Community-acquired pneumonia

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Dal-Ré, M.V. Castell, J. García-Puig" "autores" => array:3 [ 0 => array:2 [ "nombre" => "R." "apellidos" => "Dal-Ré" ] 1 => array:2 [ "nombre" => "M.V." "apellidos" => "Castell" ] 2 => array:2 [ "nombre" => "J." 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Ramírez" "autores" => array:2 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Falguera" "email" => array:1 [ 0 => "falguera@medicina.udl.cat" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M.F." "apellidos" => "Ramírez" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Medicina Interna, Hospital Universitari Arnau de Vilanova, Lleida, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neumonía adquirida en la comunidad" ] ] "textoCompleto" => "BackgroundAccording to recent studies, the incidence of community-acquired pneumonia (CAP) in adults is 3–20 cases per 1000 inhabitants/year, with an upward trend.<a class="elsevierStyleCrossRefs" href="#bib0405">1,2</a> There is an indisputable relationship between the incidence of CAP and advanced age, tobacco or alcohol consumption, low weight (body mass index <16) and, probably, morbid obesity and close contact with children.<a class="elsevierStyleCrossRefs" href="#bib0405">1–4</a> Chronic obstructive pulmonary disease (COPD), cerebrovascular disorders, advanced human immunodeficiency virus (HIV) infection and, probably, cardiovascular diseases increase the risk 2 to 4-fold.<a class="elsevierStyleCrossRefs" href="#bib0405">1,5</a>We can cautiously include the fact that a number of authors have found relationships between CAP and a work environment subject to dust and abrupt temperature changes and between CAP and poor dental hygiene, relationships that seem reasonable.<a class="elsevierStyleCrossRef" href="#bib0430">6</a> The seasonal relationship between Legionnaires’ disease and warm periods is perfectly documented; however, a recent study also established a relationship with rainy climate conditions, while winter causes an increase in the incidence of pneumococcal pneumonia.<a class="elsevierStyleCrossRef" href="#bib0435">7</a>An intense debate has arisen regarding certain drugs and the increased or decreased incidence of CAP. The controversy is not resolved, but perhaps if we put aside the possible pernicious role of inhaled corticosteroids and the consumption of benzodiazepines, the evidence does not side with the increased risk that proton pump inhibitors can play or with the reduction in risk attributable to angiotensin II inhibitors and statins.<a class="elsevierStyleCrossRefs" href="#bib0425">5,8–13</a>Aspiration pneumonia deserves a separate chapter. As its name suggests, this condition requires the presence of a number of predisposing factors that have been well established for decades, including alcoholism, neurological disease, gastrointestinal disease that impedes upper intestinal transit and conditions that cause a reduced level of consciousness.<a class="elsevierStyleCrossRef" href="#bib0470">14</a>The hopes placed in the pneumococcal polysaccharide vaccination, which has been available for decades, have been largely frustrated by numerous studies that, at best, attribute to it a slight benefit in terms of severity indicator parameters but not in terms of incidence and mortality.<a class="elsevierStyleCrossRef" href="#bib0475">15</a> The excellent results published after the massive vaccination of the pediatric population with the conjugate vaccination have renewed hopes for the adult population. Preliminary studies have suggested that the pneumococcal vaccine achieves a significant reduction in pneumococcal infections caused by the vaccine serotypes but has less impact on the overall incidence of CAP.<a class="elsevierStyleCrossRef" href="#bib0480">16</a> Similarly, the benefits of the influenza vaccination are undebatable, although they appear to be limited.<a class="elsevierStyleCrossRef" href="#bib0485">17</a>Approximately 30–40% of patients with CAP require hospitalization, and 2–10% require hospitalization in an intensive care unit (ICU). The overall mortality rate during hospitalization is 2.7%, a figure that increases significantly if we include the immediate aftermath (8% at 90 days, 21% at 12 months and 36% at 5 years).<a class="elsevierStyleCrossRefs" href="#bib0405">1,2,18</a> All of this results in very high overall healthcare expenditures, particularly in terms of hospitalization expenses, which represent more than 90% of the total cost.Clinical diagnosisThe medical history is the key element in the diagnosis of the disease. The presence of 2 or more symptoms or clinical signs (fever, cough, expectoration, dyspnea, pleuritic pain and characteristic physical signs) is considered essential in any study that assesses patients with CAP. Any clinician with certain experience knows that a simple reduction in the level of consciousness in an elderly individual could be due to pneumonia. The same is true when faced with a patient with fever with no respiratory manifestations.<a class="elsevierStyleCrossRef" href="#bib0495">19</a> However, the lack of specific clinical data forces us to rule out other diagnostic options. The presence of pleuritic pain or very obvious symptomatology can be of considerable use.<a class="elsevierStyleCrossRefs" href="#bib0405">1,19,20</a>Chest radiography confirms the clinical diagnosis, with findings that are easy to recognize in young patients with no previous respiratory diseases and when the X-rays are performed in good conditions.<a class="elsevierStyleCrossRef" href="#bib0495">19</a> Nevertheless, we are not always faced with such circumstances. Small condensations, which are difficult to observe in a plain X-ray, are obvious if we conduct chest computed tomography. Chest ultrasonography is an alternative diagnostic technique in the hands of experts and it enables us to detect the presence of pleural effusion with increased accuracy.<a class="elsevierStyleCrossRef" href="#bib0505">21</a>The differentiation between patients with typical or atypical clinical conditions (based on the presence or absence, respectively, of 3 or more of the following manifestations: sudden onset, chills, pleuritic pain, purulent expectoration, marked symptomatology and leukocytosis) has no absolute predictive usefulness. However, the differentiation correlates with a greater or lesser probability of conventional or atypical bacterial agents and is still of practical usefulness, particularly for patients with nonsevere CAP.<a class="elsevierStyleCrossRefs" href="#bib0510">22,23</a>Apart from these general clinical variables, various pathogens have been correlated with specific clinical and epidemiological findings (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Recent studies have shown that Streptococcus pneumoniae (S. pneumoniae) is still the most common etiological agent, followed by conventional bacteria and, particularly among individuals with underlying diseases, Haemophilus influenzae (H. influenzae), Staphylococcus aureus (S. aureus), Moraxella catarrhalis, Pseudomonas aeruginosa (P. aeruginosa) and other Gram-negative bacilli.<a class="elsevierStyleCrossRefs" href="#bib0405">1,19</a>P. aeruginosa and Gram-negative enteric bacilli frequently appear in patients with severe CAP, immunosuppression, advanced COPD and bronchiectasis and in those treated systemically with corticosteroids, although cases of pneumonia by P. aeruginosa and Acinetobacter spp. have been documented in previously healthy individuals.<a class="elsevierStyleCrossRefs" href="#bib0520">24,25</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Among the atypical agents, Mycoplasma pneumoniae (M. pneumoniae) constitutes the prototype microorganism responsible for clinical conditions with few symptoms, affecting young individuals and causing a subacute clinical condition with low severity. However, severe or fulminant episodes have been reported.<a class="elsevierStyleCrossRefs" href="#bib0405">1,26</a> Its epidemic character, at times within the same family group, is well known but is often not taken into account.<a class="elsevierStyleCrossRef" href="#bib0535">27</a>Chlamydophila pneumoniae, Chlamydophila psittaci and Coxiella burnetii complete the spectrum of these agents, with greater of lesser relative importance according to epidemiological studies based on the diagnostic tests performed, the presence of disease outbreaks and the geographical regions considered.<a class="elsevierStyleCrossRefs" href="#bib0495">19,28</a>Legionella pneumophila deserves special mention. This agent is associated with severe clinical conditions that frequently require hospitalization in ICUs and can be associated with particular clinical manifestations. A number of centers have fairly accurate predictive scales for this etiology.<a class="elsevierStyleCrossRef" href="#bib0545">29</a> Neurological or gastrointestinal abnormalities or hyponatremia constitute factors that have been typically related to this pathogen, along with the previously mentioned epidemiological characteristics (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRefs" href="#bib0405">1,30</a>The importance of the virus as a direct cause of CAP is undebatable after the recent pandemic caused by the influenza virus H1N1, which was responsible for very severe multilobar processes. Even in these cases, however, the association with other pathogenic bacteria (mainly S. pneumoniae and S. aureus) was common.<a class="elsevierStyleCrossRef" href="#bib0555">31</a> Studies based on molecular diagnostic techniques dramatically raise the frequency with which the virus is isolated in patients with CAP, but the actual relationship between the virus and pulmonary involvement is more questionable. The presence of extrapulmonary manifestations, such as headache and rhinorrhea, or a bilateral patchy image suggest a viral etiology.<a class="elsevierStyleCrossRef" href="#bib0560">32</a>In individuals infected by HIV, S. pneumoniae is the most common etiology when immunity is acceptable and Pneumocystis jiroveci when immunodeficiency is intense (CD4+ lymphocyte count below 200/mm3).<a class="elsevierStyleCrossRef" href="#bib0565">33</a> The relative importance of anaerobes and oropharyngeal flora is debatable, and their role might be greater than previously thought, even apart from patients with aspiration pneumonia.<a class="elsevierStyleCrossRef" href="#bib0570">34</a>S. aureus is characterized by the severe clinical conditions it causes, with bilateral infiltrates, often cavitated and associated with pleural effusion and previous influenza virus infection. Its potential methicillin resistance increases the relevance of this microorganism.<a class="elsevierStyleCrossRef" href="#bib0575">35</a>Finally, there have been various studies in recent years that compared CAP with pulmonary tuberculosis. The latter disease is characterized by a more overlapping clinical condition whose evolution is long and at times afebrile. The disease is associated with anorexia and weight loss and with a clear predilection for affecting the upper lobes.<a class="elsevierStyleCrossRef" href="#bib0580">36</a>Additional testsBiomarkersOver the last decade, numerous studies have assessed the diagnostic and prognostic usefulness of biomarkers in CAP. C-reactive protein (CRP) has been used to differentiate pneumonia from other respiratory infections such as tuberculosis, which express lower values. CRP has also been used to differentiate CAP of bacterial etiology from CAP of viral etiology or CAP caused by atypical microorganisms, which are also characterized by lower values.<a class="elsevierStyleCrossRefs" href="#bib0405">1,23,37</a> Applied to pleural fluid samples, CRP is useful for differentiating patients with simple pleural effusion from those with complicated pleural effusion.<a class="elsevierStyleCrossRef" href="#bib0590">38</a> Procalcitonin appears to fulfill similar functions and even shows more favorable results.Both CRP and procalcitonin have been incorporated into prognostic scales, thereby increasing their predictive value.