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Căn nguyên gây nhiễm khuẩn huyết Phạm Hồng Nhung Bộ môn Vi sinh, Đại học Y Hà Nội Khoa Vi sinh, Bệnh viện Bạch Mai 43 (26) rinary tract 31 (14) 32 (19) sociated, when they occur in patients with significant prior health ed from https://academic.oup.com/cid/article/48/Supplement_4/S238/293217 by guest on 05 December 2021 57 (26) from https://academic.oup.com/cid/article/48/Supplement_4/S238/293217 by guest on 05 December 2021 r tigate deep-seated sources ofofBSIcatheter-related include radiography, PCR-based methods and of fluorescence in micrositu hybridizationcluding for direct species identification isolates from monitoring for positivity A diagnosis BSI transAddress correspondence to Kevin B Laupland, klaupland@g exposure, associated, in other cases The most tigate sources of BSI include radiography, trans-or community thoracic anddeep-seated transesophageal echocardiography, CT, care positron ization for direct species identification of isolates from scopically positive blood BSI cultures [15,Escherichia 16], as well asCopyright PCRmicrorequires the semiautomated blood culture system to detect common a CT, positron © 2014, American Society for Microbiology All Ri ntestinal or biliary tract 27 (13) 18 (11) causes of community-onset include thoracic and transesophageal echocardiography, emission tomography, and MRI Laboratory investigations, inscopically positive blood cultures [15, 16], as well as PCR techniques to directly identify methicillin-resistant Staphylodoi:10.1128/CMR.00002-14 coli, Staphylococcus aureus, and Streptococcus pneumoniae Antitory tract 20 (9) 12 (7) positive resultcluding for the central venous catheter sample at emission tomography, andprotein MRI.blood Laboratory investigations, WBC count, C-reactive level measurement, and in-coccustechniques directly identify methicillin-resistant StaphyloLaupland and Church aureus fromtoblood cultures showing gram-positive cocci microbial-resistant organisms, including methicillin-resistant (4) 15 (9) least h earlierpossibly, thancluding it procalcitonin detects a positive result for the peripheral WBC count, C-reactive protein level measurement, and level measurement, may help to evaluate coccus[17] aureus from blood cultures gram-positive in clusters Methods for the directshowing identification of mi- cocci possibly, procalcitonin levelofmeasurement, may help to evaluate blood sample the [14] E SSTI, skin and soft-tissue infection Source: Diekema et al [12] clinical course and severity infectious disease Identifiin clusters [17] Methods for the direct identification crobial DNA from blood by various amplification methods areof miclinical course and severity of infectious disease IdentifiOctoberfor 2014 Volume 27 Number Clinical Microbiology Reviews p 647– 664 urces are for culture-confirmed cases crobial DNA from blood by various cationthe of have the underlying source of reduce infection is essential Several approaches been examined to the time currently being developed, but their reviewamplification is beyond themethods scope are TABLE Definitions of bloodstream infectionimplementation and cation associated entities of the underlying source of infectionsurgical is essential for currently being developed, but their review is beyond the scope of adequate treatment, including into microbial species identification in the diagnosis of BSI, inof this article implementation of adequate treatment, including surgical inof this article tervention when appropriate Treatment a BSI but Entity Definition cluding PCR-based methods and fluorescence in that situ clears hybridtervention when appropriate Treatment that clears a BSI but leaves an undiagnosed, underlying source is unlikely to be sucdeep-seated sources of BSIContamination include radiography, transDEFINITIONS OF present BACTEREMIA AND BSI of blood cultures ization for direct species cultures are positivesource for growth due tobe organisms that were not in the bloodstream identification of isolates from microleaves Blood an undiagnosed, underlying is unlikely to sucDEFINITIONS OF BACTEREMIA AND BSI cessful in the medium-to-long term and may delay effective c and transesophageal echocardiography, CT, positron Bacteremia Presence of viable bacteria in and the blood cultures positive for bacterial growth of where scopically positive cessful blood [15, 16], asterm well asblood; PCRdelay incultures the medium-to-long may effective Bacteremia is defined as the presence viable microorganisms therapy for a life-threatening complication Bacteremia is defined as the presence of viable microorganisms on tomography, and MRI Laboratory investigations, incontamination has been ruled out therapy for a life-threatening complication in the bloodstream and can be categorized as transient, intertechniques to directly identifystudy methicillin-resistant StaphyloIn a landmark conducted in the early 1990s in the in the bloodstream and can be categorized as transient, interFungemia viableconducted fungi in the blood; positive for fungal(figure growth g WBC count, C-reactive protein level measurement, and In aPresence landmarkof study in the