The Clinical Value of Satellite Blood Culture in the Early Diagnosis of Sepsis

Background: Early antibiotic treatment is a key component of therapy for sepsis. However, current blood culture can’t fulll it. The aim of this study was to assess whether satellite blood cultures (immediate incubation of blood cultures in the ICU) can improve turnaround times, antibiotic switching and patient prognosis. Methods: This a observational single-center study, satellite blood culture and medical microbiology laboratory blood culture were performed separately in two groups. septic patients are collected from department of critical care medicine, Henan Provincial People`s Hospital from February 5,2018, to January 19, 2019.All septic patients are older than 18 and diagnosed sepsis according sepsis-3 criteria, who have been stayed hospital stay longer than 48 hour admitted to ICU. Results: In total, we analyzed 299 blood culture sets from 73 ICU patients, including:149 from the medical microbiology laboratory blood culture group and 150 from the satellite blood culture group. There is no signicant difference between the two group in positive rate. Comparing to laboratory blood culture group, the median time from specimen collection until incubation as reduced by 3.02h in satellite blood culture group (P < 0.001); the median time from specimen collection to notify blood culture positivity to the clinicians was reduced by 9.76h in satellite blood culture group(P <0.001).The median time was 54.05h in medical microbiology laboratory blood culture group and 30.97h in satellite blood culture group until the rst change of antibiotic therapy regimen (P = 0.056).There was no difference in duration of ICU stay (cid:0) duration of hospital stay (cid:0) medical cost between the two group. Conclusion: We have found that satellite blood culture may reduced turnaround times and it may speed up antibiotic switching and benet on patients outcomes.


Introduction
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection [1],which is the leading cause of death worldwide [1][2][3][4]. It is important for improving the outcome of patients with sepsis by early detection and timely treatment [5]. Each hour of delay in antimicrobial administration was associated with an average decrease in survival of 7.6% [6]. Antibiotic treatment is a key component of therapy for sepsis. Early targeted therapy relays on the identi cation of the underlying pathogen. Blood culture and susceptibility are needed to guide antibiotic treatment. However, current culture-based pathogen detection -the current gold standard diagnostic method -is impaired by a delayed time to result [7]. An earlier time to positivity likely to be achieved by satellite blood culture(SBC), which is a blood culture system set up in a clinical department outside the hospital microbiology laboratory to meet the requirement for timely specimen submission. A method to increase the speed of blood culture detection.
Satellite blood culture is able to signi cantly reduces time to obtain test results and speeds up antibiotic adjustment [8,9]. It is useful for the early diagnosis and treatment of sepsis.
Based on this, this study retrospectively collected patients with sepsis February 5,2018, to January 19, 2019 and compared them with medical microbiology laboratory blood culture(LBC) to explore our hypothesis that satellite blood culture could shorten the turnround time and accelerated antibiotic switching, and might improve patient prognosis. With this goal, we assessed the effect of satellite blood culture on turnaround times: time to blood culture incubation, time to knowledge of positivity, time to antibiotic change; and duration of ICU stay duration of hospital stay medical cost are included.

Setting
This study was performed in department of Critical Care Medicine, Henan Provincial People`s Hospital, China. Enrollment commenced on February 5,2018, and concluded on January 19, 2019.

Inclusion Criteria
Patients are older than 18 with con rmed sepsis admitted to the ICUs during the study period were included in the analysis. Beside, hospital stay longer than 48 hour.

Study Design
This is a retrospective single-centre study, ICU patients with sepsis were analyzed to study the impact of satellite blood culture compared to medical microbiology laboratory blood culture at the following time

Statistical Analysis
Data are presented as mean and SD, or median and interquartile range (IQR) based on the distribution of the quantitative variables. Means for continuous variables were compared using independent group T tests when the data were normally distributed; otherwise, the Mann-Whitney test was used. Proportions for categorical variables were compared using the χ2 test, although the Fisher exact test was used when the data were limited.

Result
According to the inclusion criteria, the patients from February 5 2018 to July 30 2018 were collected as medical microbiology laboratory blood culture group,the patients from August 1, 2018 to January 19, 2019 collected as the satellite blood culture group. In total, 299 blood culture sets from 73 sepsis patients ( 35 in the medical microbiology laboratory blood culture group, 38 in the satellite blood culture group) were processed: 149 sets in the medical microbiology laboratory blood culture group and 150 sets in the satellite blood culture group.
Patient Characteristics summarizes the baseline demographic and clinical characteristics of each group. There were no signi cant differences between the two groups at baseline except the age and gender. ( Table 1)