<a class="elsevierStyleCrossRef" href="#bib0595">39</a> Higher levels are associated with increased severity, more aggressive etiologies and a risk of bacteremia or empyema. Their greatest practical usefulness probably lies in monitoring patient progress. The lack of a significant reduction during the patient's evolution warns of the possibility of complications and is associated with a poorer prognosis.<a class="elsevierStyleCrossRefs" href="#bib0600">40,41</a>It is difficult to list all the remaining parameters that have been associated in some way with the diagnosis and prognosis of CAP (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Among the most investigated are proadrenomedullin, various interleukins, dimer-D, copeptin and natriuretic peptides. The more routine substances and values that have also shown predictive ability include pH values, pCO2 and vitamin D. Although they have actual prognostic ability, it is very unlikely that most of these markers will end up being used in actual clinical applications.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Microbiological studiesUltimately, we have no truly useful technique for establishing the etiological diagnosis of CAP, although we still should use these techniques in certain circumstances.Blood cultures are recommended for all patients who require hospitalization; however, only approximately 10% will present bacteremia.<a class="elsevierStyleCrossRefs" href="#bib0405">1,42</a> According to certain studies, it seems reasonable to limit its use to patients with more severe CAP, particularly if they have septic shock, are immunosuppressed or have a clinical condition suggestive of bacterial infection. If this is not the case, the recent use of antibiotics will reduce its benefits.<a class="elsevierStyleCrossRefs" href="#bib0405">1,43</a> We should consider that samples aimed at isolating the microorganism through cultures should be extracted before starting antibiotic treatment. Thus, the laboratory results predictive of bacteremia, the case for some biomarkers, will have little importance in practice.The controversy over the use of sputum examination has dogged CAP for several decades and no short-term outcome is in sight. In certain centers experienced in obtaining good quality samples and that have microbiologists on call 24h a day, good results have been achieved with Gram staining and subsequent culture; however, saliva samples or late processed samples are not cost-effective. Obtaining samples using invasive methods, particularly from patients in ICU, improves the results.<a class="elsevierStyleCrossRef" href="#bib0620">44</a> It has been reported that the absence of S. aureus in nasal smears rules out this microorganism as a potential pathogen.<a class="elsevierStyleCrossRef" href="#bib0625">45</a>The presence of pleural fluid in sufficient quantities, which occurs in approximately 20% of patients, requires a sample to detect patients with empyema or complicated pleural effusion. The microbiological study of the fluid provides valuable information in approximately 20% of cases.<a class="elsevierStyleCrossRef" href="#bib0630">46</a>Antigen detection in urine is another regularly used technique. This test undoubtedly provides a greater number of diagnoses among patients with pneumococcal pneumonia, increasing by 11% the number of cases detected by the other techniques. According to a recent study, this test enables the identification of the pneumococcal serotype involved.<a class="elsevierStyleCrossRefs" href="#bib0635">47,48</a> Taking warfarin (but not antibiotics) could reduce the sensitivity of the technique, which has high specificity.<a class="elsevierStyleCrossRef" href="#bib0645">49</a> However, this test has 2 fundamental disadvantages: (1) it does not provide information on antibacterial sensitivity and (2) it only enables the detection of the presence of this microorganism, whose coverage is always considered in any empirical regimen. Consequently, at best we can only expect benefits related to a reduction in the antibacterial spectrum of the treatment and in the adverse effects associated with the treatment, but no benefits in terms of survival. Additionally, the price of the test is higher than that of the antibiotic regimens employed, and a calculation of the cost-benefit balance turns out negative, especially if used indiscriminately, as happens in many centers.<a class="elsevierStyleCrossRefs" href="#bib0405">1,50</a>For its part, detecting the Legionella antigen in urine has become virtually the technique of choice for diagnosing this etiology, given that the remaining tests are cumbersome and lack of good sensitivity. Nevertheless, the test shares the same drawbacks we mentioned for the pneumococcus antigen, and the cost-benefit balance is also unfavorable.<a class="elsevierStyleCrossRef" href="#bib0655">51</a> Therefore, a number of centers reserve this test for patients with criteria suggestive of Legionella infection.The polymerase chain reaction (PCR) technique represents the eternal promise that it can resolve, once and for all, the etiological diagnosis of CAP. There is no doubt that its sensitivity is superior to that of the other diagnostic methods. However, PCR requires a specific study of each pathogen, which represents its principal disadvantage, moreover if we consider that what is most useful clinically is the isolation of certain unusual microorganisms that require specific treatments, such as P. aeruginosa and S. aureus.<a class="elsevierStyleCrossRef" href="#bib0495">19</a> At present, PCR has not achieved a defined role within the routinely employed diagnostic techniques, if we exclude the influenza virus infection. It has also been suggested that PCR could be of clinical importance in detecting the resistance of M. pneumoniae to macrolides.<a class="elsevierStyleCrossRef" href="#bib0660">52</a>We will end by stating that serologies represent the past, when compared with PCR. There are those who still support the usefulness of IgM in diagnosing M. pneumoniae infection, although it does not appear that it will become a reference technique.PrognosisWe should emphasize the extraordinary success that Fine et al. had when they published their prognostic scale (PSI) in 1997. The scale sought to stratify patients with CAP into subgroups based on outcome criteria.<a class="elsevierStyleCrossRef" href="#bib0665">53</a> Since then, there have been an extraordinary number of published articles with new prognostic scales, with variants of the same or to validate these scales for various goals and in certain patient subpopulations.Due to its simplicity, the CURB-65 scale has been added to the PSI scale. The inclusion of various biomarkers or the substitution of some of the 5 variables of the CURB-65 scale by others that take into account, for example, oxygen saturation and comorbidity, seem to increase, in a number of studies, the scale's predictive value, although there is no sign that they will substitute the scale.<a class="elsevierStyleCrossRef" href="#bib0670">54</a>The main success of these 2 scales has been to facilitate objective data to ensure that patients do not require extended hospitalization. As expected, however, when employed for making other decisions, the scales’ predictive value has been lower. Thus, other criteria have had to be employed to select patients who require hospitalization in the ICU.<a class="elsevierStyleCrossRef" href="#bib0675">55</a> Other predictive scales have proliferated for this purpose, the most widely used of which was published a few years ago in the CAP management guidelines of the American Thoracic Society and Infectious Diseases Society of America.<a class="elsevierStyleCrossRef" href="#bib0610">42</a> This scale has been validated in various studies, a number of which have incorporated certain variants that will have difficulty succeeding.<a class="elsevierStyleCrossRefs" href="#bib0495">19,56</a>Ever since the high percentage of patients with cardiovascular complications during the acute phase of CAP was recognized, there has been a search for prognostic markers of such events. Thus, high troponin levels at admission, some interleukins and certain clinical factors, which have not been consistent among various authors, have been associated with cardiovascular risk.<a class="elsevierStyleCrossRefs" href="#bib0685">57,58</a>Numerous factors have been individually related to a poor short-term prognosis: age, chronic renal failure, low weight, delirium, empyema, bacteremia, low albumin and pO2 levels, leukopenia, high glycemia and pCO2 levels and a number of biomarkers (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRefs" href="#bib0405">1,2,14,42</a> In contrast, no correlation had been found between poorer outcomes and obesity, COPD or inhaled corticosteroid treatment. In terms of inhaled corticosteroid treatment, a beneficial effect has also been suggested.<a class="elsevierStyleCrossRef" href="#bib0695">59</a> The presence of specific units for managing patients with CAP could increase survival rates.Achieving clinical stability, i.e., the normalization of basic constants, is the main objective for hospitalized patients. Its failure results in an increased risk of complications and death. For those patients who persist with clinical manifestations, mainly fever, but with no clinical deterioration, biomarker analysis can be useful for discriminating a slow resolution (showing a significant reduction in biomarker levels) from poor evolution (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRefs" href="#bib0605">41,60,61</a>Finally, numerous authors have evaluated longer-term patient outcomes, either at 90 days or 1 year after the CAP. In all cases, the mortality risk was associated with the patient's characteristics, i.e., the underlying diseases, more than with the characteristics of the acute episode.<a class="elsevierStyleCrossRef" href="#bib0710">62</a> In a number of studies, the onset of cardiac complications during hospitalization, aspiration pneumonia and the need for intensive care were also predictive of greater long-term mortality.<a class="elsevierStyleCrossRefs" href="#bib0690">58,63,64</a> Similar circumstances also determine increased subsequent morbidity and the risk of early readmission.<a class="elsevierStyleCrossRef" href="#bib0725">65</a>The diagnosis of CAP offers an opportunity to diagnose previously unknown underlying diseases such as diabetes mellitus (e.g., among patients who have presented hyperglycemia during hospitalization), COPD, lung neoplasia and immunosuppressive conditions such as HIV infection and hematologic neoplasia. However, the study that requires the screening of these processes has not been established.TreatmentThe publication of consensus guidelines from the various medical societies has resulted in significant improvement in the management of CAP, mainly thanks to the standardization of antibiotic treatment and its application to the various patient subgroups.<a class="elsevierStyleCrossRefs" href="#bib0405">1,42</a> Several studies have shown that compliance with the guidelines and consensus protocols improves the patients’ medical care, which translates into all evolutionary parameters, including mortality.<a class="elsevierStyleCrossRef" href="#bib0405">1</a>There are 2 types of criteria that should be employed for selecting the most appropriate treatment: the severity of the clinical condition and the personal circumstances of the affected patient (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). The assessment of the clinical severity is based on the previously mentioned prognostic scales, preferably the CURB-65, and especially on correct clinical judgment.