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Kudo M, Takada T, Fujii K, Sasaki S, Yagi Y, Yano T, Tsuchido Y, Ito H, Sada KE, Fukuhara S. Added Value of Shaking Chills for Predicting Bacteremia in Patients with Suspected Infection. J Gen Intern Med 2025; 40:796-802. [PMID: 39707092 PMCID: PMC11914571 DOI: 10.1007/s11606-024-09291-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 12/06/2024] [Indexed: 12/23/2024]
Abstract
BACKGROUND Detailed grading of chills is more useful for diagnosing bacteremia than simply classifying the presence or absence of chills. However, its value added to other clinical information has not been evaluated. OBJECTIVE To evaluate the value of adding chills grading to other clinical information compared to simply noting the presence or absence of chills for predicting bacteremia in patients with suspected infection. DESIGN Prospective observational study. PARTICIPANTS Adult patients admitted to two acute-care hospitals with suspected infection from April 2018 to March 2019. MAIN MEASURES Two types of categorization for chills were applied: "presence" or "absence" (dichotomized chills); and "no chills", "mild/moderate chills", and "shaking chills" (trichotomized chills). Three multivariable logistic regression models incorporating each of dichotomized chills, trichotomized chills, and C-reactive protein (CRP) with other clinical information were developed and compared. To assess the potential consequences of using each model to identify patients with high risk of bacteremia (i.e., requiring prompt intervention), we applied a cut-off point of an estimated probability of 60%. The number of patients with bacteremia correctly identified by each model was compared. KEY RESULTS Among the 2,013 patients, 327 (16.2%) were diagnosed with bacteremia. The three models showed comparable discrimination and calibration performance. At the 60% cut-off, the dichotomized chills model correctly identified 11 patients (3.4% [95% confidence interval (CI) 1.9-3.4] of patients with bacteremia). The trichotomized chills model and CRP model correctly identified an additional 15 patients (4.6% [95% CI 2.8-7.4]) and 2 patients (0.6% [95% CI 0.1-2.3]) with bacteremia, respectively. CONCLUSIONS Differentiating shaking chills in comparison with dichotomized chills for predicting bacteremia allowed the correct identification of an additional 4.6% of patients with bacteremia. Detailed grading of chills can be assessed without additional time, cost, or burden on patients and can be recommended in the routine history taking.
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Affiliation(s)
- Masataka Kudo
- Department of General Internal Medicine, Iizuka Hospital, Fukuoka, Japan
- Department of Clinical Epidemiology, Kochi Medical School, Nankoku, Japan
- Department of Internal Medicine, Inan Hospital, Kochi, Japan
| | - Toshihiko Takada
- Department of General Medicine, Shirakawa Satellite for Teaching And Research (STAR), Fukushima Medical University, Fukushima, Japan.
| | - Kotaro Fujii
- Department of General Medicine, Shirakawa Satellite for Teaching And Research (STAR), Fukushima Medical University, Fukushima, Japan
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Academic and Research Centre, Hokkaido Centre for Family Medicine, Sapporo, Japan
| | - Sho Sasaki
- Section of Education for Clinical Research, Kyoto University Hospital, Kyoto, Japan
- Center for Innovative Research for Communities and Clinical Excellence (CiRC2LE), Fukushima Medical University, Fukushima, Japan
| | - Yu Yagi
- Department of General Internal Medicine, Iizuka Hospital, Fukuoka, Japan
| | - Tetsuhiro Yano
- Department of General Medicine, Shirakawa Satellite for Teaching And Research (STAR), Fukushima Medical University, Fukushima, Japan
| | - Yasuhiro Tsuchido
- Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hideyuki Ito
- Department of Emergency Medicine, Otsu City Hospital, Otsu, Japan
- Department of Infectious Diseases, Otsu City Hospital, Otsu, Japan
| | - Ken-Ei Sada
- Department of Clinical Epidemiology, Kochi Medical School, Nankoku, Japan
| | - Shunichi Fukuhara
- Department of General Medicine, Shirakawa Satellite for Teaching And Research (STAR), Fukushima Medical University, Fukushima, Japan
- Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Aita T, Nakagawa H, Takahashi S, Naganuma T, Anan K, Banno M, Hamaguchi S. Utility of shaking chills as a diagnostic sign for bacteremia in adults: a systematic review and meta-analysis. BMC Med 2024; 22:240. [PMID: 38863066 PMCID: PMC11167933 DOI: 10.1186/s12916-024-03467-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Accepted: 06/05/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Accurate prediction of bacteremia is essential for guiding blood culture collection and optimal antibiotic treatment. Shaking chills, defined as a subjective chill sensation with objective body shivering, have been suggested as a potential predictor of bacteremia; however, conflicting findings exist. To address the evidence gap, we conducted a systematic review and meta-analysis of studies to assess the diagnostic accuracy of shaking chills for predicting bacteremia among adult patients. METHODS We included studies reporting the diagnostic accuracy of shaking chills or chills for bacteremia. Adult patients with suspected bacteremia who underwent at least one set of blood cultures were included. Our main analysis focused on studies that assessed shaking chills. We searched these studies through CENTRAL, MEDLINE, Embase, the World Health Organization ICTRP Search Portal, and ClinicalTrials.gov. Study selection, data extraction, evaluation for risk of bias, and applicability using the QUADAS-2 tool were conducted by two independent investigators. We estimated a summary receiver operating characteristic curve and a summary point of sensitivity and specificity of the index tests, using a hierarchical model and the bivariate model, respectively. RESULTS We identified 19 studies with a total of 14,641 patients in which the accuracy of shaking chills was evaluated. The pooled sensitivity and specificity of shaking chills were 0.37 (95% confidence interval [CI], 0.29 to 0.45) and 0.87 (95% CI, 0.83 to 0.90), respectively. Most studies had a low risk of bias in the index test domain and a high risk of bias and a high applicability concern in the patient-selection domain. CONCLUSIONS Shaking chills are a highly specific but less sensitive predictor of bacteremia. Blood cultures and early initiation of antibiotics should be considered for patients with an episode of shaking chills; however, the absence of shaking chills must not lead to exclusion of bacteremia and early antibiotic treatment.
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Affiliation(s)
- Tetsuro Aita
- Department of General Internal Medicine, Fukushima Medical University, Fukushima City, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
- Department of Clinical Epidemiology, Graduate School of Medicine, Fukushima Medical University, Fukushima, Japan.
| | - Hiroaki Nakagawa
- Department of General Internal Medicine, Fukushima Medical University, Fukushima City, 1 Hikarigaoka, Fukushima, 960-1295, Japan
| | - Sei Takahashi
- Department of General Internal Medicine, Fukushima Medical University, Fukushima City, 1 Hikarigaoka, Fukushima, 960-1295, Japan
- Futaba Emergency and General Medicine Support Center, Fukushima Medical University, Fukushima, Japan
| | - Toru Naganuma
- Department of General Internal Medicine, Fukushima Medical University, Fukushima City, 1 Hikarigaoka, Fukushima, 960-1295, Japan
- Futaba Emergency and General Medicine Support Center, Fukushima Medical University, Fukushima, Japan
| | - Keisuke Anan
- Division of Respiratory Medicine, Saiseikai Kumamoto Hospital, Kumamoto, Japan
- Systematic Review Workshop Peer Support Group (SRWS-PSG), Osaka, Japan
| | - Masahiro Banno
- Systematic Review Workshop Peer Support Group (SRWS-PSG), Osaka, Japan
- Department of Psychiatry, Seichiryo Hospital, Nagoya, Japan
| | - Sugihiro Hamaguchi
- Department of General Internal Medicine, Fukushima Medical University, Fukushima City, 1 Hikarigaoka, Fukushima, 960-1295, Japan
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O'Neal HR, Sheybani R, Janz DR, Scoggins R, Jagneaux T, Walker JE, Henning DJ, Rosenman E, Mahler SA, Regunath H, Sampson CS, Files DC, Fremont RD, Noto MJ, Schneider EE, Shealey WR, Berlinger MS, Carver TC, Walker MK, Ledeboer NA, Shah AM, Tse HTK, DiCarlo D, Rice TW, Thomas CB. Validation of a Novel, Rapid Sepsis Diagnostic for Emergency Department Use. Crit Care Explor 2024; 6:e1026. [PMID: 38333076 PMCID: PMC10852401 DOI: 10.1097/cce.0000000000001026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2024] Open
Abstract
OBJECTIVES To assess the in vitro IntelliSep test, a microfluidic assay that quantifies the state of immune activation by evaluating the biophysical properties of leukocytes, as a rapid diagnostic for sepsis. DESIGN Prospective cohort study. SETTING Five emergency departments (EDs) in Louisiana, Missouri, North Carolina, and Washington. PATIENTS Adult patients presenting to the ED with signs (two of four Systemic Inflammatory Response Syndrome criteria, where one must be temperature or WBC count) or suspicion (provider-ordered culture) of infection. INTERVENTIONS All patients underwent testing with the IntelliSep using ethylene diamine tetraacetic acid-anticoagulated whole blood followed by retrospective adjudication for sepsis by sepsis-3 criteria by a blinded panel of physicians. MEASUREMENTS AND MAIN RESULTS Of 599 patients enrolled, 572 patients were included in the final analysis. The result of the IntelliSep test is reported as the IntelliSep Index (ISI), ranging from 0.1 to 10.0, divided into three interpretation bands for the risk of sepsis: band 1 (low) to band 3 (high). The median turnaround time for ISI results was 7.2 minutes. The ISI resulted band 1 in 252 (44.1%), band 2 in 160 (28.0%), and band 3 in 160 (28.0%). Sepsis occurred in 26.6% (152 of 572 patients). Sepsis prevalence was 11.1% (95% CI, 7.5-15.7%) in band 1, 28.1% (95% CI, 21.3-35.8%) in band 2, and 49.4% (95% CI, 41.4-57.4%) in band 3. The Positive Percent Agreement of band 1 was 81.6% and the Negative Percent Agreement of band 3 was 80.7%, with an area under the receiver operating characteristic curve of 0.74. Compared with band 1, band 3 correlated with adverse clinical outcomes, including mortality, and resource utilization. CONCLUSIONS Increasing ISI interpretation band is associated with increasing probability of sepsis in patients presenting to the ED with suspected infection.
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Affiliation(s)
- Hollis R O'Neal
- Pulmonary and Critical Care, Louisiana State University Health Sciences Center, Baton Rouge, LA
- Pulmonary & Critical Care, Our Lady of the Lake Regional Medical Center, Baton Rouge, LA
| | | | - David R Janz
- Pulmonary & Critical Care, University Medical Center, New Orleans, LA
| | - Robert Scoggins
- Pulmonary and Critical Care, Kootenai Health, Coeur d'Alene, ID
| | - Tonya Jagneaux
- Pulmonary and Critical Care, Louisiana State University Health Sciences Center, Baton Rouge, LA
- Pulmonary & Critical Care, Our Lady of the Lake Regional Medical Center, Baton Rouge, LA
| | - James E Walker
- Pulmonary and Critical Care, Louisiana State University Health Sciences Center, Baton Rouge, LA
- Pulmonary & Critical Care, Our Lady of the Lake Regional Medical Center, Baton Rouge, LA
| | - Daniel J Henning
- Department of Emergency Medicine, University of Washington, Seattle, WA
| | | | - Simon A Mahler
- Departments of Emergency Medicine, Epidemiology and Prevention, and Implementation Science, Wake Forest University School of Medicine, Winston-Salem, NC
| | - Hariharan Regunath
- Critical Care Medicine and Infectious Diseases, University of Maryland-Baltimore Washington Medical Center, Glen Burnie, MD
- Division of Infectious Diseases, Department of Medicine, University of Missouri School of Medicine, Columbia, MO
| | - Christopher S Sampson
- Department of Emergency Medicine, University of Missouri School of Medicine, Columbia, MO
| | - D Clark Files
- Pulmonary and Critical Care Medicine, Wake Forest University School of Medicine, Winston Salem, NC
| | | | - Michael J Noto
- Allergy, Pulmonary, and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA
| | - Erica E Schneider
- Pulmonary and Critical Care, Bon Secours Mercy Health System, Richmond, VA
| | - Wesley R Shealey
- Department of Medicine, Infectious Disease, Creighton University School of Medicine, Phoenix, AZ
| | - Matthew S Berlinger
- Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Thomas C Carver
- Division of Trauma, Critical Care, and Acute Care Surgery, Medical College of Wisconsin, Milwaukee, WI
| | - Morgan K Walker
- Critical Care Medicine, National Institutes of Health, Bethesda, MD
| | - Nathan A Ledeboer
- Department of Pathology, Medical College of Wisconsin, Milwaukee, WI
| | | | - Henry T K Tse
- Pulmonary & Critical Care, Our Lady of the Lake Regional Medical Center, Baton Rouge, LA
| | - Dino DiCarlo
- Department of Bioengineering and Biomedical Engineering, University of California, Los Angeles, CA
| | - Todd W Rice
- Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Christopher B Thomas
- Pulmonary and Critical Care, Louisiana State University Health Sciences Center, Baton Rouge, LA
- Pulmonary & Critical Care, Our Lady of the Lake Regional Medical Center, Baton Rouge, LA
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Tsai WC, Liu CF, Ma YS, Chen CJ, Lin HJ, Hsu CC, Chow JC, Chien YW, Huang CC. Real-time artificial intelligence system for bacteremia prediction in adult febrile emergency department patients. Int J Med Inform 2023; 178:105176. [PMID: 37562317 DOI: 10.1016/j.ijmedinf.2023.105176] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 07/29/2023] [Accepted: 08/04/2023] [Indexed: 08/12/2023]
Abstract
BACKGROUND Artificial intelligence (AI) holds significant potential to be a valuable tool in healthcare. However, its application for predicting bacteremia among adult febrile patients in the emergency department (ED) remains unclear. Therefore, we conducted a study to provide clarity on this issue. METHODS Adult febrile ED patients with blood cultures at Chi Mei Medical Center were divided into derivation (January 2017 to June 2019) and validation groups (July 2019 to December 2020). The derivation group was utilized to develop AI models using twenty-one feature variables and five algorithms to predict bacteremia. The performance of these models was compared with qSOFA score. The AI model with the highest area under the receiver operating characteristics curve (AUC) was chosen to implement the AI prediction system and tested on the validation group. RESULTS The study included 5,647 febrile patients. In the derivation group, there were 3,369 patients with a mean age of 61.4 years, and 50.7% were female, including 508 (13.8%) with bacteremia. The model with the best AUC was built using the random forest algorithm (0.761), followed by logistic regression (0.755). All five models demonstrated better AUC than the qSOFA score (0.560). The random forest model was adopted to build a real-time AI prediction system integrated into the hospital information system, and the AUC achieved 0.709 in the validation group. CONCLUSION The AI model shows promise to predict bacteremia in adult febrile ED patients; however, further external validation in different hospitals and populations is necessary to verify its effectiveness.
