Hematological patients are more vulnerable to pathogen infection because of long-term hospitalization, chemotherapy-induced immune suppression and antibiotic exposure, which lead to higher mortality. The common symptom of infection is fever, though noninfectious febrile episodes are often seen [2]. The gold standard of infection test is blood culture, but its application in early diagnosis is limited by huge time-consumption and low positive rate. Therefore, it is important to distinguish infectious episodes from noninfectious patients, which provides appropriate and immediate antibiotic therapy. This retrospective study was aimed to analyze the differences in clinical characteristics, pathogens distribution, antibiotics use and resistance, clinical common indicators and diagnostic efficiency between bacterial positive patients and bacterial negative patients.
We enrolled 322 patients with hematological malignancy, including 81 bacteremia (+) and 241 bacteremia (-) patients. The positive rate of 25.2% was higher than other reports from different studies, which may be due to our objects were hematological patients who were more likely to have infection because of their lower immunity [10, 11]. AML, lymphoma and ALL were the most common basic diseases in the two groups, which are consistent with other studies [1, 12–14]. In the blood culture positive group, more Gram-negative bacteria (51.9%) were isolated than Gram-positive bacteria (32.1%) and fungi (7.4%), indicating that clinicians should attach great importance to infection by Gram-negative bacteria. Meanwhile, G- bacteria were more likely resistant against penicillins, cephalosporins and quinolones, due to the abuse of broad-spectrum antibiotics, thus bringing great challenge to treatment [14, 15]. As reported, G + bacteria were more frequent in some hospitals, even more than G- bacteria, with a high prevalence in clinical laboratory test [6]. Antibiotics resistance in G + bacteria was more common in penicillins, quinolones, tetracyclines and erythromycin in the present study. Our results were similar with other reports that empirical antibiotics treatment would increase resistance rate, bringing huge burden to clinical staff and patients [3, 6]. According to blood culture and antibiotics resistance results, meropenem, imipenem and cephalosporins were used more frequently because they were all advanced antibiotics to treat infection. Patients without specific infection often receive empirical antibiotics treatment, including these advanced antibiotics, which often cause resistance.
Multivariate logistic analysis found that patients with complications, high PCT, GLU, IL-6 and D-D, and low ALB were more likely to have infection. As we all know, hematological malignancy patients are often accompanied with complications due to their immunocompromised status [1]. Moreover, patients with low ALB concentration are more likely to have lower immunity to resist bacterial infection [16, 17]. The indicators, including PCT, IL-6 and D-D, are inflammation biomarkers to assist in infection diagnosis. In a word, changes of the above factors might indicate the occurrence of infection.
Inflammation biomarkers often serve as assistant indicators in diagnosis, including WBC, PLT, CRP, PCT, IL-6 and D-D. We used ROC curves to investigate the diagnostic efficiency of these biomarkers. WBC is commonly used to indicate inflammation with the level increasing, but we found WBC counts were lower in the bacteremia group. The reason may be that the hematological patients under lower immunity status were accompanied with chemotherapy or marrow suppression. Meanwhile, the sensitivity and specificity of WBC were relatively low, which were insufficient for diagnosis of infection. Platelets, circulating blood cells from megakaryocytes, are pivotal in many physical activities, including clot formation, stop of bleeding, innate immune reply, and inflammation. As reported, PLT plays an important role not only in hemostasis, but also in antibacterial [18]. Platelets have a direct antibacterial defense effect through recognizing microbial antigens and secreting antimicrobial peptides and kinocidins, which can enhance innate immune effectors (including complement, neutrophils) and coordinate adaptive immunity (APS, T cells and B cells) [19]. However, in our study, PLT levels decreased in the bacteremia group compared with the non-bacteremia group with an AUC of 0.5803 to differentiate these two groups and the specificity was too low, which needs further research. Moreover, CRP, PCT, IL-6 and D-D levels significantly rose in the bacteremia group than the non-bacteremia group and performed well in differentiating these two groups. In comparison, PCT, IL-6 and D-D outperformed CRP in differentiating G-/+ groups, with AUC all above 0.75. CRP and PCT are commonly applied for infection detection. However, CRP concentrations often increase in non-infectious complications and are nonspecific for infection [20]. PCT is rapidly produced by thyroid gland C cells and several other types of cells, and is stimulated by bacterial endotoxins, lipopolysaccharids or inflammatory modulators (e.g. tumor necrosis factor-α, IL-6, IL-1) [21]. PCT reportedly can distinguish infection from non-infection. Yang et al. also found that PCT outperformed CRP in separating G- and G + infection in hematological malignancy patients [1, 22]. IL-6 secreted into the blood initiates division of both B cells and T cells and generation of antibodies and acute stage proteins during acute stage infections. IL-6 is also involved in the activation of cytokine cascade in sepsis. IL-6 seems helpful in early assessment of sepsis and is related to disease severity [8, 9]. Our results demonstrated that IL-6 performed well in differentiating not only infections from non-infections, but also G- from G + patients, which were consistent with previous studies [21, 23]. D-D, which results from fibrin degradation by fibrinolysis, is commonly used to screen venous thromboembolism clinically. In recent years, the relationship between inflammatory cytokines and biomarkers of the coagulation system has been widely studied, especially in critical patients with sepsis [7, 24–26]. Previous study found that the D-D level increased in pediatric hematological patients with E.coli bacteremia, which may be a clue for physicians to distinguish patients at higher risk for shock and mortality [7]. Though our data were all from hematological patients, D-D level increased in the bacteremia patients with a sensitivity of 88.89% and specificity of 70.95%, and performed well in distinguishing G- or G + patients. However, some reports demonstrate no significant diagnostic value for patients in early phases of sepsis [27]. Thus, the function of D-D needs further research.
This retrospective study has several limitations. First, it was conducted at a single center hospital, which may not be generalizable to other settings. Second, we can not compare the laboratory parameters with clinical course due to some insufficient data from patients. Despite these limitations, our study may serve as a reference to guide clinicians in treating patients with bacterial infection, especially hematological episodes.ith prognosis of different conditions.