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

Can the Number of Coagulase-negative Staphylococci Specimens Detected be an Alternative Quality Indicator to the Blood Culture Contamination Rate? | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Can the Number of Coagulase-negative Staphylococci Specimens Detected be an Alternative Quality Indicator to the Blood Culture Contamination Rate? Kei Yamamoto, Kazuhisa Mezaki, Norio Ohmagari This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-558271/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract 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. Clinical Pharmacology Scientific Communication General Microbiology coagulase-negative staphylococci contamination rate antimicrobial-resistant bacteria Figures Figure 1 Figure 2 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 coefficients 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 , with AUCs (95% confidence interval) of 0.85 (0.78 to 0.93), 0.93 (0.88 to 0.98), 0.95 (0.92 to 0.99), 0.97 (0.93 to 1.00), respectively. On comparing the AUCs for each indicator, we found that A vs. B, A vs. C, and A vs. D were statistically significant with Holm correction (Supplementary Table 1). The sensitivity was 78.6%, 92.9%, 92.9%, and 100%, and the specificities were 78.7%, 80.0%, 87.5%, and 87.5%, with cut-off values of 33 sets, 23, 19, and 19 cases for indicators A–D, respectively; all with a high negative predictive value of 91.3–100%. 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 specificity 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. Methods 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 Certificate 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. Identification 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 identification and susceptibilities to the predefined antimicrobials were determined in accordance with the Clinical and Laboratory Standard Institutions criteria (M100) [ 4 , 5 ] by matrix assisted laser desorption/ionization-time of flight 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 ]. The values of the four indicators were aggregated as follows: the number of CoNS-positive sets (Indicator A), CoNS-positive cases (Indicator B), cases with only one CoNS-positive blood culture set (Indicator C), and cases of CoNS contamination (Indicator D). Statistical analysis Correlation coefficients were calculated using Pearson’s correlation test. Receiver operating characteristic (ROC) curves were prepared for all indicators with a ConR of ≥ 2.5, as the objective variable, and cut-off values were calculated using Youden's index. The area under the curves (AUCs) were compared using the Delong method with the Holm correlation. Statistical analysis was performed using EZR for Windows version 1.54 [ 6 ]. Figures were created using IBM SPSS Statistics software for Windows (version 26.0; IBM Corp., Armonk, NY, USA). The probability of significance was calculated to be 5%. Declarations Acknowledgements None Funding None Authors' contributions KY came up with the conception and design of the study, and analysed and interpretated of data. KY and KM acquired data. KY wrote drafting the article, and KM and NO revised it critically for important intellectual content. All authors reviewed the manuscript and approved the final version to be submitted. has nothing to declare. K.Y. has received research grants from Fujirebio, Inc., Mizuho Medy, Co., Ltd., and VisGene Inc., outside the submitted work. N.O. has received grants from Sanofi Pasteur and Eiken Chemical Co., Ltd., outside the submitted work. K.M. declare no competing interests. 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. References Souvenir, D. J et al . Blood cultures positive for coagulase-negative staphylococci: antisepsis, pseudobacteremia, and therapy of patients. J. Clin Microbiol . 36, 1923–1926 (1998). doi: 10.1128/JCM.36.7.1923-1926.1998 Alahmadi, Y. M. et al. Clinical and economic impact of contaminated blood cultures within the hospital setting. J. Hosp Infect . 77, 233–236 (2011). https://doi.org/10.1016/j.jhin.2010.09.033 Baron, E. J. et al. CUMITECH 1C, Blood cultures IV . ASM Press, Washington DC (2005). Clinical and Laboratory Standards Institute . Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement M100-S22 (Clinical and Laboratory Standards Institute, 2012). Clinical and Laboratory Standards Institute . Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Sixth Informational Supplement M100-S26 (Clinical and Laboratory Standards Institute, 2015). Kanda, Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48, 452–458 (2013). https://doi.org/10.1038/bmt.2012.244 Garcia, R. A., Spitzer, E. D., Kranz, B., Barnes, S. A national survey of interventions and practices in the prevention of blood culture contamination and associated adverse health care events. Am J. Infect Control. 