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Affiliation(s)
- Wei-Chun Tsai
- Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pediatrics, Chi Mei Medical Center, Tainan, Taiwan
| | - Chung-Feng Liu
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| | - Yu-Shan Ma
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| | - Chia-Jung Chen
- Department of Information Systems, Chi Mei Medical Center, Tainan, Taiwan
| | - Hung-Jung Lin
- Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Emergency Medicine, Taipei Medical University, Taipei, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Chien-Chin Hsu
- Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Julie Chi Chow
- Department of Pediatrics, Chi Mei Medical Center, Tainan, Taiwan
| | - Yu-Wen Chien
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
| | - Chien-Cheng Huang
- Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Emergency Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Guo Q, Qu P, Cui W, Liu M, Zhu H, Chen W, Sun N, Geng S, Song W, Li X, Lou A. Organism type of infection is associated with prognosis in sepsis: an analysis from the MIMIC-IV database. BMC Infect Dis 2023; 23:431. [PMID: 37365506 DOI: 10.1186/s12879-023-08387-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/08/2023] [Indexed: 06/28/2023] Open
Abstract
BACKGROUND Sepsis has a high mortality rate, which is expensive to treat, and is a major drain on healthcare resources; it seriously impacts the quality of human life. The clinical features of positive or non-positive blood cultures have been reported, but the clinical features of sepsis with different microbial infections and how they contribute to clinical outcomes have not been adequately described. METHODS We extracted clinical data of septic patients with a single pathogen from the online Medical Information Mart for Intensive Care(MIMIC)-IV database. Based on microbial cultures, patients were classified into Gram-negative, Gram-positive, and fungal groups. Then, we analyzed the clinical characteristics of sepsis patients with Gram-negative, Gram-positive, and fungal infections. The primary outcome was 28-day mortality. The secondary outcomes were in-hospital mortality, the length of hospital stay, the length of ICU stay, and the ventilation duration. In addition, Kaplan-Meier analysis was used for the 28-day cumulative survival rate of patients with sepsis. Finally, we performed further univariate and multivariate regression analyses for 28-day mortality and created a nomogram for predicting 28-day mortality. RESULTS The analysis showed that bloodstream infections showed a statistically significant difference in survival between Gram-positive and fungal organisms; drug resistance only reached statistical significance for Gram-positive bacteria. Through univariate and multivariate analysis, it was found that both the Gram-negative bacteria and fungi were independent risk factors for the short-term prognosis of sepsis patients. The multivariate regression model showed good discrimination, with a C-index of 0.788. We developed and validated a nomogram for the individualized prediction of 28-day mortality in patients with sepsis. Application of the nomogram still gave good calibration. CONCLUSIONS Organism type of infection is associated with mortality of sepsis, and early identification of the microbiological type of a patient with sepsis will provide an understanding of the patient's condition and guide treatment.
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Affiliation(s)
- Qiuping Guo
- Department of Emergency Medicine, Southern Medical University Nanfang Hospital, Guangzhou, 510515, China
| | - Peng Qu
- Department of Emergency Medicine, Southern Medical University Nanfang Hospital, Guangzhou, 510515, China
- Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Wanfu Cui
- Department of Emergency Medicine, Southern Medical University Nanfang Hospital, Guangzhou, 510515, China
| | - Mingrong Liu
- Department of Emergency Medicine, Southern Medical University Nanfang Hospital, Guangzhou, 510515, China
| | - Huiling Zhu
- Department of Emergency Medicine, Southern Medical University Nanfang Hospital, Guangzhou, 510515, China
| | - Weixin Chen
- Department of Emergency Medicine, Southern Medical University Nanfang Hospital, Guangzhou, 510515, China
| | - Nan Sun
- Department of Emergency Medicine, Southern Medical University Nanfang Hospital, Guangzhou, 510515, China
| | - Shiyu Geng
- Department of Emergency Medicine, Southern Medical University Nanfang Hospital, Guangzhou, 510515, China
| | - Weihua Song
- Department of Emergency Medicine, Southern Medical University Nanfang Hospital, Guangzhou, 510515, China
| | - Xu Li
- Department of Emergency Medicine, Southern Medical University Nanfang Hospital, Guangzhou, 510515, China.
- Key Laboratory of Emergency and Trauma, Ministry of Education, College of Emergency and Trauma, Hainan Medical University, Haikou, 571199, China.
| | - Anni Lou
- Department of Emergency Medicine, Southern Medical University Nanfang Hospital, Guangzhou, 510515, China.
- Key Laboratory of Emergency and Trauma, Ministry of Education, College of Emergency and Trauma, Hainan Medical University, Haikou, 571199, China.
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Rodic S, Hryciw BN, Selim S, Wang CQ, Lepage MF, Goyal V, Nguyen LH, Fergusson DA, van Walraven C. Concurrent external validation of bloodstream infection probability models. Clin Microbiol Infect 2023; 29:61-69. [PMID: 35872173 DOI: 10.1016/j.cmi.2022.07.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 06/15/2022] [Accepted: 07/12/2022] [Indexed: 01/26/2023]
Abstract
OBJECTIVE Accurately estimating the likelihood of bloodstream infection (BSI) can help clinicians make diagnostic and therapeutic decisions. Many multivariate models predicting BSI probability have been published. This study measured the performance of BSI probability models within the same patient sample. METHODS We retrieved validated BSI probability models included in a recently published systematic review that returned a patient-level BSI probability for adults. Model applicability, discrimination, and accuracy was measured in a simple random sample of 4485 admitted adults having blood cultures ordered in the emergency department or the initial 48 hours of hospitalization. RESULTS Ten models were included (publication years 1991-2015). Common methodological threats to model performance included overfitting and continuous variable categorization. Restrictive inclusion criteria caused seven models to apply to <15% of validation patients. Model discrimination was less than originally reported in derivation groups (median c-statistic 60%, range 48-69). The observed BSI risk frequently deviated from expected (median integrated calibration index 4.0%, range 0.8-12.4). Notable disagreement in expected BSI probabilities was seen between models (median (25th-75th percentile) relative difference between expected risks 68.0% (28.6-113.6%)). DISCUSSION In a large randomly selected external validation population, many published BSI probability models had restricted applicability, limited discrimination and calibration, and extensive inter-model disagreement. Direct comparison of model performance is hampered by dissimilarities between model-specific validation groups.
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Affiliation(s)
- Stefan Rodic
- Department of Medicine, University of Ottawa, Canada
| | | | - Shehab Selim
- Department of Medicine, University of Ottawa, Canada
| | - Chu Qi Wang
- Department of Medicine, University of Ottawa, Canada
| | | | - Vineet Goyal
- Department of Medicine, University of Ottawa, Canada
| | | | - Dean A Fergusson
- Department of Medicine, University of Ottawa, Canada; Department of Epidemiology & Community Medicine, University of Ottawa, Ottawa Hospital Research Institute, ICES (formerly Institute for Clinical Evaluative Sciences), Canada
| | - Carl van Walraven
- Department of Medicine, University of Ottawa, Canada; Department of Epidemiology & Community Medicine, University of Ottawa, Ottawa Hospital Research Institute, ICES (formerly Institute for Clinical Evaluative Sciences), Canada.
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Associations between interleukin-1-B gene -511G/A polymorphism and sepsis risk: A meta-analysis. Cytokine 2022; 157:155953. [PMID: 35834950 DOI: 10.1016/j.cyto.2022.155953] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 06/04/2022] [Accepted: 06/21/2022] [Indexed: 11/20/2022]
Abstract
The role of the cytokine (IL) gene has been indicated in the progression of sepsis. Nevertheless, the outcomes remain controversial. This meta-analysis aimed to examine the relationship of IL-1B gene -511G/A polymorphism and the risk of sepsis. To perform a retrospective database analysis, the CNKI PubMed,EMBASE and Cochrane Library databases were searched for related articles. Then, the combined odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated using a fixed- or a random-effects model. A total of six related articles were discovered. The result of the meta-analysis showed that IL-1B -511G/A polymorphism was not significantly correlated with sepsis risk in the total population, but in the subgroup analysis we found that IL-1B -511G/A polymorphism was associated with sepsis risk in Caucasian populations (A vs. G: OR = 1.22, 95 %CI = 1.01-1.48; AA vs. GG: OR = 2.14, 95 %CI = 1.33-3.43; Recessive model: OR = 2.59, 95 %CI = 1.68-4.01). This meta-analysis showed that the IL-1B -511A allele might be a low-penetrant risk factor for sepsis in Caucasians.
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Retamar-Gentil P, López-Cortés LE. Predicting bacteremia in the Emergency Room: How and why. ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA (ENGLISH ED.) 2022; 40:99-101. [PMID: 35249677 DOI: 10.1016/j.eimce.2021.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 12/29/2021] [Indexed: 06/14/2023]
Affiliation(s)
- Pilar Retamar-Gentil
- Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva Hospital Universitario Virgen Macarena/CSIC/Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain; Departamento de Medicina, Universidad de Sevilla, Spain.
| | - Luis Eduardo López-Cortés
- Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva Hospital Universitario Virgen Macarena/CSIC/Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain
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Predicting bacteremia in the Emergency Room: How and why. Enferm Infecc Microbiol Clin 2022. [DOI: 10.1016/j.eimc.2021.12.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Fukui S, Inui A, Saita M, Kobayashi D, Naito T. Clinical prediction rule for bacteremia with pyelonephritis and hospitalization judgment: chi-square automatic interaction detector (CHAID) decision tree analysis model. J Int Med Res 2022; 50:3000605211065658. [PMID: 34986702 PMCID: PMC8743944 DOI: 10.1177/03000605211065658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Objective This study was performed to identify predictive factors for bacteremia among patients with pyelonephritis using a chi-square automatic interaction detector (CHAID) decision tree analysis model. Methods This retrospective cross-sectional survey was performed at Juntendo University Nerima Hospital, Tokyo, Japan and included all patients with pyelonephritis from whom blood cultures were taken. At the time of blood culture sample collection, clinical information was extracted from the patients’ medical charts, including vital signs, symptoms, laboratory data, and culture results. Factors potentially predictive of bacteremia among patients with pyelonephritis were analyzed using Student’s t-test or the chi-square test and the CHAID decision tree analysis model. Results In total, 198 patients (60 (30.3%) men, 138 (69.7%) women; mean age, 74.69 ± 15.27 years) were included in this study, of whom 92 (46.4%) had positive blood culture results. The CHAID decision tree analysis revealed that patients with a white blood cell count of >21,000/μL had a very high risk (89.5%) of developing bacteremia. Patients with a white blood cell count of ≤21,000/μL plus chills plus an aspartate aminotransferase concentration of >19 IU/L constituted the high-risk group (69.0%). Conclusion The present results are extremely useful for predicting the results of bacteremia among patients with pyelonephritis.
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Affiliation(s)
- Sayato Fukui
- Department of General Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - Akihiro Inui
- Department of General Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - Mizue Saita
- Department of General Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - Daiki Kobayashi
- Department of Internal Medicine, St. Luke's International Hospital, Tokyo, Japan
| | - Toshio Naito
- Department of General Medicine, Juntendo University School of Medicine, Tokyo, Japan
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Prediction of Bacteremia Based on 12-Year Medical Data Using a Machine Learning Approach: Effect of Medical Data by Extraction Time. Diagnostics (Basel) 2022; 12:diagnostics12010102. [PMID: 35054269 PMCID: PMC8774637 DOI: 10.3390/diagnostics12010102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 12/29/2021] [Accepted: 12/31/2021] [Indexed: 12/12/2022] Open
Abstract
Early detection of bacteremia is important to prevent antibiotic abuse. Therefore, we aimed to develop a clinically applicable bacteremia prediction model using machine learning technology. Data from two tertiary medical centers’ electronic medical records during a 12-year-period were extracted. Multi-layer perceptron (MLP), random forest, and gradient boosting algorithms were applied for machine learning analysis. Clinical data within 12 and 24 hours of blood culture were analyzed and compared. Out of 622,771 blood cultures, 38,752 episodes of bacteremia were identified. In MLP with 128 hidden layer nodes, the area under the receiver operating characteristic curve (AUROC) of the prediction performance in 12- and 24-h data models was 0.762 (95% confidence interval (CI); 0.7617–0.7623) and 0.753 (95% CI; 0.7520–0.7529), respectively. AUROC of causative-pathogen subgroup analysis predictive value for Acinetobacter baumannii bacteremia was the highest at 0.839 (95% CI; 0.8388–0.8394). Compared to primary bacteremia, AUROC of sepsis caused by pneumonia was highest. Predictive performance of bacteremia was superior in younger age groups. Bacteremia prediction using machine learning technology appeared possible for acute infectious diseases. This model was more suitable especially to pneumonia caused by Acinetobacter baumannii. From the 24-h blood culture data, bacteremia was predictable by substituting only the continuously variable values.
