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Abstract

We studied procalcitonin (PCT) levels at hospital admittance and their association with aetiology and severity in patients with community-acquired pneumonia (CAP). Median PCT concentrations were higher in bacteraemic patients than in those without bacteraemia (6.11 μg/L vs 0.34 μg/L, p = 0.0002), in patients with non-bacteraemic pneumococcal aetiology than in those infected with other classic bacteria (1.18 vs 0.18, p = 0.038), and in patients with pneumococcal as compared with viral aetiology (2.43 vs 0.24, p = 0.017). When aetiology, bacteraemia and severity according to the pneumonia severity index (PSI) were included in logistic regression analyses with PCT > 0.5 as a dependent variable, the odds ratio (OR) for non-bacteraemic pneumococcal aetiology was 5.7 (p = 0.008) and 3.0 ( p = 0.1) for PSI 4-5. A separate analysis for bacteraemia and PSI 4-5 showed an OR of 17.5 (p = 0.008) and 2.7 (p = 0.092), respectively. In CAP patients, high PCT seems to be a good marker for invasive disease and pneumococcal aetiology. As a predictor of severity it appears to be less important.

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... While the majority of studies investigating the clinical utility of PCT have been in the context of differentiating between clinical syndromes that require antibiotics and those that do not, a few studies have also assessed the association between PCT levels and bacterial etiologies of pneumonia (9)(10)(11)(12)(13). However, the pertinent comparisons in these studies were made between aggregate groups, such as "classic bacterial" versus "atypical" causes of pneumonia (9,13), gram positive versus gram negative organisms (10), and pneumococcal or non-pneumococcal pneumonia (11,12). ...
... While the majority of studies investigating the clinical utility of PCT have been in the context of differentiating between clinical syndromes that require antibiotics and those that do not, a few studies have also assessed the association between PCT levels and bacterial etiologies of pneumonia (9)(10)(11)(12)(13). However, the pertinent comparisons in these studies were made between aggregate groups, such as "classic bacterial" versus "atypical" causes of pneumonia (9,13), gram positive versus gram negative organisms (10), and pneumococcal or non-pneumococcal pneumonia (11,12). Accordingly, though two studies (11,12) did report higher PCT levels for pneumococcal compared to non-pneumococcal pneumonia, no granular conclusions were reached regarding PCT values associated with speci c bacteria. ...
... However, the pertinent comparisons in these studies were made between aggregate groups, such as "classic bacterial" versus "atypical" causes of pneumonia (9,13), gram positive versus gram negative organisms (10), and pneumococcal or non-pneumococcal pneumonia (11,12). Accordingly, though two studies (11,12) did report higher PCT levels for pneumococcal compared to non-pneumococcal pneumonia, no granular conclusions were reached regarding PCT values associated with speci c bacteria. Another crucial limitation of these studies is that they were generally limited to community-acquired pneumonia (CAP) due to relatively drug-susceptible organisms, with only a small proportion of cases being due to bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. ...
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Background: Accurate determination of the microbial etiology of pneumonia has important consequences for appropriate administration of antimicrobials and antimicrobial stewardship. Procalcitonin (PCT) is a biomarker that is finding increasing diagnostic and prognostic utility in lower respiratory infections, however, it remains unclear whether it can be helpful in predicting the bacterial etiology of pneumonia. In this study, we examined the relationship between serial PCT measurements and bacterial etiology in hospitalized patients with community-acquired pneumonia, including those at high risk for infections due to multi-drug resistant organisms (MDRO), to determine whether PCT at admission and its trajectory early in the hospital course of patients provides distinguishing information between different bacterial causes of pneumonia. Methods: We analyzed data collected from a prospective cohort study of 505 patients admitted to a tertiary care center with a clinical syndrome consistent with pneumonia. Bacterial etiology of pneumonia was determined from high quality respiratory samples, blood cultures and other relevant diagnostic tests according to standard protocols in conjunction with clinical review. Daily plasma procalcitonin levels were measured for these patients serially during the first four days of hospitalization. We compared procalcitonin levels associated with different bacterial etiologies of pneumonia over the first four days of admission, using the Mann-Whitney-U test to assess for statistical significance. Results: Out of 505 patients, the diagnosis of pneumonia was adjudicated in 322, and bacterial etiology determined in 64 cases. The predominant pathogens were Staphylococcus aureus (n = 19; 12 Methicillin Resistant (MRSA) and 7 Methicillin Susceptible (MSSA)), Pseudomonas aeruginosa (n = 12), Streptococcus pneumoniae (n = 6), and Haemophilus influenza (n=5). We found higher procalcitonin values for S. pneumoniae relative to other etiologies, a delayed rise for Pseudomonas over time, and consistently low PCT values for infections due to multiple bacteria. In addition, our results also suggest that procalcitonin values on the second day of hospitalization, rather than at admission, may have the most utility in distinguishing between bacterial etiologies. Conclusion: Serial procalcitonin values during the early course of bacterial pneumonia reveal a difference between pneumococcal and other bacterial etiologies, and may have an adjunct role in guiding antibiotic choice and duration.
... Inflammatory biomarkers may provide support for initiating and de-escalation of antibiotics, prognosis assessment, choice of level of care and discharge from hospital [67]. The potential of inflammatory biomarkers to distinguish between bacterial and viral aetiology has also been studied [67][68][69]. ...
... However, only three of 14 studies included patients with CAP. Swedish studies have shown an association between high levels of PCT and severe pneumonia as well as with pneumococcal aetiology [68,69]. ...
... S. pneumoniae is the predominant aetiology in CAP and is associated with the highest mortality compared to other common aetiologies [28,69,176]. For this reason, all empirical antibiotic regimens must have good expected efficacy against S. pneumoniae (Aþ). ...
Article
Based on expert group work, Swedish recommendations for the management of community-acquired pneumonia in adults are here updated. The management of sepsis-induced hypotension is addressed in detail, including monitoring and parenteral therapy. The importance of respiratory support in cases of acute respiratory failure is emphasized. Treatment with high-flow oxygen and non-invasive ventilation is recommended. The use of statins or steroids in general therapy is not found to be fully supported by evidence. In the management of pleural infection, new data show favourable effects of tissue plasminogen activator and deoxyribonuclease installation. Detailed recommendations for the vaccination of risk groups are afforded.
... Procalcitonin (PCT) can be used as a marker to differentiate bacterial infection from other non-bacterial infections or non-infectious inflammation [2][3][4]. Many investigators have reported the clinical usefulness of PCT for assessing the severity of pneumonia or pathogen involved, and for guiding antibiotic use [5][6][7]. Elderly patients, although representing the large majority of cases of CAP admitted to acute-care hospital wards, are often excluded from clinical studies due to the possible presence of multiple confounders. Although pneumonia occurs mainly in the elderly, the usefulness or clinical significance of PCT in these patients has not been studied extensively. ...
... PCT has been used to differentiate between infectious and noninfectious inflammatory respiratory diseases, or bacterial and non-bacterial respiratory infectious diseases [2][3][4]. Many investigators have reported the clinical usefulness of PCT in patients with CAP [5][6][7][17][18][19][20][21][22][23][24][25][26], HCAP [37,38], ventilator-associated pneumonia (VAP) [39][40][41][42][43], and hospital-acquired pneumonia (HAP) [44]. Although these studies included many elderly patients, the clinical usefulness of PCT in those patients was not consistent. ...
