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Blood cultures in the emergency department: Do we need a new approach?
Hemocultivos en los servicios de urgencias, ¿hacia un nuevo enfoque?
Pere Tudelaa,
Corresponding author
ptudela.germanstrias@gencat.net

Corresponding author.
, Montserrat Giménezb, Josep María Mòdola, Cristina Pratb,c
a Unidad de Corta Estancia-Observación de Urgencias, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain
b Servicio de Microbiología, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain
c Centros de Investigación Biomédica en Red (CIBER), Instituto de Salud Carlos III, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Emergency departments &#40;EDs&#41; provide care to many patients with infectious diseases&#59; it has been estimated that these account for 14&#46;3&#37; of all visits<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">1</span></a> in our community setting&#46; In this context&#44; clinicians often raise the possibility of taking blood cultures&#44; since the detection of bacteraemia is a fact with potential diagnostic&#44; prognostic and therapeutic significance&#46; Clinical practice in this regard is variable in different EDs and extractions range from 1 to 25&#37; of visits&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">2</span></a> However&#44; the indication of blood cultures is still a poorly defined aspect&#44; and subject of several controversies&#46; So far&#44; the indications have been remarkably generic&#44; such as suspected focal infection&#44; sepsis or endocarditis&#44; and the presence of fever&#44; chills&#44; leukocytosis or leukopenia&#44; or multiorgan failure&#44; unclarified&#46; With this approach the fraction of positive blood cultures&#44; variable depending on the series&#44; ranges from 4 to 21&#37;&#44; with a contamination rate of 3&#8211;7&#37;&#46; It has been estimated that the acceptable range would be between 5 and 15&#37; positive with a contamination rate of 2&#8211;3&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">3&#8211;6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">But in recent years&#44; many authors have questioned these results&#44; evaluating different aspects&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">7&#8211;9</span></a> On the one hand&#44; it was considered that the criteria for the indication of blood cultures should be more specific than those currently exposed&#46; And those questioned were mainly the ones conducted for EDs patients&#44; without hospital admissions&#46; In addition&#44; their clinical performance could be increased both quantitatively &#40;in percentage of isolates&#41; and qualitatively&#44; since it has been found that positive blood cultures do not always have a healthcare impact&#44; as sometimes they do not modify the therapeutic approach&#46; Do not forget that the practice of these cultures is not without drawbacks&#46; We must assess their economic costs and their workload&#44; and sometimes the problems associated with contamination and its different consequences&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The current situation is complex&#44; including numerous clinical studies as well as the emergence of different biomarkers &#40;BM&#41; in an attempt to predict the existence of bacteraemia&#46; Moreover&#44; we should not lose sight of the fact that in the near future the development of new molecular techniques could mean a radical change in the paradigm of all these issues&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Predicting bacteraemia</span><p id="par0020" class="elsevierStylePara elsevierViewall">The key consideration regarding patients with clinically suspected bacteraemia is to assess whether there are risk factors &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; which are present in 86&#37; of cases&#44; and logically determine the event probability&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">5&#44;10</span></a> In addition&#44; the possible existence of related factors should be assessed&#59; numerous studies have proposed different clinical and analytical variables as predictors of bacteraemia &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">10&#8211;20</span></a> The variability of populations&#44; settings&#44; source of bacteraemia&#44; and lab testing parameter cut-offs has made it difficult to reach a definitive diagnosis scheme in this regard&#46; A comprehensive analysis of different studies shows that the variables with greater predictive power are the presence of chills &#40;defined as &#8220;cold feeling with shaking&#8221;&#41; and hypotension or <span class="elsevierStyleItalic">shock</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">9</span></a> By contrast&#44; other variables such as clinical suspicion&#44; tachycardia&#44; temperature&#44; leukocytosis &#40;15&#44;000&#47;&#956;l&#41;&#44; thrombocytopenia&#44; lymphopenia or the neutrophils&#47;lymphocytes ratio are not useful&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The importance of the clinical context is highlighted in the Coburn et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">9</span></a> paper&#44; which allows to stratify the likelihood of bacteraemia in 3 levels&#46; In the low level &#40;2&#8211;13&#37;&#41; we have skin infections&#44; pneumonia and fever of unknown origin&#59; at the intermediate level &#40;19&#8211;25&#37;&#41;&#44; urinary tract infections &#40;UTI&#41;&#59; while the high level &#40;38&#8211;69&#37;&#41; corresponds to meningitis&#44; sepsis and septic <span class="elsevierStyleItalic">shock</span>&#46; When indicating the practice of blood cultures&#44; the authors propose to estimate the probability depending on the context&#44; not considering their indication in cases of isolated fever or leukocytosis&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The tendency