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12
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Spoto S, Lupoi DM, Valeriani E, Fogolari M, Locorriere L, Beretta Anguissola G, Battifoglia G, Caputo D, Coppola A, Costantino S, Ciccozzi M, Angeletti S. Diagnostic Accuracy and Prognostic Value of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Septic Patients outside the Intensive Care Unit. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:medicina57080811. [PMID: 34441017 PMCID: PMC8399559 DOI: 10.3390/medicina57080811] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/29/2021] [Accepted: 07/31/2021] [Indexed: 12/29/2022]
Abstract
Background and Objectives: The aim of this study was to evaluate the diagnostic accuracy and prognostic value of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios and to compare them with other biomarkers and clinical scores of sepsis outside the intensive care unit. Materials and methods: In this retrospective study, 251 patients with sepsis and 126 patients with infection other than sepsis were enrolled. NLR and PLR were calculated as the ratio between absolute values of neutrophils, lymphocytes, and platelets by complete blood counts performed on whole blood by Sysmex XE-9000 (Dasit, Italy) following the manufacturer’s instruction. Results: The best NLR value in diagnosis of sepsis was 7.97 with sensibility, specificity, AUC, PPV, and NPV of 64.26%, 80.16%, 0.74 (p < 0.001), 86.49%, and 53.18%, respectively. The diagnostic role of NLR significantly increases when PLR, C-reactive protein (PCR), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) values, as well as systemic inflammatory re-sponse syndrome (SIRS), sequential organ failure assessment (SOFA), and quick-sequential organ failure assessment (qSOFA) scores, were added to the model. The best value of NLR in predicting 90-day mortality was 9.05 with sensibility, specificity, AUC, PPV, and NPV of 69.57%, 61.44%, 0.66 (p < 0.0001), 28.9%, and 89.9%, respectively. Sensibility, specificity, AUC, PPV, and NPV of NLR increase if PLR, PCR, PCT, MR-proADM, SIRS, qSOFA, and SOFA scores are added to NLR. Conclusions: NLR and PLR represent a widely useful and cheap tool in diagnosis and in predict-ing 90-day mortality in patients with sepsis.
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Affiliation(s)
- Silvia Spoto
- Diagnostic and Therapeutic Medicine Department, University Campus Bio-Medico of Rome, 00128 Roma, Italy; (S.S.); (D.M.L.); (E.V.); (L.L.); (G.B.A.); (G.B.); (S.C.)
| | - Domenica Marika Lupoi
- Diagnostic and Therapeutic Medicine Department, University Campus Bio-Medico of Rome, 00128 Roma, Italy; (S.S.); (D.M.L.); (E.V.); (L.L.); (G.B.A.); (G.B.); (S.C.)
| | - Emanuele Valeriani
- Diagnostic and Therapeutic Medicine Department, University Campus Bio-Medico of Rome, 00128 Roma, Italy; (S.S.); (D.M.L.); (E.V.); (L.L.); (G.B.A.); (G.B.); (S.C.)
| | - Marta Fogolari
- Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, 00128 Roma, Italy;
- Correspondence: ; Tel.: +39-0622-541-1461
| | - Luciana Locorriere
- Diagnostic and Therapeutic Medicine Department, University Campus Bio-Medico of Rome, 00128 Roma, Italy; (S.S.); (D.M.L.); (E.V.); (L.L.); (G.B.A.); (G.B.); (S.C.)
| | - Giuseppina Beretta Anguissola
- Diagnostic and Therapeutic Medicine Department, University Campus Bio-Medico of Rome, 00128 Roma, Italy; (S.S.); (D.M.L.); (E.V.); (L.L.); (G.B.A.); (G.B.); (S.C.)
| | - Giulia Battifoglia
- Diagnostic and Therapeutic Medicine Department, University Campus Bio-Medico of Rome, 00128 Roma, Italy; (S.S.); (D.M.L.); (E.V.); (L.L.); (G.B.A.); (G.B.); (S.C.)
| | - Damiano Caputo
- Department of Surgery, University Campus Bio-Medico of Rome, 00128 Roma, Italy; (D.C.); (A.C.)
| | - Alessandro Coppola
- Department of Surgery, University Campus Bio-Medico of Rome, 00128 Roma, Italy; (D.C.); (A.C.)
| | - Sebastiano Costantino
- Diagnostic and Therapeutic Medicine Department, University Campus Bio-Medico of Rome, 00128 Roma, Italy; (S.S.); (D.M.L.); (E.V.); (L.L.); (G.B.A.); (G.B.); (S.C.)
| | - Massimo Ciccozzi
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, 00128 Roma, Italy;
| | - Silvia Angeletti
- Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, 00128 Roma, Italy;
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13
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Development and validation of a novel sepsis biomarker based on amino acid profiling. Clin Nutr 2021; 40:3668-3676. [PMID: 34130013 DOI: 10.1016/j.clnu.2021.05.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 05/12/2021] [Accepted: 05/14/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Sepsis is a potentially fatal condition influenced by pathogens and host factors. Current sepsis biomarkers such as white blood cell count and C-reactive protein and procalcitonin levels show unsatisfactory performance in terms of diagnostic sensitivity and specificity in clinical practice. Thus, we developed and validated a new sepsis biomarker based on amino acid profiling. METHODS We used two independent groups. The training and validation groups included 161 and 22 healthy controls, 123 and 50 patients with systemic inflammatory response syndrome, and 115 and 45 patients with sepsis, respectively. Using mass spectrometry, we measured and analyzed serum amino acid levels to select candidate amino acids that could differentiate sepsis from other conditions. Then, several possible multivariate indexes were developed by generating formulae with different combinations of candidate amino acids. The formula showing the best performance was selected and validated further. RESULTS Kynurenine, tryptophan, phenylalanine, arginine, aspartic acid, glutamic acid, and glutamine were selected as candidate amino acids. Ten possible formulae were generated, and the formula with the highest diagnostic performance, which included kynurenine, tryptophan, phenylalanine, and arginine, was selected. In the validation group, the area under the receiving operating characteristic curve of the selected multivariate index (0.931) was similar to that of procalcitonin (0.945). Moreover, the generated multivariate index showed potential as a prognostic marker. CONCLUSIONS Serum amino acid composition in patients with sepsis differs significantly from that in healthy individuals and patients with inflammation only. The newly developed multivariate index is expected to be implementable as a sepsis biomarker in clinical practice in the near future.
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14
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Spoto S, Nobile E, Carnà EPR, Fogolari M, Caputo D, De Florio L, Valeriani E, Benvenuto D, Costantino S, Ciccozzi M, Angeletti S. Best diagnostic accuracy of sepsis combining SIRS criteria or qSOFA score with Procalcitonin and Mid-Regional pro-Adrenomedullin outside ICU. Sci Rep 2020; 10:16605. [PMID: 33024218 PMCID: PMC7538435 DOI: 10.1038/s41598-020-73676-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 09/03/2020] [Indexed: 12/17/2022] Open
Abstract
Early diagnosis and treatment significantly reduce sepsis mortality. Currently, no gold standard has been yet established to diagnose sepsis outside the ICU. The aim of the study was to evaluate the diagnostic accuracy of sepsis defined by SIRS Criteria of 1991, Second Consensus Conference Criteria of 2001, modified Second Consensus Conference Criteria of 2001 (obtaining SIRS Criteria and SOFA score), Third Consensus Conference of 2016, in addition to the dosage of Procalcitonin (PCT) and MR-pro-Adrenomedullin (MR-proADM). In this prospective study, 209 consecutive patients with clinical diagnosis of sepsis were enrolled (May 2014-June 2018) outside intensive care unit (ICU) setting. A diagnostic protocol could include SIRS criteria or qSOFA score evaluation, rapid testing of PCT and MR-proADM, and SOFA score calculation for organ failure definition. Using this approach outside the ICU, a rapid diagnostic and prognostic evaluation could be achieved, also in the case of negative SIRS, qSOFA or SOFA scores with high post-test probability to reduce mortality and improve outcomes.
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Affiliation(s)
- Silvia Spoto
- Diagnostic and Therapeutic Medicine Department, University Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Rome, Italy.
| | - Edoardo Nobile
- Diagnostic and Therapeutic Medicine Department, University Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Rome, Italy
| | - Emanuele Paolo Rafano Carnà
- Diagnostic and Therapeutic Medicine Department, University Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Rome, Italy
| | - Marta Fogolari
- Unit of Clinical Laboratory Science, University Campus Bio-Medico, Rome, Italy
| | - Damiano Caputo
- Department of Surgery, University Campus Bio-Medico, Rome, Italy
| | - Lucia De Florio
- Unit of Clinical Laboratory Science, University Campus Bio-Medico, Rome, Italy
| | - Emanuele Valeriani
- Diagnostic and Therapeutic Medicine Department, University Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Rome, Italy
| | - Domenico Benvenuto
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico, Rome, Italy
| | - Sebastiano Costantino
- Diagnostic and Therapeutic Medicine Department, University Campus Bio-Medico, Via Alvaro del Portillo 200, 00128, Rome, Italy
| | - Massimo Ciccozzi
- Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico, Rome, Italy
| | - Silvia Angeletti
- Unit of Clinical Laboratory Science, University Campus Bio-Medico, Rome, Italy
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15
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Fabre V, Sharara SL, Salinas AB, Carroll KC, Desai S, Cosgrove SE. Does This Patient Need Blood Cultures? A Scoping Review of Indications for Blood Cultures in Adult Nonneutropenic Inpatients. Clin Infect Dis 2020; 71:1339-1347. [PMID: 31942949 DOI: 10.1093/cid/ciaa039] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 01/13/2020] [Indexed: 12/15/2022] Open
Abstract
Guidance regarding indications for initial or follow-up blood cultures is limited. We conducted a scoping review of articles published between January 2004 and June 2019 that reported the yield of blood cultures and/or their impact in the clinical management of fever and common infectious syndromes in nonneutropenic adult inpatients. A total of 2893 articles were screened; 50 were included. Based on the reported incidence of bacteremia, syndromes were categorized into low, moderate, and high pretest probability of bacteremia. Routine blood cultures are recommended in syndromes with a high likelihood of bacteremia (eg, endovascular infections) and those with moderate likelihood when cultures from the primary source of infection are unavailable or when prompt initiation of antibiotics is needed prior to obtaining primary source cultures. In syndromes where blood cultures are low-yield, blood cultures can be considered for patients at risk of adverse events if a bacteremia is missed (eg, patient with pacemaker and severe purulent cellulitis). If a patient has adequate source control and risk factors or concern for endovascular infection are not present, most streptococci or Enterobacterales bacteremias do not require routine follow-up blood cultures.
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Affiliation(s)
- Valeria Fabre
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Sima L Sharara
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Alejandra B Salinas
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Karen C Carroll
- Department of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Sanjay Desai
- Department of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Sara E Cosgrove
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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16
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17
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Rothe K, Wantia N, Spinner CD, Schneider J, Lahmer T, Waschulzik B, Schmid RM, Busch DH, Katchanov J. Antimicrobial resistance of bacteraemia in the emergency department of a German university hospital (2013-2018): potential carbapenem-sparing empiric treatment options in light of the new EUCAST recommendations. BMC Infect Dis 2019; 19:1091. [PMID: 31888581 PMCID: PMC6937826 DOI: 10.1186/s12879-019-4721-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 12/22/2019] [Indexed: 12/21/2022] Open
Abstract
Background This study investigated predominant microorganisms causing community-onset bacteraemia at the medical emergency department (ED) of a tertiary-care university hospital in Germany from 2013 to 2018 and their antimicrobial susceptibility patterns. Methods Antimicrobial resistance patterns in patients with positive blood cultures presenting to an internal medicine ED were retrospectively analysed. Results Blood cultures were obtained at 5191 of 66,879 ED encounters, with 1013 (19.5%) positive results, and true positive results at 740 encounters (diagnostic yield, 14.3%). The most frequently isolated relevant microorganisms were Enterobacterales (n = 439, 59.3%), Staphylococcus aureus (n = 92, 12.4%), Streptococcus pneumoniae (n = 34, 4.6%), Pseudomonas aeruginosa (n = 32, 4.3%), Streptococcus pyogenes (n = 16, 2.2%), Enterococcus faecalis (n = 18, 2.4%), and Enterococcus faecium (n = 12, 1.6%). Antimicrobial susceptibility testing revealed a high proportion of resistance against ampicillin-sulbactam in Enterobacterales (42.2%). The rate of methicillin-resistant Staphylococcus aureus was low (0.4%). Piperacillin-tazobactam therapy provided coverage for 83.2% of all relevant pathogens using conventional breakpoints. Application of the new European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations increased the percentage of susceptible isolates to high-dose piperacillin-tazobactam to 92.8% (p < 0.001). Broad-spectrum carbapenems would only cover an additional 4.8%. The addition of vancomycin or linezolid extended coverage by just 1.7%. Conclusions Using an ureidopenicillin-beta-lactamase inhibitor combination at the high dose suggested by the new EUCAST recommendations provided nearly 93% coverage for relevant pathogens in patients with suspected bloodstream infection in our cohort. This might offer a safe option to reduce the empiric use of carbapenems. Our data support the absence of a general need for glycopeptides or oxazolidinones in empiric treatment.