46, 571–576 (2018). https://doi.org/10.1016/j.ajic.2017.11.009 Schifman, R. B., Strand, C. L., Meier, F. A., Howanitz, P. J. Blood culture contamination: a College of American Pathologists Q-Probes study involving 640 institutions and 497134 specimens from adult patients. Arch Pathol Lab Med . 122, 216–221 (1998). PMID: 9823858 Dargère, S., Cormier, H., Verdon, R. Contaminants in blood cultures: importance, implications, interpretation and prevention. Clin Microbiol Infect . 24, 964–969 (2018). https://doi.org/10.1016/j.cmi.2018.03.030 Rupp, M. E., Cavalieri, R. J., Marolf, C., Lyden, E. Reduction in blood culture contamination through use of initial specimen diversion device. Clin Infect Dis. 65, 201–5 (2017). https://doi.org/10.1093/cid/cix304 Gibb, A. P., Hill, B., Chorel, B., Brant, R. Reduction in blood culture contamination rate by feedback to phlebotomists. Arch Pathol Lab Med . 121, 503–7 (1997). PMID: 9167605 Additional Declarations Competing interest reported. K.Y. has received research grants from Fujirebio, Inc., Mizuho Medy, Co., Ltd., and VisGene Inc., outside the submitted work. N.O. has received grants from Sanofi Pasteur and Eiken Chemical Co., Ltd., outside the submitted work. K.M. declare no competing interests. Supplementary Files SupplementaryFigure1.tif SupplementaryTable.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 05 Jul, 2021 Reviews received at journal 29 Jun, 2021 Reviewers agreed at journal 22 Jun, 2021 Reviewers invited by journal 15 Jun, 2021 Editor assigned by journal 15 Jun, 2021 Editor invited by journal 03 Jun, 2021 Submission checks completed at journal 02 Jun, 2021 First submitted to journal 24 May, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-558271","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":30652777,"identity":"d1781a9d-8c0d-41d6-b46a-5bdbd9f801e7","order_by":0,"name":"Kei Yamamoto","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDklEQVRIiWNgGAWjYBACCTiLvQdVhpmQFgkGnjMka5HIIdJhkjOSn274mWNTxy/59uDDnzsY8vj7VycwfqlgYDfHoUVaIs3sZu+2NAnJ2XnJxrxnGIolbrzdwCxzhoHZsgG7FjmJBLMbvNsOSxjczjGTZmxjSNwgcXYDs2QbA7PBAVxa0r/d/AvScvOMmeRPYrRIS+SY3QbbcoPHTIIXpIW/dwPjRzxaJHvelN2W3ZYmObMnxxjoF4nEGTd4NxxmOCOB0y8Sx9O33Xy7zYafn/2MITDEbBL7+89ufPijwiYZV4gxCCQgcRgbgPEkkcBwmIdBItkAlxb+AyhaICKMPxgY7HBqGQWjYBSMgpEGALfYXAay9UQ0AAAAAElFTkSuQmCC","orcid":"","institution":"National Center For Global Health and Medicine","correspondingAuthor":true,"prefix":"","firstName":"Kei","middleName":"","lastName":"Yamamoto","suffix":""},{"id":30652778,"identity":"7e0c1427-b816-4560-94a4-31b13e1d2098","order_by":1,"name":"Kazuhisa Mezaki","email":"","orcid":"","institution":"National Center For Global Health and Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kazuhisa","middleName":"","lastName":"Mezaki","suffix":""},{"id":30652779,"identity":"f90d6e5b-92c5-44cf-8a22-1da209f22645","order_by":2,"name":"Norio Ohmagari","email":"","orcid":"","institution":"National Center For Global Health and Medicine","correspondingAuthor":false,"prefix":"","firstName":"Norio","middleName":"","lastName":"Ohmagari","suffix":""}],"badges":[],"createdAt":"2021-05-25 00:44:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-558271/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-558271/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":9941010,"identity":"c195f254-9475-4db8-9a56-06f4a1958cc9","added_by":"auto","created_at":"2021-06-03 14:39:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":51212,"visible":true,"origin":"","legend":"Scatter plot of correlation of ConR of each group (Indicator A–D)\na: Number of CoNS detected per specimen\nb: Number of CoNS detected per case\nc: Cases with only one set of positive CoNS\nd: Contamination cases by CoNS\nConR: contamination rate; CoNS: coagulase-negative staphylococci\n","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-558271/v1/a7a18fb92a1bddc51f7ccae3.png"},{"id":9941228,"identity":"2167007b-2111-4fb3-8575-765f583b9bb9","added_by":"auto","created_at":"2021-06-03 14:42:33","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":27172,"visible":true,"origin":"","legend":"ROC curve predicting ConR 2.5 or higher and AUC comparison \nCoNS: coagulase-negative staphylococci; ConR: contamination rate; AUC: Area under the curve; ROC: Receiver operating characteristic\n","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-558271/v1/9d0df8568328daade4fc9508.png"},{"id":13697048,"identity":"75c5175f-5561-4a68-b26c-ab967642ea9c","added_by":"auto","created_at":"2021-09-17 13:07:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":340576,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-558271/v1/35b0f0b5-1382-4ef2-b22b-52f58ccf741f.pdf"},{"id":9941227,"identity":"57a3cf7c-94fa-42f5-a6c1-e065de712cd5","added_by":"auto","created_at":"2021-06-03 