earlyblood 1990scultures in themittent, or persistent 1) where [6] Transient bacteremia lasts coccus aureus from showing cocci Unitedblood Statescultures by Weinstein et al gram-positive [10], 843 episodes of bactermittent, or persistent (figure 1) [6] Transient bacteremia lasts contamination has ruled United States by Weinstein et been al [10], 843out episodes of bacter-for minutes y, procalcitonin level measurement, may help to evaluate or a few hours and most frequently occurs after in clusters [17] for the identification emiaMethods and fungemia weredirect analyzed for their portalofofmientry BSIs for minutes or a few hours and most frequently occurs after Transient bacteremia/fungemia Brief episode of bacteremia/fungemia that is not associated with emia and fungemia were analyzed for their portal of entry BSIs manipulation ofinfection nonsterile body sites—for example, during nical course and severity of infectious disease Identifiwere considered to be primary in 44.7% methods of cases: inare 19.1% of crobial DNA from blood by various amplification manipulation of nonsterile body sites—for example, during Bloodstream infection Bacteremia/fungemia is associated infection were considered to be primarythat in 44.7% of cases:with in 19.1% of of the underlying source of infection is essential for cases, an intravascular catheter was the sourcethe of infection, and currently being developed, but their review is beyond scope cases, Bloodstream an intravascular catheter was source of infection, and drawn) Ն48 h after hospital admission and Hospital-onset bloodstream infection infection thatthe is first identified (culture of cases had an unknown portal of entry The most mentation of adequate treatment, including surgical inof this article.25.6%25.6% ofwithin cases had unknown portal discharge of entry The most 48 han following hospital frequent secondary sources were the genitourinary tract ion when appropriate Treatment that clears bloodstream a BSI but infection frequent secondary infection sources were the genitourinary tract Community-onset Bloodstream occurring in an outpatient or first identified (culture drawn) Ͻ48 h (17.4%), the respiratory tract (12.3%), the abdomen (12.1%), an undiagnosed, underlying source is unlikely to be suc(17.4%), the respiratory tract (12.3%), the abdomen (12.1%), DEFINITIONS OF BACTEREMIA AND following admission toBSI hospital and the skin and skin structure (6.3%) [10] In an analysis of and the skin and skin structure (6.3%) [10] In an analysis of with significant prior health care exposure in the medium-to-long term andcare-associated may delay effective Health community-onset Community-onset bloodstream infection associated 111 patients with BSI in French hospitals, 29% had primary Bacteremia is defined as the presence of viable microorganisms 111 patients with BSI in French hospitals, 29% had primary y for a life-threatening complication bloodstream infection (as evidenced by recent hospitalization, specialized in-home medical services, care in a infections defined source, 26% had catheter-related in the bloodstream andwithout can bea categorized assource, transient, interinfections without a defined 26% had catheter-related hospital-based clinic or hemodialysis unit, or residence in a nursing home) landmark study conducted in the early 1990s in the infections, and 45% had infection secondary to other sources infections, and 45% had infection secondary to other mittent, or persistent (figure 1) [6] Transient bacteremia lasts Community-associated communityCommunity-onset bloodstream infection notsources fulfilling criteria for health care-associated infection States by Weinstein et al [10], 843 episodes of bacter[11] Although colonized (“infected”) catheters are the most [11] Although colonized (“infected”) catheters are the most for minutes orfrequently a few hours andsource, most infection frequently occurs after infection nd fungemia were analyzed foronset theirbloodstream portal of entry BSIs identified at numerous other other sites sites frequently identified source, infection at numerous Polymicrobial bloodstream infection Episode of bloodstream infection associated with two or more different organisms isolated within manipulation can of also nonsterile body sites—for example, during BSIs For in a prospective study study inonsidered to be primary in 44.7% of cases: in 19.1% of cancause also cause BSIs.example, For example, in a prospective in48 h of each other volving patients from 2from US hospitals, catheters were the source volving patients US hospitals, catheters were the source an intravascular catheter was the source of infection, and of infection in 26% nosocomial BSI episodes, whereas the the of infection in of 26% of nosocomial BSI episodes, whereas of cases had an unknown portal of entry The most sourcesource was described as genitourinary in 14%, gastrointestinal was described as genitourinary in 14%, gastrointestinalFigure Commonly used classification of bacteremias into catent secondary sources were the genitourinary tract Figure Commonly used classification of bacteremias into cateor biliary in 13%, in 9%,inand softortissue in or biliary