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Affiliation(s)
- Kathrin Rothe
- Technical University of Munich, School of Medicine, Institute for Medical Microbiology, Immunology and Hygiene, Trogerstr. 30, 81675, Munich, Germany. .,German Centre for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
| | - Nina Wantia
- Technical University of Munich, School of Medicine, Institute for Medical Microbiology, Immunology and Hygiene, Trogerstr. 30, 81675, Munich, Germany.,German Centre for Infection Research (DZIF), Partner Site Munich, Munich, Germany
| | - Christoph D Spinner
- German Centre for Infection Research (DZIF), Partner Site Munich, Munich, Germany.,Department of Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Jochen Schneider
- German Centre for Infection Research (DZIF), Partner Site Munich, Munich, Germany.,Department of Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Tobias Lahmer
- German Centre for Infection Research (DZIF), Partner Site Munich, Munich, Germany.,Department of Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Birgit Waschulzik
- Institute of Medical Informatics, Statistics, and Epidemiology, Technical University of Munich, Munich, Germany
| | - Roland M Schmid
- German Centre for Infection Research (DZIF), Partner Site Munich, Munich, Germany.,Department of Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
| | - Dirk H Busch
- Technical University of Munich, School of Medicine, Institute for Medical Microbiology, Immunology and Hygiene, Trogerstr. 30, 81675, Munich, Germany.,German Centre for Infection Research (DZIF), Partner Site Munich, Munich, Germany
| | - Juri Katchanov
- German Centre for Infection Research (DZIF), Partner Site Munich, Munich, Germany.,Department of Medicine II, Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany
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18
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Imai Y, Taniguchi K, Iida R, Nitta M, Uchiyma K, Takasu A. Diagnostic accuracy of presepsin in predicting bacteraemia in elderly patients admitted to the emergency department: prospective study in Japan. BMJ Open 2019; 9:e030421. [PMID: 31843822 PMCID: PMC6924853 DOI: 10.1136/bmjopen-2019-030421] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE Early prediction of bacteraemia in the elederly is needed in the emergency department (ED). DESIGN, SETTING AND PARTICIPANTS A prospective study in Japan; single-centre trial in patients who satisfied the sepsis criteria was conducted between September 2014 and March 2016. Forty-six elderly patients aged ≥70 years were included. The study protocol was approved by the ethics committee of Osaka Medical College. Ethics Committee approval number was 1585. INTERVENTIONS Blood sampling to evaluate C-reactive protein (CRP), procalcitonin (PCT) and presepsin plasma levels; two sets of blood sampling for bacterial cultures; and evaluations of the Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation scores were performed on arrival at the ED. The results were compared between patients with bacteraemia and those without bacteraemia. MAIN OUTCOME MEASURE The accuracy of detecting bacteraemia. RESULTS The presepsin value was significantly higher in the bacteraemia group than in the non-bacteraemia group (866.6±184.6 vs 639.9±137.1 pg/mL, p=0.03). The PCT and CRP did not significantly differ between the groups. The area under the receiver operating characteristic curve values were not significantly different among presepsin (0.69), PCT (0.61) and CRP (0.53). Multivariate analysis showed that presepsin was independently associated with bacteraemia (OR 8.84; 95% CI 0.95 to 81.79; p=0.02). CONCLUSION Presepsin could be a good biomarker to predict bacteraemia in elderly patients with sepsis criteria admitted to the ED.
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Affiliation(s)
- Yoshiro Imai
- Department of Emergency Medicine, Osaka Medical College, Takatsuki, Japan
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Japan
| | - Kohei Taniguchi
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Japan
| | - Ryo Iida
- Department of Emergency Medicine, Osaka Medical College, Takatsuki, Japan
| | - Masahiko Nitta
- Department of Emergency Medicine, Osaka Medical College, Takatsuki, Japan
| | - Kazuhisa Uchiyma
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Japan
| | - Akira Takasu
- Department of Emergency Medicine, Osaka Medical College, Takatsuki, Japan
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19
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Schwarzenbacher J, Kuhn SO, Vollmer M, Scheer C, Fuchs C, Rehberg S, Balau V, Hahnenkamp K, Bohnert JA, Gründling M. On-site blood culture incubation shortens the time to knowledge of positivity and microbiological results in septic patients. PLoS One 2019; 14:e0225999. [PMID: 31826003 PMCID: PMC6905563 DOI: 10.1371/journal.pone.0225999] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 11/19/2019] [Indexed: 12/29/2022] Open
Abstract
Introduction To determine whether on-site incubation of blood cultures at the intensive care unit (ICU) improves not only the time to incubation but also time to positivity, time to knowledge of positivity and time to results (identification and antibiotic susceptibility testing). Methods This observational single-centre study in ICU patients with severe sepsis and septic shock investigated the impact of blood culture incubation immediately on-site at the ICU (ICU group) by comparison with traditional processing in a remote laboratory (LAB group) on different time intervals of blood culture diagnostics from obtaining blood to clinician notification of final result. The effect of on-site incubation was evaluated in Kaplan-Meier estimates for the time to positivity, time to knowledge of positivity and time to microbiological results and a linear mixed model was built. Results A total of 3,549 blood culture sets from 657 ICU patients were analysed: 2,381 in the LAB group and 1,168 in the ICU group. Overall, 660 (18.6%) blood culture sets were positive and 2,889 (81.4%) sets remained negative. On-site incubation was associated with reduced time to knowledge of positivity (46.9 h [CI 43.4–50.8 h] vs. 28.0 h [CI 23.6–32.2 h], p < 0.001) and reduced time to result (61.4 h [CI 58.4–64.8 h] vs. 42.1 h [CI 39.1–47.5 h], p < 0.001). In blood cultures processed instantaneously at the ICU compared to incubation in the remote laboratory within 4 h, the time to microbiological result was significantly reduced by 8.5 h (p < 0.001). Pre-existing anti-infective therapy had no significant impact on diagnostic time intervals. Conclusions Instantaneous incubation of blood cultures in the ICU compared to incubation in a remote laboratory significantly improves time to knowledge to positivity and time to result. These effects are even more pronounced during off-hours of the microbiological laboratory. The results underline the importance of 24/7 diagnostics to provide round-the-clock processing of blood culture samples in patients with sepsis and septic shock and an immediate to communication of the results to the clinicians.
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Affiliation(s)
| | - Sven-Olaf Kuhn
- Department of Anesthesiology, University Hospital of Greifswald, Greifswald, Germany
- * E-mail:
| | - Marcus Vollmer
- Institute of Bioinformatics, University Medicine Greifswald, Greifswald, Germany
| | - Christian Scheer
- Department of Anesthesiology, University Hospital of Greifswald, Greifswald, Germany
| | - Christian Fuchs
- Department of Anesthesiology, University Hospital of Greifswald, Greifswald, Germany
| | - Sebastian Rehberg
- Department of Anesthesiology, Intensive Care, Emergency Medicine, Transfusion Medicine and Pain Therapy, Protestant Hospital of the Bethel Foundation, Bielefeld, Germany
| | - Veronika Balau
- IMD Labor Greifswald, MVZ Labor Greifswald GmbH, Greifswald, Germany
| | - Klaus Hahnenkamp
- Department of Anesthesiology, University Hospital of Greifswald, Greifswald, Germany
| | - Jürgen A. Bohnert
- Friedrich Loeffler Institute of Microbiology, University Hospital Greifswald, Greifswald, Germany
| | - Matthias Gründling
- Department of Anesthesiology, University Hospital of Greifswald, Greifswald, Germany
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20
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Lee KH, Dong JJ, Jeong SJ, Chae MH, Lee BS, Kim HJ, Ko SH, Song YG. Early Detection of Bacteraemia Using Ten Clinical Variables with an Artificial Neural Network Approach. J Clin Med 2019; 8:jcm8101592. [PMID: 31581716 PMCID: PMC6832527 DOI: 10.3390/jcm8101592] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 09/21/2019] [Accepted: 09/23/2019] [Indexed: 12/20/2022] Open
Abstract
An adequate model for predicting bacteraemia has not yet been developed. This study aimed to evaluate the performance of an artificial neural network (ANN)-based prediction model in comparison with previous statistical models. The performance of multi-layer perceptron (MLP), a representative ANN model, was verified via comparison with a non-neural network model. A total of 1260 bacteraemia episodes were identified in 13,402 patients. In MLP with 128 hidden layer nodes, the area under the receiver operating characteristic curve (AUC) of the prediction performance was 0.729 (95% confidence interval [CI]; 0.712–0.728), while in MLP with 256 hidden layer nodes, it was 0.727 (95% CI; 0.713–0.727). In a conventional Bayesian statistical method, the AUC was 0.7. The aforementioned two MLP models exhibited the highest sensitivity (0.810). The ranking of clinical variables was used to describe the influential power of the prediction. Serum alkaline phosphatase was one of the most influential clinical variables, and one-out search was the best ranking method for measuring the influence of the clinical variables. Furthermore, adding variables beyond the 10 top-ranking ones did not significantly affect the prediction of bacteraemia. The ANN model is not inferior to conventional statistical approaches. Bacteraemia can be predicted using only the top 10 clinical variables determined by a ranking method, and the model can be used in clinical practice by applying real-time monitoring.
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Affiliation(s)
- Kyoung Hwa Lee
- Division of Infectious Diseases, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 06273, Korea.
| | - Jae June Dong
- Department of Family Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea.
| | - Su Jin Jeong
- Division of Infectious Diseases, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.
| | - Myeong-Hun Chae
- Selvas Artificial Intelligence Incorporate, Seoul 08594, Korea.
| | - Byeong Soo Lee
- Selvas Artificial Intelligence Incorporate, Seoul 08594, Korea.
| | - Hong Jae Kim
- Department of Medical Information, Gangnam Severance Hospital, Seoul 06273, Korea.
| | - Sung Hun Ko
- Department of Medical Information, Gangnam Severance Hospital, Seoul 06273, Korea.
| | - Young Goo Song
- Division of Infectious Diseases, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 06273, Korea.
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21
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Li XJ, Tan EL, Zhao CP, Yan J. Accuracy of intercellular adhesion molecule-1 for diagnosing sepsis: A systematic review and meta-analysis protocol. Medicine (Baltimore) 2019; 98:e16019. [PMID: 31192950 PMCID: PMC6587476 DOI: 10.1097/md.0000000000016019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND Sepsis is a complex and life-threatening systemic disease. A positive blood culture is the criterion standard of diagnosis for sepsis; however, it does not produce results for 24 to 72 hours. Besides, the clinical manifestations of sepsis are variable and nonspecific. Therefore, a new diagnostic biomarker for diagnosis of sepsis should be developed. The present study aims to assess the diagnostic value of intercellular adhesion molecule-1 (ICAM-1) in individuals with sepsis. METHODS The literature will be searched in PubMed, EMBASE, the Cochrane Library, and Web of Science databases from the inception of each database up to June 2019. The methodological quality of eligible study will be assessed by Quality Assessment of Diagnostic Accuracy Studies tool-2 (QUADAS-2). Stata 15.1 software (version 15.1, Stata Corporation) will be used to calculate the pooled sensitivity, pooled specificity, pooled positive likelihood ratio, pooled negative likelihood ratio, pooled diagnostic odds ratio, pre-test probability, post-test probability, and summary receiver-operating characteristic curve for diagnostic value of ICAM-1. The I statistic will be used to test heterogeneity. Subgroup analysis will be used to explore the source of inconsistency. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system will be used to assess the certainty of evidence. This study will be conducted fully following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of diagnostic test accuracy. RESULTS AND CONCLUSIONS Our study will detect the potential of ICAM-1 for diagnosing the patients with sepsis and the results will be submitted to a peer-reviewed journal. DISCUSSION The evidence will indicate that ICAM-1 is a valuable biomarker for detecting sepsis. This is a protocol of systematic review and meta-analysis, so the ethical approval and patient consent are not required.
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Affiliation(s)
| | | | - Cheng-peng Zhao
- Department of Oncology, the First Hospital of Lanzhou University
| | - Juan Yan
- Clinical College of Traditonal Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
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22
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Lambregts MMC, Bernards AT, van der Beek MT, Visser LG, de Boer MG. Time to positivity of blood cultures supports early re-evaluation of empiric broad-spectrum antimicrobial therapy. PLoS One 2019; 14:e0208819. [PMID: 30601829 PMCID: PMC6314566 DOI: 10.1371/journal.pone.0208819] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Accepted: 11/25/2018] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Blood cultures are considered the gold standard to distinguish bacteremia from non-bacteremic systemic inflammation. In current clinical practice, bacteraemia is considered unlikely if blood cultures have been negative for 48-72 hours. Modern BC systems have reduced this time-to-positivity (TTP), questioning whether the time frame of 48-72 hrs is still valid. This study investigates the distribution of TTP, the probability of blood culture positivity after 24 hours, and identifies clinical predictors of prolonged TTP. METHODS Adult patients with monomicrobial bacteremia in an academic hospital were included retrospectively over a three-year period. Clinical data were retrieved from the medical records. Predictors of TTP >24 hours were determined by uni- and multivariate analyses. The residual probability of bacteremia was estimated for the scenario of negative BCs at 24 hours after bedside collection. RESULTS The cohort consisted of 801 patients, accounting for 897 episodes of bacteremia. Mean age was 65 years (IQR 54-73), 534 (59.5%) patients were male. Median TTP was 15.7 (IQR 13.5-19.3) hours. TTP was ≤24 hours in 85.3% of episodes. Antibiotic pre-treatment (adjusted OR 1.77; 95%CI 1.14-2.74, p<0.01) was independently associated with prolonged TTP. The probability of bacteremia, if BC had remained negative for 24 hours, was 1.8% (95% CI 1.46-2.14). CONCLUSION With adequate hospital logistics, the probability of positive blood cultures after 24 hours of negative cultures was low. Combined with clinical reassessment, knowledge of this low probability may contribute to prioritization of the differential diagnosis and decisions on antimicrobial therapy. As a potential antibiotic stewardship tool, this strategy warrants further prospective investigation.
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Affiliation(s)
- Merel M. C. Lambregts
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - Alexandra T. Bernards
- Department of Microbiology, Leiden University Medical Center, Leiden, The Netherlands
| | | | - Leo G. Visser
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - Mark G. de Boer
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
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23
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Huerta LE, Rice TW. Pathologic Difference between Sepsis and Bloodstream Infections. J Appl Lab Med 2018; 3:654-663. [PMID: 31639733 DOI: 10.1373/jalm.2018.026245] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 10/09/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND Sepsis, defined as life-threatening organ failure caused by a dysregulated host response to infection, is a major cause of morbidity and mortality in hospitalized patients. Understanding the features that distinguish sepsis from bloodstream infections (and other types of infection) can help clinicians appropriately and efficiently target their diagnostic workup and therapeutic interventions, especially early in the disease course. CONTENT In this review, sepsis and bloodstream infections are both defined, with a focus on recent changes in the sepsis definition. The molecular and cellular pathways involved in sepsis pathogenesis are described, including cytokines, the coagulation cascade, apoptosis, and mitochondrial dysfunction. Laboratory tests that have been evaluated for their utility in sepsis diagnosis are discussed. SUMMARY Sepsis is defined not only by the presence of an infection, but also by organ dysfunction from a dysregulated host response to that infection. Numerous pathways, including proinflammatory and antiinflammatory cytokines, the coagulation cascade, apoptosis, and mitochondrial dysfunction, help determine if a bloodstream infection (or any other infection) progresses to sepsis. Many biomarkers, including C-reactive protein, procalcitonin, and lactic acid have been evaluated for use in sepsis diagnosis, although none are routinely recommended for that purpose in current clinical practice. While some laboratory tests can help distinguish the 2, the presence of organ dysfunction is what separates sepsis from routine infections.