14:42:33","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":180614,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-558271/v1/1a76453ffbbecdb866a02804.tif"},{"id":9941013,"identity":"1fbeff03-9df0-47fe-a466-fdf2ae9f2547","added_by":"auto","created_at":"2021-06-03 14:39:33","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":176236,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable.pdf","url":"https://assets-eu.researchsquare.com/files/rs-558271/v1/51df45ac7f509306f4866ee2.pdf"}],"financialInterests":"Competing interest reported. K.Y. has received research grants from Fujirebio, Inc., Mizuho Medy, Co., Ltd., and VisGene Inc., outside the submitted work. \nN.O. has received grants from Sanofi Pasteur and Eiken Chemical Co., Ltd., outside the submitted work.\nK.M. declare no competing interests.","formattedTitle":"\u003cp\u003eCan the Number of Coagulase-negative Staphylococci Specimens Detected be an Alternative Quality Indicator to the Blood Culture Contamination Rate?\u003c/p\u003e","fulltext":[{"header":"Introduction","content":" \u003cp\u003eRelevant 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 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Although the blood culture contamination rate (ConR) is calculated retrospectively based on certain criteria [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], its calculation is time-consuming and requires some labour. Coagulase-negative staphylococci (CoNS) are the most frequently detected bacteria on blood culture contamination [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Therefore, we intended to investigate a simple real-time indicator of CoNS to predict the increase in ConR.\u003c/p\u003e "},{"header":"Results","content":" \u003cp\u003eA 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.\u0026nbsp;1). The correlation coefficients with ConR for indicators A\u0026ndash;D were 0.71, 0.85, 0.91, and 0.93, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The ROC curve is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, with AUCs (95% confidence interval) of 0.85 (0.78 to 0.93), 0.93 (0.88 to 0.98), 0.95 (0.92 to 0.99), 0.97 (0.93 to 1.00), respectively. On comparing the AUCs for each indicator, we found that A vs. B, A vs. C, and A vs. D were statistically significant with Holm correction (Supplementary Table\u0026nbsp;1). The sensitivity was 78.6%, 92.9%, 92.9%, and 100%, and the specificities were 78.7%, 80.0%, 87.5%, and 87.5%, with cut-off values of 33 sets, 23, 19, and 19 cases for indicators A\u0026ndash;D, respectively; all with a high negative predictive value of 91.3\u0026ndash;100%.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e "},{"header":"Discussion","content":" \u003cp\u003eThese results suggest that the number of CoNS-positive cases correlated with ConR to predict a ConR of \u0026ge;\u0026thinsp;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 specificity for predicting ConR\u0026thinsp;\u0026ge;\u0026thinsp;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 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Indicators A and B may be good predictors for ConR in such institutes.\u003c/p\u003e \u003cp\u003eConR of \u0026le;\u0026thinsp;3.0 is often used as a standard for the quality of blood culture tests [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In this study, we set the predicted ConR to be \u0026ge;\u0026thinsp;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\u0026nbsp;2). ConR is related to disinfection of the puncture site, collection method, hand hygiene, education, and feedback methods regarding collection [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Recently, the usefulness of a blood collection device has also been reported [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. 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 [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. 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.\u003c/p\u003e \u003cp\u003eHowever, the situation regarding blood cultures varies from hospital to hospital [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. 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\u0026rsquo;s own institution before using it as a simple indicator.\u003c/p\u003e "},{"header":"Methods","content":"\u003ch2\u003eStudy design\u003c/h2\u003e\n\u003cp\u003eWe 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\u0026rsquo; consent. The protocol of this study including the opt-out consent method was approved by the Certificate 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.\u003c/p\u003e\n\u003ch2\u003eThe registry data of blood culture surveillance\u003c/h2\u003e\n\u003cp\u003eFor 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 [\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]. Undetermined cases and those with pending determination were excluded from the study.