in respiratory 13%, respiratory 9%,skin andorskin soft tissue ingories: gories: transient (bacteremia lasts for a short of timeofand transient (bacteremia lasts for a amount short amount timecan and can %), the respiratory tract (12.3%), the abdomen (12.1%), (table 1) [12] The distribution of sources of the BSIs was be caused by the actions such assuch brushing of teethof orteeth afterorgastrointestinal 4% (table 1) [12] The distribution of sources ofoverall BSIs was be caused byspeciesactions brushing after gastrointestinal mographics, shifts in health care delivery4% models, and increasing to first define and then orasorganism groupe skin and skin structure (6.3%) [10] In an analysis of biopsy),biopsy), intermittent (recurring bacteremia due to due discontinuous seeding broadly similarsimilar for community-onset infections [12] [12] intermittent (recurring bacteremia to discontinuous broadly forbeen community-onset infections globalization, the epidemiology of community-onset BSI has specific burden of community-onset BSI Following this, we such asseeding of the same organisms, which can be caused by infections of the same organisms, which can be caused by infections such as tients with BSI in French hospitals, 29% had primary For the of BSIs to intravascular devices, a Fordiagnosis the diagnosis of related BSIs related to intravascular devices, a changing in recent decades In addition,meta-analysis antimicrobial-resistant briefly highlight the importance of of (bacteremia resistant or- occurring abscesses), andthe persistent or sustained occurring over aover a abscesses), andemergence persistent or sustained (bacteremia of 51 of studies revealed that paired quantitative ons without a defined source, 26% had catheter-related meta-analysis 51 studies revealed that paired quantitativeprolonged period that is usually associated with infections such as inprolonged periodBSI that is usually associated with infections such as inorganisms, most notably methicillin-resistant Staphylococcus auganisms as agents of community-onset blood blood cultures were the most diagnostic test, whereas cultures were the accurate most accurate diagnostic test, whereasfective fective ons, and 45% had infection secondary to other sources endocarditis) Red and indicateindicate the presence and and endocarditis) Redgreen and arrows green arrows the presence reus (MRSA) and extended-spectrum ␤-lactamase (ESBL)/metalother methods, such as catheter-segment culture and acridine other methods, such as catheter-segment culture and acridine absence, respectively, of bacteria in blood cultures obtained at different absence, respectively, of bacteria in blood cultures obtained at different Although colonized (“infected”) catheters are the most ESTABLISHING THE OF AND DEFINING lo-␤-lactamase-producing Enterobacteriaceae, haveleukocyte emerged as had orangeorange leukocyte cytospin, also acceptable sensitivity, spec- PRESENCE (in minutes, unless hours [h] is specified) cytospin, also had acceptable sensitivity, spec-time points time points (in minutes, unless hours [h] is specified) ntly identified source, infection at numerous other sites important etiologies of community-onset BSI However, despite COMMUNITY-ONSET BLOODSTREAM INFECTION o cause BSIs For example, in a prospective study inand classification its importance and extensive investigation, as a result of inconsis- There are a number of diagnostic Microbiological Findings and BSIs CID •2009:48 (Suppl(Suppl 4) • S239 Microbiological Findings and•considerations BSIs CID 2009:48 4) • S239 g patients from US hospitals, catheters were the source tent application of definitions and a reliance on hospital-based related to ascertainment of the presence of a BSI episode Howction in 26% of nosocomial BSI episodes, whereas the Downloaded from https://academic.oup.com/cid/article/48/Supplement_4/S238/293217 by guest on 05 December 2021 Định nghĩa nhiễm khuẩn huyết vãng khuẩn huyết Influence of blood culture systems and other laboratory-based determinants Determining the Significance of Positive Blood Cultures Factors to consider in classifying positive blood cultures (i) Identified organism(s) (ii) Number and timing of positive cultures (iii) Transient bacteremia (iv) Clinical variables Approaches to classification of positive blood cultures Classification of Community-Onset Bloodstream Infections Community-associated versus health care-associated community-onset disease BURDEN OF COMMUNITY-ONSET BLOODSTREAM INFECTION Overall Populations Community-Onset Bloodstream Infection Specific Etiologies Escherichia coli Staphylococcus aureus Streptococcus pneumoniae Klebsiella species Salmonella enterica Other Enterobacteriaceae Haemophilus influenzae Pseudomonas aeruginosa Beta-hemolytic streptococci Enterococci Anaerobes Candida species Coagulase-negative staphylococci and other Gram-positive organisms Other Gram-negative bacteria EMERGENCE OF RESISTANT COMMUNITY-ONSET BLOODSTREAM INFECTIONS Community-Onset MRSA Bloodstream Infection Enterobacteriaceae CONCLUSIONS REFERENCES AUTHOR BIOS Định nghĩa nhiễm khuẩn huyết vãng khuẩn huyết SUMMARY Bloodstream infection (BSI) is a major cause