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Affiliation(s)
- Luis E Huerta
- Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN.
| | - Todd W Rice
- Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN
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24
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Tan M, Lu Y, Jiang H, Zhang L. The diagnostic accuracy of procalcitonin and C‐reactive protein for sepsis: A systematic review and meta‐analysis. J Cell Biochem 2018; 120:5852-5859. [PMID: 30417415 DOI: 10.1002/jcb.27870] [Citation(s) in RCA: 125] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Accepted: 09/19/2018] [Indexed: 01/28/2023]
Affiliation(s)
- Meichun Tan
- Department of Emergency (EICU) Shanghai Baoshan Traditional Chinese Medicine—Integrated Hospital Shanghai China
| | - Yunxia Lu
- Department of Emergency (EICU) Shanghai Baoshan Traditional Chinese Medicine—Integrated Hospital Shanghai China
| | - Hao Jiang
- Department of Emergency (EICU) Shanghai Baoshan Traditional Chinese Medicine—Integrated Hospital Shanghai China
| | - Liandong Zhang
- Department of Emergency (EICU) Shanghai Baoshan Traditional Chinese Medicine—Integrated Hospital Shanghai China
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25
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Machine learning for fast identification of bacteraemia in SIRS patients treated on standard care wards: a cohort study. Sci Rep 2018; 8:12233. [PMID: 30111827 PMCID: PMC6093921 DOI: 10.1038/s41598-018-30236-9] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 07/16/2018] [Indexed: 01/09/2023] Open
Abstract
Bacteraemia is a life-threating condition requiring immediate diagnostic and therapeutic actions. Blood culture (BC) analyses often result in a low true positive result rate, indicating its improper usage. A predictive model might assist clinicians in deciding for whom to conduct or to avoid BC analysis in patients having a relevant bacteraemia risk. Predictive models were established by using linear and non-linear machine learning methods. To obtain proper data, a unique data set was collected prior to model estimation in a prospective cohort study, screening 3,370 standard care patients with suspected bacteraemia. Data from 466 patients fulfilling two or more systemic inflammatory response syndrome criteria (bacteraemia rate: 28.8%) were finally used. A 29 parameter panel of clinical data, cytokine expression levels and standard laboratory markers was used for model training. Model tuning was performed in a ten-fold cross validation and tuned models were validated in a test set (80:20 random split). The random forest strategy presented the best result in the test set validation (ROC-AUC: 0.729, 95%CI: 0.679–0.779). However, procalcitonin (PCT), as the best individual variable, yielded a similar ROC-AUC (0.729, 95%CI: 0.679–0.779). Thus, machine learning methods failed to improve the moderate diagnostic accuracy of PCT.
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26
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New Technologies for the Diagnosis of Infection. DIAGNOSTIC PATHOLOGY OF INFECTIOUS DISEASE 2018. [PMCID: PMC7152403 DOI: 10.1016/b978-0-323-44585-6.00006-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Cha JK, Kwon KH, Byun SJ, Ryoo SR, Lee JH, Chung JW, Huh HJ, Chae SL, Park SY. Clinical value of procalcitonin for suspected nosocomial bloodstream infection. Korean J Intern Med 2018; 33:176-184. [PMID: 29108401 PMCID: PMC5768543 DOI: 10.3904/kjim.2016.119] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Revised: 09/09/2016] [Accepted: 09/13/2016] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND/AIMS Procalcitonin (PCT) may prove to be a useful marker to exclude or predict bloodstream infection (BSI). However, the ability of PCT levels to differentiate BSI from non-BSI episodes has not been evaluated in nosocomial BSI. METHODS We retrospectively reviewed the medical records of patients ≥ 18 years of age with suspected BSI that developed more than 48 hours after admission. RESULTS Of the 785 included patients, 105 (13.4%) had BSI episodes and 680 (86.6%) had non-BSI episodes. The median serum PCT level was elevated in patients with BSI as compared with those without BSI (0.65 ng/mL vs. 0.22 ng/mL, p = 0.001). The optimal PCT cut-off value of BSI was 0.27 ng/mL, with a corresponding sensitivity of 74.6% (95% confidence interval [CI], 66.4% to 81.7%) and a specificity of 56.5% (95% CI, 52.7% to 60.2%). The area under curve of PCT (0.692) was significantly larger than that of C-reactive protein (CRP; 0.526) or white blood cell (WBC) count (0.518). However, at the optimal cut-off value, PCT failed to predict BSI in 28 of 105 cases (26.7%). The PCT level was significantly higher in patients with an eGFR < 60 mL/min/1.73 m2 than in those with an eGFR ≥ 60 mL/min/1.73 m2 (0.68 vs. 0.17, p = 0.01). CONCLUSIONS PCT was more useful for predicting nosocomial BSI than CRP or WBC count. However, the diagnostic accuracy of predicting BSI remains inadequate. Thus, PCT is not recommended as a single diagnostic tool to avoid taking blood cultures in the nosocomial setting.
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Affiliation(s)
- Joo Kyoung Cha
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Ki Hwan Kwon
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Seung Joo Byun
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Soo Ryeong Ryoo
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Jeong Hyeon Lee
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Jae-Woo Chung
- Department of Laboratory Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Hee Jin Huh
- Department of Laboratory Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Seok Lae Chae
- Department of Laboratory Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Seong Yeon Park
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
- Correspondence to Seong Yeon Park, M.D. Division of Infectious Diseases, Department of Internal Medicine, Dongguk University Ilsan Hospital, 27 Dongguk-ro, Ilsandong-gu, Goyang 10326, Korea Tel: +82-31-961-7140 Fax: +82-31-961-8331 E-mail:
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Wiehr S, Warnke P, Rolle AM, Schütz M, Oberhettinger P, Kohlhofer U, Quintanilla-Martinez L, Maurer A, Thornton C, Boschetti F, Reischl G, Autenrieth IB, Pichler BJ, Autenrieth SE. New pathogen-specific immunoPET/MR tracer for molecular imaging of a systemic bacterial infection. Oncotarget 2017; 7:10990-1001. [PMID: 26934329 PMCID: PMC4905453 DOI: 10.18632/oncotarget.7770] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Accepted: 02/20/2016] [Indexed: 01/12/2023] Open
Abstract
The specific and rapid detection of Enterobacteriaceae, the most frequent cause of gram-negative bacterial infections in humans, remains a major challenge. We developed a non-invasive method to rapidly detect systemic Yersinia enterocolitica infections using immunoPET (antibody-targeted positron emission tomography) with [64Cu]NODAGA-labeled Yersinia-specific polyclonal antibodies targeting the outer membrane protein YadA. In contrast to the tracer [18F]FDG, [64Cu]NODAGA-YadA uptake co-localized in a dose dependent manner with bacterial lesions of Yersinia-infected mice, as detected by magnetic resonance (MR) imaging. This was accompanied by elevated uptake of [64Cu]NODAGA-YadA in infected tissues, in ex vivo biodistribution studies, whereas reduced uptake was observed following blocking with unlabeled anti-YadA antibody. We show, for the first time, a bacteria-specific, antibody-based, in vivo imaging method for the diagnosis of a Gram-negative enterobacterial infection as a proof of concept, which may provide new insights into pathogen-host interactions.
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Affiliation(s)
- Stefan Wiehr
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Philipp Warnke
- Institute of Medical Microbiology and Hygiene, Eberhard Karls University, Tübingen, Germany.,Institute of Medical Microbiology, Virology and Hygiene, Rostock University Hospital, Rostock, Germany
| | - Anna-Maria Rolle
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Monika Schütz
- Institute of Medical Microbiology and Hygiene, Eberhard Karls University, Tübingen, Germany
| | - Philipp Oberhettinger
- Institute of Medical Microbiology and Hygiene, Eberhard Karls University, Tübingen, Germany
| | - Ursula Kohlhofer
- Institute of Pathology, Eberhard Karls University Tübingen, Tübingen, Germany
| | | | - Andreas Maurer
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Christopher Thornton
- Biosciences and ISCA Diagnostics Ltd., University of Exeter, Exeter, United Kingdom
| | | | - Gerald Reischl
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Ingo B Autenrieth
- Institute of Medical Microbiology and Hygiene, Eberhard Karls University, Tübingen, Germany
| | - Bernd J Pichler
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Stella E Autenrieth
- Department of Internal Medicine II, University Hospital Tübingen, Tübingen, Germany
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29
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Chin-Hong PV. Still ironing out the best way to diagnose infection. Liver Transpl 2017; 23:1499-1500. [PMID: 29087021 DOI: 10.1002/lt.24967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 10/30/2017] [Indexed: 01/13/2023]
Affiliation(s)
- Peter V Chin-Hong
- Division of Infectious Diseases, University of California, San Francisco San Francisco, CA
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30
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Bahloul M, Baccouch N, Chtara K, Turki M, Turki O, Hamida CB, Chelly H, Ayedi F, Chaari A, Bouaziz M. Value of Serum Cholinesterase Activity in the Diagnosis of Septic Shock Due to Bacterial Infections. J Intensive Care Med 2017; 32:346-352. [DOI: 10.1177/0885066616636549] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
Background: We aimed to investigate whether serum cholinesterase (SChE) activity can be helpful for the diagnosis of septic shock and to evaluate its usefulness in comparison with procalcitonin (PCT) and C-reactive protein (CRP). Methods: A prospective single-blinded study conducted in an intensive care unit of university hospital. Patients were classified as having cardiogenic shock, septic shock, or hemorrhagic shock. We also included a control group without neither hemodynamic instability nor sepsis. For all included patients, SChE, PCT, and CRP were simultaneously sampled. Results: The comparison of sepsis markers between all groups showed that the mean values of PCT and CRP were significantly higher in patients with septic shock. However, SChE activity was significantly lower in this group. The SChE activity was found to be more accurate than PCT and CRP for the diagnosis of septic shock. In fact, an SChE activity ≤ 4000 UI/L predicted the diagnosis of septic shock with a sensitivity of 78%, a specificity of 89%, a predictive negative value of 97%, and a predictive positive value of 65%. However, the prognostic value of SChE activity was poor in multivariate analysis. Conclusion: The SChE activity level was significantly decreased in patients with septic shock. However, its prognostic value is poor. Our results suggest that SChE activity is useful for the diagnosis of septic shock. Further studies are warranted to confirm our findings.
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Affiliation(s)
- Mabrouk Bahloul
- Service de Réanimation Médicale, CHU Habib Bourguiba, Sfax, Tunisie
| | - Najeh Baccouch
- Service de Réanimation Médicale, CHU Habib Bourguiba, Sfax, Tunisie
| | - Kamilia Chtara
- Service de Réanimation Médicale, CHU Habib Bourguiba, Sfax, Tunisie
| | - Mouna Turki
- Laboratoire de Biochimie, CHU Habib Bourguiba, Sfax, Tunisie
| | - Olfa Turki
- Service de Réanimation Médicale, CHU Habib Bourguiba, Sfax, Tunisie
| | | | - Hedi Chelly
- Service de Réanimation Médicale, CHU Habib Bourguiba, Sfax, Tunisie
| | - Fatma Ayedi
- Laboratoire de Biochimie, CHU Habib Bourguiba, Sfax, Tunisie
| | - Anis Chaari
- Service de Réanimation Médicale, CHU Habib Bourguiba, Sfax, Tunisie
| | - Mounir Bouaziz
- Service de Réanimation Médicale, CHU Habib Bourguiba, Sfax, Tunisie
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31
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Heredia-Rodríguez M, Bustamante-Munguira J, Lorenzo M, Gómez-Sánchez E, Álvarez FJ, Fierro I, Conejo E, Tamayo E. Procalcitonin and white blood cells, combined predictors of infection in cardiac surgery patients. J Surg Res 2017; 212:187-194. [PMID: 28550906 DOI: 10.1016/j.jss.2017.01.021] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2016] [Revised: 12/20/2016] [Accepted: 01/20/2017] [Indexed: 11/24/2022]
Abstract
BACKGROUND Sepsis is strongly associated with an increased risk of postoperative mortality, longer length of hospital stay, and elevated health care costs. Early clinical symptoms overlap with those of systemic inflammatory response syndrome, a response that commonly occurs after cardiac surgery with cardiopulmonary bypass. Since a combination of biomarkers has been demonstrated to improve the prediction of postoperative infection, the objective of the present study was to test whether the combination of C-reactive protein (CRP), white blood cells (WBC), and procalcitonin (PCT) is able to predict postoperative infection in a large cohort of cardiac surgery patients. MATERIAL AND METHODS Case-control study involving 423 patients who underwent cardiac surgery with cardiopulmonary bypass. Patients were retrospectively classified into two groups based on whether they developed severe sepsis or septic shock during the postoperative period. Blood samples for biological measurements (PCT, CRP, and WBC) were drawn on the first day in the intensive care unit, then once daily in the morning until the 10th postoperative day. RESULTS CRP median values were similar in both groups. WBC and PCT median values were significantly higher in patients with infection than without during the first 10 postoperative days. With elevation cutoffs ≤3 times (OR: 4.058; 95% CI: 2.206-7.463; P = 0.001) and ≥4 times (OR: 10.274, 95% CI: 3.690-28.604; P < 0.001), the median value for PCT (1.7 ng/mL) and/or WBC (13,000 cells/mm3) on the second postoperative day was significantly associated with the development of infection. CONCLUSIONS The goal of this study was to use a large cohort of cardiac surgery patients to ensure that the results were representative of this population. The combination of PCT and WBC levels over the first three postoperative days was able to predict postoperative infection within the 30 d following cardiac surgery.