... Though many investigators have studied the utility of PCT in predicting mortality in various types of pneumonia including CAP [5][6][7][17][18][19][20][21][22][23][24][25][26], HCAP [37,38], VAP [39][40][41][42][43] and HAP [44], their results were not consistent While some reported PCT to be a reliable predictor for mortality [17][18][19][20][21][22][23][24][25][26], others showed that PCT was inferior to other markers such as PSI, CURB-65 [52], CRP, IL-6 [53], or BUN/albumin ratio [54] for predicting mortality. Several investigators reported that serial measurements of PCT were useful for predicting mortality [21,50,55]. ...
Article
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Background Procalcitonin (PCT) is a useful marker for pneumonia. However, its clinical usefulness in elderly patients has not been studied extensively. This study aimed to assess the relationship between PCT and prognosis and pneumonia severity in elderly patients with pneumonia acquired outside the hospital. Methods Data considered relevant to pneumonia severity and prognosis were retrospectively obtained from clinical charts of all patients with pneumonia who were admitted to our hospital from 2010 to 2017. The primary outcome was 30-day mortality in elderly patients (aged ≥75 years), and the relationship between PCT levels and pneumonia severity, as determined by the pneumonia severity index (PSI) was also examined. Results Data were collected from 667 patients, of which 436 were elderly patients. Multivariate and receiver operating characteristic curve analysis revealed that albumin, body mass index, and PSI class rather than PCT are important factors related to 30-day mortality in elderly patients. PCT was also not an independent prognostic factor in younger patients. PCT levels significantly differed by pneumonia severity (mild, moderate, and severe) in both younger (p < 0.001) and elderly (p < 0.0001) patients, with levels increasing as severity increased. In contrast, C-reactive protein (CRP) levels and white blood cell counts did not significantly differ by pneumonia severity in younger and elderly patients. A subgroup analysis focused on Streptococcus pneumoniae pneumonia revealed that PCT levels differed by severity in elderly patients (p = 0.03), with levels increasing as severity increased. Conclusion PCT was not an independent predictor of 30-day mortality in both of elderly and younger patients. PCT levels, but not CRP levels, significantly increased with increasing pneumonia severity in younger and elderly patients, although the degree of increase tended to be lower in elderly patients compared to younger patients for the same severity. PCT levels also significantly increased with increasing pneumonia severity in elderly patients with Streptococcus pneumoniae pneumonia.
... Several studies have evaluated the utility of inflammatory markers to predict both the etiology and the outcome of CAP. Thereby, serum procalcitonin (PCT) levels have proven more effective than C-reactive protein (CRP) to distinguish typical bacterial from atypical bacterial or viral pneumonia [16][17][18][19]. Also, higher PCT values indicated bacteremia [17,20,21] and a worse outcome of pneumonias, e.g. higher rates of ICU admission and mortality [22][23][24]. ...
... Although many studies have proven the excellent performance of PCT in the differentiation of typical bacterial from viral pneumonia [16][17][18][19], the differentiation between atypical bacterial from typical bacterial and viral pneumonia has remained difficult. ...
Article
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Background Discriminating Mycoplasma pneumoniae (MP) from Streptococcus pneumoniae (SP) and viral etiologies of community-acquired pneumonia (CAP) is challenging but has important implications regarding empiric antibiotic therapy. We investigated patient parameters upon hospital admission to predict MP infection. Methods All patients hospitalized in a tertiary care hospital between 2013 and 2017 for CAP with a confirmed etiology were analyzed using logistic regression analyses and area under the receiver operator characteristics (ROC) curves (AUC) for associations between demographic, clinical and laboratory features and the causative pathogen. Results We analyzed 568 patients with CAP, including 47 (8%) with MP; 152 (27%) with SP and 369 (65%) with influenza or other viruses. Comparing MP and SP by multivariate logistic regression analysis, younger age (odds ration [OR] 0.56 per 10 years, 95% CI 0.42–0.73), a lower neutrophil/lymphocyte ratio (OR 0.9, 0.82–0.99) and an elevated C-reactive protein/procalcitonin (CRP/PCT) ratio (OR 15.04 [5.23–43.26] for a 400 mg/μg cut-off) independently predicted MP. With a ROC curve AUC of 0.91 (0.80 for the >400 mg/μg cutoff), the CRP/PCT ratio was the strongest predictor of MP vs. SP. The discriminatory value resulted from significantly lower PCT values (p < 0.001) for MP, while CRP was high in both groups (p = 0.057). Comparing MP and viral infections showed similar results with again the CRP/PCT ratio providing the best information (AUC 0.83; OR 5.55 for the >400 mg/μg cutoff, 2.26–13.64). Conclusions In patients hospitalized with CAP, a high admission CRP/PCT ratio predicts M. pneumoniae infection and may improve empiric management.
... Viral infections do not usually affect the number of leukocytes, and therefore the use of acute-phase reactants, such as procalcitonin, as biomarkers may be of great help in reaching a diagnosis [33]. The production of procalcitonin depends on the presence of circulating tumor necrosis factor (TNF-α); in viral infections, macrophages produce interferon-α that can inhibit TNF-α, suppressing the elevation of procalcitonin, thus suggesting a viral origin [34]. We showed that the CRP/albumin ratio has much better sensitivity and specificity than procalcitonin in COVID-19 patients' follow-up. ...
... Respecto a los reactantes de fase aguda, las infecciones víricas no suelen modificar la cifra de leucocitos, por lo que el uso de biomarcadores como la procalcitonina puede ser de gran ayuda en la aproximación diagnóstica 14 . La producción de procalcitonina depende de la presencia del factor de necrosis tumoral circulante (TNF-␣); en las infecciones víricas los macrófagos producen interferón-␣ capaz de inhibir el TNF-␣, lo que condiciona la no elevación de procalcitonina, sugiriendo el origen viral 15 . ...
Article
Although bacteria are the main pathogens involved in community-acquired pneumonia, a significant number of community-acquired pneumonia are caused by viruses, either directly or as part of a co-infection. The clinical picture of these different pneumonias can be very similar, but viral infection is more common in the pediatric and geriatric populations, leukocytes are not generally elevated, fever is variable, and upper respiratory tract symptoms often occur; procalcitonin levels are not generally affected. For years, the diagnosis of viral pneumonia was based on cell culture and antigen detection, but since the introduction of polymerase chain reaction techniques in the clinical setting, identification of these pathogens has increased and new microorganisms such as human bocavirus have been discovered. In general, influenza virus type A and syncytial respiratory virus are still the main pathogens involved in this entity. However, in recent years, outbreaks of deadly coronavirus and zoonotic influenza virus have demonstrated the need for constant alert in the face of new emerging pathogens. Neuraminidase inhibitors for viral pneumonia have been shown to reduce transmission in cases of exposure and to improve the clinical progress of patients in intensive care; their use in common infections is not recommended. Ribavirin has been used in children with syncytial respiratory virus, and in immunosuppressed subjects. Apart from these drugs, no antiviral has been shown to be effective. Prevention with anti-influenza virus vaccination and with monoclonal antibodies, in the case of syncytial respiratory virus, may reduce the incidence of pneumonia. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.
... 53 In contrast, other studies argue against the association between biomarkers of inflammation and outcomes. 54,55 Moreover, cost-effectiveness is another concern for using such biomarkers. 56,57 It was suggested that when a novel biomarker becomes available to help facilitate risk prediction, it is essential to measure the improvement compared with the existing practice tool, that is, combining different biomarkers and clinical scores to further increase the AUROC. ...