of most groups has been to develop predictive models &#40;PM&#41;&#44; to estimate the probability of bacteraemia objectively&#46; Recently&#44; in the article by Eliakim-Raz et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">11</span></a> it was proposed to select the models that meet two requirements&#58; firstly&#44; those that incorporate internal validation&#44; and secondly&#44; those that allow stratifying the likelihood of bacteraemia in low or high &#40;arbitrarily defined as less than 3&#37; and above 30&#37;&#44; respectively&#41;&#46; 15 studies were analysed&#59; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the main characteristics of those conducted in patients with fever of undetermined origin&#46; One of the most striking findings of the analysis was that although the diagnostic yield of the models was acceptable&#44; the authors confirmed that none of them had been implemented in clinical practice&#46; The explanation for this finding may be that the PM are complicated&#44; requiring variables that are not available in the EDs&#44; or that clinicians do not want to dispense with the additional information that blood cultures can provide&#44; even when the likelihood is remote&#46; Perhaps we should value more the virtues of the different PM proposed and apply them as support of the clinical assessment&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Blood cultures in patients with fever of known focus</span><p id="par0035" class="elsevierStylePara elsevierViewall">Until recently&#44; blood cultures have been systematic in patients diagnosed in the EDs of major infectious syndromes&#44; such as pneumonia&#44; UTI&#44; cellulite and gastroenteritis&#46; However&#44; in recent years&#44; different papers have questioned this practice and is currently under debate&#46; In the case of UTI&#44; for uncomplicated pyelonephritis&#44; different studies show that blood cultures may be irrelevant if identification and sensitivity through urine culture is available&#46; Of the 10&#8211;25&#37; of patients who will have bacteraemia&#44; only 1&#46;9&#37; of them will have the treatment modified&#44; that is why some authors have proposed not to use blood cultures&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">21</span></a> On the contrary&#44; complicated pyelonephritis&#44; the difficulty in obtaining a sample for urine culture &#40;or risk of contamination&#41; and the possible existence of resistant organisms would not allow this approach&#46; However&#44; far from establishing a general premise&#44; decisions should always be individualized&#44; considering these various factors in each case&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">For pneumonia&#44; since the frequency of positive blood cultures is low&#44; around 1&#8211;16&#37; depending on the series&#44; systematic indication is also questioned&#46; In fact&#44; it has been shown that only 0&#8211;5&#37; of cases experience therapeutic modifications based on blood cultures&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">22</span></a> The general recommendation&#44; therefore&#44; is limited to severe clinical forms&#44; as these conditions are most likely caused by microorganisms other than <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> &#40;such as <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#44; <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> and other Gram-negative bacilli&#41; which are not covered with the usual guidelines&#46; They are also indicated in patients that are immunocompromised&#44; coming from other health centres and when there is evidence of cavitation or pleural effusion&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">23</span></a> However&#44; it is difficult to establish a recommendation as exhaustive as in UTI cases&#44; given that the etiologic diagnosis of pneumonia is not obtained so easily&#44; only 40&#8211;60&#37; of cases&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Gastroenteritis could have a similar approach to the UTI&#44; and if we have a sample for stool culture and&#47;or investigation of microorganisms &#40;toxins&#41;&#44; blood cultures would not be indicated systematically&#46; Although frequently requested in clinical practice&#44; the fact is that the clinical guides of reference consider their indication only in selected cases&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">24</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Regarding skin and subcutaneous tissue infections&#44; although the overall yield of blood cultures is considered relatively low&#44; it is highly variable depending on the series &#40;4&#8211;35&#37;&#41; probably due to differences in patient characteristics&#46; Some factors determine a higher bacteraemia frequency&#44; such as cirrhosis&#44; HIV disease&#44; lymphedema or head and neck cellulitis&#46; Several authors have considered that the impact on therapy is very limited and that they would only be indicated in immunosuppressed patients&#44; of complicated progression or exposed to unusual organisms&#44;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">25</span></a> although this approach is debatable&#44; considering the frequent absence of alternative samples for culture and the growing possibility of resistant microorganisms &#40;Methicillin resistant <span class="elsevierStyleItalic">S&#46; aureus</span>&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Blood cultures in patients with fever without a focus</span><p id="par0055" class="elsevierStylePara elsevierViewall">Patients with fever without a focus&#44; which have been studied numerous times&#44; still represent a challenge for EDs clinicians&#46; Their frequency is estimated at 7&#8211;15&#37; of all patients with fever in the ED&#59; it is therefore a common situation&#46; An important part of these&#44; 33&#8211;58&#37; are sent