of infectious disease morbidity and mortality worldwide While a positive blood culture is mandatory for establishment of the presence of a BSI, there are a number of determinants that must be considered for establishment of this entity Community-onset BSIs are those that occur in outpatients or are first identified Ͻ48 h after admission to hospital, and they may be subclassified further as health care associated, when they occur in patients with significant prior health care exposure, or community associated, in other cases The most common causes of community-onset BSI include Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae Antimicrobial-resistant organisms, including methicillin-resistant Staphylococcus aureus and extended-spec tallo-␤-lactamase/carbapenemase-produc have emerged as important etiologies of co INTRODUCTION B loodstream infection (BSI) is a major ease morbidity and mortality worldw number of determinants, not limited to ch Address correspondence to Kevin B Laupland, klaupla Copyright © 2014, American Society for Microbiology doi:10.1128/CMR.00002-14 FIG Diagnostic hierarchy from positive blood cultures to community-onset bloodstream infection BSI, bloodstream infection; HO, hospital onset; HCA, health care associated; CA, community associated The overall triangular area indicates all positive cultures, contamination (first October 2014blood Volume 27 Number which may represent Clinical Microbiology Reviews p 647– 664 level), transient bacteremia/fungemia (second level), or “true” BSI (third level) Bloodstream infections are further classified into the three mutually exclusive categories of hospital-associated, health care-associated community-onset, and community-associated community-onset BSIs Gánh nặng nhiễm trùng huyết Bloodstream in Community Hospitals in the • Mỗi năm cóInfections khoảng 250 000 triệu ca NTH/năm st • Mỗi năm có khoảng 9 000000 ca tử vong trẻ 21 Century: A Multicenter Cohort Study • TỷJ lệ tử vong: 35% Deverick Anderson *, Rebekah W Moehring , Richard Sloane , Kenneth E Schmader , sơ sinh, trong 70% do NKH David J Weber , Vance G Fowler Jr , Emily Smathers , Daniel J Sexton 1,2 1,2 1,2 Duke University Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina, United States of America, Duke Infection Control Outreach Network, Durham, North Carolina, United States of America, Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina, United States of America, Department of Medicine-Geriatrics, Duke University Medical Center and Geriatric Research Education and Clinical Center (GRECC), Durham VA Medical Center, Durham, North Carolina, United States of America, Department of Hospital Epidemiology, University of North Carolina Health System, Chapel Hill, North Carolina, United States of America • Nguyên nhân hàng đầu gây tử vong ICU •Abstract 35000 ca tử vong/năm • 50% xảy nước châu Á Sub-Sahran Africa African Journal of Emergency Medicine (2015) 5, 127–135 Background: While the majority of healthcare in the US is provided in community hospitals, the epidemiology and treatment of bloodstream infections in this setting is unknown • Tỷ lệ tử vong tăng 7,6% sau liệu pháp điều African Federation for Emergency Medicine • Nguyên nhân hàng đầu gây tử vong ICU Methods and Findings: We undertook this multicenter, retrospective cohort study to 1) describe the epidemiology of bloodstream infections (BSI) in a network of community hospitals and 2) determine risk factors for inappropriate therapy for bloodstream infections in community hospitals 1,470 patients were identified as having a BSI in community hospitals in the southeastern US from 2003 through 2006 The majority of BSIs were community-onset, healthcare associated (n = 823, 56%); 432 (29%) patients had community-acquired BSI, and 215 (15%) had hospital-onset, healthcare-associated BSI BSIs due to multidrug-resistant pathogens occurred in 340 patients (23%) Overall, the three most common pathogens were S aureus (n = 428, 28%), E coli (n = 359, 24%), coagulase-negative Staphylococci (n = 148, 10%), though type of infecting organism varied by location of acquisition (e.g., community-acquired) Inappropriate empiric antimicrobial therapy was given to 542 (38%) patients Proportions of inappropriate therapy varied by hospital (median = 33%, range 21–71%) Multivariate logistic regression identified the following factors independently associated with failure to receive appropriateCLINICAL REVIEW • empiric antimicrobial therapy: hospital where the patient received care (p,0.001), assistance with $3 ADLs (p = 0.005), Charlson score (p = 0.05), community-onset, healthcare-associated infection (p = 0.01), and hospital-onset, healthcareassociated infection (p = 0.02) Important interaction was observed between Charlson score and location of acquisition Sepsis, severe sepsis, and trị bị chậm trễ African Journal of Emergency Medicine www.afjem.com www.sciencedirect.com • $37 000/ca septic shock: A review of the literature Bloodstream Infections in Community Hospitals in the st Conclusions: Our large,A multicenter study providesCohort the most complete picture of BSIs in community hospitals in the US to 21date Century: Multicenter