Article
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Several studies argue against the association between admission hyperglycemia and adverse outcomes in infected diabetic patients. When investigating the association, it is necessary to consider preexisting hyperglycemia. The objective of this study was to assess whether stress-induced hyperglycemia, determined by the glycemic gap between admission glucose levels and A1c-derived average glucose levels adversely affects outcomes in diabetic patients admitted to hospital with community-acquired pneumonia (CAP). We retrospectively analyzed the glycemic gap and adverse outcomes of diabetic patients hospitalized because of CAP from June 1, 2007 to August 31, 2012 in single medical center in Taiwan. A total of 203 patients admitted with principal diagnosis of CAP and available data of glycemic gap. Patients with glycemic gaps ≥40 mg/dL had greater AUROC values for the development of adverse outcomes compared with acute hyperglycemia and long-term glycemic controls. Patients with an elevated glycemic gap had an odds ratio of 3.84 for the incidence of combined adverse outcomes. Incorporation of the glycemic gap into pneumonia severity index, CURB-65 or SMART-COP scores, increased the discriminative performance of predicting the development of adverse outcomes. Glycemic gaps were associated with adverse outcomes of diabetic CAP patients. The discriminative performance of the calculated glycemic gaps was comparable with those of current clinical scoring systems and may further increase the AUROC of each system.
... It should be noticed that authors didn't show the etiology of CAP; this information could be relevant since PCT arises especially in bacterial instead of viral pneumonia. The increase of PCT has been also associated to lobar consolidation, known to be the most important radiographic finding of pneumococcal infections [36][37][38][39]. Our study showed no association between serum PCT and lobar consolidation on chest X-rays, probably because most patients enrolled in our study, remarkably children, showed a viral, mixed or unknown etiology which are peculiar of pediatric age and commonly associated to interstitial pneumonia [40]. ...
Article
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Objectives: Although the importance of serum Procalcitonin (PCT) levels at diagnosis is well established in adult Community-Acquired Pneumonia (CAP), its use remains controversial in pediatric CAP. The aim of our study is to investigate the role of PCT and C-Reactive Protein (CRP) in the assessment of pediatric CAP severity defined by the extent of consolidation on chest X-rays and the presence of pleural effusion. In this particular setting, no clinical severity score is available at present and chest X-ray, although important for diagnosis confirmation, is not recommended as routine test. Design and methods: The study involved 119 children admitted to the Department of Pediatric Infectious Disease for radiographically documented CAP aged 1 year to 14 years, without chronic diseases. Baseline PCT, CRP and routine laboratory tests were performed on admission. Results: The median PCT (μg/L) and CRP (mg/L) were 0.11 (0.05–0.58) and 21.3 (4.2–48.1), respectively. PCT showed a good correlation with CRP, neutrophils and WBC (r = 0.538, P < 0.001; r = 0.377, P < 0.001; r = 0.285, P0.002, respectively). CRP, but not PCT, was associated with lobar consolidation (P = 0.007) and pleural effusion (P = 0.002). Logistic regression analysis revealed that only CRP was a predictor of lobar consolidation (OR: 1.078; 95% CI: 1.017–1.143; P = 0.011) and pleural effusion (OR: 1.076; 95% CI: 1.005–1.153; P = 0.036). Conclusion: Our findings revealed that PCT is correlated to the main inflammatory markers in children with CAP. CRP, unlike PCT, is able to predict the extent of chest X-ray infiltration and ultimately the severity of the disease confirming its usefulness in the management of pneumonia
... Johansson et al. found that median PCT levels were higher in bacteremic patients (than in those without bacteremia), in patients with non-bacteremic pneumococcal etiology (than in those infected with other bacteria) and in patients with pneumococcal etiology (as compared with viral etiology). They suggested high level of PCT to be a good marker for invasive disease and pneumococcal etiology (19). ...
Article
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Background: The first decision confronting clinicians in the management of patients with community acquired pneumonia (CAP) is whether the patient is to be hospitalized or not. We sought to validate the pneumonia scoring system and assess the power of procalcitonin (PCT) level to predict in-hospital mortality (IHM) and intensive vasopressor and respiratory support (IVRS) requirements in patients with CAP. Materials and methods: A total of 120 patients with CAP were evaluated for severity of illness based on the defined scoring systems including pneumonia severity index (PSI), confusion, urea, respiratory rate, blood pressure, age>65 (CURB-65), confusion, respiratory rate, blood pressure, age>65 (CRB-65), infectious diseases society of America/American thoracic society 2007 criteria (IDSA/ATS 2007) and systolic blood pressure, multilobar infiltrate, albumin, respiratory rate, tachycardia, confusion, low oxygen, low pH (SMART-COP). Demographic, clinical, laboratory and radiographic data were collected prospectively. The accuracy of each scoring system in predicting IVRS requirement and IHM was assessed from the area under the receiver operating characteristic (ROC) curve (AUC). Level of PCT was determined by semi-quantitative PCT-Q method (BRAHMS). The accuracy of the defined scoring systems, PCT levels and each scoring system plus PCT levels in prediction of IHM and IVRS requirement was analyzed. Results: The accuracy of PCT levels in predicting IHM and IVRS requirement based on AUC was 0.542 and 0.658, respectively and the best threshold was ≥ 2ng/mL for both of them. Adding the level of procalcitonin to different scoring systems (based on the defined scoring systems) improved the accuracy of all systems. Conclusion: We do not suggest using the PCT level alone as a predictor for mortality and IVRS requirement. Instead, we suggest PSI plus PCT and IDSA/ATS 2007 plus PCT as accurate predictors for IHM and SMART-COP plus PCT for IVRS requirement in patients who presented with CAP.
... 14 Procalcitonin production depends on the presence of circulating tumor necrosis factor (TNF-␣); in viral infections, macrophages produce interferon-␣ that can inhibit TNF-␣, suppressing the elevation of procalcitonin, thus suggesting a viral origin. 15 Despite these assertions, there is no gold standard for differentiating the etiology of pneumonia. 16 Moreover, we must not forget that CAP, whether viral or bacterial, is a dynamic entity: differences in biomarker values or the appearance of infiltrates on radiology are only snapshots of an active process that can vary widely from day to day. ...
... In patients with CAP, the inflammatory biomarker procalcitonin has been used to establish the diagnosis, 18 define the etiology, 19,20 and predict prognosis. 21 We found that procalcitonin actually had among the lowest pooled specificity values and positive likelihood ratios, suggesting poor prediction of high-risk patients. ...
Article
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Objectives: The Pneumonia Severity Index and CURB-65 are risk assessment tools widely used in community-acquired pneumonia (CAP). However, limitations in these prognostic scores have led to increasing interest in finding biomarkers that might provide additional information. To date, the role of these biomarkers has not been fully elucidated. Methods: We systematically searched the Medline, Web of Knowledge, Science Direct, and LILACS databases. We included studies that assessed the accuracy of biomarkers for the prediction of in-hospital or ≤30-day mortality, in hospitalized adults with CAP. Two independent investigators extracted patient and study characteristics, which were thereafter pooled using a random effects model. Relationships between sensitivity and specificity of biomarkers and prognostic scores were plotter using the area under the receiver operator characteristic curve (AUC). Results: We included 24 articles and 2 databases from 1,069 reviewed abstracts, which provided 10,319 patients for analysis. Reported mortality rates varied from 2.4% to 34.6%. The highest AUC values for predicting mortality were associated with pro-adrenomedullin (0.80) and prohormone forms of atrial natriuretic peptide (0.79), followed by cortisol (0.78), procalcitonin (0.75), copeptin (0.71), and C-reactive protein (0.62). There were no statistically significant differences between the AUCs of the studied biomarkers, other than for copeptin and C-reactive protein, which performed comparatively poorly. When compared with the CAP-specific scores, the AUCs were not significantly different from those of most biomarkers. Conclusions: The identified biomarkers are able to predict mortality with moderate to good accuracy in CAP. However, biomarkers have no clear advantage over CAP-specific scores for predicting mortality.