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Therefore, in the first group we would find patients who experience mild CAP. These patients, generally young and with no underlying diseases, may be treated at home, perhaps after a short period of observation. The infection will most likely be caused by pneumococcus or one of the atypical agents. Treatment with amoxicillin and azithromycin would be indicated. If this regimen cannot be followed then quinolone, preferentially moxifloxacin, may be employed. The use of beta-lactam agents could involve clinical and environmental benefits (development of resistance) and precedes the use of quinolones as the first choice. In selected cases where a pneumococcal etiology appears highly likely, clinicians may dispense with the macrolide. Subgroups of patients with mild CAP can have significant underlying diseases that could result in an increased risk of more resistant pathogens, mainly H. influenzae. For these groups, replacing amoxicillin with amoxicillin-clavulanate or cefditoren seems reasonable.<a class="elsevierStyleCrossRefs" href="#bib0405">1,19,42,66,67</a>In the second group, we would find patients with severe CAP, who require hospitalization in conventional wards. The spectrum of potential pathogens should be broadened to include H. influenzae and a number of Gram-negative bacilli. The recommended regimen in the majority of guidelines is the combination of a beta-lactam agent (ceftriaxone or amoxicillin-clavulanate) with a macrolide.<a class="elsevierStyleCrossRefs" href="#bib0405">1,19,42,67</a> As with the previous group, quinolones with pneumococcal activity are the most reasonable alternative. However, this general regimen is not without controversy. There is a debate on the need to include the macrolide in this initial empiric regimen. On one hand, we have the alleged cardiotoxicity associated with macrolides,<a class="elsevierStyleCrossRef" href="#bib0740">68</a> and on the other, we have its potential benefits, both in terms of increasing the antimicrobial coverage and its anti-inflammatory effects. We can conclude that although most studies favor the combined treatment, these studies are usually observational.<a class="elsevierStyleCrossRef" href="#bib0745">69</a> A recently published, prospective randomized trial with more than 2000 patients assigned to 3 branches (beta-lactam agent/beta-lactam agent plus macrolide/quinolone) found no differences in terms of mortality at 90 days.<a class="elsevierStyleCrossRef" href="#bib0750">70</a>Furthermore, the use of parenteral corticosteroids has generated significant controversy. Although the results are conflicting, these corticosteroids could provide certain benefits for patients with more severe CAP, both in terms of survival and earlier functional recovery.<a class="elsevierStyleCrossRefs" href="#bib0735">67,71,72</a>Finally, there are other minor points of discussion. The use of statins combined with antibiotic treatment has generated certain expectations that seem as if they will not be confirmed.<a class="elsevierStyleCrossRef" href="#bib0765">73</a> In another vein, the results of noninvasive mechanical ventilation do not seem encouraging.<a class="elsevierStyleCrossRef" href="#bib0770">74</a>The reference general empiric antibiotic regimen should undergo changes for patients with particular risk factors. Patients with aspiration pneumonia therefore require effective treatment against anaerobes and Gram-negative bacilli. It would therefore be preferable to employ a regimen that includes amoxicillin-clavulanate as a beta-lactam agent or, for severely ill patients or those with underlying diseases, piperacillin–tazobactam or a carbapenem.<a class="elsevierStyleCrossRefs" href="#bib0405">1,75</a> A similar reasoning should be applied to patients with empyema, in whom the coverage of anaerobes and Gram-positive germs is a priority.<a class="elsevierStyleCrossRef" href="#bib0630">46</a>The regimen should also be modified depending on the microorganism responsible (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). Thus, a diagnosis or high suspicion of pneumonia by P. aeruginosa or by resistant Gram-negative bacilli, mainly in immunosuppressed patients or those who meet various criteria associated with this pathogen (recent hospitalization, previous antibiotic treatment, advanced COPD, bronchiectasis or systemic corticosteroid treatment), requires the preferential application of an antipseudomonal beta-lactam agent, combined perhaps with amikacin.<a class="elsevierStyleCrossRefs" href="#bib0405">1,24,42,67</a> For treating pneumonia by methicillin-resistant S. aureus, the efficacy of linezolid appears to be superior to that of vancomycin, although ceftaroline, which has recently been approved, could very well take its place.<a class="elsevierStyleCrossRefs" href="#bib0780">76,77</a> In those areas where the resistance of M. pneumoniae to macrolides is high, tetracyclines appear to be an effective alternative.<a class="elsevierStyleCrossRef" href="#bib0790">78</a> Regarding Legionnaires’ disease, it is likely that the efficacies of quinolone and azithromycin are comparable; however, experience recommends using the former when dealing with severely ill patients.<a class="elsevierStyleCrossRef" href="#bib0550">30</a> Finally, oseltamivir should be added when the epidemiological circumstances or microbiological results recommend its use.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>The antibiotic treatment regimens for patients hospitalized in ICU or for those who met healthcare-associated pneumonia criteria do not differ considerably from the recommendations for patients included in the previous section, although the clinical severity will favor the use of regimens with greater coverage in a higher percentage of cases.<a class="elsevierStyleCrossRefs" href="#bib0405">1,19,42,79</a> The combination of a broad-spectrum beta-lactam agent and a quinolone has frequently been used for critically ill patients. A recent study, however, found no differences compared with the beta-lactam agent plus macrolide regimen.<a class="elsevierStyleCrossRef" href="#bib0800">80</a>Lastly, it is worth noting that antibiotic treatment should be started as soon as possible, within the emergency department, which commonly uses excessively long treatment regimens. It has been shown that treatment lasting 5–7 days, for patients lacking local complications (empyema or cavitations) and with good clinical evolution, would be sufficient.<a class="elsevierStyleCrossRefs" href="#bib0405">1,19</a>Conflicts of interestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres797713" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec795737" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres797714" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec795738" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Background" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinical diagnosis" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Additional tests" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Biomarkers" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Microbiological studies" ] ] ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Prognosis" ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Treatment" ] 9 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec795737" "palabras" => array:7 [ 0 => "Community-acquired pneumonia" 1 => "Risk factors" 2 => "Epidemiology" 3 => "Clinical manifestations" 4 => "Diagnosis" 5 => "Biomarkers" 6 => "Prognosis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec795738" "palabras" => array:7 [ 0 => "Neumonía adquirida en la comunidad" 1 => "Factores de riesgo" 2 => "Epidemiología" 3 => "Manifestaciones clínicas" 4 => "Diagnóstico" 5 => "Biomarcadores" 6 => "Pronóstico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "This article not only reviews the essential aspects of community-acquired pneumonia for daily clinical practice, but also highlights the controversial issues and provides the newest available information. Community-acquired pneumonia is considered in a broad sense, without excluding certain variants that, in recent years, a number of authors have managed to delineate, such as healthcare-associated pneumonia. The latter form is nothing more than the same disease that affects more frail patients, with a greater number of risk factors, both sharing an overall common approach." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El presente artículo no revisa únicamente aquellos aspectos de la neumonía adquirida en la comunidad fundamentales para la práctica clínica diaria, sino que incide en los temas polémicos, y aporta la información más novedosa disponible. Se considera la neumonía adquirida en la comunidad en un sentido amplio, sin excluir ciertas variantes que, durante los últimos años, algunos autores han llegado a deslindar, como la neumonía asociada a cuidados sanitarios. Esta última no es más que la misma enfermedad que incide en pacientes más frágiles, con un mayor número de factores de riesgo, compartiendo ambas un planteamiento global común." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Falguera M, Ramírez MF. Neumonía adquirida en la comunidad. Rev Clin Esp. 2015;215:458–467." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Abbreviations: COPD, chronic obstructive pulmonary disease." "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Microorganisms \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">Epidemiological data \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">Clinical and radiological data \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Streptococcus pneumoniae \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The most common in any situation. Winter predominance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Typical clinical condition: chills, rust-colored sputum, pleuritic pain, leukocytes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Haemophilus influenzae \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Individuals with underlying diseases, especially smokers and patients with COPD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Typical clinical condition: chills, rust-colored sputum, pleuritic pain, leukocytes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Staphylococcus aureus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Drug addiction, previous influenza virus infection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Very severe conditions with bilateral infiltrates, cavitations and pleural effusion. Frequent bacteremia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Methicillin-resistant Staphylococcus aureus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Healthcare centers with a high rate of colonization, previous antibiotic therapy, recent hospitalization \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Very severe conditions with bilateral infiltrates, cavitations and pleural effusion. Frequent bacteremia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Gram-negative bacilli and Pseudomonas aeruginosa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Immunosuppression, patients with advanced COPD, treatment with systemic corticosteroids or bronchiectasis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Very severe clinical condition with septic shock. Radiological cavitation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Anaerobes and oral cavity flora \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Patients with aspiration pneumonia (altered level of consciousness or swallowing disorder), alcoholism or poor oral hygiene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cavitated infiltrate with foul-smelling sputum. Presence of empyema or complicated pleural effusion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mycoplasma pneumoniae \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Young individuals with no underlying diseases. Outbreaks in communities or relatives \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Generally mild clinical condition and slightly symptomatic (atypical clinical condition) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Chlamydophila pneumoniae \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Equally affects all population subgroups \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clinical condition without particular characteristics \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Coxiella burnetii \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">More common in mountainous regions; contact with livestock \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mildly symptomatic conditions or febrile syndrome without focus. Hepatic disorder \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Legionella pneumophila \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Predominantly summer, related to rainy periods. Disease outbreaks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe clinical conditions. Neurological and gastrointestinal (diarrhea) disorders, hyponatremia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Virus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Disease outbreaks. During pandemics, obese individuals and pregnant women are mostly affected \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Upper respiratory tract symptoms and headache Patchy multilobar infiltrate \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1337986.