\u003c/p\u003e\n\u003ch2\u003eIdentification of bacterial species\u003c/h2\u003e\n\u003cp\u003eAll 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\u0026deg;C (Depending on the situation, other media may be added or the environment may be changed, such as anaerobic incubation). Conventional bacterial identification and susceptibilities to the predefined antimicrobials were determined in accordance with the Clinical and Laboratory Standard Institutions criteria (M100) [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e] by matrix assisted laser desorption/ionization-time of flight 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 \u003cem\u003eStaphylococcus aureus\u003c/em\u003e and \u003cem\u003eS. lugdunensis\u003c/em\u003e, were treated as CoNS.\u003c/p\u003e\n\u003ch2\u003eIndicators\u003c/h2\u003e\n\u003cp\u003eWe calculated the monthly ConR [(total number of contaminated cases per month) / (total number of blood culture sets collected per month) \u0026times; 100] [\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]. The values of the four indicators were aggregated as follows: the number of CoNS-positive sets (Indicator A), CoNS-positive cases (Indicator B), cases with only one CoNS-positive blood culture set (Indicator C), and cases of CoNS contamination (Indicator D).\u003c/p\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003eStatistical analysis\u003c/h2\u003e\n\u003cp\u003eCorrelation coefficients were calculated using Pearson\u0026rsquo;s correlation test. Receiver operating characteristic (ROC) curves were prepared for all indicators with a ConR of \u0026ge;\u0026thinsp;2.5, as the objective variable, and cut-off values were calculated using Youden's index. The area under the curves (AUCs) were compared using the Delong method with the Holm correlation. Statistical analysis was performed using EZR for Windows version 1.54 [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]. Figures were created using IBM SPSS Statistics software for Windows (version 26.0; IBM Corp., Armonk, NY, USA). The probability of significance was calculated to be 5%.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003ch2\u003eFunding\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003ch2\u003eAuthors' contributions\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eKY came up with the conception and design of the study, and analysed and interpretated of data. KY and KM acquired data. KY wrote drafting the article, and KM and NO revised it critically for important intellectual content. All authors reviewed the manuscript and approved the final version to be submitted.\u003c/p\u003e\n\u003ch2\u003ehas nothing to declare.\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eK.Y. has received research grants from Fujirebio, Inc., Mizuho Medy, Co., Ltd., and VisGene Inc., outside the submitted work.\u003c/p\u003e\n\u003cp\u003eN.O. has received grants from Sanofi Pasteur and Eiken Chemical Co., Ltd., outside the submitted work.\u003c/p\u003e\n\u003cp\u003eK.M. declare no competing interests.\u003c/p\u003e\n\u003ch2\u003eEthics approval:\u003c/h2\u003e\n\u003cp\u003eThe 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).\u003c/p\u003e\n\u003ch2\u003eConsent to participate:\u003c/h2\u003e\n\u003cp\u003eThe study information was presented on the Web for the possibility of opting out of consent.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSouvenir, D. J \u003cem\u003eet al\u003c/em\u003e. Blood cultures positive for coagulase-negative staphylococci: antisepsis, pseudobacteremia, and therapy of patients. \u003cem\u003eJ. Clin Microbiol\u003c/em\u003e. \u003cstrong\u003e36,\u003c/strong\u003e 1923\u0026ndash;1926 (1998). doi: \u003ca href=\"https://doi.org/10.1128/jcm.36.7.1923-1926.1998\"\u003e10.1128/JCM.36.7.1923-1926.1998\u003c/a\u003e\u003c/li\u003e\n\u003cli\u003eAlahmadi, Y. M. \u003cem\u003eet al.\u003c/em\u003e Clinical and economic impact of contaminated blood cultures within the hospital setting. \u003cem\u003eJ. Hosp Infect\u003c/em\u003e. \u003cstrong\u003e77,\u003c/strong\u003e 233\u0026ndash;236 (2011). \u003ca href=\"https://doi.org/10.1016/j.jhin.2010.09.033\"\u003ehttps://doi.org/10.1016/j.jhin.2010.09.033\u003c/a\u003e\u003c/li\u003e\n\u003cli\u003eBaron, E. J. \u003cem\u003eet al.\u003c/em\u003e CUMITECH 1C, \u003cem\u003eBlood cultures IV\u003c/em\u003e. ASM Press, Washington DC (2005).\u003c/li\u003e\n\u003cli\u003eClinical and Laboratory Standards Institute\u003cem\u003e.\u003c/em\u003e Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement M100-S22 (Clinical and Laboratory Standards Institute, 2012).\u003c/li\u003e\n\u003cli\u003eClinical and Laboratory Standards Institute\u003cem\u003e.