... Therefore PCT displayed diversity in patients with respiratory infections, mainly related with the type of pathogens, severity of infection and systemic inflammatory response. PCT in patients with bacterial pneumonia was higher than that of virus, atypical pathogens and mycobacterium tuberculosis [8][9][10][11][12]. But PCT wouldn't increase in all patients with bacterial pneumonia, it is reported that, PCT was less than 0.5 ng/ml in nearly 50% patients with bacterial pneumonia and was less than 0.1 ng/ml in 28% patients with bacterial pneumonia. ...
Article
Purpose: This study observed the relationship between procalcitonin (PCT) and results of sputum culture, the relationship between PCT and results of blood culture to evaluate and compare the value of PCT in respiratory and bloodstream infections. Methods: We analyzed 1616 patients in which PCT and sputum culture were concurrently ordered and analyzed, and 1096 patients in which PCT and blood culture were concurrently ordered and analyzed from January 2014 to May 2015. PCT concentrations were measured by on a Roche Cobas E601 ECL analyzer. Results: The average values of PCT from patients with sputum culture positive and negative were 0.42 (0.17-2.16) and 0.12 (0.06-0.57) ng/ml respectively, and the average values of PCT from patients with blood culture positive and negative were 9.54 (2.10-48.47) and 0.28 (0.10-1.23) ng/ml respectively. In sputum culture, positive rate of PCT in cases with growth of pathogens was 47.1%. In blood culture, positive rate of PCT in cases with growth of pathogens was 89.2%. Conclusions: PCT is useful in early diagnosis of respiratory infections and bloodstream infections, but the specificity of PCT in diagnosing respiratory infections is not as high as it is in bloodstream infections.
... Measurement of PCT gives information about the severity of the disease and may help physicians to differentiate typical bacterial aetiology from atypical aetiology. A study by Johansson et al. 73 showed that high PCT levels are related to invasive disease and pneumococcal aetiology. Higher levels of PCT are associated with bacterial pneumonia 74 . ...
Article
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Despite the development of new diagnostic tests, new antimicrobial agents, and the implementation of international guidelines in recent decades, community-acquired pneumonia still has high morbidity and mortality worldwide and is associated with moderate health costs. Streptococcus pneumoniae is still the most frequent pathogen related to microbial aetiology of community-acquired pneumonia, although almost 50% of cases of pneumonia still have no microbiological diagnosis. However, the development of molecular techniques such as real-time polymerase chain reaction in the past five years has revealed respiratory viruses to be major causative agents in community-acquired pneumonia. With the explosion of information from the many studies focusing on community-acquired pneumonia epidemiology, microbial aetiology and management in the last 15 years, the introduction of predictive tools, and advances in the pathophysiology of the disease, management of community-acquired pneumonia has also improved over this time due to the implementation of international guidelines proposed by different scientific associations. This review focuses on the new data in the management of community-acquired pneumonia. (BRN Rev. 2016;2:253-73)
... Measurement of PCT gives information about the severity of the disease and may help physicians to differentiate typical bacterial aetiology from atypical aetiology. A study by Johansson et al. 73 showed that high PCT levels are related to invasive disease and pneumococcal aetiology. Higher levels of PCT are associated with bacterial pneumonia 74 . ...
Article
Full-text available
Despite the development of new diagnostic tests, new antimicrobial agents, and the implementation of international guidelines in recent decades, community-acquired pneumonia (CAP) still has high morbidity and mortality worldwide and is associated with moderate health costs. Streptococcus pneumoniae is still the most frequent pathogen related to microbial etiology of CAP, although almost 50% of cases of pneumonia still have no microbiological diagnosis. However, the development of molecular techniques such as real time PCR in the past five years has revealed respiratory viruses to be major causative agents in CAP. With the explosion of information from the many studies focusing on CAP epidemiology, microbial etiology and management in the last 15 years, the introduction of predictive tools and advances in the pathophysiology of the disease, management of CAP has also improved over this time due to the implementation and of international guidelines proposed by different scientific associations. This review focuses on the new data in the management of CAP.
... Комментарии. Уровень ПКТ коррелирует с тяжестью пневмонии и пневмококковой этиологией заболевания [62,63]. При определении уровня ПКТ значимо сокращались продолжительность применения АБП и летальность у пациентов ОРИТ с вероятной бактериальной инфекцией [64]. ...
Article
Community-acquired pneumonia is one of the most common acute infectious diseases that has a significant share in the structure of mortality from respiratory diseases. It is extremely important to select rational antibiotic therapy which ensures optimal clinical efficacy, improved outcome, reduced rate of antibiotic resistance selection, and minimization of side effects. Methods . The target audience of these clinical recommendations are therapists, general practitioners, pulmonologists, anesthesiologist-resuscitators, and clinical pharmacologists. Each thesis-recommendation about diagnostic and therapeutic procedures has been scored according to the scale of classes of recommendations from 1 to 5 and A, B, C scale of the levels of evidence. The clinical recommendations also contain comments and explanations to these theses, algorithms for the diagnosis and treatment, and reference materials on the use of antibacterial drugs and microbiological (culture) tests. Conclusion . The presented clinical guidelines cover current information about the etiology, clinical manifestations, diagnosis and treatment tactics for community-acquired pneumonia. The presented clinical guidelines have been approved by the Scientific and Practical Council of the Ministry of Health of the Russian Federation in 2021.
... In our trial positive correlation of serum PCT level and PSI score was found to be significant with p b .01. Same result was found in several trials [31][32][33]. Especially stronger correlation was observed between the level of PCT and PSI in GP NP than that in GN NP. That can be explained by following two reasons. ...
Article
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Purpose: We evaluated the diagnostic accuracy of PCT to distinguish between gram-negative (GN) and gram-positive (GP) bloodstream infections nosocomial pneumonia (NP) patients and compared PCT levels with the pneumonia severity index (PSI) for predicting mortality. Methods: Data were collected retrospectively for blood culture-positive NP patients between January 2014 and August 2016. PCT levels were compared between patients with GN versus GP infections. Outcome variables included 28- and 60-day mortality. Results: PCT level was higher in GN infections than in GP infections. PCT could differentiate between GN and GP infections with an AUC value of 0.706. At a PCT cutoff of 5.4 ng/mL, the specificity for GN infections were 80.3%. The AUCs for 28- and 60-day mortality were 0.758 and 0.759 for PSI, and 0.620 and 0.634 for PCT. Serum PCT level was less predictive of mortality in GN NP patients compared with that for GP NP patients. There was a significantly positive correlation between PCT and PSI, and the correlation in GP NP patients was better than that in GN NP patients. Conclusions: PCT could differentiate between GN and GP bloodstream infections in patients with NP. However, PCT levels were less predictive of mortality compared with the PSI.
... In the study of Naderi et al., the PCT levels were determined to be higher in parients with CURB-65≥3 and SMART-COP≥3 20 . The median PCT level was observed to be higher in patients with high PSI in the study of Johansson et al. 21 . In our study, the PCT levels were found to be significantly higher in patients with CURB-65≥2 and SMART-COP≥2 (p:0.004 and p:0.001, respectively). ...
