Can the Number of Coagulase-negative Staphylococci Specimens Detected be an Alternative Quality Indicator to the Blood Culture Contamination Rate?

Purpose: Coagulase-negative staphylococci (CoNS) are the most frequent contaminating bacteria; hence, we aimed to investigate an indicator of CoNS to predict the increase in blood culture contamination rate (ConR). Methods: We performed a retrospective study of selected patients who underwent blood culture testing. Results: Cases with CoNS-positive blood cultures correlated with ConR (r=0.85). The area under the receiver operating characteristic curves for the number of cases with ConR ≥ 2.5 did not differ statistically from that of the number of cases contaminated by CoNS. Conclusion: The number of CoNS-positive cases could help predict an increase in ConR ≥ 2.5.


Introduction
Relevant culture tests are important for the appropriate use of antimicrobial agents to combat antimicrobial-resistant bacteria. However, these tests can result in increased contamination, leading to an excessive use of antimicrobial agents, contributing to longer hospital stays and higher costs [1,2]. Although the blood culture contamination rate (ConR) is calculated retrospectively based on certain criteria [3], its calculation is time-consuming and requires some labour. Coagulase-negative staphylococci (CoNS) are the most frequently detected bacteria on blood culture contamination [2]. Therefore, we intended to investigate a simple real-time indicator of CoNS to predict the increase in ConR.

Results
A total of 104,853 sets of blood cultures were collected during the study period. Of these, 14,227 sets were culture-positive and 1,149 sets were excluded due to pending determination in 190 cases and no determination in 404 cases. A total of 2,142 cases were determined as contaminated; of these, 1,689 (78.9%) cases were contaminated with CoNS. The ConR was 2.5% or higher for 28 months of the total study period (25.9%) ( Supplementary Fig. 1). The correlation coe cients with ConR for indicators A-D were 0.71, 0.85, 0.91, and 0.93, respectively (Fig. 1). The ROC curve is shown in Fig. 2

Discussion
These results suggest that the number of CoNS-positive cases correlated with ConR to predict a ConR of ≥ 2.5, as well as the number of CoNS-contaminated cases. However, high negative predictive rates were observed for all indicators, indicating that if the number of cases with CoNS detection or CoNS positivity remained low, it was unlikely that the ConR would increase. Although the sensitivity and speci city for predicting ConR ≥ 2.5 were higher when indicators C or D were used, the former requires time until another blood culture set collected at the same time is determined to be negative, and the latter requires human resources and time to determine contamination. In contrast, indicators A and B do not require much human resources and can be displayed in real time. As for the calculation of ConR, most hospitals do it once a month; however, only less than 30% of the facilities report it over a longer span of time [7].
Indicators A and B may be good predictors for ConR in such institutes.
ConR of ≤ 3.0 is often used as a standard for the quality of blood culture tests [8]. In this study, we set the predicted ConR to be ≥ 2.5. As the cut-off was increased, the predictive power of each index increased because the number of months covered decreased; however, there was no difference in the trend of AUC between 2.5% or higher and 3.0% or higher (Supplementary Table 2). ConR is related to disinfection of the puncture site, collection method, hand hygiene, education, and feedback methods regarding collection [9].
Recently, the usefulness of a blood collection device has also been reported [10]. These relevant factors can be reviewed when CoNS-positive cases increase. In addition, it has been reported that feedback from monitoring results alone can improve the ConR [9,11]. Therefore, establishing a system that provides real-time feedback on the number of cases of CoNS detection may be a countermeasure to reduce contamination without requiring additional labour.
However, the situation regarding blood cultures varies from hospital to hospital [7]. For example, in facilities with many patients with central venous catheters, true infection by CoNS is more common.
Therefore, the results of this study, especially the cut-off values, may not be directly applicable to other facilities. However, as CoNS is the most commonly detected organism in contamination, a similar result can be predicted. It would be desirable to set a cut-off and determine the correlation with ConR at least once at one's own institution before using it as a simple indicator.

Study design
We performed a retrospective study of patients who underwent blood culture testing at the National Center for Global Health and Medicine between April 2012 and March 2021. The need for informed consent was waived due to the retrospective nature of the study design. The study information was presented on the Web for the possibility of opting out of consent. This was substituted for the participants' consent. The protocol of this study including the opt-out consent method was approved by the Certi cate Review Board of National Center for Global Health and Medicine (NCGM-G-004168-00) and conformed to the amended Declaration of Helsinki. The data were compiled from the registry of blood culture surveillance, including data on contamination, and the microbiology laboratory.
The registry data of blood culture surveillance For every case, two or more infectious disease physicians of the National Center for Global Health and Medicine determined whether the case was contaminated from a clinical point of view by reviewing clinical records and laboratory data in accordance with the CUMITECH criteria [3]. Undetermined cases and those with pending determination were excluded from the study.

Identi cation of bacterial species
All blood culture samples were collected into standard aerobic and anaerobic culture bottles (92F or 94F and 93F, 23F or 20F and 24F Becton Dickinson Microbiology Systems, Sparks, MD, USA) and processed using the BACTEC 9240, 9120, and FX systems (Becton, Dickinson and Company, Franklin Lakes, NJ, USA). These samples were routinely monitored for at least 144 h. The bottles that tested positive were removed and subjected to Gram staining. The specimens were then inoculated into 5% sheep blood agar and BTB agar media (Nissui Pharmaceutical Co., Ltd., Tokyo, Japan), and incubated at 35°C (Depending on the situation, other media may be added or the environment may be changed, such as anaerobic incubation). Conventional bacterial identi cation and susceptibilities to the prede ned antimicrobials were determined in accordance with the Clinical and Laboratory Standard Institutions criteria (M100) [4,5] by matrix assisted laser desorption/ionization-time of ight mass spectrometry system (MALDI Biotyper system; Bruker, Billerica, MA, USA) and automated broth micro dilution system (MicroScan WalkAway 96 SI system; Beckman Coulter, Brea, CA, USA). All Staphylococci species, except Staphylococcus aureus and S. lugdunensis, were treated as CoNS.

Indicators
We calculated the monthly ConR [(total number of contaminated cases per month) / (total number of blood culture sets collected per month) × 100] [3].

Ethics approval:
The need for informed consent was waived due to the retrospective nature of the study design. The study information was presented on the Web for the possibility of opting out of consent. The protocol was approved by the institutional review board of the National Center for Global Health and Medicine (NCGM-G-004168-00).

Consent to participate:
The study information was presented on the Web for the possibility of opting out of consent.