back home&#44; although 9&#37; of these may require hospitalization later&#46; In 13&#37; of cases there is no final diagnosis obtained&#44; and 4&#37; are not infectious&#44; but up to 35&#37; have bacterial infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">26&#8211;28</span></a> An interesting study by Gur et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">28</span></a> showed that among patients who had been discharged&#44; most had viral infections&#44; but occasionally bacteraemia and malaria was also detected&#44; and among those admitted&#44; the most frequent diagnoses were bacteraemia and endocarditis&#46; Blood cultures were positive in 12&#8211;20&#37; of cases&#44; of which nearly half were bacteraemia of unknown origin&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">26&#44;28</span></a> Therefore&#44; in most cases with serious diagnoses&#44; blood cultures represented a key element&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">From the point of view of emergency care&#44; and after ruling out some specific entities &#40;such as primary infection by HIV or malaria&#44; which usually occur in a given context&#41;&#44; the key issue is to assess these patients regarding the risk of having primary bacteraemia &#40;PB&#41;&#44; leaving aside other entities that do not require preferential treatment &#40;such as viral infections&#44; malignancies&#44; autoimmune diseases&#41;&#46; Reference to PB is made when there is no evidence of a clear focus&#44; being sometimes called occult bacteraemia due to its similarity to the paediatric setting&#44; although the latter nomenclature can be confusing because it refers to bacteraemia detected in non-hospitalized patients&#44; which&#44; in most cases&#44; do not correspond to patients without diagnosis and adequate treatment&#46; So the subgroup subject of concern is the one made up of patients with PB&#44; of uncertain origin&#44; who come to represent 15&#8211;20&#37; of all non-hospitalized bacteremias&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">29&#8211;31</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Therefore&#44; the question is to be able to indicate blood cultures in patients at risk of PB&#44; but not indiscriminately&#46; In order to achieve this&#44; assessing the presence of risk factors seems the most reasonable approach &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; It should be noted that in cases where blood cultures are already underway&#44; it would be advisable to display an expectant attitude&#44; keeping the patient in observation or short stay units until the results are received&#46; But the indication is much more questionable in those without risk factors&#44; especially if their good general condition points towards a prompt discharge&#46; Many authors have spoken against it&#44; mentioning its low profitability&#44; since less than 3&#37; are positive&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">32</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Blood cultures in patients not admitted to hospital</span><p id="par0070" class="elsevierStylePara elsevierViewall">The indication of blood cultures has been specially and repeatedly questioned in patients who are discharged from the EDs&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">7</span></a> But the reality is that&#44; quite often&#44; in most EDs&#44; detection of bacteraemia is observed in non-admitted patients&#44; representing 3&#8211;29&#37; of all detected&#46; Since the analysis of our initial experience&#44; different studies have provided data and considerations over the years about this issue&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">29&#8211;31</span></a> This wealth of experience allows us to confirm that there are 2 fundamental subgroups that should be interpreted in very different ways&#58; on the one hand&#44; a majority &#40;27&#8211;69&#37;&#41; of UTI with almost always appropriate diagnosis and treatment where&#44; as previously raised&#44; blood cultures could have been avoided&#59; and on the other&#44; a 12&#8211;39&#37; corresponding to undiagnosed and untreated PB&#44; where the case should always be reconsidered&#46; The processes thus detected are not trivial and include endocarditis&#44; osteomyelitis&#44; catheter infection&#44; cholangitis&#44; diverticulitis and bacteraemia of unknown origin&#44; among others&#46; It is noteworthy that out of the total number of patients&#44; 17&#8211;41&#37; required treatment modification&#44; and 14&#8211;82&#37; required admission&#44; in some cases to intensive care&#46; Although null in several studies&#44; mortality is not negligible&#44; since in some series it is found between 1&#46;2 and 5&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">29&#8211;31</span></a> When blood cultures performed on an outpatient basis are specifically analysed&#44; a very low yield is observed&#44; only 2&#46;4&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">32</span></a> The only variables related to bacteraemia were age and having received health care in the previous 2 weeks&#46; Therefore&#44; the indication is very questionable&#44; especially when considering that&#44; in up to 40&#37; of cases&#44; the initial assumption was that of a non-infectious or probably viral disease&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Therefore&#44; we should be able to act with greater discrimination&#46; For patients with a focal infection and no admission&#44; blood cultures would not be indicated in the vast majority of cases&#46; Moreover&#44; in fevers of unknown origin with potential PB&#44; due to existing risk factors&#44; the practice of blood cultures should be accompanied by an expectant attitude in observation or short stay units&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">33</span></a> In cases of fever without a focus and