Adjustment Of Antibiotics And Patient Outcomes
In medical microbiology laboratory blood culture group, 66 (44.3%) of 149 blood culture sets are positive, while in the satellite blood culture group, 78 (52%) of 150 blood culture sets are positive, but there was no signi cant difference in positivity rate between two groups. ( Table 3) Compared with the medical microbiology laboratory blood culture group, TI(4.48 vs 1.46)and TK (27.83 vs 18.07) is signi cantly shorten in satellite blood culture group, there was a statistical difference in TI and TK between the two groups(P < 0.001).However, although TA was reduced by 23.08 h in satellite blood culture group, we found no signi cant difference in TA between the two group(P = 0.056). (Table 2) In the study, antibiotics were adjusted according to the blood culture results in part of patients, but there was no signi cant differences in the rate of antibiotics adjustment between the two groups(P = 0.09). (   Table 4) Furthermore, we compared the duration of ICU stay duration of hospital stay and medical cost of patients between these two groups, the length of ICU stay(15vs12)and the length of hospital stay(23vs15) was shorter as well as medical cost was less in satellite blood culture group, but there was no signi cant difference between the two groups, which is related to the small sample size.

Discussion
Our research suggested that satellite blood culture signi cantly reduces turnaround time including TI and TK(P < 0.001), which is similar with the previous studies [8,9]. In our study, compared with medical microbiology laboratory blood culture group, TI was reduced by 3.02 h and TK was reduced by 9.76 h in satellite blood culture group. It indicated that when TI was only 3 hours earlier, TK was roughly 10 hours earlier, which is related to work ow in the lab [10].Schwarzenbacher et al. controled the incubation time within 1 h in satellite blood culture group, even if in the medical microbiology laboratory blood culture group, the incubation time were not more than 8h [9].which is better than our data. Maybe it because we didn't train the staffs to get blood culture incubated as soon as possible. A study shown that after improving awareness of sepsis in the staff associated with improving pre-analytical phase procedures in blood culture collection,the isolation of bacteria by blood culture increased 3.25-fold [11]. Which might explain our results and lead us to make improvements in future research. Janapatla.et al proved that there is no difference in the time to positive detection of pathogens which was observed in bottles processed during the day and after overnight delay [12]. It's the opposite of what we thought it was and deserve more research to explore.
In Schwarzenbacher's study, the time to know positive was more length than ours, which might owe to the staffs 24 h on duty in our hospital so that we can learn about the positive outcome quickly. However, when it comes to TA, the study didn't demonstrate that satellite blood culture is better than medical microbiology laboratory blood culture (p = 0.056),although the median time from specimen collection to adjust antibiotic was reduced by 23.08 h in satellite blood culture group. It is contrary to Schwarzenbacher's ndings [9]. Small sample size maybe the main reason for it.
Besides, because lack of staff during off-hours, there is an increased risk of death among patients hospitalized during off-duty [13].Timely intervention for positive blood culture results during weekends,the duration of hospital stay with the hospital-acquired bacteremia patients was signi cantly reduced during after controlling for confounders [14].
The probability of cultures positive result decreased of 16% while the laboratory was closed. Further, the positive rate of blood culture may decrease by 0.3% for every one hour delay from blood sample collection to incubation [10]. We found that although the positive rate is increased in satellite blood culture group, there is no signi cant difference between the two groups, which is opposite of the Schwarzenbacher's study [9].Small scale of patients maybe account for it. Further to analysis, we indicated that the percentage of antibiotic regimen adjustment is rising in satellite blood culture group, but there is no signi cant difference between the two groups. Which is correspond with results published by Kerremans et al [8].In addition, a study showed that blood cultures collected during 24 hours after admission yielded more positive results than those collected later [15]. Lambregts et al reported that if blood culture had remained negative for 24 hours, The probability of bacteremia was 1.8% which may contribute to decisions on antimicrobial therapy [16].when the time of culture incubation is more than 48 hours, few true bloodstream infection could be detected [17]. Evaluation of the blood volume can also improve the rate of blood culture positivity [18,19]. So clinicians may adjust empirical antibiotic coverage at this time with little risk for subsequent bacterial pathogen detection.
Procop have shown that shorten process time (specimen collection to positive blood culture detection)could decrease hospital stays and mortality rates [20].However, we found that there is no signi cant differences in duration of ICU stay duration of hospital stay and medical cost between the two groups, while the three factors is lower in satellite blood culture group. But these ndings are consistent with research of Kerremans et al [8].One possible explanation is the higher proportion of old patients in satellite blood culture group. Another explanation might be the aw of design of our study. Beside our sample size was too small. Therefore, it need to do further research to explore the impact of shorten process time on hospital stays, mortality rates, and medical cost.
The limitation of our study is that this was a non-randomized controlled study and the baseline was not perfectly balanced, so we cannot exclude an analytical bias. and in addition, The sample size is too small for the adjustment of antibiotic regimen length of hospital stay and medical costs. In the future, we will design a randomized controlled study and increase the sample size to provide more robust evidence for satellite blood cultures.

Conclusion
In conclusion, satellite blood culture may signi cantly reduced turnaround times, which could result in earlier change s in antibiotic therapy and bene t on patients outcomes. Figure 1 Flow chart of study design