Study The epidemiology of BSIs in community hospitals has changed: community-onset, healthcare-associated BSI is mostSeptice´mie, septice´mie grave et choc septique: e´tude bibliographique • common, S aureus is the most common cause, and of patients with a BSI receives inappropriate empiric antimicrobial Deverick J Anderson1,2*, Rebekah W Moehring1,2, Richard Sloane3, Kenneth E Schmader4, Keegan Tupchong a, Alex Koyfman b,*, Mark Foran a therapy Our 5data suggest that appropriateness of empiric antimicrobial therapy is an important and needed performance 1,2 , Vanceand G Fowler , Emily Smathers , Daniel J Sextonhospitals David J Weber a Department of Emergency Medicine, New York University School of Medicine, Bellevue Hospital Center, New York, NY, USA metric for physicians hospitalJr.stewardship programs in community b Duke University Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina, United States of America, Duke Infection Control Outreach Division of Emergency Medicine, UT Southwestern Medical Center/Parkland Memorial Hospital, Dallas, TX, Network, Durham, North Carolina, United States of America, Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North African Journal of Emergency Medicine (2015) 5, 127–135 st 25 November 2013; revised 14 April 2014; accepted 25 May 2014; available online August 2014 Citation: Anderson DJ, Moehring RW, Sloane R, SchmaderDuke KE, University Weber DJ, et al (2014) Infections Community Hospitals A Carolina, United States of America, Department of Medicine-Geriatrics, Medical Center andBloodstream Geriatric Research Educationin and Clinical Center (GRECC), in the 21 Century: Received Multicenter Cohort Study PLoSNorth ONECarolina, 9(3): e91713 doi:10.1371/journal.pone.0091713 Durham VA Medical Center, Durham, United States of America, Department of Hospital Epidemiology, University of North Carolina Health System, Chapel Hill, Paul NorthJ.Carolina, States University, of America United States of America Editor: Planet,United Columbia USA the southeastern US from 2003 through 2006 The majority of BSIs were community-onset, healthcare associated (n = 823, 56%); 432 (29%) patients had community-acquired BSI, and 215 (15%) had hospital-onset, healthcare-associated BSI BSIs due to multidrug-resistant pathogens occurred in 340 patients (23%) Overall, the three most common pathogens were S aureus (n = 428, 28%), E coli (n = 359, 24%), coagulase-negative Staphylococci (n = 148, 10%), though type of infecting BSI in Community Hospitals organism varied by location of acquisition (e.g., community-acquired) Inappropriate empiric antimicrobial therapy was given to 542 (38%) patients Proportions of inappropriate therapy varied by hospital (median = 33%, range 21–71%) Multivariate logistic regression identified the following factors independently associated with failure to receive appropriate empiric antimicrobial therapy: hospital where the patient received care (p,0.001), assistance with $3 ADLs (p = 0.005), Charlson score (p = 0.05), community-onset, healthcare-associated infection (p = 0.01), and hospital-onset, healthcareassociated (p = 0.02) Important interaction Charlson hospitals, score and location of acquisition patients withinfection bloodstream infection (BSI)wasinobserved nine between community 2003– Nguồn gốc nhiễm trùng huyết Table Infection and Treatment Data for 1,470 2006a Conclusions: Our large, multicenter study provides the most complete picture of BSIs in community hospitals in the US to date The epidemiology of BSIs in community hospitals has changed: community-onset, healthcare-associated BSI is most common, S aureus is the most common cause, and of patients with a BSI receives inappropriate empiric antimicrobial therapy Our data suggest that appropriateness of empiric antimicrobial therapy is an important and needed performance metric for physicians and hospital in community hospitals Patients who did not stewardship programs Patients who received receive appropriate empiric Documented infection in past year appropriate empiric Total cohort Citation: Anderson DJ, Moehring RW, Sloane R, Schmader KE, Weber DJ, et al (2014) Bloodstream Infections in Community Hospitals in the 21st Century: A antimicrobial therapy antimicrobial therapy P-value Multicenter Cohort Study PLoS ONE 9(3): e91713 doi:10.1371/journal.pone.0091713 N = 1470 Editor: Paul J Planet, Columbia University, United States of America n (%) Copyright: ß 2014 Anderson et al This is an open-access article n (%) n distributed (%) under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited 273 (20) Funding: This work was supported by the Robert Wood Johnson Foundation [#66327 to DJA] and the National Institute of Health/National Institute of Allergy 106 (20) 167 0.58 and Infectious Diseases [K23 AIO95357 to DJA; K24 AI093969 to VGF] The(19) funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript BSI DATA Type of BSI N = 542 N = 906 Received August 22, 2013; Accepted February 13, 2014; Published March 18, 2014 Competing Interests: DJA has received research support from the CDC, AHRQ, and Merck, Inc., and receives royalties from UpToDate, Online KES receives research