when admission is not anticipated&#44; blood culture indication should be questioned if there are no underlying diseases&#46; In any case&#44; having in place a healthcare circuit that ensures the quick location and reassessment of the patient if necessary is a must&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">4&#44;30&#44;33&#44;34</span></a> However&#44; it would be advantageous if these clinical decisions could have an additional element of support&#46; It is in this scenario where the infection BM may have a role in helping the EDs&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Role of biomarkers</span><p id="par0080" class="elsevierStylePara elsevierViewall">Of the more than 170 molecules related to systemic bacterial infection&#44; a small group has been proposed as predictors of bacteraemia and severity&#46; These are cytokines&#44; cell markers or receptors&#44; acute phase proteins&#44; endothelial or vasodilator factors&#44; among others&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">35</span></a> But data and experience on many of them is limited&#46; Interleukins 1 and 6 and tumour necrosis factor &#945; have been evaluated&#44; but they present difficulties due to their lab instability and rapid kinetics&#46; Endocan&#44; nitric oxide and lactate are mainly related to severity&#46; The truth is that most of the studies are centred around C-reactive protein &#40;CRP&#41; and procalcitonin &#40;PCT&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">35&#44;36</span></a> CRP is a sensitive inflammation marker&#44; but very unspecific and with relatively slow kinetics&#44; both in elevation as well as decline&#46; However&#44; PCT is more specific as a marker for systemic bacterial infection&#44; early elevation and high negative predictive value &#40;NPV&#41;&#46; Therefore&#44; numerous studies have proposed PCT determination to rule bacteraemia out&#46; Specifically&#44; a value lower than 0&#46;4&#8211;0&#46;5<span class="elsevierStyleHsp" style=""></span>ng&#47;ml has a NPV of 95&#8211;98&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">35&#8211;37</span></a> In our experience&#44; the combination of a Charlson index lower than 2 and a PCT lower than 0&#46;4<span class="elsevierStyleHsp" style=""></span>ng&#47;ml delimits a group &#40;25&#37; of the sample&#41; of low probability of bacteraemia &#40;0 to 2&#46;9&#37;&#41; with a NPV of 95&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">19</span></a> However&#44; it is worth recalling some limitations such as false positives in cases of multiple injuries and recent surgeries&#44; <span class="elsevierStyleItalic">shock</span>&#44; pancreatitis&#44; autoimmune diseases&#44; paraneoplastic syndromes&#44; heat stroke and immunomodulatory treatments before considering its clinical implementation&#46; And false negatives in infections caused by <span class="elsevierStyleItalic">Mycoplasma</span>&#44; tuberculosis&#44; <span class="elsevierStyleItalic">Chlamydia&#44; Legionella&#44; Candida</span> and <span class="elsevierStyleItalic">Pneumocystis jirovecii</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">35&#44;36</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Among the new BM&#44; soluble triggering receptor expressed on myeloid cells&#44; soluble urokinase receptor&#44; pentraxin-3 and proadrenomedullin could play a significant role&#44; but more oriented to the prediction of severity&#46; Presepsin seems to be more promising as a diagnostic tool&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">35</span></a> But if we consider its availability&#44; already in many hospitals&#44; the technique&#39;s speed and clinical experience&#44; the PCT is&#44; by far&#44; the BM of reference&#46; Admittedly we do not have an ideal BM&#44; probably because to expect great precision from a single molecule is simplify in excess something which is highly complex&#46; We must recall that the response mechanisms to bacterial infection involve multiple cellular mediators&#44; microorganism-specific factors and host-dependent factors&#46; The BM seek&#44; with more or less success&#44; to measure this response&#46; But despite these limitations&#44; and given the difficulty of predicting bacteraemia&#44; the PCT may be useful as complementary data on clinical assessment&#44; given its high NPV&#44; especially in those situations which we described as doubtful in connection with blood culture indication&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">The problem of contamination</span><p id="par0090" class="elsevierStylePara elsevierViewall">Contamination of blood cultures&#44; usually by skin bacteria or via the hands of healthcare staff&#44; have a negative impact on patients and the healthcare system&#46; The main problem derives from the difficulty in differentiating true bacteraemia from contamination&#44; essentially when faced with <span class="elsevierStyleItalic">Staphylococcus epidermidis</span> isolates&#46; When interpreting the result&#44; evaluating the time to positivity of blood cultures can be helpful&#44; as it is usually more than 24<span class="elsevierStyleHsp" style=""></span>h in contamination cases&#44; or the proportion of positive blood cultures&#44; which usually corresponds to only one of the samples in contamination cases&#46; However&#44; these dubious situations tend to involve taking new samples for culture&#44; performing other examinations or starting antibiotic treatment&#44; all really unnecessary and with the risks of adverse reactions&#44; generation of resistance&#44; or opportunist infections&#46; This represents an economic cost estimated at about 4500&#8211;10&#44;000<span class="elsevierStyleHsp" style=""></span>USD per contaminated blood culture&#44; and an extended hospital stay of about 1&#8211;5 days&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">EDs are at particular risk