antibiotic treatment. A delay in the application of effective initial empirical antibiotics has been reported to lead to poor outcomes in patients with BSI, especially critical patients(21). Therefore, increasing attention needs to be paid to initial empirical antibiotic therapy in patients with suspected infections. However, 41.3% of patients required combination therapy that was not received; for example, some patients had two pathogens that could not be treated by only one antibiotic. It is more difficult to administer adequate antibiotic therapy in patients with PBSI than in patients with monomicrobial BSI. One antibiotic is not enough to treat multiple pathogens, even if it is a broad-spectrum antibiotic (14). To provide adequate empirical coverage, it is vital to measure clinical characteristics and evaluate risk factors for acquiring PBSI. We also discovered that WBC > 11.2 × 109 and platelet ≤ 54 × 109 were optimal cut-off points as another two prognostic factors. Leukocytosis and thrombocytopenia were common hematologic findings in BSI, which means widespread systemic inflammation (1). It is an exaggerated defense response triggered by some pathogens. Additionally, Systemic inflammatory response syndrome (SIRS) will lead to dysregulated cytokine storm and even massive inflammatory cascade. These may resulted in organ dysfunction and death(22).
Gram-negative organisms were the most frequent pathogens in our study, similar to other reports(6, 14). Among the gram-negative organisms, Klebsiella pneumoniae and Acinetobacter spp. were the most frequent causative agents. With the wider use of carbapenems, the carbapenem resistance rates of Klebsiella spp. and Acinetobacter spp. have increased to 37% and 69%, and few treatment options are available for these pathogens currently(21). Among the gram-positive organisms, Enterococcus spp. and coagulase-negative staphylococci were the most frequent. A report on PBSI in patients with cancer obtained the same conclusion(6). In contrast with our study, another report on PBSI in patients in the emergency department excluded patients infected with coagulase-negative staphylococci from their study and found that streptococci were the most frequent gram-positive bacteria(14). One study analyzed the isolated microorganisms in community-acquired BSIs and identified Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae as the most common organisms(23). Considering the small sample sizes in the existing studies on PBSI, relatively large sample sizes are required to help us fully understand the microbiology of PBSIs, which will provide valuable information for empirical antimicrobial treatment.
We found that PBSI patients infected with fungi had poor outcomes. Candida spp. was the most frequent fungal species in our study (77.5%). A report comparing Candida with other isolated pathogens found that BSI patients infected with Candida had increased ICU mortality(21). Traditional initial empirical treatment does not always cover fungi. Waiting to administer antifungal therapy until culture results are returned may be detrimental to some patients. Only 62.5% of patients infected with fungi received antifungal therapy during the period of PBSI in our study. Some patients died before the culture results were returned. Therefore, we believe that timely antifungal treatment may improve the prognosis of patients with PBSI, if the patients are highly suspect co-infection with fungi.
Besides, we also evaluated some prognostic systems, which have been reported link with mortality of patients with BSI(24, 25). We found that the SOFA ,APACHE II and SAPS II all had good predictive accuracy in our study. The SOFA exhibited a higher AUROC than the other two, and the Z-test showed that the probability p value was less than 0.05. Therefore, we believe that SOFA was the better one. The SOFA score is used to evaluate the trend of organ dysfunction in patients(26). Multiorgan dysfunction is common in patients with BSI. It was reported that the SOFA performed well in predicting organ dysfunction in some patients with BSI(24). However, no previous study has considered the SOFA score in patients with PBSI. In some large-scale validation studies on the Sepsis-3 criteria for BSI patients, the median SOFA scores were 6 (IQR 3–9) in the US(27) and 5 (IQR 3–8) in Australia and New Zealand(28). The patients in our study had a median SOFA score of 9 (IQR 5–14). Patients with PBSI had a higher SOFA score than patients with BSI, suggesting severe clinical manifestations.
This study had some major limitations. First, it was a single-center study, which limited its generalizability. Second, the long-term prognosis of these patients was not analyzed in this study.