support from Merck, Inc DJW has consulting relationships with Merck, Pfizer, ASP, and Clorox and is on speaker’s bureaus for Merck and Pfizer VGF has 0.57 and receives royalties from consulting relationships with Merck, Pfizer, Novartis, Galderma, Novadigm, Durata, Achaogen, Affinium, Cerex, and MedImmune, UpToDate, Online DJS receives royalties from UpToDate, Online RWM, RS, and ES report no other relationships or activities that readers could perceive to have 107or(20) 194 (21) influenced give the appearance of potentially influencing the submitted work These potential competing interests not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials Secondary 303 (21) Urine 173 (12) Wound 33 (2) Pneumonia 59 (4) Introduction 21 (4) Other 38 (3) Bloodstream suffering 13 (2) infections (BSIs) are a leading cause of25 (3) and death in the US As many as 250,000 BSIs occur each year 434 (80) rate of 35% and costs of up to $37,000 710 (79) [1], with a mortality per case [2,3] In fact, BSI was one of the top causes of death in the US in 2008, leading to more than 35,000 deaths [4] The majority of healthcare in the US is performed in smaller, non-teaching community hospitals._ENREF_4 The mean size of No secondary source identified or due to central venous catheter 61deverick.anderson@duke.edu (11) * E-mail: 111 (12) 13 (2) 1163 (79) Location of acquisition 20 (2) 36 (4) hospitals in the US was 160 beds in 2009, and 72% of hospitals had fewer than 200 beds [4]._ENREF_4 Of the 39 million hospital discharges in the US in 2010, 19.9 million (51%) were from non-teaching facilities [5] Our understanding about the causes and risk factors for BSI in these community hospitals, however, is alarmingly inadequate Prior studies on BSIs in community hospitals have been limited to specific organisms [6,7], single institutions, intensive ,0.001 care units [8] and/or patients admitted prior to the emergence and spread of epidemiologically 432 (29) 126 (23) 302 (33) Bloodstream Infections in Community Hospitals in the st Community-onset, healthcare-associated 823 (56) 314 (58) 501 (55) 21 Century: A Multicenter Cohort Study PLOS ONE | www.plosone.org March 2014 | Volume | Issue | e91713 Hospital-onset, healthcare-associated 215 (15)Bloodstream 102 (19) Infections in Community 103 (11) Hospitals in the W Moehring , Richard Sloane , Kenneth E Schmader , st In intensive care unit prior to BSIDeverick J Anderson 87 (6) *, Rebekah 40 (7) 44 (5) 0.05 21 Century: A Multicenter , Daniel J Sexton Cohort Study David J Weber , Vance G Fowler Jr , Emily Smathers Community-associated 1,2 Central line present at BSI 1,2 1,2 289 (20) 116 (22) 163 (19) Duke University Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina, United States of America, Duke Infection Control Outreach 1,2 1,2 0.08 Community-acquired BSI / Healthcare-associated BSI CAP/HCAP Intra-abdominal infection UTI S pneumoniae Enterobacteriaceae Haemophilus spp (including ESBL-PE) Enterobacteriaceae Enterobacteriaceae Anaerobes (including ESBL-PE) S aureus Enterococcus spp Meningitis Endocarditis S pneumoniae S aureus N meningitidis Streptococcus spp L monocytogenes Enterococcus spp SSTI S aureus β-hemolytic streptococci Enterobacteriaceae Anaerobes Bloodstream infection in critically ill patients Enterobacteriaceae P aeruginosa A baumannii S aureus HAP/VAP Enterobacteriaceae Enterobacteriaceae Enterobacteriaceae P aeruginosa Enterococcus spp P aeruginosa Staphylococcus spp Candida spp Enterococcus spp Enterococcus spp Variable depending on the site Enterobacteriaceae P aeruginosa Candida spp Candida spp Intra-abdominal infection UTI Catheter-related Surgical site infection infection Primary BSI Hospital-acquired BSI / ICU-acquired BSI Intensive Care MedCAP (2020)community-acquired 46:266–284 Fig Bloodstream infections in critically ill patients: main sources and leading pathogens BSI bloodstream infection, Candida Proteus Enterobacter 10 (1) 58 (4) infection due to to 0.07 a multidrug-resistant organism was strongly from 0.05 associated with failure to receive appropriate empiric hospitals antibiotic in the US was 160 beds in 2009, and 72% of hospitals Introduction therapy (OR = 2.17, 95% CI 1.48–3.18, p,0.001), majority hadthefewer than of 200 beds [4]._ENREF_4 Of the 39 million Bloodstream (BSIs)identified are a leading cause of suffering hospital discharges in the US in 2010, 19.9 million (51%) were theinfections predictors in Model remained independently st and death in the US As many as 250,000 BSIs occur each year from non-teaching associated with failure to receive appropriate empiric antibiotic facilities [5] Our understanding about the [1], with a mortality rate of 35% and costs of up to $37,000 per causes and risk factors for BSI in these community hospitals, with adjustment MDR 5) The exception case [2,3] Intherapy fact, BSI even was one of the top causes offor death in the(Table US 1,2 1,2 is alarmingly inadequate however, Prior E studies on BSIs4, in Deverick J Anderson *, Rebekah W Moehring Richard Sloane3, Kenneth Schmader to this trendthan was35,000 Charlson score, for which the community p-value, changed in 2008, leading to more deaths [4] hospitals