of blood culture contamination&#44; and often their rates are above the reference 3&#37;&#46; A high staff turnover&#44; the pressure to start early antibiotic treatment and the department&#39;s saturation have been considered as potential causes for this situation&#46; A high level of saturation has been associated with an increase of 23&#37; in the contamination rate&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">38</span></a> Multiple strategies have been developed in order to reduce contamination rates&#46; Of all these&#44; the use of sterile extraction <span class="elsevierStyleItalic">kits</span> and the implementation of phlebotomists teams have shown to be the most cost-effective&#46; For these reasons&#44; it is important to limit the maximum number of contaminated blood cultures&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Future prospects and conclusions</span><p id="par0100" class="elsevierStylePara elsevierViewall">Microbiological diagnosis has experienced significant advances in recent years&#46; One of them is the reduction of time intervals&#44; which can have a positive impact on patient treatment&#46; According to recent findings&#44; a prompt identification based on positive blood culture with mass spectrometry &#40;MALDI-TOF&#41; contributes to treatment improvements&#46; However&#44; blood cultures&#44; which are still the reference method&#44; have a fundamental limitation&#44; that is&#44; the time to positivity detection&#44; which is around 15<span class="elsevierStyleHsp" style=""></span>h on average&#46; In recent years&#44; new molecular methods are being developed to detect nucleic acids using polymerase chain reaction&#44; which allow&#44; directly from the patient&#39;s blood&#44; to obtain a result in just 6&#8211;8<span class="elsevierStyleHsp" style=""></span>h&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">39</span></a> These also allow the detection of slow-growing microorganisms&#44; non-culturable on artificial media&#44; or in cases where the patient has received antibiotic treatment&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">In the meantime&#44; while waiting for the further development of these innovative techniques&#44; we will need to optimize the performance of blood cultures using more conventional tools&#46; In some studies&#44; in order to adapt the indication and the blood culture technique&#44; a clinical intervention has been developed through recommendation guides&#44; with positive results&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">40</span></a> We must also consider that there might be a scope for improvement beyond infectious disease indications&#46; This would include patients with unclear diagnosis &#40;nonspecific deterioration&#44; ill-defined signs and symptoms&#41;&#44; in which blood cultures are performed randomly&#44; without a clear suspicion of infection&#46; We have found that this section is not negligible&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">41</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Perhaps the best strategy would be to define the subgroup with very low probability of bacteraemia &#40;&#60;3&#37;&#41;&#44; in which blood cultures would not be indicated&#46; This subgroup may include up to 25&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">19</span></a> The PM and some BM are helpful in this regard&#46; Also&#44; in an attempt to outline the different approaches that have been described&#44; we could stratify the indications of blood cultures according to the clinical context and the degree of proven utility&#46; Thus 3 large groups are defined&#44; from less to more controversial &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41; with group C where the indication is probably not justified&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">In conclusion&#44; to increase the diagnostic yield of blood cultures&#44; its efficiency&#44; and limit contamination associated complications&#44; better defined indication criteria should be considered&#46; We should also consider an added benefit related to a stricter indication&#44; that of a very likely improvement in the use of antibiotic treatment and hospital admissions&#46; Hopefully&#44; we will be witnessing the development of a new approach to these issues in the near future&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflict of interests</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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          "titulo" => "Blood cultures in patients with fever of known focus"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Tudela P&#44; Gim&#233;nez M&#44; M&#242;dol JM&#44; Prat C&#46; Hemocultivos en los servicios de urgencias&#44; &#191;hacia un nuevo enfoque&#63; Med Clin &#40;Barc&#41;&#46; 2016&#59;146&#58;455&#8211;459&#46;</p>"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">ESR&#44; erythrocyte sedimentation rate&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Signs and symptoms</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Temperature&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Tachycardia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypotension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Comorbidity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Shaking chills&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vomiting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Acute abdomen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Altered mental status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vascular catheter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Immunosuppression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Blood&#47;lab test</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Leukopenia or leukocytosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Bands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lymphopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Thrombocytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Elevated creatinine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypoalbuminemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Elevated alkaline phosphatase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>C-reactive protein&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ESR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Procalcitonin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Variables proposed as predictors of bacteraemia in febrile cases&#46;</p>"