\u003c/em\u003e Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Sixth Informational Supplement M100-S26 (Clinical and Laboratory Standards Institute, 2015).\u003c/li\u003e\n\u003cli\u003eKanda, Y. Investigation of the freely available easy-to-use software \u0026lsquo;EZR\u0026rsquo; for medical statistics. \u003cem\u003eBone Marrow Transplant\u003c/em\u003e \u003cstrong\u003e48,\u003c/strong\u003e 452\u0026ndash;458 (2013). https://doi.org/10.1038/bmt.2012.244\u003c/li\u003e\n\u003cli\u003eGarcia, R. A., Spitzer, E. D., Kranz, B., Barnes, S. A national survey of interventions and practices in the prevention of blood culture contamination and associated adverse health care events. \u003cem\u003eAm J. Infect Control.\u003c/em\u003e \u003cstrong\u003e46,\u003c/strong\u003e 571\u0026ndash;576 (2018). \u003ca href=\"https://doi.org/10.1016/j.ajic.2017.11.009\"\u003ehttps://doi.org/10.1016/j.ajic.2017.11.009\u003c/a\u003e\u003c/li\u003e\n\u003cli\u003eSchifman, R. B., Strand, C. L., Meier, F. A., Howanitz, P. J. Blood culture contamination: a College of American Pathologists Q-Probes study involving 640 institutions and 497134 specimens from adult patients. \u003cem\u003eArch Pathol Lab Med\u003c/em\u003e. \u003cstrong\u003e122,\u003c/strong\u003e 216\u0026ndash;221 (1998). PMID: \u003ca href=\"http://www.ncbi.nlm.nih.gov/pubmed/9823858\"\u003e9823858\u003c/a\u003e\u003c/li\u003e\n\u003cli\u003eDarg\u0026egrave;re, S., Cormier, H., Verdon, R. Contaminants in blood cultures: importance, implications, interpretation and prevention. \u003cem\u003eClin Microbiol Infect\u003c/em\u003e. \u003cstrong\u003e24,\u003c/strong\u003e 964\u0026ndash;969 (2018). \u003ca href=\"https://doi.org/10.1016/j.cmi.2018.03.030\"\u003ehttps://doi.org/10.1016/j.cmi.2018.03.030\u003c/a\u003e\u003c/li\u003e\n\u003cli\u003eRupp, M. E., Cavalieri, R. J., Marolf, C., Lyden, E. Reduction in blood culture contamination through use of initial specimen diversion device. \u003cem\u003eClin Infect Dis.\u003c/em\u003e \u003cstrong\u003e65,\u003c/strong\u003e 201\u0026ndash;5 (2017). \u003ca href=\"https://doi.org/10.1093/cid/cix304\"\u003ehttps://doi.org/10.1093/cid/cix304\u003c/a\u003e\u003c/li\u003e\n\u003cli\u003eGibb, A. P., Hill, B., Chorel, B., Brant, R. Reduction in blood culture contamination rate by feedback to phlebotomists. \u003cem\u003eArch Pathol Lab Med\u003c/em\u003e. \u003cstrong\u003e121,\u003c/strong\u003e 503\u0026ndash;7 (1997). PMID: \u003ca href=\"http://www.ncbi.nlm.nih.gov/pubmed/9167605\"\u003e9167605\u003c/a\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"coagulase-negative staphylococci, contamination rate, antimicrobial-resistant bacteria","lastPublishedDoi":"10.21203/rs.3.rs-558271/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-558271/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eCoagulase-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).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: We performed a retrospective study of selected patients who underwent blood culture testing.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e 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. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The number of CoNS-positive cases could help predict an increase in ConR ≥2.5.\u003c/p\u003e","manuscriptTitle":"Can the Number of Coagulase-negative Staphylococci Specimens Detected be an Alternative Quality Indicator to the Blood Culture Contamination Rate?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-06-03 14:39:31","doi":"10.21203/rs.3.rs-558271/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2021-07-05T08:05:50+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-06-29T13:55:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"a14ff47c-42b1-42aa-9ef8-fbec635ddb70","date":"2021-06-23T01:59:38+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-06-16T00:23:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-06-15T23:59:55+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-06-03T08:01:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-06-02T06:48:30+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2021-05-25T00:42:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e1ee85b4-2121-4f29-b418-e602f6bd9184","owner":[],"postedDate":"June 3rd, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":4774237,"name":"Clinical Pharmacology"},{"id":4774238,"name":"Scientific Communication"},{"id":4774239,"name":"General Microbiology"}],"tags":[],"updatedAt":"2021-08-19T07:44:10+00:00","versionOfRecord":[],"versionCreatedAt":"2021-06-03 14:39:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-558271","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-558271","identity":"rs-558271","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}