have been limited1,2 to specific organisms [6,7], , Vance G Fowler Jr , Emily Smathers , Daniel J Sexton David J Weber The majority of 0.05 healthcare in the US is performed in smaller, from to 0.07 single institutions, intensive care units [8] and/or patients 30 (2) a Isolates that led toSerratia ,10 bloodstream infections are not included 13 (1) doi:10.1371/journal.pone.0091713.t003 Citrobacter 11 (1) Căn nguyên gây bệnh Acinetobacter 10 (1) Anaerobes 14 (1) Candida 10 (1) a Isolates that led to ,10 bloodstream infections are not included doi:10.1371/journal.pone.0091713.t003 Bloodstream Infections in Community Hospitals in the 21 Century: A Multicenter Cohort Study non-teaching1 community The mean size of Medical Duke Universityhospitals._ENREF_4 Division of Infectious Diseases, Duke University Center, Durham, Unitedand States of America, Duke Infection Control Outrea admitted prior toNorth the Carolina, emergence spread of epidemiologically Network, Durham, North Carolina, United States of America, Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, No Carolina, United States of America, Department of Medicine-Geriatrics, Duke University Medical Center and Geriatric Research Education and Clinical Center (GREC Durham VA Medical Center, Durham, North Carolina, United States of America, Department of Hospital Epidemiology, University of North Carolina Health Syste PLOS ONE | www.plosone.org March 2014 | Volume | Issue | e91713 Chapel Hill, North Carolina, United States of America Bloodstream Infections in Community Hospitals in the Abstract 21st Century: A Multicenter Cohort Study Background: While the majority of healthcare in the US is provided in community hospitals, the epidemiology and 1,2 1,2 Deverick J Anderson *, Rebekah W Moehring , Richard treatment of bloodstream infections in this setting is Sloane unknown., Kenneth E Schmader , 1,2 David J Weber , Vance G Fowler Jr , Emily Smathers , Daniel J Sexton Methods and Findings: We undertook this multicenter, retrospective cohort study to 1) describe the epidemiology of Duke University Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina, United States of America, Duke Infection Control Outreach bloodstream infections (BSI) in a network of community hospitals and 2) determine risk factors for inappropriate therapy for Network, Durham, North Carolina, United States of America, Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North bloodstream infections in community hospitals 1,470 patients were identified as having a BSI in community hospitals in Carolina, United States of America, Department of Medicine-Geriatrics, Duke University Medical Center and Geriatric Research Education and Clinical Center (GRECC), the southeastern US from 2003 through 2006 The majority of BSIs were community-onset, healthcare associated (n = 823, Durham VA Medical Center, Durham, North Carolina, United States of America, Department of Hospital Epidemiology, University of North Carolina Health System, 56%); 432 (29%) patients had community-acquired BSI, and 215 (15%) had hospital-onset, healthcare-associated BSI BSIs Chapel Hill, North Carolina, United States of America due to multidrug-resistant pathogens occurred in 340 patients (23%) Overall, the three most common pathogens were S aureus (n = 428, 28%), E coli (n = 359, 24%), coagulase-negative Staphylococci (n = 148, 10%), though type of infecting organism varied by location of acquisition (e.g., community-acquired) Inappropriate empiric antimicrobial therapy was Abstract given to 542 (38%) patients Proportions of inappropriate therapy varied by hospital (median = 33%, range 21–71%) Multivariate logistic regression identified the following factors independently associated with failure to receive appropriate Background: While the majority of healthcare the US is provided in community hospitals, the assistance epidemiology empiric antimicrobial therapy: in hospital where the patient received care (p,0.001), with and $3 ADLs (p = 0.005), treatment of bloodstream infections in this setting is unknown Charlson score (p = 0.05), community-onset, healthcare-associated infection (p = 0.01), and hospital-onset, healthcareassociated infection (p = 0.02) Important interaction was observed between Charlson score and location of acquisition Methods and Findings: We undertook this multicenter, retrospective cohort study to 1) describe the epidemiology of bloodstream infections (BSI) in aOur network communitystudy hospitals and 2) risk factors for of inappropriate therapyhospitals for Conclusions: large,ofmulticenter provides thedetermine most complete picture BSIs in community in the US to bloodstream infections community hospitals patients were identified as havingcommunity-onset, a BSI in community hospitals in date in The epidemiology of BSIs1,470 in community hospitals has changed: healthcare-associated BSI is most the southeastern US from 2003 through 2006 Thecommon majoritycause, of BSIsand were (n = 823, common, S aureus is the most ofcommunity-onset, patients with a healthcare BSI receivesassociated inappropriate empiric antimicrobial 56%); 432 (29%) patients BSI, and 215 (15%) had