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Microorganisms responsible for community-acquired pneumonia and their correlation with specific clinical and epidemiological characteristics." ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "Abbreviations: MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinase." "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Biomarkers \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">Clinical diagnosis<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>,<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \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">Etiological diagnosis<a class="elsevierStyleCrossRef" href="#tblfn0015">c</a> \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">Complications and mortality \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">Progress monitoring \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Albumin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Beta-defensin 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Leukocyte count \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>,<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Leukocyte count \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Leukocyte count \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Copeptin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Cortisol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">D dimers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Tumor necrosis factor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Interleukin 6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Interleukin 8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Interleukin 10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Kallistatin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Lactate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Lipocalin 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">MMP-9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">MMP-9/TIMP-1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">pCO2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Natriuretic peptide. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">pH<7.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Proadrenomedullin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Procalcitonin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>,<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">C-Reactive Protein \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>,<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">O2 saturation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Sodium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Urea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Vitamin D (deficiency) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1337988.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Pneumonia versus tuberculosis." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Pneumonia versus acute bronchitis or COPD exacerbation." ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "Bacterial exacerbation versus viral pneumonia or by atypical agents." ] ] ] "descripcion" => array:1 [ "en" => "Potential usefulness of various plasma biomarkers in managing patients with community-acquired pneumonia." ] ] 2 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient subgroup \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">Most likely microorganisms \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">Recommended empiric treatment \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mild pneumonia with no underlying diseases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Streptococcus pneumoniae, atypical agents and virus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Option: amoxicillin±macrolide Alternative: quinolone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mild pneumonia with underlying diseases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Streptococcus pneumoniae, atypical agents and virus, Haemophilus influenzae, Gram-negative bacilli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Option: amoxicillin-clavulanate or cefditoren±macrolide Alternative: quinolone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Severe pneumonia with no risk factors \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Streptococcus pneumoniae, atypical agents and virus, Haemophilus influenzae, Gram-negative bacteria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Option: ceftriaxone±macrolide Alternative: quinolone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Very severe pneumonia with risk factors for Pseudomonas aeruginosa or Gram-negative bacilli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Streptococcus pneumoniae, atypical agents and virus, Haemophilus influenzae, Gram-negative bacteria, Pseudomonas aeruginosa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Option: cefepime or piperacillin–tazobactam or carbapenem±macrolide or quinolone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Aspiration pneumonia or empyema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Streptococcus pneumoniae, other Gram-positive cocci, anaerobic, Gram-negative bacilli \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Option: amoxicillin-clavulanate or piperacillin–tazobactam or carbapenem<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> Alternative: quinolone+clindamycin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Pneumonia with criteria of methicillin-resistant Staphylococcus aureus infection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Streptococcus pneumoniae, atypical agents and virus, Haemophilus influenzae, Gram-negative bacteria, Pseudomonas aeruginosa, Staphylococcus aureus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Option: amoxicillin-clavulanate or ceftriaxone or piperacillin–tazobactam or carbapenem±macrolide+linezolid or vancomycin Alternative: ceftaroline±macrolide \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1337985.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "a" "nota" => "Depending on the relative risk of other microorganisms." ] ] ] "descripcion" => array:1 [ "en" => "Etiology and recommended empiric treatment according to the various patient subgroups." ] ] 3 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Microorganism isolated \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">Recommended treatment \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Streptococcus pneumoniae \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Option: amoxicillin Alternative: quinolone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Legionella pneumophila \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Option: quinolone Alternative: azithromycin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mycoplasma pneumoniae \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Option: macrolide Alternatives: tetracyclines<a class="elsevierStyleCrossRef" href="#tblfn0025">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Methicillin-resistant Staphylococcus aureus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Option: linezolid Alternatives: vancomycin or ceftaroline \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Pseudomonas aeruginosa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Antipseudomonal beta-lactam<a class="elsevierStyleCrossRef" href="#tblfn0030">b</a>±amikacin Alternative: quinolone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Influenza virus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ceftriaxone+macrolide+oseltamivir Alternative: quinolone+oseltamivir \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1337987.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "a" "nota" => "In areas with high rates of resistance to macrolides." ] 1 => array:3 [ "identificador" => "tblfn0030" "etiqueta" => "b" "nota" => "Based on the results of the antibiogram." ] ] ] "descripcion" => array:1 [ "en" => "Targeted treatment depending on the microorganism isolated." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:80 [ 0 => array:3 [ "identificador" => "bib0405" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "e1–19" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guía multidisciplinar para la valoración pronóstica, diagnóstico y tratamiento de la neumonía adquirida en la comunidad" 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which has been available for decades&#44; have been largely frustrated by numerous studies that&#44; at best&#44; attribute to it a slight benefit in terms of severity indicator parameters but not in terms of incidence and mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">15</span></a> The excellent results published after the massive vaccination of the pediatric population with the conjugate vaccination have renewed hopes for the adult population&#46; Preliminary studies have suggested that the pneumococcal vaccine achieves a significant reduction in pneumococcal infections caused by the vaccine serotypes but has less impact on the overall incidence of CAP&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">16</span></a> Similarly&#44; the benefits of the influenza vaccination are undebatable&#44; although they appear to be limited&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">17</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Approximately 30&#8211;40&#37; of patients with CAP require hospitalization&#44; and 2&#8211;10&#37; require hospitalization in an intensive care unit &#40;ICU&#41;&#46; The overall mortality rate during hospitalization is 2&#46;7&#37;&#44; a figure that increases significantly if we include the immediate aftermath &#40;8&#37; at 90 days&#44; 21&#37; at 12 months and 36&#37; at 5 years&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;2&#44;18</span></a> All of this results in very high overall healthcare expenditures&#44; particularly in terms of hospitalization expenses&#44; which represent more than 90&#37; of the total cost&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical diagnosis</span><p id="par0035" class="elsevierStylePara elsevierViewall">The medical history is the key element in the diagnosis of the disease&#46; The presence of 2 or more symptoms or clinical signs &#40;fever&#44; cough&#44; expectoration&#44; dyspnea&#44; pleuritic pain and characteristic physical signs&#41; is considered essential in any study that assesses patients with CAP&#46; Any clinician with certain experience knows that a simple reduction in the level of consciousness in an elderly individual could be due to pneumonia&#46; The same is true when faced with a patient with fever with no respiratory manifestations&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">19</span></a> However&#44; the lack of specific clinical data forces us to rule out other diagnostic options&#46; The presence of pleuritic pain or very obvious symptomatology can be of considerable use&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;19&#44;20</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Chest radiography confirms the clinical diagnosis&#44; with findings that are easy to recognize in young patients with no previous respiratory diseases and when the X-rays are performed in good conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">19</span></a> Nevertheless&#44; we are not always faced with such circumstances&#46; Small condensations&#44; which are difficult to observe in a plain X-ray&#44; are obvious if we conduct chest computed tomography&#46; Chest ultrasonography is an alternative diagnostic technique in the hands of experts and it enables us to detect the presence of pleural effusion with increased accuracy&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">21</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The differentiation between patients with typical or atypical clinical conditions &#40;based on the presence or absence&#44; respectively&#44; of 3 or more of the following manifestations&#58; sudden onset&#44; chills&#44; pleuritic pain&#44; purulent expectoration&#44; marked symptomatology and leukocytosis&#41; has no absolute predictive usefulness&#46; However&#44; the differentiation correlates with a greater or lesser probability of conventional or atypical bacterial agents and is still of practical usefulness&#44; particularly for patients with nonsevere CAP&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">22&#44;23</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Apart from these general clinical variables&#44; various pathogens have been correlated with specific clinical and epidemiological findings &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Recent studies have shown that <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> &#40;<span class="elsevierStyleItalic">S</span>&#46; <span class="elsevierStyleItalic">pneumoniae</span>&#41; is still the most common etiological agent&#44; followed by conventional bacteria and&#44; particularly among individuals with underlying diseases&#44; <span class="elsevierStyleItalic">Haemophilus influenzae</span> &#40;<span class="elsevierStyleItalic">H&#46; influenzae</span>&#41;&#44; <span class="elsevierStyleItalic">Staphylococcus aureus</span> &#40;<span class="elsevierStyleItalic">S&#46; aureus</span>&#41;&#44; <span class="elsevierStyleItalic">Moraxella catarrhalis</span>&#44; <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> &#40;<span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#41; and other Gram-negative bacilli&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;19</span></a><span class="elsevierStyleItalic">P&#46; aeruginosa</span> and Gram-negative enteric bacilli frequently appear in patients with severe CAP&#44; immunosuppression&#44; advanced COPD and bronchiectasis and in those treated systemically with corticosteroids&#44; although cases of pneumonia by <span class="elsevierStyleItalic">P&#46; aeruginosa</span> and <span class="elsevierStyleItalic">Acinetobacter spp</span>&#46; have been documented in previously healthy individuals&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">24&#44;25</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Among the atypical agents&#44; <span class="elsevierStyleItalic">Mycoplasma pneumoniae</span> &#40;<span class="elsevierStyleItalic">M</span>&#46; <span class="elsevierStyleItalic">pneumoniae</span>&#41; constitutes the prototype microorganism responsible for clinical conditions with few symptoms&#44; affecting young individuals and causing a subacute clinical condition with low severity&#46; However&#44; severe or fulminant episodes have been reported&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;26</span></a> Its epidemic character&#44; at times within the same family group&#44; is well known but is often not taken into account&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">27</span></a><span class="elsevierStyleItalic">Chlamydophila pneumoniae</span>&#44; <span class="elsevierStyleItalic">Chlamydophila psittaci</span> and <span class="elsevierStyleItalic">Coxiella burnetii</span> complete the spectrum of these agents&#44; with greater of lesser relative importance according to epidemiological studies based on the diagnostic tests performed&#44; the presence of disease outbreaks and the geographical regions considered&#46;<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">19&#44;28</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Legionella pneumophila</span> deserves special mention&#46; This agent is associated with severe clinical conditions that frequently require hospitalization in ICUs and can be associated with particular clinical manifestations&#46; A number of centers have fairly accurate predictive scales for this etiology&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">29</span></a> Neurological or gastrointestinal abnormalities or hyponatremia constitute factors that have been typically related to this pathogen&#44; along with the previously mentioned epidemiological characteristics &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;30</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The importance of the virus as a direct cause of CAP is undebatable after the recent pandemic caused by the influenza virus H1N1&#44; which was responsible for very severe multilobar processes&#46; Even in these cases&#44; however&#44; the association with other pathogenic bacteria &#40;mainly <span class="elsevierStyleItalic">S&#46; pneumoniae</span> and <span class="elsevierStyleItalic">S&#46; aureus</span>&#41; was common&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">31</span></a> Studies based on molecular diagnostic techniques dramatically raise the frequency with which the virus is isolated in patients with CAP&#44; but the actual relationship between the virus and pulmonary involvement is more questionable&#46; The presence of extrapulmonary manifestations&#44; such as headache and rhinorrhea&#44; or a bilateral patchy image suggest a viral etiology&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">32</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In individuals infected by HIV&#44; <span class="elsevierStyleItalic">S&#46; pneumoniae</span> is the most common etiology when immunity is acceptable and <span class="elsevierStyleItalic">Pneumocystis jiroveci</span> when immunodeficiency is intense &#40;CD4&#43; lymphocyte count below 200&#47;mm<span class="elsevierStyleSup">3</span>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">33</span></a> The relative importance of anaerobes and oropharyngeal flora is debatable&#44; and their role might be greater than previously thought&#44; even apart from patients with aspiration pneumonia&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">34</span></a><span class="elsevierStyleItalic">S&#46; aureus</span> is characterized by the severe clinical conditions it causes&#44; with bilateral infiltrates&#44; often cavitated and associated with pleural effusion and previous influenza virus infection&#46; Its potential methicillin resistance increases the relevance of this microorganism&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">35</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Finally&#44; there have been various studies in recent years that compared CAP with pulmonary tuberculosis&#46; The latter disease is characterized by a more overlapping clinical condition whose evolution is long and at times afebrile&#46; The disease is associated with anorexia and weight loss and with a clear predilection for affecting the upper lobes&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">36</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Additional tests</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Biomarkers</span><p id="par0080" class="elsevierStylePara elsevierViewall">Over the last decade&#44; numerous studies have assessed the diagnostic and prognostic usefulness of biomarkers in CAP&#46; C-reactive protein &#40;CRP&#41; has been used to differentiate pneumonia from other respiratory infections such as tuberculosis&#44; which express lower values&#46; CRP has also been used to differentiate CAP of bacterial etiology from CAP of viral etiology or CAP caused by atypical microorganisms&#44; which are also characterized by lower values&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;23&#44;37</span></a> Applied to pleural fluid samples&#44; CRP is useful for differentiating patients with simple pleural effusion from those with complicated pleural effusion&#46;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">38</span></a> Procalcitonin appears to fulfill similar functions and even shows more favorable results&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Both CRP and procalcitonin have been incorporated into prognostic scales&#44; thereby increasing their predictive value&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">39</span></a> Higher levels are associated with increased severity&#44; more aggressive etiologies and a risk of bacteremia or empyema&#46; Their greatest practical usefulness probably lies in monitoring patient progress&#46; The lack of a significant reduction during the patient&#39;s evolution warns of the possibility of complications and is associated with a poorer prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0600"><span class="elsevierStyleSup">40&#44;41</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">It is difficult to list all the remaining parameters that have been associated in some way with the diagnosis and prognosis of CAP &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Among the most investigated are proadrenomedullin&#44; various interleukins&#44; dimer-D&#44; copeptin and natriuretic peptides&#46; The more routine substances and values that have also shown predictive ability include pH values&#44; pCO<span class="elsevierStyleInf">2</span> and vitamin D&#46; Although they have actual prognostic ability&#44; it is very unlikely that most of these markers will end up being used in actual clinical applications&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Microbiological studies</span><p id="par0095" class="elsevierStylePara elsevierViewall">Ultimately&#44; we have no truly useful technique for establishing the etiological diagnosis of CAP&#44; although we still should use these techniques in certain circumstances&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Blood cultures are recommended for all patients who require hospitalization&#59; however&#44; only approximately 10&#37; will present bacteremia&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;42</span></a> According to certain studies&#44; it seems reasonable to limit its use to patients with more severe CAP&#44; particularly if they have septic shock&#44; are immunosuppressed or have a clinical condition suggestive of bacterial infection&#46; If this is not the case&#44; the recent use of antibiotics will reduce its benefits&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;43</span></a> We should consider that samples aimed at isolating the microorganism through cultures should be extracted before starting antibiotic treatment&#46; Thus&#44; the laboratory results predictive of bacteremia&#44; the case for some biomarkers&#44; will have little importance in practice&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The controversy over the use of sputum examination has dogged CAP for several decades and no short-term outcome is in sight&#46; In certain centers experienced in obtaining good quality samples and that have microbiologists on call 24<span class="elsevierStyleHsp" style=""></span>h a day&#44; good results have been achieved with Gram staining and subsequent culture&#59; however&#44; saliva samples or late processed samples are not cost-effective&#46; Obtaining samples using invasive methods&#44; particularly from patients in ICU&#44; improves the results&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">44</span></a> It has been reported that the absence of <span class="elsevierStyleItalic">S&#46; aureus</span> in nasal smears rules out this microorganism as a potential pathogen&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">45</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The presence of pleural fluid in sufficient quantities&#44; which occurs in approximately 20&#37; of patients&#44; requires