Article
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Know the result of disease severity and clinical results in community-acquired pneumonia (CAP) are preconditions for treatment options and management for health care resources. Various scoring systems as CURB-65 and SMART-COP have been developed to facilitate these awareness. We aimed to investigate the relationship between these two scoring systems with procalcitonin level in the diagnosis of CAP. The study was conducted on a total of 124 cases. 72 of the cases had a CURB-65 score of 2 or more and 49 of the cases had a SMART-COP score of 3 or above. The cases’ procalcitonin levels which had 2 ng/ml or above scores for CURB-65 had higher statistical significance than the cases that had 2 or less scores for CURB-65 (P: 0,004; p<0,05). The cases’ procalcitonin levels that had 3 or above scores for SMART-COP had higher statistical significance than the cases which had 2 or less scores for SMART-COP (p: 0,001; p<0,05). Conclusions High procalcitonin levels were associated with the patients who had high scores in both scoring systems, and had a relationship with the severity and course of the disease.
... However, opinions vary on PCT between the groups. The research by Johansson suggested that the PCT level of patients infected by Streptococcus pneumoniae is higher than that of other bacteria [22]. Some studies found that Gram-negative bacteria results in higher PCT levels than Gram-positive bacteria in patients with neutropenia [23][24][25]. ...
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Background To explore differences between hospital- (HASS) and community-acquired septic shock (CASS) in patient characteristics, pathogens, complications, outcomes, and risk factors in pediatric intensive care unit (PICU) children. Methods This retrospective study enrolled septic shock children from January 1, 2016, to December 31, 2019. The patients were followed up until 28 days after shock or death and were divided into HASS and CASS groups. After comparison, logistic regression analyses were used to identify risk factors for mortality. Results A total of 298 children were enrolled. 65.9% of HASS patients (N = 91) had hematological/tumor diseases and were mainly bloodstream infections of Gram-negative bacteria (47.3%). 67.7% of CASS (N = 207) had no obvious underlying disease and were mostly infected with Gram-positive bacteria (30.9%) of the respiratory or central nervous system. 28-day mortality was 62.6% and 32.7% in HASS and CASS groups, respectively (p < 0.001). The factor associated with 28-day mortality of HASS and CASS was MODS (OR:11.524; 95% CI: 2.140-62.051) and needed invasive mechanical ventilation therapy (OR:6.884; 95% CI: 1.499–31.624), respectively. Conclusions The underlying diseases, pathogens, complications, prognosis and mortality varied widely. 28-day mortality is associated with MODS and need for invasive mechanical ventilation therapy in HASS and CASS patients.
... Наряду с определением концентрации СРБ имеющиеся на сегодняшний день данные свидетельствуют об актуальности исследования уровня прокальцитонина (ПКТ) в сыворотке крови. Установлено, что ПКТ наиболее значимо повышается при пневмонии тяжелого течения и пневмококковой этиологии заболевания [44,45]. По данным систематического обзора рандомизированных клинических исследований (РКИ), использование ПКТ в диагностическом алгоритме при респираторных инфекциях приводило к уменьшению частоты и сокра-щению длительности АБТ, нежелательных лекарственных реакций, связанных с применением антибиотиков, и летальности, однако в исследования включались преимущественно пациенты без ВП [46]. ...
Article
The article provides an overview of literature on severe community-acquired pneumonia (CAP) and the most recent data on the epidemiology and etiology of CAP, and describes the antibiotic susceptibility of Streptococcus pneumoniae - the leading causative agent of CAP. The article discusses demonstrative diagnostic data and emphasizes the need to determine as early as possible the oxygen saturation of arterial blood using a pulse oximeter, as well as to dynamically measure the concentration of inflammatory markers in blood and carry out a comprehensive microbiological examination. The authors argue for the advantages of computed tomography over conventional x-ray examination and point out the usefulness of ultrasound to diagnose and dynamically assess the condition of lung tissue in the course of treatment. The article also provides up-to-date recommendations for the differential antibiotic treatment of severe CAP patients based on the existence of risk factors making them susceptible to the infection with certain microorganisms, and suggests etiotropic therapy regimens for cases where the causative agent has been identified. It also emphasizes the need for a timely prescription of combined antibiotic therapy with intravenous administration, suggesting the possibility of de-escalation based on microbiological data. A substantial portion of the overview focuses on the respiratory therapy for CAP, outlining a graded algorithm for the treatment of acute respiratory failure based on stage, and describing in detail the most effective and safe invasive and non-invasive respiratory support strategies. The proposed adjuvant therapies include glucocorticosteroids if it is impossible to stabilize hemodynamics by means of adequate hydration and vasopressor support, as well as parenteral anticoagulants to prevent thromboembolic complications. Pneumococcal and influenza vaccines are suggested as CAP prevention strategies for high-risk patients. The publication seeks to highlight the most critical aspects of the draft of the updated clinical recommendations for CAP and encourage their wide discussion across the community of Russian intensive care anesthesiologists and intensivists.
... Our findings support previous studies which reported similar findings. 15,16 There was a lack of correlation with other clinical signs of disease severity. This might be because the age of the study population and the disease category were different from previous studies which involved rather serious diseases such as acute respiratory distress syndrome, cardiovascular disease, and sepsis in adults. ...
Article
Background: Pentraxin 3 (PTX-3) is an acute-phase protein that increases in the plasma during inflammation. Objective: We aimed to evaluate the usefulness of PTX-3 as a clinical marker in children with lower respiratory tract infection (LRTI) and examine the correlation of PTX-3 with other biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT). Methods: We enrolled 117 consecutive patients admitted to Seoul St. Mary's Hospital with LRTI using the WHO criteria. We recorded data on fever duration and peak temperature before admission, duration of fever after admission, respiratory rate, heart rate, oxygen saturation upon admission, duration of oxygen supplementation, and duration of hospital stay. Upon admission, white blood cell (WBC) count, erythrocyte sedimentation rate, CRP level were measured. Multiplex respiratory virus polymerase chain reaction was performed using nasal swabs. PTX-3, PCT, and various cytokines were measured after the study had been completed. Results: We found that there was no significant difference in the level of PTX-3 according to the type of viral infection. PTX-3 levels showed a significant correlation with PCT levels, but not with levels of CRP. The level of PTX-3 showed a significant correlation with peak temperature and duration of fever before admission as well as interleukin (IL)-6 levels. PCT levels showed a significant correlation with IL-6 and granulocyte-colony stimulating factor levels, peak temperature, and duration of fever before admission, and duration of hospital stay. CRP levels showed a significant correlation with duration of fever before admission, total WBC count, and neutrophil count. PCT levels significantly predicted a hospital stay of 7 days or more. PTX-3, PCT, and CRP levels showed no correlation with any other clinical features. Conclusion: PTX-3 reflected disease severity but failed to predict length of hospital stay. Further studies evaluating the use of PTX-3 as a biomarker in mild LRTI would be useful.
Article
Background.: Lower procalcitonin (PCT) concentrations are associated with reduced risk of bacterial community-acquired pneumonia (CAP) in adults, but data in children are limited. Methods.: We analyzed serum PCT concentrations from children hospitalized with radiographically confirmed CAP enrolled in the Centers for Disease Control and Prevention's Etiology of Pneumonia in the Community (EPIC) Study. Blood and respiratory specimens were tested using multiple pathogen detection methods for typical bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus), atypical bacteria (Mycoplasma pneumoniae and Chlamydophila pneumoniae), and respiratory viruses. Multivariable regression was used to assess associations between PCT concentrations and etiology and severity. Results.: Among 532 children (median age, 2.4 years; interquartile range [IQR], 1.0-6.3), patients with typical bacteria had higher PCT concentrations (±viruses; n = 54; median, 6.10; IQR, 0.84-22.79 ng/mL) than those with atypical bacteria (±viruses; n = 82; median, 0.10; IQR, 0.06-0.39 ng/mL), viral pathogens only (n = 349; median, 0.33; IQR, 0.12-1.35 ng/mL), or no pathogen detected (n = 47; median, 0.44; IQR, 0.10-1.83 ng/mL) (P < .001 for all). No child with PCT <0.1 ng/mL had typical bacteria detected. Procalcitonin <0.25 ng/mL featured a 96% negative predictive value (95% confidence interval [CI], 93-99), 85% sensitivity (95% CI, 76-95), and 45% specificity (95% CI, 40-50) in identifying children without typical bacterial CAP. Conclusions.: Lower PCT concentrations in children hospitalized with CAP were associated with a reduced risk of typical bacterial detection and may help identify children who would not benefit from antibiotic treatment.