hospital-onset, healthcare-associated therapy.had Ourcommunity-acquired data suggest that appropriateness of empiric antimicrobial therapy is an importantBSI andBSIs needed performance due to multidrug-resistant pathogens occurred in 340 patients (23%) Overall, the three most common pathogens were S metric for physicians and hospital stewardship programs in community hospitals aureus (n = 428, 28%), E coli (n = 359, 24%), coagulase-negative Staphylococci (n = 148, 10%), though type of infecting organism varied by location of acquisition (e.g., community-acquired) Inappropriate empiric antimicrobial therapy was Citation: AndersonProportions DJ, Moehring RW, Sloane R, Schmader KE, Weber DJ, et al Bloodstream Infections in Community Hospitals in the 21st Century: A given to 542 (38%) patients of inappropriate therapy varied by(2014) hospital (median = 33%, range 21–71%) Multicenter Cohort Study PLoS ONE 9(3): e91713 doi:10.1371/journal.pone.0091713 Multivariate logistic regression identified the following factors independently associated with failure to receive appropriate Editor:therapy: Paul J Planet, Columbia University, States of America empiric antimicrobial hospital where the United patient received care (p,0.001), assistance with $3 ADLs (p = 0.005), scoreofReceived (pbloodstream = 0.05),August community-onset, healthcare-associated infection (p = 0.01), and hospital-onset, healthcare22, infection 2013; Accepted February 13, 2014; Published March 18, 2014 Figure Distribution of pathogens based on location ofCharlson acquisition (BSI) among 1,470 patients admitted Distribution of pathogens based on [FOOTNOTE] location of acquisition of bloodstream infection (BSI) among 1,470 patients admitted associated infection (p = 0.02) Important interaction observed between and of acquisition to community hospitals, 2003–2006 * CA = community-acquired, CO-HCA = community-onset, healthcare-associate, HO-HCA; Copyright: ß 2014 Anderson et al This is anwas open-access article distributedCharlson under the score terms of the location Creative Commons Attribution License, which permits Figure in any medium, provided the original author and sourceHO-HCA; are credited to community hospitals, 2003–2006 CoNS [FOOTNOTE] CA = community-acquired, CO-HCAand=reproduction community-onset, healthcare-associate, hospital-onset, healthcare-associated, = coagulase*negative Staphylococci.unrestricted use, distribution, Conclusions: OurFunding: large, multicenter study provides the most complete picture of BSIs in community hospitals in the US to doi:10.1371/journal.pone.0091713.g001 This work was supported by the Robert Wood Johnson Foundation [#66327 to DJA] and the National Institute of Health/National Institute of Allergy hospital-onset, healthcare-associated, CoNS = coagulase negative date Staphylococci The epidemiology of BSIs in community hospitals has changed: community-onset, healthcare-associated BSI most decision to publish, or and Infectious Diseases [K23 AIO95357 to DJA; K24 AI093969 to VGF] The funders had no role in study design, data collection andisanalysis, common, S aureus is the most common cause, and of patients with a BSI receives inappropriate empiric antimicrobial doi:10.1371/journal.pone.0091713.g001 preparation of the manuscript PLOS ONE | www.plosone.org therapy Our data suggest that appropriateness empiric antimicrobial therapy is anMerck, important needed performance Competing Interests: DJA has receivedofresearch support from the CDC, AHRQ, and Inc., and and receives royalties from UpToDate, Online KES receives March 2014 | Volume |with Issue Pfizer, | e91713 metric for 6physicians and hospital stewardship programs in community hospitals research support from Merck, Inc DJW has consulting relationships Merck, ASP, and Clorox and is on speaker’s bureaus for Merck and Pfizer VGF has consulting relationships with Merck, Pfizer, Novartis, Galderma, Novadigm, Durata, Achaogen, Affinium, Cerex, and MedImmune, and receives royalties from Total (%) Total (%) Căn nguyên gây bệnh P = 0.045, R² = 0.459 30 Gram positives 20 Gram negatives 40 30 20 10 2001 Table 1: Bloodstream infection isolates, 2001 to 2009, by organism 2002 2003 10 2004 2005 2006 2007 2008 2009 2001 Year Keywords: bloodstream infections, gram positive organisms, gram negative organi CHANGINGP = 0.0002, EPIDEMIOLOGY OF BLOODSTREAM R² = 0.869 epidemiology, antimicrobial susceptibility INFECTION PATHOGENS OVER TIME IN ADULT NONGram positives SPECIALTY PATIENTS AN AUSTRALIAN TERTIARY GramAT negatives HOSPITAL Ar 2002 Kar Aung, J 2005 Skinner,2006 Felicity2007 J Lee,2008 Allen C2009 Cheng 2003 Matthew 2004 CDI Year 2001 Year 2002 2003 2004 n % n % n % Gram positives 189 48.7 250 61.0 216 51.3 S aureus 100 25.8 138 33.7 107 25.4 2005 2006 ated from cultures) ents aged mean age ) patients r period, h group positive ates and analysed, lst 1,261 nity onset 04 (51%) tes while %) gram 44 (11%) Peer-reviewed articles roportion over time ) with a of gram in 2009, set BSIs rends in athogens positive trast, no over time igure 4) atistically negative nfections ge group t evident e gative xcluded excluded

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