a sample to detect patients with empyema or complicated pleural effusion&#46; The microbiological study of the fluid provides valuable information in approximately 20&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">46</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Antigen detection in urine is another regularly used technique&#46; This test undoubtedly provides a greater number of diagnoses among patients with pneumococcal pneumonia&#44; increasing by 11&#37; the number of cases detected by the other techniques&#46; According to a recent study&#44; this test enables the identification of the pneumococcal serotype involved&#46;<a class="elsevierStyleCrossRefs" href="#bib0635"><span class="elsevierStyleSup">47&#44;48</span></a> Taking warfarin &#40;but not antibiotics&#41; could reduce the sensitivity of the technique&#44; which has high specificity&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">49</span></a> However&#44; this test has 2 fundamental disadvantages&#58; &#40;1&#41; it does not provide information on antibacterial sensitivity and &#40;2&#41; it only enables the detection of the presence of this microorganism&#44; whose coverage is always considered in any empirical regimen&#46; Consequently&#44; at best we can only expect benefits related to a reduction in the antibacterial spectrum of the treatment and in the adverse effects associated with the treatment&#44; but no benefits in terms of survival&#46; Additionally&#44; the price of the test is higher than that of the antibiotic regimens employed&#44; and a calculation of the cost-benefit balance turns out negative&#44; especially if used indiscriminately&#44; as happens in many centers&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;50</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">For its part&#44; detecting the <span class="elsevierStyleItalic">Legionella</span> antigen in urine has become virtually the technique of choice for diagnosing this etiology&#44; given that the remaining tests are cumbersome and lack of good sensitivity&#46; Nevertheless&#44; the test shares the same drawbacks we mentioned for the pneumococcus antigen&#44; and the cost-benefit balance is also unfavorable&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">51</span></a> Therefore&#44; a number of centers reserve this test for patients with criteria suggestive of <span class="elsevierStyleItalic">Legionella</span> infection&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The polymerase chain reaction &#40;PCR&#41; technique represents the eternal promise that it can resolve&#44; once and for all&#44; the etiological diagnosis of CAP&#46; There is no doubt that its sensitivity is superior to that of the other diagnostic methods&#46; However&#44; PCR requires a specific study of each pathogen&#44; which represents its principal disadvantage&#44; moreover if we consider that what is most useful clinically is the isolation of certain unusual microorganisms that require specific treatments&#44; such as <span class="elsevierStyleItalic">P&#46; aeruginosa</span> and <span class="elsevierStyleItalic">S&#46; aureus</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">19</span></a> At present&#44; PCR has not achieved a defined role within the routinely employed diagnostic techniques&#44; if we exclude the influenza virus infection&#46; It has also been suggested that PCR could be of clinical importance in detecting the resistance of <span class="elsevierStyleItalic">M&#46; pneumoniae</span> to macrolides&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">52</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">We will end by stating that serologies represent the past&#44; when compared with PCR&#46; There are those who still support the usefulness of IgM in diagnosing <span class="elsevierStyleItalic">M&#46; pneumoniae</span> infection&#44; although it does not appear that it will become a reference technique&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Prognosis</span><p id="par0135" class="elsevierStylePara elsevierViewall">We should emphasize the extraordinary success that Fine et al&#46; had when they published their prognostic scale &#40;PSI&#41; in 1997&#46; The scale sought to stratify patients with CAP into subgroups based on outcome criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">53</span></a> Since then&#44; there have been an extraordinary number of published articles with new prognostic scales&#44; with variants of the same or to validate these scales for various goals and in certain patient subpopulations&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Due to its simplicity&#44; the CURB-65 scale has been added to the PSI scale&#46; The inclusion of various biomarkers or the substitution of some of the 5 variables of the CURB-65 scale by others that take into account&#44; for example&#44; oxygen saturation and comorbidity&#44; seem to increase&#44; in a number of studies&#44; the scale&#39;s predictive value&#44; although there is no sign that they will substitute the scale&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">54</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">The main success of these 2 scales has been to facilitate objective data to ensure that patients do not require extended hospitalization&#46; As expected&#44; however&#44; when employed for making other decisions&#44; the scales&#8217; predictive value has been lower&#46; Thus&#44; other criteria have had to be employed to select patients who require hospitalization in the ICU&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">55</span></a> Other predictive scales have proliferated for this purpose&#44; the most widely used of which was published a few years ago in the CAP management guidelines of the American Thoracic Society and Infectious Diseases Society of America&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">42</span></a> This scale has been validated in various studies&#44; a number of which have incorporated certain variants that will have difficulty succeeding&#46;<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">19&#44;56</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Ever since the high percentage of patients with cardiovascular complications during the acute phase of CAP was recognized&#44; there has been a search for prognostic markers of such events&#46; Thus&#44; high troponin levels at admission&#44; some interleukins and certain clinical factors&#44; which have not been consistent among various authors&#44; have been associated with cardiovascular risk&#46;<a class="elsevierStyleCrossRefs" href="#bib0685"><span class="elsevierStyleSup">57&#44;58</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Numerous factors have been individually related to a poor short-term prognosis&#58; age&#44; chronic renal failure&#44; low weight&#44; delirium&#44; empyema&#44; bacteremia&#44; low albumin and pO<span class="elsevierStyleInf">2</span> levels&#44; leukopenia&#44; high glycemia and pCO<span class="elsevierStyleInf">2</span> levels and a number of biomarkers &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;2&#44;14&#44;42</span></a> In contrast&#44; no correlation had been found between poorer outcomes and obesity&#44; COPD or inhaled corticosteroid treatment&#46; In terms of inhaled corticosteroid treatment&#44; a beneficial effect has also been suggested&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">59</span></a> The presence of specific units for managing patients with CAP could increase survival rates&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Achieving clinical stability&#44; i&#46;e&#46;&#44; the normalization of basic constants&#44; is the main objective for hospitalized patients&#46; Its failure results in an increased risk of complications and death&#46; For those patients who persist with clinical manifestations&#44; mainly fever&#44; but with no clinical deterioration&#44; biomarker analysis can be useful for discriminating a slow resolution &#40;showing a significant reduction in biomarker levels&#41; from poor evolution &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0605"><span class="elsevierStyleSup">41&#44;60&#44;61</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Finally&#44; numerous authors have evaluated longer-term patient outcomes&#44; either at 90 days or 1 year after the CAP&#46; In all cases&#44; the mortality risk was associated with the patient&#39;s characteristics&#44; i&#46;e&#46;&#44; the underlying diseases&#44; more than with the characteristics of the acute episode&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">62</span></a> In a number of studies&#44; the onset of cardiac complications during hospitalization&#44; aspiration pneumonia and the need for intensive care were also predictive of greater long-term mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0690"><span class="elsevierStyleSup">58&#44;63&#44;64</span></a> Similar circumstances also determine increased subsequent morbidity and the risk of early readmission&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">65</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The diagnosis of CAP offers an opportunity to diagnose previously unknown underlying diseases such as diabetes mellitus &#40;e&#46;g&#46;&#44; among patients who have presented hyperglycemia during hospitalization&#41;&#44; COPD&#44; lung neoplasia and immunosuppressive conditions such as HIV infection and hematologic neoplasia&#46; However&#44; the study that requires the screening of these processes has not been established&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Treatment</span><p id="par0175" class="elsevierStylePara elsevierViewall">The publication of consensus guidelines from the various medical societies has resulted in significant improvement in the management of CAP&#44; mainly thanks to the standardization of antibiotic treatment and its application to the various patient subgroups&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;42</span></a> Several studies have shown that compliance with the guidelines and consensus protocols improves the patients&#8217; medical care&#44; which translates into all evolutionary parameters&#44; including mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">1</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">There are 2 types of criteria that should be employed for selecting the most appropriate treatment&#58; the severity of the clinical condition and the personal circumstances of the affected patient &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; The assessment of the clinical severity is based on the previously mentioned prognostic scales&#44; preferably the CURB-65&#44; and especially on correct clinical judgment&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0185" class="elsevierStylePara elsevierViewall">Therefore&#44; in the first group we would find patients who experience mild CAP&#46; These patients&#44; generally young and with no underlying diseases&#44; may be treated at home&#44; perhaps after a short period of observation&#46; The infection will most likely be caused by pneumococcus or one of the atypical agents&#46; Treatment with amoxicillin and azithromycin would be indicated&#46; If this regimen cannot be followed then quinolone&#44; preferentially moxifloxacin&#44; may be employed&#46; The use of beta-lactam agents could involve clinical and environmental benefits &#40;development of resistance&#41; and precedes the use of quinolones as the first choice&#46; In selected cases where a pneumococcal etiology appears highly likely&#44; clinicians may dispense with the macrolide&#46; Subgroups of patients with mild CAP can have significant underlying diseases that could result in an increased risk of more resistant pathogens&#44; mainly <span class="elsevierStyleItalic">H&#46; influenzae&#46;</span> For these groups&#44; replacing amoxicillin with amoxicillin-clavulanate or cefditoren seems reasonable&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;19&#44;42&#44;66&#44;67</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">In the second group&#44; we would