Article
Background: The optimal duration of antibiotic treatment has not been established for pneumonia patients. Some investigators reported procalcitonin (PCT)-guided antimicrobial stewardship reduces the duration of antibiotic use without increasing mortality in pneumonia patients. Material and methods: We prospectively enrolled hospitalized community-acquired pneumonia or healthcare-associated pneumonia patients with PCT levels >0.20 ng/mL on admission, who were admitted between 2014 and 2017. PCT levels were measured on days 5, 8 and 11 and every 3 days thereafter if needed. Physicians were encouraged and strongly encouraged to discontinue antibiotics when PCT levels decreased below 0.20 ng/mL and 0.10 ng/mL, respectively. Those admitted between 2010 and 2014 were included in the study as historical controls. Primary endpoints were duration of antibiotic treatment and recurrence of pneumonia within 30 days after antibiotic discontinuation. Results: The PCT-guided and control groups consisted of 116 patients each. Background factors including pneumonia severity and PCT levels did not differ between the 2 groups. Median duration of antibiotic treatment was 8.0 and 11 days in the PCT-guided and control groups, respectively (P < 0.001). Multivariable regression analysis revealed that PCT-guided antibiotic discontinuation (partial regression coefficient [PRC] -1.9319, P < 0.001), PCT (PRC 0.1501, P = 0.0059) and albumin (PRC -1.4398, P = 0.0096) were significantly related to duration of antibiotic treatment. Pneumonia recurrence within 30 days after antibiotic discontinuation was not statistically different between the 2 groups (4.3% vs. 6.0%, P = 0.5541). Conclusions: PCT-guided antibiotic discontinuation might be useful for shortening the duration of antibiotic treatment without increasing pneumonia recurrence.
Article
Sepsis and pneumonia cause significant morbidity and mortality worldwide. Despite improvements in diagnostic methodologies for organism identification, the early recognition and further risk stratification of these infections can be challenging. Although traditional clinical scoring systems are beneficial for the management of sepsis and pneumonia, biomarkers supporting the diagnosis and management of these infectious diseases are needed. Many biomarkers have been identified and there is no lack of studies and meta-analyses assessing the utility of biomarkers. Focusing primarily on sepsis and pneumonia, this article discusses the most commonly used biomarkers for which clinical laboratory testing methods are available.
Article
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Introduction Clinically diagnosed pneumonia in children is a leading cause of paediatric hospitalisation and mortality. The aetiology is usually bacterial or viral, but malaria can cause a syndrome indistinguishable from clinical pneumonia. There is no method with high sensitivity to detect a bacterial infection in these patients and, as result, antibiotics are frequently overprescribed. Conversely, unrecognised concomitant bacterial infection in patients with malarial infections occur with omission of antibiotic therapy from patients with bacterial infections. Previously, we identified two combinations of blood proteins with 96% sensitivity and 86% specificity for detecting bacterial disease. The current project aimed to validate and improve these combinations by evaluating additional biomarkers in paediatric patients with clinical pneumonia. Our goal was to describe combinations of a limited number of proteins with high sensitivity and specificity for bacterial infection to be incorporated in future point-of-care tests. Furthermore, we seek to explore signatures to prognosticate clinical pneumonia. Methods and analysis Patients (n=900) aged 2–59 months presenting with clinical pneumonia at two Gambian hospitals will be enrolled and classified according to criteria for definitive bacterial aetiology (based on microbiological tests and chest radiographs). We will measure proteins at admission using Luminex-based immunoassays in 90 children with definitive and 160 with probable bacterial aetiology, and 160 children classified according to the prognosis of their disease. Previously identified diagnostic signatures will be assessed through accuracy measures. Moreover, we will seek new diagnostic and prognostic signatures through machine learning methods, including support vector machine, penalised regression and classification trees. Ethics and dissemination Ethics approval has been obtained from the Gambia Government/Medical Research Council Unit The Gambia Joint Ethics Committee (protocol 1616) and the institutional review board of Boston University Medical Centre (STUDY00000958). Study results will be disseminated to the staff of the study hospitals, in scientific seminars and meetings, and in publications. Trial registration number H-38462.
Article
Objective: To detect the level of serum procalcitonin (PCT) in the patients with community acquired pneumonia (CAP), and to clarify its significance in diagnosis and treatment of CAP. Methods: 127 CAP patients and 30 cases of normal individuals were selected. According to the sputum bacterial culture results, 127 CAP patients were divided into positive bacteria culture group (n=54) and negative bacteria culture group (n=73); according to the diagnostic criteria of severe pneumonia, the bacteria culture positive group was divided into severe pneumonia group (n=13) and non-severe pneumonia group (n = 41). The levels of serum PCT, the white blood cell (WBC) count, neutrophil percentage (NEUT%) and levels of C-reactive protein (CRP) of the objects were detected by double antibody sandwich method. Results: After treated for 8 d, the levels of serum PCT of the objects in positive bacteria culture group and negative bacteria culture group and normal control group had no significant differences. After treated for 8 d, the levels of serum PCT of the objects in positive bacteria culture group and negative bacteria culture group were lower than that of the objects on the first day after treatment. The level of serum PCT of the patients in severe pneumonia group was significantly higher than that in non-severe pneumonia group; the WBC count, NEUT% and CRP level of the patients in severe pneumonia group were higher than those in non-severe pneumonia group, but the difference was not statistically significant. When consindering the bacterial culture as the gold standard for diagnosis of bacterial infection, the sensitivity and specificity of the serum level in diagnosis of bacterial CAP were superior to NEUT% and WBC count. Conclusion: The level of serum PCT plays a role in the diagnosis of CAP, and it could help to judge whether the CAP patient gets a bacterial infection and assess the severity of pneumonia and the discontinuation of antibiotics.
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The purpose of the updated guidelines is to provide specialists, primarily, anesthesiologists and intensive care physicians with modern evidence-based data on ethiology, epidemiology methods od diagnostic, treatment and prophylaxis of severe community- aquired pneumonia in adults. In the preparation of the current document, the high quality scientific studies, systematic reviews, meta-analyses, and the latest recommendations of Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS), and the European Respiratory Society/European Society of Intensive Care Medicine/European Society of Clinical Micribiology and Infectious Diseases/Asociacion Latinoamericana del Torax (ERS/ESICM/ESCMID/ALAT) as well as other leading professional communities have been analyzed, localized and implemented. Current guidelines provide up-to-date recommendations for the differential antibiotic treatment of severe CAP patients based on the existence of risk factors making them susceptible to the infection with certain microorganisms, and suggests etiotropic therapy regimens for cases where the causative agent has been identified. A substantial portion of the document focuses on the respiratory therapy for CAP, outlining a graded algorithm for the treatment of acute respiratory failure based on stage, and describing in detail the most effective and safe invasive and non-invasive respiratory support strategies. The proposed adjuvant therapies include glucocorticosteroids if it is impossible to stabilize hemodynamics by means of adequate hydration and vasopressor support, as well as parenteral anticoagulants to prevent thromboembolic complications. Pneumococcal and influenza vaccines are suggested as CAP prevention strategies for high-risk patients. The criteria on the quality of medical care are presented.