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          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">AUC&#44; area under the curve&#59; AP&#44; alkaline phosphatase&#59; HR&#44; heart rate&#59; RR&#44; respiratory rate&#59; RF&#44; renal failure&#59; SBP&#44; systolic blood pressure&#59; CRP&#44; C-reactive protein&#59; PCT&#44; procalcitonin&#59; <span class="elsevierStyleItalic">T</span>&#44; temperature&#59; ESR&#44; erythrocyte sedimentation rate&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Adapted from Eliakim-Raz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">11</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Variables included</th><th class="td" title="table-head  " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Diagnostic yield</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Signs of sepsis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">History&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Laboratory&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">AUC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Probability&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Low risk&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">High risk&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bates et al&#46;&#44; 1990<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">12</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>38&#46;3&#176;&#44; shaking chills&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Comorbidity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#8211;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Leibovici et al&#46;&#44; 1991<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Shaking chills&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Comorbidity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RF&#44; &#8595; Albumin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#8211;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65&#8211;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mozes et al&#46;&#44; 1993<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">14</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>39&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Immunosuppressant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8593; AP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#8211;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#8211;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bates et al&#46;&#44; 1997<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Altered consciousness&#46; Abdominal focus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Liver disease&#44; Hickman catheter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&#8211;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#8211;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lizarralde et al&#46;&#44; 2004<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">16</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>38&#46;3&#176;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bands&#44; ESR &#62;70&#44; CRP &#62;12&#44; &#8595; platelets&#44; &#8593; urea&#44; &#8595; albumin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#8211;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65&#8211;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Shapiro et al&#46;&#44; 2008<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>39&#46;5&#176;&#44; 38&#46;3&#8211;39&#46;4&#176;&#46; Vomiting&#44; SBP &#60;90&#44; chills&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vascular catheter&#44; suspected endocarditis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Leucocytes &#62;18&#44;000 bands &#62;5&#37;&#44; &#8595; platelets&#44; creatinine &#62;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&#8211;0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#8211;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lipsky et al&#46;&#44; 2010<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>35&#46;6&#176; or &#62;38&#176;&#46; HR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>49 or &#62;125&#46; RR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10 or &#62;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Health care&#44; male&#44; coronary artery disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bands &#62;7&#37;&#44; leukocytes &#62;11&#44;000&#44; &#8595; Albumin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#8211;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&#8211;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tudela et al&#46;&#44; 2010<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Charlson &#62;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PCT<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#8211;2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#8211;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Jin et al&#46;&#44; 2013<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fever&#44; hypothermia&#44; HR &#8595;&#44; &#8595; SBP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Corticoid treatment&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;4&#8211;1&#46;9&nbsp;\t\t\t\t\t\t\n
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