find patients with severe CAP&#44; who require hospitalization in conventional wards&#46; The spectrum of potential pathogens should be broadened to include <span class="elsevierStyleItalic">H&#46; influenzae</span> and a number of Gram-negative bacilli&#46; The recommended regimen in the majority of guidelines is the combination of a beta-lactam agent &#40;ceftriaxone or amoxicillin-clavulanate&#41; with a macrolide&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;19&#44;42&#44;67</span></a> As with the previous group&#44; quinolones with pneumococcal activity are the most reasonable alternative&#46; However&#44; this general regimen is not without controversy&#46; There is a debate on the need to include the macrolide in this initial empiric regimen&#46; On one hand&#44; we have the alleged cardiotoxicity associated with macrolides&#44;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">68</span></a> and on the other&#44; we have its potential benefits&#44; both in terms of increasing the antimicrobial coverage and its anti-inflammatory effects&#46; We can conclude that although most studies favor the combined treatment&#44; these studies are usually observational&#46;<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">69</span></a> A recently published&#44; prospective randomized trial with more than 2000 patients assigned to 3 branches &#40;beta-lactam agent&#47;beta-lactam agent plus macrolide&#47;quinolone&#41; found no differences in terms of mortality at 90 days&#46;<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">70</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Furthermore&#44; the use of parenteral corticosteroids has generated significant controversy&#46; Although the results are conflicting&#44; these corticosteroids could provide certain benefits for patients with more severe CAP&#44; both in terms of survival and earlier functional recovery&#46;<a class="elsevierStyleCrossRefs" href="#bib0735"><span class="elsevierStyleSup">67&#44;71&#44;72</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Finally&#44; there are other minor points of discussion&#46; The use of statins combined with antibiotic treatment has generated certain expectations that seem as if they will not be confirmed&#46;<a class="elsevierStyleCrossRef" href="#bib0765"><span class="elsevierStyleSup">73</span></a> In another vein&#44; the results of noninvasive mechanical ventilation do not seem encouraging&#46;<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">74</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">The reference general empiric antibiotic regimen should undergo changes for patients with particular risk factors&#46; Patients with aspiration pneumonia therefore require effective treatment against anaerobes and Gram-negative bacilli&#46; It would therefore be preferable to employ a regimen that includes amoxicillin-clavulanate as a beta-lactam agent or&#44; for severely ill patients or those with underlying diseases&#44; piperacillin&#8211;tazobactam or a carbapenem&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;75</span></a> A similar reasoning should be applied to patients with empyema&#44; in whom the coverage of anaerobes and Gram-positive germs is a priority&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">46</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">The regimen should also be modified depending on the microorganism responsible &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; Thus&#44; a diagnosis or high suspicion of pneumonia by <span class="elsevierStyleItalic">P&#46; aeruginosa</span> or by resistant Gram-negative bacilli&#44; mainly in immunosuppressed patients or those who meet various criteria associated with this pathogen &#40;recent hospitalization&#44; previous antibiotic treatment&#44; advanced COPD&#44; bronchiectasis or systemic corticosteroid treatment&#41;&#44; requires the preferential application of an antipseudomonal beta-lactam agent&#44; combined perhaps with amikacin&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;24&#44;42&#44;67</span></a> For treating pneumonia by methicillin-resistant <span class="elsevierStyleItalic">S&#46; aureus</span>&#44; the efficacy of linezolid appears to be superior to that of vancomycin&#44; although ceftaroline&#44; which has recently been approved&#44; could very well take its place&#46;<a class="elsevierStyleCrossRefs" href="#bib0780"><span class="elsevierStyleSup">76&#44;77</span></a> In those areas where the resistance of <span class="elsevierStyleItalic">M&#46; pneumoniae</span> to macrolides is high&#44; tetracyclines appear to be an effective alternative&#46;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">78</span></a> Regarding Legionnaires&#8217; disease&#44; it is likely that the efficacies of quinolone and azithromycin are comparable&#59; however&#44; experience recommends using the former when dealing with severely ill patients&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">30</span></a> Finally&#44; oseltamivir should be added when the epidemiological circumstances or microbiological results recommend its use&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0215" class="elsevierStylePara elsevierViewall">The antibiotic treatment regimens for patients hospitalized in ICU or for those who met healthcare-associated pneumonia criteria do not differ considerably from the recommendations for patients included in the previous section&#44; although the clinical severity will favor the use of regimens with greater coverage in a higher percentage of cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;19&#44;42&#44;79</span></a> The combination of a broad-spectrum beta-lactam agent and a quinolone has frequently been used for critically ill patients&#46; A recent study&#44; however&#44; found no differences compared with the beta-lactam agent plus macrolide regimen&#46;<a class="elsevierStyleCrossRef" href="#bib0800"><span class="elsevierStyleSup">80</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Lastly&#44; it is worth noting that antibiotic treatment should be started as soon as possible&#44; within the emergency department&#44; which commonly uses excessively long treatment regimens&#46; It has been shown that treatment lasting 5&#8211;7 days&#44; for patients lacking local complications &#40;empyema or cavitations&#41; and with good clinical evolution&#44; would be sufficient&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1&#44;19</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflicts of interest</span><p id="par0225" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "identificador" => "xres797713"
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              "identificador" => "abst0005"
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          "identificador" => "xpalclavsec795737"
          "titulo" => "Keywords"
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          "clase" => "keyword"
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          "palabras" => array:7 [
            0 => "Community-acquired pneumonia"
            1 => "Risk factors"
            2 => "Epidemiology"
            3 => "Clinical manifestations"
            4 => "Diagnosis"
            5 => "Biomarkers"
            6 => "Prognosis"
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            0 => "Neumon&#237;a adquirida en la comunidad"
            1 => "Factores de riesgo"
            2 => "Epidemiolog&#237;a"
            3 => "Manifestaciones cl&#237;nicas"
            4 => "Diagn&#243;stico"
            5 => "Biomarcadores"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">This article not only reviews the essential aspects of community-acquired pneumonia for daily clinical practice&#44; but also highlights the controversial issues and provides the newest available information&#46; Community-acquired pneumonia is considered in a broad sense&#44; without excluding certain variants that&#44; in recent years&#44; a number of authors have managed to delineate&#44; such as healthcare-associated pneumonia&#46; The latter form is nothing more than the same disease that affects more frail patients&#44; with a greater number of risk factors&#44; both sharing an overall common approach&#46;</p></span>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El presente art&#237;culo no revisa &#250;nicamente aquellos aspectos de la neumon&#237;a adquirida en la comunidad fundamentales para la pr&#225;ctica cl&#237;nica diaria&#44; sino que incide en los temas pol&#233;micos&#44; y aporta la informaci&#243;n m&#225;s novedosa disponible&#46; Se considera la neumon&#237;a adquirida en la comunidad en un sentido amplio&#44; sin excluir ciertas variantes que&#44; durante los &#250;ltimos a&#241;os&#44; algunos autores han llegado a deslindar&#44; como la neumon&#237;a asociada a cuidados sanitarios&#46; Esta &#250;ltima no es m&#225;s que la misma enfermedad que incide en pacientes m&#225;s fr&#225;giles&#44; con un mayor n&#250;mero de factores de riesgo&#44; compartiendo ambas un planteamiento global com&#250;n&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Please cite this article as&#58; Falguera M&#44; Ram&#237;rez MF&#46; Neumon&#237;a adquirida en la comunidad&#46; Rev Clin Esp&#46; 2015&#59;215&#58;458&#8211;467&#46;</p>"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; COPD&#44; chronic obstructive pulmonary disease&#46;</p>"
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                  <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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Microorganisms&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">Epidemiological data&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">Clinical and radiological data&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" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Streptococcus pneumoniae</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The most common in any situation&#46; Winter predominance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Typical clinical condition&#58; chills&#44; rust-colored sputum&#44; pleuritic pain&#44; leukocytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Haemophilus influenzae</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Individuals with underlying diseases&#44; especially smokers and patients with COPD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Typical clinical condition&#58; chills&#44; rust-colored sputum&#44; pleuritic pain&#44; leukocytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Staphylococcus aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Drug addiction&#44; previous influenza virus infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Very severe conditions with bilateral infiltrates&#44; cavitations and pleural effusion&#46; Frequent bacteremia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Healthcare centers with a high rate of colonization&#44; previous antibiotic therapy&#44; recent hospitalization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Very severe conditions with bilateral infiltrates&#44; cavitations and pleural effusion&#46; Frequent bacteremia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Gram-negative bacilli and <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Immunosuppression&#44; patients with advanced COPD&#44; treatment with systemic corticosteroids or bronchiectasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Very severe clinical condition with septic shock&#46; Radiological cavitation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Anaerobes and oral cavity flora&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Patients with aspiration pneumonia &#40;altered level of consciousness or swallowing disorder&#41;&#44; alcoholism or poor oral hygiene&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cavitated infiltrate with foul-smelling sputum&#46; Presence of empyema or complicated pleural effusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Mycoplasma pneumoniae</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Young individuals with no underlying diseases&#46; Outbreaks in communities or relatives&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Generally mild clinical condition and slightly symptomatic &#40;atypical clinical condition&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Chlamydophila pneumoniae</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Equally affects all population subgroups&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clinical condition without particular characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Coxiella burnetii</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">More common in mountainous regions&#59; contact with livestock&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mildly symptomatic conditions or febrile syndrome without focus&#46; Hepatic disorder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Legionella pneumophila</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Predominantly summer&#44; related to rainy periods&#46; Disease outbreaks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Severe clinical conditions&#46; Neurological and gastrointestinal &#40;diarrhea&#41; disorders&#44; hyponatremia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Virus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Disease outbreaks&#46; During pandemics&#44; obese individuals and pregnant women are mostly affected&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Upper respiratory tract symptoms and headache Patchy multilobar infiltrate&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">Microorganisms responsible for community-acquired pneumonia and their correlation with specific clinical and epidemiological characteristics&#46;</p>"