Article
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The inflammatory response in community-acquired pneumonia (CAP) depends on the host and on the challenge of the causal microorganism. Here, we analyze the patterns of inflammatory cytokines, procalcitonin (PCT), and C-reactive protein (CRP) in order to determine their diagnostic value. This was a prospective study of 658 patients admitted with CAP. PCT and CRP were analyzed by immunoluminometric and immunoturbidimetric assays. Cytokines (tumor necrosis factor-α [TNF-α], IL-1β, IL-6, IL-8, and IL-10) were measured using enzyme immunoassay. The lowest medians of CRP, PCT, TNF-α, and IL-6 were found in CAP of unknown cause, and the highest were found in patients with positive blood cultures. Different cytokine profiles and biomarkers were found depending on cause: atypical bacteria (lower PCT and IL-6), viruses (lower PCT and higher IL-10), Enterobacteriaceae (higher IL-8), Streptococcus pneumoniae (high PCT), and Legionella pneumophila (higher CRP and TNF-α). PCT ≥ 0.36 mg/dL to predict positive blood cultures showed sensitivity of 85%, specificity of 42%, and negative predictive value (NPV) of 98%, whereas a cutoff of ≤ 0.5 mg/dL to predict viruses or atypicals vs bacteria showed sensitivity of 89%/81%, specificity of 68%/68%, positive predictive value of 12%/22%, and NPV of 99%/97%. In a multivariate Euclidean distance model, the lowest inflammatory expression was found in unknown cause and the highest was found in L pneumophila, S pneumoniae, and Enterobacteriaceae. Atypical bacteria exhibit an inflammatory pattern closer to that of viruses. Different inflammatory patterns elicited by different microorganisms may provide a useful tool for diagnosis. Recognizing these patterns provides additional information that may facilitate a broader understanding of host inflammatory response to microorganisms.
Article
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Previous randomized controlled trials suggest that using clinical algorithms based on procalcitonin levels, a marker of bacterial infections, results in reduced antibiotic use without a deleterious effect on clinical outcomes. However, algorithms differed among trials and were embedded primarily within the European health care setting. Herein, we summarize the design, efficacy, and safety of previous randomized controlled trials and propose adapted algorithms for US settings. We performed a systematic search and included all 14 randomized controlled trials (N = 4467 patients) that investigated procalcitonin algorithms for antibiotic treatment decisions in adult patients with respiratory tract infections and sepsis from primary care, emergency department (ED), and intensive care unit settings. We found no significant difference in mortality between procalcitonin-treated and control patients overall (odds ratio, 0.91; 95% confidence interval, 0.73-1.14) or in primary care (0.13; 0-6.64), ED (0.95; 0.67-1.36), and intensive care unit (0.89; 0.66-1.20) settings individually. A consistent reduction was observed in antibiotic prescription and/or duration of therapy, mainly owing to lower prescribing rates in low-acuity primary care and ED patients, and shorter duration of therapy in moderate- and high-acuity ED and intensive care unit patients. Measurement of procalcitonin levels for antibiotic decisions in patients with respiratory tract infections and sepsis appears to reduce antibiotic exposure without worsening the mortality rate. We propose specific procalcitonin algorithms for low-, moderate-, and high-acuity patients as a basis for future trials aiming at reducing antibiotic overconsumption.
Article
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Aim of this study was to evaluate the correlation of inflammatory markers procalcitonin (PCT), C-reactive protein (CRP) and leukocyte count (WBC) with microbiological etiology of CAP. We enrolled 1337 patients (62 +/- 18 y, 45% f) with proven CAP. Extensive microbiological workup was performed. In all patients PCT, CRP, WBC and CRB-65 score were determined. Patients were classified according to microbial diagnosis and CRB-65 score. In patients with typical bacterial CAP, levels of PCT, CRP and WBC were significantly higher compared to CAP of atypical or viral etiology. There were no significant differences in PCT, CRP and WBC in patients with atypical or viral etiology of CAP. In contrast to CRP and WBC, PCT markedly increased with severity of CAP as measured by CRB-65 score (p < 0.0001). In ROC analysis for discrimination of patients with CRB-65 scores > 1, AUC for PCT was 0.69 (95% CI 0.66 to 0.71), which was higher compared to CRP and WBC (p < 0.0001). CRB-65, PCT, CRP and WBC were higher (p < 0.0001) in hospitalised patients in comparison to outpatients. PCT, CRP and WBC are highest in typical bacterial etiology in CAP but do not allow individual prediction of etiology. In contrast to CRP and WBC, PCT is useful in severity assessment of CAP.
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Calcitonin was discovered in the early 1960s [1], at which time it was assumed to be a single hormone with a yet-to-be-determined role in human physiology. Since then it has been found to be only one entity among a large array of related circulating peptides, at least one of which has a pivotal role in the host response to microbial infections [2, 3]. The aim of this review is to describe this metamorphosis of an endocrine hormone to a new class of hormokine mediators in infectious diseases.
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Community-acquired pneumonia (CAP) is the most frequent infection-related cause of death. The reference standard to diagnose CAP is a new infiltrate on chest radiograph in the presence of recently acquired respiratory signs and symptoms. This study aims to evaluate the diagnostic and prognostic accuracy of clinical signs and symptoms and laboratory biomarkers for CAP. 545 patients with suspected lower respiratory tract infection, admitted to the emergency department of a university hospital were included in a pre-planned post-hoc analysis of two controlled intervention trials. Baseline assessment included history, clinical examination, radiography and measurements of procalcitonin (PCT), highly sensitive C-reactive protein (hsCRP) and leukocyte count. Of the 545 patients, 373 had CAP, 132 other respiratory tract infections, and 40 other final diagnoses. The AUC of a clinical model including standard clinical signs and symptoms (i.e. fever, cough, sputum production, abnormal chest auscultation and dyspnea) to diagnose CAP was 0.79 [95% CI, 0.75-0.83]. This AUC was significantly improved by including PCT and hsCRP (0.92 [0.89-0.94]; p < 0.001). PCT had a higher diagnostic accuracy (AUC, 0.88 [0.84-0.93]) in differentiating CAP from other diagnoses, as compared to hsCRP (AUC, 0.76 [0.69-0.83]; p < 0.001) and total leukocyte count (AUC, 0.69 [0.62-0.77]; p < 0.001). To predict bacteremia, PCT had a higher AUC (0.85 [0.80-0.91]) as compared to hsCRP (p = 0.01), leukocyte count (p = 0.002) and elevated body temperature (p < 0.001). PCT, in contrast to hsCRP and leukocyte count, increased with increasing severity of CAP, as assessed by the pneumonia severity index (p < 0.001). PCT, and to a lesser degree hsCRP, improve the accuracy of currently recommended approaches for the diagnosis of CAP, thereby complementing clinical signs and symptoms. PCT is useful in the severity assessment of CAP.