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Affiliation(s)
- María Heredia-Rodríguez
- BioCritic. Group for biomedical Research in Critical Care Medicine, Valladolid, Spain; Department of Anesthesiology and Surgical Critical Care, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | | | - Mario Lorenzo
- Department of Anesthesiology and Surgical Critical Care, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - Esther Gómez-Sánchez
- BioCritic. Group for biomedical Research in Critical Care Medicine, Valladolid, Spain; Department of Anesthesiology and Surgical Critical Care, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - F Javier Álvarez
- Department of Pharmacology and Therapeutics, Valladolid University Physicians College, Valladolid, Spain
| | - Inmaculada Fierro
- Department of Pharmacology and Therapeutics, Valladolid University Physicians College, Valladolid, Spain
| | - Esther Conejo
- BioCritic. Group for biomedical Research in Critical Care Medicine, Valladolid, Spain; Department of Anesthesiology and Surgical Critical Care, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - Eduardo Tamayo
- BioCritic. Group for biomedical Research in Critical Care Medicine, Valladolid, Spain; Department of Anesthesiology and Surgical Critical Care, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
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Wiehr S, Rolle AM, Warnke P, Kohlhofer U, Quintanilla-Martinez L, Reischl G, Autenrieth IB, Pichler BJ, Autenrieth SE. The Positron Emission Tomography Tracer 3'-Deoxy-3'-[18F]Fluorothymidine ([18F]FLT) Is Not Suitable to Detect Tissue Proliferation Induced by Systemic Yersinia enterocolitica Infection in Mice. PLoS One 2016; 11:e0164163. [PMID: 27701464 PMCID: PMC5049782 DOI: 10.1371/journal.pone.0164163] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 09/20/2016] [Indexed: 11/25/2022] Open
Abstract
Most frequently, gram-negative bacterial infections in humans are caused by Enterobacteriaceae and remain a major challenge in medical diagnostics. We non-invasively imaged moderate and severe systemic Yersinia enterocolitica infections in mice using the positron emission tomography (PET) tracer 3’-deoxy-3’-[18F]fluorothymidine ([18F]FLT), which is a marker of proliferation, and compared the in vivo results to the ex vivo biodistributions, bacterial loads, and histologies of the corresponding organs. Y. enterocolitica infection is detectable with histology using H&E staining and immunohistochemistry for Ki 67. [18F]FLT revealed only background uptake in the spleen, which is the main manifestation site of systemic Y. enterocolitica-infected mice. The uptake was independent of the infection dose. Antibody-based thymidine kinase 1 (Tk-1) staining confirmed the negative [18F]FLT-PET data. Histological alterations of spleen tissue, observed via Ki 67-antibody-based staining, can not be detected by [18F]FLT-PET in this model. Thus, the proliferation marker [18F]FLT is not a suitable tracer for the diagnosis of systemic Y. enterocolitica infection in the C57BL/6 animal model of yersiniosis.
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Affiliation(s)
- Stefan Wiehr
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Anna-Maria Rolle
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Philipp Warnke
- Institute of Medical Microbiology and Hygiene, Eberhard Karls University Tübingen, Tübingen, Germany
- Institute of Medical Microbiology, Virology and Hygiene, University Medicine Rostock, Rostock, Germany
| | - Ursula Kohlhofer
- Institute of Pathology, Eberhard Karls University Tübingen, Tübingen, Germany
| | | | - Gerald Reischl
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Ingo B. Autenrieth
- Institute of Medical Microbiology and Hygiene, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Bernd J. Pichler
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Stella E. Autenrieth
- Department of Internal Medicine II, University Hospital Tübingen, Tübingen, Germany
- * E-mail:
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Ordonez AA, Weinstein EA, Bambarger LE, Saini V, Chang YS, DeMarco VP, Klunk MH, Urbanowski ME, Moulton KL, Murawski AM, Pokkali S, Kalinda AS, Jain SK. A Systematic Approach for Developing Bacteria-Specific Imaging Tracers. J Nucl Med 2016; 58:144-150. [PMID: 27635025 DOI: 10.2967/jnumed.116.181792] [Citation(s) in RCA: 79] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 08/22/2016] [Indexed: 12/24/2022] Open
Abstract
The modern patient is increasingly susceptible to bacterial infections including those due to multidrug-resistant organisms (MDROs). Noninvasive whole-body analysis with pathogen-specific imaging technologies can significantly improve patient outcomes by rapidly identifying a source of infection and monitoring the response to treatment, but no such technology exists clinically. METHODS We systematically screened 961 random radiolabeled molecules in silico as substrates for essential metabolic pathways in bacteria, followed by in vitro uptake in representative bacteria-Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and mycobacteria. Fluorine-labeled analogs, that could be developed as PET-based imaging tracers, were evaluated in a murine myositis model. RESULTS We identified 3 novel, nontoxic molecules demonstrating selective bacterial uptake: para-aminobenzoic acid (PABA), with uptake in all representative bacteria including Mycobacterium tuberculosis; mannitol, with selective uptake in S. aureus and E. coli; and sorbitol, accumulating only in E. coli None accumulated in mammalian cells or heat-killed bacteria, suggesting metabolism-derived specificity. In addition to an extended bacterial panel of laboratory strains, all 3 molecules rapidly accumulated in respective clinical isolates of interest including MDROs such as methicillin-resistant S. aureus, extended-spectrum β-lactamase-producing, and carbapenem-resistant Enterobacteriaceae. In a murine myositis model, fluorine-labeled analogs of all 3 molecules could rapidly detect and differentiate infection sites from sterile inflammation in mice (P = 0.03). Finally, 2-deoxy-2-[F-18]fluoro-d-sorbitol (18F-FDS) can be easily synthesized from 18F-FDG. PET, with 18F-FDS synthesized using current good manufacturing practice, could rapidly differentiate true infection from sterile inflammation to selectively localize E. coli infection in mice. CONCLUSION We have developed a systematic approach that exploits unique biochemical pathways in bacteria to develop novel pathogen-specific imaging tracers. These tracers have significant potential for clinical translation to specifically detect and localize a broad range of bacteria, including MDROs.
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Affiliation(s)
- Alvaro A Ordonez
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Edward A Weinstein
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; and
| | - Lauren E Bambarger
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Vikram Saini
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Yong S Chang
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Vincent P DeMarco
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Mariah H Klunk
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Michael E Urbanowski
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.,Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Kimberly L Moulton
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Allison M Murawski
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Supriya Pokkali
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Alvin S Kalinda
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sanjay K Jain
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, Maryland .,Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Long B, Koyfman A. Best Clinical Practice: Blood Culture Utility in the Emergency Department. J Emerg Med 2016; 51:529-539. [PMID: 27639424 DOI: 10.1016/j.jemermed.2016.07.003] [Citation(s) in RCA: 77] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2016] [Revised: 06/01/2016] [Accepted: 07/19/2016] [Indexed: 11/26/2022]
Abstract
BACKGROUND Bacteremia affects 200,000 patients per year, with the potential for significant morbidity and mortality. Blood cultures are considered the most sensitive method for detecting bacteremia and are commonly obtained in patients with fever, chills, leukocytosis, focal infections, and sepsis. OBJECTIVE We sought to provide emergency physicians with a review of the literature concerning blood cultures in the emergency department. DISCUSSION The utility of blood cultures has been a focus of controversy, prompting research evaluating effects on patient management. Bacteremia is associated with increased mortality, and blood cultures are often obtained for suspected infection. False-positive blood cultures are associated with harm, including increased duration of stay and cost. This review suggests that blood cultures are not recommended for patients with cellulitis, simple pyelonephritis, and community-acquired pneumonia, because the chance of a false-positive culture is greater than the prevalence of true positive cultures. Blood cultures are recommended for patients with sepsis, meningitis, complicated pyelonephritis, endocarditis, and health care-associated pneumonia. Clinical prediction rules that predict true positive cultures may prove useful. The clinical picture should take precedence. If cultures are obtained, two bottles of ≥7 mL should be obtained from separate peripheral sites. CONCLUSIONS Blood cultures are commonly obtained but demonstrate low yield in cellulitis, simple pyelonephritis, and community-acquired pneumonia. The Shapiro decision rule for predicting true bacteremia does show promise, but clinical gestalt should take precedence. To maximize utility, blood cultures should be obtained before antibiotic therapy begins. At least two blood cultures should be obtained from separate peripheral sites.
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Affiliation(s)
- Brit Long
- Department of Emergency Medicine, San Antonio Military Medical Center, Fort Sam Houston, Texas
| | - Alex Koyfman
- Department of Emergency Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas
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Ketchum P, Parsonnet J, Stotts L, Novitsky T, Schlain B, Bates D, AMCC SEPSIS Project. Utilization of a chromogenic Limulus amebocyte lysate blood assay in a multi-center study of sepsis. ACTA ACUST UNITED AC 2016. [DOI: 10.1177/096805199700400102] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
We conducted a prospective study of a chromogenic LAL assay in 346 patients with sepsis syndrome, as defined by a modification of the Bone criteria, and 131 healthy volunteers at eight member centers of the Academic Medical College Consortium (AMCC). We identified patients with endotoxemia (> 0.40 EU/ml) by measuring LAL-reactive material in whole blood, extracted by the Tamura nitric acid method, with the chromogenic LAL (Pyrochrome®) assay. The mean result in sepsis patients with detectable endotoxemia (n = 241) was 1.07 ± 1.57 EU/ml, and the mean result in 131 volunteers was 0.151 ± 0.113 EU/ml, with 73% of the volunteers' results falling below the detectable limit. The average incidence of endotoxemia in sepsis patients was 33%, but varied 2.7-fold among the clinical centers (range 16-44%). Assay results were repeatable when samples tested frozen at the clinical sites were compared to results on frozen samples tested at Associates of Cape Cod, Inc. (ACC). Multiple samples were obtained from 40 patients at 18-24 h interval(s). Fourteen multidraw patients (35%) were endotoxemic at one or more draw(s) and eight of these patients had two or more draws with endotoxin levels > 1.0 EU/ml. The presence of sulfa drugs gave false positive results in two patient samples. A positive LAL test did not correlate with culture-proven bacterial infection and did not significantly correlate with mortality. There was a correlation ( P = 0.014) between a patient having a positive LAL test and the presence of a fungal infection when mixed fungal and bacterial infections were included. There was no correlation with a positive LAL test when only a fungal infection was present (P = 0.425) or when only a fungal and a Gram-positive infection was present ( P = 0.087).
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Affiliation(s)
- P.A. Ketchum
- Associates of Cape Cod, Inc., Woods Hole, Massachusetts, USA
| | - J. Parsonnet
- Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
| | - L.S. Stotts
- Associates of Cape Cod, Inc., Woods Hole, Massachusetts, USA
| | - T.J. Novitsky
- Associates of Cape Cod, Inc., Woods Hole, Massachusetts, USA
| | - B. Schlain
- Brian Schlain, Inc., Boston, Massachusetts, USA
| | - D.W. Bates
- Division of General Medicine and Primary Care, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
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Fukui S, Uehara Y, Fujibayashi K, Takahashi O, Hisaoka T, Naito T. Bacteraemia predictive factors among general medical inpatients: a retrospective cross-sectional survey in a Japanese university hospital. BMJ Open 2016; 6:e010527. [PMID: 27388348 PMCID: PMC4947759 DOI: 10.1136/bmjopen-2015-010527] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVES The precise criteria for obtaining blood cultures have not been established; they depend on the physician's judgement. We examined clinical parameters to determine predictive factors of bacteraemia and the need for blood cultures among general medical inpatients. DESIGN A retrospective cross-sectional survey. SETTING A Japanese university hospital. PARTICIPANTS All general inpatients who had blood cultures taken from 1 January 2011 to 31 December 2012. MAIN MEASURES Clinical information at or just before blood culture sampling was extracted from medical charts. Factors potentially predictive of bacteraemia were analysed using Fisher's exact test, followed by multivariable logistic regression model analysis. MAIN RESULTS A total of 200 patients (male: female=119:81, 64.3±19.1 years old) comprised this study; 57 (28.5%) had positive blood culture results. Multivariable logistic regression analysis revealed that age >60 years (OR=2.75, 95% CI 1.23 to 6.48, p=0.015), female sex (OR=2.21, 95% CI 1.07 to 4.67, p=0.038), pulse rate >90 bpm (OR=5.18, 95% CI 2.25 to 12.48, p<0.001) and neutrophil percentage >80% (OR=3.61, 95% CI 1.71 to 8.00, p=0.001) were independent risk factors for positive blood culture results. The area under the receiver operating characteristic curve analysis of this model was 0.796. CONCLUSIONS Our results emphasise the importance of taking blood cultures if the pulse rate is >90 bpm, in elderly patients and in women, and for ordering a differential white cell count.
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Affiliation(s)
- Sayato Fukui
- Department of General Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - Yuki Uehara
- Department of General Medicine, Juntendo University School of Medicine, Tokyo, Japan
- Department of Infection Control Science, Faculty of Medicine, Juntendo University, Tokyo, Japan
| | - Kazutoshi Fujibayashi
- Department of General Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - Osamu Takahashi
- Center for Clinical Epidemiology, St. Luke's Life Science Institute, Tokyo, Japan
| | - Teruhiko Hisaoka
- Department of General Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - Toshio Naito
- Department of General Medicine, Juntendo University School of Medicine, Tokyo, Japan
- Department of Infection Control Science, Faculty of Medicine, Juntendo University, Tokyo, Japan
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Linsenmeyer K, Gupta K, Strymish JM, Dhanani M, Brecher SM, Breu AC. Culture if spikes? Indications and yield of blood cultures in hospitalized medical patients. J Hosp Med 2016; 11:336-40. [PMID: 26762577 DOI: 10.1002/jhm.2541] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Revised: 12/07/2015] [Accepted: 12/16/2015] [Indexed: 11/09/2022]
Abstract
BACKGROUND Although optimal utilization of blood cultures has been studied in populations, including emergency room and intensive care patients, less is known about the use of blood cultures in populations consisting exclusively of patients on a medical service. OBJECTIVE To identify the physician-selected indication and yield of blood cultures ordered after hospitalization to an acute medical service and to identify populations in which blood cultures may not be necessary. DESIGN, SETTING, AND PATIENTS A prospective cohort study was performed at a single Veterans Affairs Medical Center from October 1, 2014 through April 15, 2015. Participants included all hospitalized patients on a medical service for whom a blood culture was ordered. MEASUREMENTS The main outcomes were the rate of true positive blood cultures and the predictors of true positive cultures. RESULTS The true positive rate was 3.6% per order. The most common physician-selected indications were fever and leukocytosis, neither of which alone was highly predictive of true positive blood cultures. The only indication significantly associated with a true positive blood culture was "follow-up previous positive" (likelihood ratio [LR]+ 3.4, 95% confidence interval [CI]: 1.8-6.5). The only clinical predictors were a working diagnosis of bacteremia/endocarditis (LR+ 3.7, 95% CI: 2.5-5.7) and absence of antibiotic exposure within 72 hours of the culture (LR+ 2.4, 95% CI: 1.2-4.9). CONCLUSIONS The rate of true positive blood cultures among patients on a medical service was lower than previously studied. Using objective and easily obtainable clinical characteristics, including antibiotic exposure and working diagnosis, may improve the likelihood of true positive blood cultures. Journal of Hospital Medicine 2016;11:336-340. © 2016 Society of Hospital Medicine.