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          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; MMP&#44; matrix metalloproteinase&#59; TIMP&#44; tissue inhibitor of metalloproteinase&#46;</p>"
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                  <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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Biomarkers&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">Clinical diagnosis<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&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">Etiological diagnosis<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&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">Complications and mortality&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">Progress monitoring&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" title="table-entry  " align="left" valign="top">Albumin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Beta-defensin 2&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="left" valign="top">Yes&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Leukocyte count&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&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="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Leukocyte count&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Leukocyte count&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Copeptin&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="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Cortisol&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="left" valign="top">Yes&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">D dimers&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="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Tumor necrosis factor&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="" 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></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Interleukin 6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&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="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Interleukin 8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&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="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Interleukin 10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&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="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Kallistatin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&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="left" valign="top">Yes&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Lactate&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="left" valign="top">Yes&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Lipocalin 2&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="left" valign="top">Yes&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">MMP-9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&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="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">MMP-9&#47;TIMP-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&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="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">pCO<span class="elsevierStyleInf">2</span>&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="left" valign="top">Yes&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Natriuretic peptide&#46;&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="left" valign="top">Yes&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">pH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>7&#46;30&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="left" valign="top">Yes&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Proadrenomedullin&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="left" valign="top">Yes&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Procalcitonin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</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">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">C-Reactive Protein&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</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">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">O<span class="elsevierStyleInf">2</span> saturation&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="left" valign="top">Yes&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Sodium&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="left" valign="top">Yes&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Urea&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="left" valign="top">Yes&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></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Vitamin D &#40;deficiency&#41;&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="left" valign="top">Yes&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></tr></tbody></table>
                  """
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                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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient subgroup&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">Most likely microorganisms&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">Recommended empiric treatment&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" title="table-entry  " align="left" valign="top">Mild pneumonia with no underlying diseases&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">Streptococcus pneumoniae</span>&#44; atypical agents and virus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Option&#58; amoxicillin<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>macrolide<br>Alternative&#58; quinolone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Mild pneumonia with underlying diseases&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">Streptococcus pneumoniae</span>&#44; atypical agents and virus&#44; <span class="elsevierStyleItalic">Haemophilus influenzae</span>&#44; Gram-negative bacilli&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Option&#58; amoxicillin-clavulanate or cefditoren<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>macrolide<br>Alternative&#58; quinolone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Severe pneumonia with no risk factors&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">Streptococcus pneumoniae</span>&#44; atypical agents and virus&#44; <span class="elsevierStyleItalic">Haemophilus influenzae</span>&#44; Gram-negative bacteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Option&#58; ceftriaxone<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>macrolide<br>Alternative&#58; quinolone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Very severe pneumonia with risk factors for <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> or Gram-negative bacilli&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">Streptococcus pneumoniae</span>&#44; atypical agents and virus&#44;<br><span class="elsevierStyleItalic">Haemophilus influenzae</span>&#44;<br>Gram-negative bacteria&#44;<br><span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Option&#58; cefepime or piperacillin&#8211;tazobactam or carbapenem<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>macrolide or quinolone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Aspiration pneumonia or empyema&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">Streptococcus pneumoniae</span>&#44;<br>other Gram-positive cocci&#44; anaerobic&#44; Gram-negative bacilli&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Option&#58; amoxicillin-clavulanate or piperacillin&#8211;tazobactam or carbapenem<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a><br>Alternative&#58; quinolone<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>clindamycin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Pneumonia with criteria of methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span> infection&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">Streptococcus pneumoniae</span>&#44;<br>atypical agents and virus&#44;<br><span class="elsevierStyleItalic">Haemophilus influenzae</span>&#44;<br>Gram-negative bacteria&#44;<br><span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&#44;<br><span class="elsevierStyleItalic">Staphylococcus aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Option&#58; amoxicillin-clavulanate or ceftriaxone or piperacillin&#8211;tazobactam or carbapenem<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>macrolide<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>linezolid or vancomycin<br>Alternative&#58; ceftaroline<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>macrolide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Etiology and recommended empiric treatment according to the various patient subgroups&#46;</p>"
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Option&#58; amoxicillin<br>Alternative&#58; quinolone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Legionella pneumophila</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Option&#58; quinolone<br>Alternative&#58; azithromycin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Mycoplasma pneumoniae</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Option&#58; macrolide<br>Alternatives&#58; tetracyclines<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Option&#58; linezolid<br>Alternatives&#58; vancomycin or ceftaroline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Antipseudomonal beta-lactam<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>amikacin<br>Alternative&#58; quinolone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Influenza virus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ceftriaxone<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>macrolide<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>oseltamivir<br>Alternative&#58; quinolone<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>oseltamivir&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Targeted treatment depending on the microorganism isolated&#46;</p>"
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      "titulo" => "References"
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        0 => array:2 [
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