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Affiliation(s)
- Katherine Linsenmeyer
- Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts
- Boston University School of Medicine, Boston, Massachusetts
| | - Kalpana Gupta
- Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts
- Boston University School of Medicine, Boston, Massachusetts
| | - Judith M Strymish
- Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts
- Harvard Medical School, Boston, Massachusetts
| | - Muhammad Dhanani
- Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts
- Boston University School of Medicine, Boston, Massachusetts
| | - Stephen M Brecher
- Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts
- Boston University School of Medicine, Boston, Massachusetts
| | - Anthony C Breu
- Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts
- Harvard Medical School, Boston, Massachusetts
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Tudela P, Giménez M, Mòdol JM, Prat C. Hemocultivos en los servicios de urgencias, ¿hacia un nuevo enfoque? Med Clin (Barc) 2016; 146:455-9. [DOI: 10.1016/j.medcli.2015.11.026] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Revised: 11/24/2015] [Accepted: 11/26/2015] [Indexed: 01/10/2023]
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Takeshima T, Yamamoto Y, Noguchi Y, Maki N, Gibo K, Tsugihashi Y, Doi A, Fukuma S, Yamazaki S, Kajii E, Fukuhara S. Identifying Patients with Bacteremia in Community-Hospital Emergency Rooms: A Retrospective Cohort Study. PLoS One 2016; 11:e0148078. [PMID: 27023336 PMCID: PMC4811592 DOI: 10.1371/journal.pone.0148078] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 03/14/2016] [Indexed: 12/23/2022] Open
Abstract
Objectives (1) To develop a clinical prediction rule to identify patients with bacteremia, using only information that is readily available in the emergency room (ER) of community hospitals, and (2) to test the validity of that rule with a separate, independent set of data. Design Multicenter retrospective cohort study. Setting To derive the clinical prediction rule we used data from 3 community hospitals in Japan (derivation). We tested the rule using data from one other community hospital (validation), which was not among the three “derivation” hospitals. Participants Adults (age ≥ 16 years old) who had undergone blood-culture testing while in the ER between April 2011 and March 2012. For the derivation data, n = 1515 (randomly sampled from 7026 patients), and for the validation data n = 467 (from 823 patients). Analysis We analyzed 28 candidate predictors of bacteremia, including demographic data, signs and symptoms, comorbid conditions, and basic laboratory data. Chi-square tests and multiple logistic regression were used to derive an integer risk score (the “ID-BactER” score). Sensitivity, specificity, likelihood ratios, and the area under the receiver operating characteristic curve (i.e., the AUC) were computed. Results There were 241 cases of bacteremia in the derivation data. Eleven candidate predictors were used in the ID-BactER score: age, chills, vomiting, mental status, temperature, systolic blood pressure, abdominal sign, white blood-cell count, platelets, blood urea nitrogen, and C-reactive protein. The AUCs was 0.80 (derivation) and 0.74 (validation). For ID-BactER scores ≥ 2, the sensitivities for derivation and validation data were 98% and 97%, and specificities were 20% and 14%, respectively. Conclusions The ID-BactER score can be computed from information that is readily available in the ERs of community hospitals. Future studies should focus on developing a score with a higher specificity while maintaining the desired sensitivity.
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Affiliation(s)
- Taro Takeshima
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University, Tochigi, Japan
- * E-mail:
| | - Yosuke Yamamoto
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan
| | - Yoshinori Noguchi
- Department of General Internal Medicine, Japanese Red Cross Nagoya Daini Hospital, Aichi, Japan
| | - Nobuyuki Maki
- Department of Emergency Medicine, Shizuoka General Hospital, Shizuoka, Japan
| | - Koichiro Gibo
- Biostatistics Center, Kurume University, Kurume, Fukuoka, Japan
| | - Yukio Tsugihashi
- Department of Home Care Medicine, Tenri Hospital, Nara, Japan, Tenri Hospital, Nara, Japan
| | - Asako Doi
- Department of General Internal Medicine and Infectious Diseases, Kobe City Medical Center General Hospital, Hyogo, Japan
| | - Shingo Fukuma
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan
| | - Shin Yamazaki
- Center for Environmental Health Sciences, National Institute for Environmental Studies, Ibaraki, Japan
| | - Eiji Kajii
- Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University, Tochigi, Japan
| | - Shunichi Fukuhara
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Center for Innovative Research for Communities and Clinical Excellence (CIRC2LE), Fukushima Medical University, Fukushima, Japan
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Serum Procalcitonin and Procalcitonin Clearance as a Prognostic Biomarker in Patients with Severe Sepsis and Septic Shock. BIOMED RESEARCH INTERNATIONAL 2016; 2016:1758501. [PMID: 27088084 PMCID: PMC4818793 DOI: 10.1155/2016/1758501] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/23/2016] [Revised: 03/01/2016] [Accepted: 03/02/2016] [Indexed: 12/29/2022]
Abstract
We evaluated the tendency of the plasma concentration and procalcitonin (PCT) clearance (PCTc) to act as biomarkers of prognosis in patients with severe sepsis and septic shock. From 2011 to 2013, we prospectively analyzed patients with sepsis admitted to the intensive care unit (ICU). The serum PCT was evaluated at the time of sepsis diagnosis and again after 48 h (day 3) and 96 h (day 5). PCTc after 48 h (PCTc-day 3) and 96 h (PCTc-day 5) was also calculated to evaluate the prognostic value for survival in patients with sepsis. A total of 48 patients were included. Overall mortality was 16.7% (8 patients). PCTc was higher in survivors than in nonsurvivors, with significant differences on day 3 and day 5 (p = 0.033; p = 0.002, resp.); however, serum PCT levels on day 1, day 3, and day 5 were not significant prognostic factors for survival. The prognosis of patients with severe sepsis and septic shock may be associated with PCTc. Dynamic changes of PCT reflected as PCTc at 48 h (day 3) and 96 h (day 5) after admission to the ICU may serve as a predictor of survival in critically ill patients with severe sepsis.
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Yanai M, Gon Y, Suzuki K, Hayashi Y, Hasumi S, Otsuka H, Soma M. Clinical usefulness of serum 2'-5'-oligoadenylate synthetase for early diagnosis of viral infections among febrile adult patients. Infect Dis (Lond) 2015; 48:338-42. [PMID: 26624960 DOI: 10.3109/23744235.2015.1118531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND This study aimed to evaluate the clinical usefulness of serum 2'-5'-oligoadenylate synthetase (2-5AS) levels in diagnosing viral infection. METHODS 2-5AS, procalcitonin (PCT) and C-reactive protein (CRP) serum levels and leukocyte counts were evaluated in 104 febrile patients (26 viral and 55 bacterial infections, 23 non-infectious diseases). RESULTS Assessment of areas under the receiver-operator characteristic curves revealed that 2-5AS and CRP levels and the age of the patient differentiated between viral and bacterial infections, 2-5AS levels differentiated between viral infection and non-infectious disease and PCT levels differentiated between bacterial infection and non-infectious disease. The decision tree constructed according to the results correctly classified the origin of fever in 88 of 104 patients (85%). CONCLUSIONS 2-5AS is a useful diagnostic biomarker for viral infections and combining it with the PCT and CRP levels and leukocyte counts improves determination of causes of fever.
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Affiliation(s)
| | - Yasuhiro Gon
- b Division of Respiratory Medicine, Department of Internal Medicine , Nihon University School of Medicine , Tokyo , Japan
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Oussalah A, Ferrand J, Filhine-Tresarrieu P, Aissa N, Aimone-Gastin I, Namour F, Garcia M, Lozniewski A, Guéant JL. Diagnostic Accuracy of Procalcitonin for Predicting Blood Culture Results in Patients With Suspected Bloodstream Infection: An Observational Study of 35,343 Consecutive Patients (A STROBE-Compliant Article). Medicine (Baltimore) 2015; 94:e1774. [PMID: 26554775 PMCID: PMC4915876 DOI: 10.1097/md.0000000000001774] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Previous studies have suggested that procalcitonin is a reliable marker for predicting bacteremia. However, these studies have had relatively small sample sizes or focused on a single clinical entity. The primary endpoint of this study was to investigate the diagnostic accuracy of procalcitonin for predicting or excluding clinically relevant pathogen categories in patients with suspected bloodstream infections. The secondary endpoint was to look for organisms significantly associated with internationally validated procalcitonin intervals. We performed a cross-sectional study that included 35,343 consecutive patients who underwent concomitant procalcitonin assays and blood cultures for suspected bloodstream infections. Biochemical and microbiological data were systematically collected in an electronic database and extracted for purposes of this study. Depending on blood culture results, patients were classified into 1 of the 5 following groups: negative blood culture, Gram-positive bacteremia, Gram-negative bacteremia, fungi, and potential contaminants found in blood cultures (PCBCs). The highest procalcitonin concentration was observed in patients with blood cultures growing Gram-negative bacteria (median 2.2 ng/mL [IQR 0.6-12.2]), and the lowest procalcitonin concentration was observed in patients with negative blood cultures (median 0.3 ng/mL [IQR 0.1-1.1]). With optimal thresholds ranging from ≤0.4 to ≤0.75 ng/mL, procalcitonin had a high diagnostic accuracy for excluding all pathogen categories with the following negative predictive values: Gram-negative bacteria (98.9%) (including enterobacteria [99.2%], nonfermenting Gram-negative bacilli [99.7%], and anaerobic bacteria [99.9%]), Gram-positive bacteria (98.4%), and fungi (99.6%). A procalcitonin concentration ≥10 ng/mL was associated with a high risk of Gram-negative (odds ratio 5.98; 95% CI, 5.20-6.88) or Gram-positive (odds ratio 3.64; 95% CI, 3.11-4.26) bacteremia but dramatically reduced the risk of PCBCs or fungemia. In this large real-life setting experience with more than 35,000 patients, procalcitonin was highly effective at excluding bloodstream infections regardless of pathogen categories. The results from our study are limited by its cross-sectional design and deserve to be validated in prospective longitudinal studies.
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Affiliation(s)
- Abderrahim Oussalah
- From the Department of Molecular Medicine and Personalized Therapeutics, Department of Biochemistry, Molecular Biology, Nutrition, and Metabolism, University Hospital of Nancy (AO, PF-T, IA-G, FN, MG, J-LG); INSERM, U954, NGERE - Nutrition, Genetics, and Environmental Risk Exposure, Faculty of Medicine of Nancy, University of Lorraine (AO, IA-G, FN, J-LG); Department of Bacteriology, University Hospital of Nancy (JF, NA, AL), and EA7300, Stress Immunity Pathogens Laboratory, Faculty of Medicine of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France (JF, NA, AL)
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Hodgson LE, Dragolea N, Venn R, Dimitrov BD, Forni LG. An external validation study of a clinical prediction rule for medical patients with suspected bacteraemia. Emerg Med J 2015; 33:124-9. [PMID: 26246024 DOI: 10.1136/emermed-2015-204926] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Accepted: 07/06/2015] [Indexed: 11/04/2022]
Abstract
OBJECTIVE The objective of this study was to externally validate a clinical prediction rule (CPR)-the 'Shapiro criteria'-to predict bacteraemia in an acute medical unit (AMU). METHODS Prospectively collected data, retrospectively evaluated over 11 months in an AMU in the UK. From 4810 admissions, 635 patients (13%) had blood cultures (BCs) performed. The 100 cases of true bacteraemia were compared with a randomly selected sample of 100 control cases where BCs were sterile. RESULTS To predict bacteraemia (at a cut-off score of two points), the Shapiro criteria had a sensitivity of 97% (95% CIs 91% to 99%), specificity 37% (28% to 47%), positive likelihood ratio 1.54 (1.3 to 1.8) and a negative likelihood ratio of 0.08 (0.03 to 0.25). The area under the receiver operating curve was 0.80 (0.74 to 0.86), and the Hosmer-Lemeshow p value was 0.45. CONCLUSIONS A cut-off score of two points on the Shapiro criteria had high sensitivity to predict bacteraemia in a study of acute general medical admissions. Application of the rule in patients being considered for a BC could identify those at low risk of bacteraemia. Though the model demonstrated good discrimination, the lengthy number of variables (13) and difficulty automating the CPR may limit its use.
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Affiliation(s)
- Luke Eliot Hodgson
- Intensive Care Department, Western Sussex Hospitals NHS Foundation Trust, Worthing Hospital, Worthing, West Sussex, UK
| | - Nicholas Dragolea
- Brighton and Sussex Medical School, Royal Sussex County Hospital, Brighton, East Sussex, UK
| | - Richard Venn
- Intensive Care Department, Western Sussex Hospitals NHS Foundation Trust, Worthing Hospital, Worthing, West Sussex, UK
| | - Borislav D Dimitrov
- Primary Care and Population Sciences, University of Southampton, Southampton General Hospital, Southampton, Hampshire, UK
| | - Lui G Forni
- Intensive Care Department, The Royal Surrey County Hospital NHS Foundation Trust, Guildford, Surrey, UK
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Wu J, Hu L, Zhang G, Wu F, He T. Accuracy of Presepsin in Sepsis Diagnosis: A Systematic Review and Meta-Analysis. PLoS One 2015; 10:e0133057. [PMID: 26192602 PMCID: PMC4507991 DOI: 10.1371/journal.pone.0133057] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Accepted: 06/23/2015] [Indexed: 02/06/2023] Open
Abstract
Objective It’s difficult to differentiate sepsis from non-sepsis, especially non-infectious SIRS, because no good standard exists for proof of infection. Soluble CD14 subtype (sCD14-ST), recently re-named presepsin, was identified as a new marker for the diagnosis of sepsis in several reports. However, the findings were based on the results of individual clinical trials, rather than a comprehensive and overall estimation. Thus, we conducted this systematic review and meta-analysis to estimate the pooled accuracy of presepsin in patients with sepsis suspect. Methods A comprehensive electronic search was performed via internet retrieval system up to 15 December 2014. Methodological quality assessment was applied by using the QUADAS2 tool. The diagnostic value of presepsin in sepsis was evaluated by using the pooled estimate of sensitivity, specificity, likelihood ratio, and diagnostic odds ratio, as well as summary receiver operating characteristics curve. Results Nine studies with 10 trials and 2159 cases were included in the study. Only two trials had low concerns regarding applicability, whereas all trials were deemed to be at high risk of bias. Heterogeneity existed in the non-threshold effect, but not in the threshold effect. The pooled sensitivity of presepsin for sepsis was 0.78 (0.76–0.80), pooled specificity was 0.83 (0.80–0.85), pooled positive likelihood ratio was 4.63 (3.27–6.55), pooled negative likelihood ratio was 0.22 (0.16–0.30), and pooled diagnostic odds ratio was 21.73 (12.81–36.86). The area under curve of summary receiver operating characteristics curve was 0.89 (95%CI: 0.84 to 0.94) and Q* index was 0.82 (95%CI: 0.77 to 0.87). Conclusion This meta-analysis demonstrates that presepsin had some superiority in the management of patients, and may be a helpful and valuable biomarker in early diagnosis of sepsis. However, presepsin showed a moderate diagnostic accuracy in differentiating sepsis from non-sepsis which prevented it from being recommended as a definitive test for diagnosing sepsis in isolation, but the results should be interpreted cautiously.
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Affiliation(s)
- Jiayuan Wu
- Nutritional Department, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China
- * E-mail: (JW); (TH)
| | - Liren Hu
- Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Medical College, Zhanjiang, Guangdong, China
| | - Gaohua Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Medical College, Zhanjiang, Guangdong, China
| | - Fenping Wu
- Department of Radiotherapy, The Seventh People's Hospital of Chengdu, The Oncology Hospital of Chengdu, Chengdu, Sichuan Province, China
| | - Taiping He
- School of Public Health, Guangdong Medical College, Zhanjiang, Guangdong Province, China
- * E-mail: (JW); (TH)
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Weinstein EA, Ordonez AA, DeMarco VP, Murawski AM, Pokkali S, MacDonald EM, Klunk M, Mease RC, Pomper MG, Jain SK. Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography. Sci Transl Med 2015; 6:259ra146. [PMID: 25338757 DOI: 10.1126/scitranslmed.3009815] [Citation(s) in RCA: 177] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The Enterobacteriaceae are a family of rod-shaped Gram-negative bacteria that normally inhabit the gastrointestinal tract and are the most common cause of Gram-negative bacterial infections in humans. In addition to causing serious multidrug-resistant, hospital-acquired infections, a number of Enterobacteriaceae species are also recognized as biothreat pathogens. As a consequence, new tools are urgently needed to specifically identify and localize infections due to Enterobacteriaceae and to monitor antimicrobial efficacy. In this report, we used commercially available 2-[(18)F]-fluorodeoxyglucose ((18)F-FDG) to produce 2-[(18)F]-fluorodeoxysorbitol ((18)F-FDS), a radioactive probe for Enterobacteriaceae, in 30 min. (18)F-FDS selectively accumulated in Enterobacteriaceae, but not in Gram-positive bacteria or healthy mammalian or cancer cells in vitro. In a murine myositis model, (18)F-FDS positron emission tomography (PET) rapidly differentiated true infection from sterile inflammation with a limit of detection of 6.2 ± 0.2 log10 colony-forming units (CFU) for Escherichia coli. Our findings were extended to models of mixed Gram-positive and Gram-negative thigh co-infections, brain infection, Klebsiella pneumonia, and mice undergoing immunosuppressive chemotherapy. This technique rapidly and specifically localized infections due to Enterobacteriaceae, providing a three-dimensional holistic view within the animal. Last, (18)F-FDS PET monitored the efficacy of antimicrobial treatment, demonstrating a PET signal proportionate to the bacterial burden. Therapeutic failures associated with multidrug-resistant, extended-spectrum β-lactamase (ESBL)-producing E. coli infections were detected in real time. Together, these data show that (18)F-FDS is a candidate imaging probe for translation to human clinical cases of known or suspected infections owing to Enterobacteriaceae.
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Affiliation(s)
- Edward A Weinstein
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Alvaro A Ordonez
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Vincent P DeMarco
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Allison M Murawski
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Supriya Pokkali
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Elizabeth M MacDonald
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Mariah Klunk
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Ronnie C Mease
- Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Martin G Pomper
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Sanjay K Jain
- Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
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Seo K, Kitazawa T, Yoshino Y, Koga I, Ota Y. Characteristics of serum endocan levels in infection. PLoS One 2015; 10:e0123358. [PMID: 25894539 PMCID: PMC4404335 DOI: 10.1371/journal.pone.0123358] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Accepted: 03/03/2015] [Indexed: 12/29/2022] Open
Abstract
Objectives Endocan is a newly recognized biomarker of sepsis. However, there have been no studies of the trends in endocan levels during infection and their associations with other clinical factors. The aim of this study was to assess the time course of endocan levels and the associations of endocan with clinical factors during infection by comparison with other biomarkers. Methods Serum samples and blood cultures were obtained from patients who were diagnosed with infection from June 2013 to March 2014. Serum endocan, C-reactive protein (CRP), and procalcitonin (PCT) levels during four periods during infection were measured (day 0, day 1-2, day 3-5, and day 6-10). Results A total of 78 patients were enrolled in this study. The median endocan level decreased by only 23% during infection, whereas both serum CRP and PCT levels decreased by more than 80%. Endocan levels were correlated to neither CRP levels nor PCT levels in each period. Endocan levels at day 0 in patients with bacteremia were higher than those without bacteremia (1.09 ng/mL vs 0.82 ng/mL, P=0.002), but neither CRP levels nor PCT levels at day 0 were different between the two groups. Areas under the receiver operator characteristic (ROC) curves of endocan, CRP, and PCT at day 0 were 0.662, 0.343, and 0.563, respectively. Positive blood cultures tended to be related to high endocan levels, but not significantly (odds ratio: 4.24, 95% CI: 0.99-10.34, P=0.05). Conclusions In bacteremic cases, serum endocan levels in bacteremia tended to be higher than in non-bacteremic cases. Although endocan level was not identified as a prognostic factor of bacteremia, further prospective study concerning the relationship between serum endocan level and bacteremia would be needed.
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Affiliation(s)
- Kazunori Seo
- Department of Internal Medicine, Teikyo University, Tokyo, Japan
| | - Takatoshi Kitazawa
- Department of Internal Medicine, Teikyo University, Tokyo, Japan
- * E-mail:
| | - Yusuke Yoshino
- Department of Internal Medicine, Teikyo University, Tokyo, Japan
| | - Ichiro Koga
- Department of Internal Medicine, Teikyo University, Tokyo, Japan
| | - Yasuo Ota
- Department of Internal Medicine, Teikyo University, Tokyo, Japan
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Prin M, Bakker J, Wagener G. Hepatosplanchnic circulation in cirrhosis and sepsis. World J Gastroenterol 2015; 21:2582-2592. [PMID: 25759525 PMCID: PMC4351207 DOI: 10.3748/wjg.v21.i9.2582] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2014] [Revised: 11/15/2014] [Accepted: 01/21/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatosplanchnic circulation receives almost half of cardiac output and is essential to physiologic homeostasis. Liver cirrhosis is estimated to affect up to 1% of populations worldwide, including 1.5% to 3.3% of intensive care unit patients. Cirrhosis leads to hepatosplanchnic circulatory abnormalities and end-organ damage. Sepsis and cirrhosis result in similar circulatory changes and resultant multi-organ dysfunction. This review provides an overview of the hepatosplanchnic circulation in the healthy state and in cirrhosis, examines the signaling pathways that may play a role in the physiology of cirrhosis, discusses the physiology common to cirrhosis and sepsis, and reviews important issues in management.
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Eliakim-Raz N, Bates DW, Leibovici L. Predicting bacteraemia in validated models--a systematic review. Clin Microbiol Infect 2015; 21:295-301. [PMID: 25677625 DOI: 10.1016/j.cmi.2015.01.023] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Revised: 01/21/2015] [Accepted: 01/22/2015] [Indexed: 11/18/2022]
Abstract
Bacteraemia is associated with high mortality. Although many models for predicting bacteraemia have been developed, not all have been validated, and even when they were, the validation processes varied. We identified validated models that have been developed; asked whether they were successful in defining groups with a very low or high prevalence of bacteraemia; and whether they were used in clinical practice. Electronic databases were searched to identify studies that underwent validation on prediction of bacteraemia in adults. We included only studies that were able to define groups with low or high probabilities for bacteraemia (arbitrarily defined as below 3% or above 30%). Fifteen publications fulfilled inclusion criteria, including 59 276 patients. Eleven were prospective and four retrospective. Study populations and the parameters included in the different models were heterogeneous. Ten studies underwent internal validation; the model performed well in all of them. Twelve performed external validation. Of the latter, seven models were validated in a different hospital, using a new independent database. In five of these, the model performed well. After contacting authors, we found that none of the models was implemented in clinical practice. We conclude that heterogeneous studies have been conducted in different defined groups of patients with limited external validation. Significant savings to the system and the individual patient can be gained by refraining from performing blood cultures in groups of patients in which the probability of true bacteraemia is very low, while the probability of contamination is constant. Clinical trials of existing or new models should be done to examine whether models are helpful and safe in clinical use, preferably multicentre in order to secure utility and safety in diverse clinical settings.
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Affiliation(s)
- N Eliakim-Raz
- Unit of Infectious Diseases Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
| | - D W Bates
- Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Health Policy and Management, Harvard School of Public Health, Boston, MA, USA
| | - L Leibovici
- Department of Medicine E, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
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Endotoxemia as a diagnostic tool for patients with suspected bacteremia caused by gram-negative organisms: a meta-analysis of 4 decades of studies. J Clin Microbiol 2015; 53:1183-91. [PMID: 25631796 DOI: 10.1128/jcm.03531-14] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The clinical significance of endotoxin detection in blood has been evaluated for a broad range of patient groups in over 40 studies published over 4 decades. The influences of Gram-negative (GN) bacteremia species type and patient inclusion criteria on endotoxemia detection rates in published studies remain unclear. Studies were identified after a literature search and manual reviews of article bibliographies, together with a direct approach to authors of potentially eligible studies for data clarifications. The concordance between GN bacteremia and endotoxemia expressed as the summary diagnostic odds ratios (DORs) was derived for three GN bacteremia categories across eligible studies by using a hierarchical summary receiver operating characteristic (HSROC) method. Forty-two studies met broad inclusion criteria, with between 2 and 173 GN bacteremias in each study. Among all 42 studies, the DORs (95% confidence interval) were 3.2 (1.7 to 6.0) and 5.8 (2.4 to 13.7) in association with GN bacteremias with Escherichia coli and those with Pseudomonas aeruginosa, respectively. Among 12 studies of patients with sepsis, the proportion of endotoxemia positivity (95% confidence interval) among patients with P. aeruginosa bacteremia (69% [57 to 79%]; P=0.004) or with Proteus bacteremia (76% [51 to 91%]; P=0.04) was significantly higher than that among patients without GN bacteremia (49% [33 to 64%]), but this was not so for patients bacteremic with E. coli (57% [40 to 73%]; P=0.55). Among studies of the sepsis patient group, the concordance of endotoxemia with GN bacteremia was surprisingly weak, especially for E. coli GN bacteremia.
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Hoeboer SH, van der Geest PJ, Nieboer D, Groeneveld ABJ. The diagnostic accuracy of procalcitonin for bacteraemia: a systematic review and meta-analysis. Clin Microbiol Infect 2015; 21:474-81. [PMID: 25726038 DOI: 10.1016/j.cmi.2014.12.026] [Citation(s) in RCA: 179] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2014] [Revised: 11/29/2014] [Accepted: 12/20/2014] [Indexed: 01/07/2023]
Abstract
The diagnostic use of procalcitonin for bacterial infections remains a matter of debate. Most studies have used ambiguous outcome measures such as sepsis instead of infection. We performed a systematic review and meta-analysis to investigate the diagnostic accuracy of procalcitonin for bacteraemia, a proven bloodstream infection. We searched all major databases from inception to June 2014 for original, English language, research articles that studied the diagnostic accuracy between procalcitonin and positive blood cultures in adult patients. We calculated the area under the summary receiver-operating characteristic (SROC) curves and pooled sensitivities and specificities. To minimize potential heterogeneity we performed subgroup analyses. In total, 58 of 1567 eligible studies were included in the meta-analysis and provided a total of 16,514 patients, of whom 3420 suffered from bacteraemia. In the overall analysis the area under the SROC curve was 0.79. The optimal and most widely used procalcitonin cut-off value was 0.5 ng/mL with a corresponding sensitivity of 76% and specificity of 69%. In subgroup analyses the lowest area under the SROC curve was found in immunocompromised/neutropenic patients (0.71), the highest area under the SROC curve was found in intensive-care patients (0.88), sensitivities ranging from 66 to 89% and specificities from 55 78%. In spite of study heterogeneity, procalcitonin had a fair diagnostic accuracy for bacteraemia in adult patients suspected of infection or sepsis. In particular low procalcitonin levels can be used to rule out the presence of bacteraemia. Further research is needed on the safety and efficacy of procalcitonin as a single diagnostic tool to avoid taking blood cultures.
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Affiliation(s)
- S H Hoeboer
- Department of Intensive Care Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
| | - P J van der Geest
- Department of Intensive Care Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
| | - D Nieboer
- Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - A B J Groeneveld
- Department of Intensive Care Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands
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