Article
The aim of this study was to investigate whether procalcitonin (PCT), neopterin, C-reactive protein (CRP), and mid regional pro-atrial natriuretic peptide (MR-proANP) levels at admission and during the clinical course can be useful for the management of patients with pneumonia. The study population consisted of 75 patients with clinical and radiological diagnosis of pneumonia. Serum samples were collected at admission and during hospitalization. Complications were defined as intensive care unit (ICU) admission or death. The levels of PCT were significantly higher in pneumonia of definite bacterial origin in comparison to probable bacterial or unknown origin. The PCT levels were higher in pneumococcal pneumonia. The PCT and MR-proANP levels increased significantly according to the Pneumonia Severity Index (PSI). All biomarkers levels are higher in patients developing complications and who were dying. The serial levels of MR-proANP remain significantly elevated in patients developing complications and in patients classified in PSI and CURB-65 risk groups. In patients not developing complications, there is a significant decrease in the PCT levels. PCT can be useful for identifying pneumonia etiology. PCT and MR-proANP levels correlate with pneumonia severity rules. PCT and MR-proANP serial measurements can be useful for predicting short-term prognosis. Systemic biomarkers can provide additional information regarding clinical evolution, because these are dynamic and can be measured daily.
Article
New methods for identifying respiratory pathogens have led to several reports of a high yield of mixed infections in patients with community-acquired pneumonia (CAP). The clinical impact of these findings has, however, not been fully evaluated. We aimed to compare patients with a pure bacterial etiology with those with findings of both bacteria and virus regarding severity of illness and length of hospital stay. Adults with CAP admitted to Karolinska University Hospital were studied prospectively (N = 184). Microbiological methods included cultures from blood, sputum and nasopharyngeal secretions; sputum samples analyzed with quantitative real-time polymerase chain reaction for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis; nasopharyngeal specimens analyzed with polymerase chain reaction and serology for Mycoplasma pneumoniae, Chlamydophila pneumoniae and viruses common in the respiratory tract; and urine antigen assays for detecting pneumococcal and Legionella pneumophila antigens. The pneumonia severity index (PSI) was used to assess the severity of illness. The likelihood of getting a score corresponding to PSI classes IV or V was higher in patients with findings of both bacteria and virus than in those with a bacterial pathogen alone (odds ratio 4.98, 95% confidence interval 2.09-11.89; p < 0.001). The median length of hospital stay was 7 days among patients with mixed infections and 4 days among those with a bacterial etiology alone (p = 0.018). Patients infected with a virus and a bacterial pathogen more often develop severe CAP and have a longer hospitalization than those with a bacterial etiology alone.
Article
About 200 million cases of viral community-acquired pneumonia occur every year-100 million in children and 100 million in adults. Molecular diagnostic tests have greatly increased our understanding of the role of viruses in pneumonia, and findings indicate that the incidence of viral pneumonia has been underestimated. In children, respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses are the agents identified most frequently in both developed and developing countries. Dual viral infections are common, and a third of children have evidence of viral-bacterial co-infection. In adults, viruses are the putative causative agents in a third of cases of community-acquired pneumonia, in particular influenza viruses, rhinoviruses, and coronaviruses. Bacteria continue to have a predominant role in adults with pneumonia. Presence of viral epidemics in the community, patient's age, speed of onset of illness, symptoms, biomarkers, radiographic changes, and response to treatment can help differentiate viral from bacterial pneumonia. However, no clinical algorithm exists that will distinguish clearly the cause of pneumonia. No clear consensus has been reached about whether patients with obvious viral community-acquired pneumonia need to be treated with antibiotics. Apart from neuraminidase inhibitors for pneumonia caused by influenza viruses, there is no clear role for use of specific antivirals to treat viral community-acquired pneumonia. Influenza vaccines are the only available specific preventive measures. Further studies are needed to better understand the cause and pathogenesis of community-acquired pneumonia. Furthermore, regional differences in cause of pneumonia should be investigated, in particular to obtain more data from developing countries.
Article
The microbial etiology of community-acquired pneumonia (CAP) is still not well characterized. During the past few years, polymerase chain reaction (PCR)-based methods have been developed for many pathogens causing respiratory tract infections. The aim of this study was to determine the etiology of CAP among adults-especially the occurrence of mixed infections among patients with CAP-by implementing a new diagnostic PCR platform combined with conventional methods. Adults admitted to Karolinska University Hospital were studied prospectively during a 12-month period. Microbiological testing methods included culture from blood, sputum, and nasopharyngeal secretion samples; sputum samples analyzed by real-time quantitative PCR for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis; nasopharyngeal specimens analyzed by use of PCR; serological testing for Mycoplasma pneumoniae, Chlamydophila pneumoniae, and viruses common in the respiratory tract; and urine antigen assays for detection of pneumococcal and Legionella pneumophila antigens. A microbial etiology could be identified for 67% of the patients (n = 124). For patients with complete sampling, a microbiological agent was identified for 89% of the cases. The most frequently detected pathogens were S. pneumoniae (70 patients [38%]) and respiratory virus (53 patients [29%]). Two or more pathogens were present in 43 (35%) of 124 cases with a determined etiology. By supplementing traditional diagnostic methods with new PCR-based methods, a high microbial yield was achieved. This was especially evident for patients with complete sampling. Mixed infections were frequent (most commonly S. pneumoniae together with a respiratory virus).
Article
Acute respiratory tract infections are caused by a large number of viruses. Diagnostic methods have until recently been available only for a limited number of these viruses. With the objective to achieve sensitive assays for all respiratory viruses, a rational workflow in the laboratory, and a short turn-around time, a real-time PCR diagnostic platform for daily rapid detection of 15 respiratory viruses was developed. The system was evaluated on 585 stored nasopharyngeal aspirates from hospitalized children. Previous analysis by immunofluorescence and virus isolation identified viruses in 37% of the samples while the new PCR diagnostic panel detected 57% virus positive samples. The new platform was introduced in the laboratory in October 2007 and has then fully replaced the standard immunofluorescence assay for rapid detection of viruses and virus isolation.
Article
There is considerable variability in rates of hospitalization of patients with community-acquired pneumonia, in part because of physicians' uncertainty in assessing the severity of illness at presentation. From our analysis of data on 14,199 adult inpatients with community-acquired pneumonia, we derived a prediction rule that stratifies patients into five classes with respect to the risk of death within 30 days. The rule was validated with 1991 data on 38,039 inpatients and with data on 2287 inpatients and outpatients in the Pneumonia Patient Outcomes Research Team (PORT) cohort study. The prediction rule assigns points based on age and the presence of coexisting disease, abnormal physical findings (such as a respiratory rate of > or = 30 or a temperature of > or = 40 degrees C), and abnormal laboratory findings (such as a pH <7.35, a blood urea nitrogen concentration > or = 30 mg per deciliter [11 mmol per liter] or a sodium concentration <130 mmol per liter) at presentation. There were no significant differences in mortality in each of the five risk classes among the three cohorts. Mortality ranged from 0.1 to 0.4 percent for class I patients (P=0.22), from 0.6 to 0.7 percent for class II (P=0.67), and from 0.9 to 2.8 percent for class III (P=0.12). Among the 1575 patients in the three lowest risk classes in the Pneumonia PORT cohort, there were only seven deaths, of which only four were pneumonia-related. The risk class was significantly associated with the risk of subsequent hospitalization among those treated as outpatients and with the use of intensive care and the number of days in the hospital among inpatients. The prediction rule we describe accurately identifies the patients with community-acquired pneumonia who are at low risk for death and other adverse outcomes. This prediction rule may help physicians make more rational decisions about hospitalization for patients with pneumonia.
Article
The diagnostic value of admission serum levels of procalcitonin (PCT) and C-reactive protein (CRP) as indicators of the etiology and prognosis was prospectively investigated. 96 patients, 50-85 years of age, treated in the hospital for community-acquired pneumonia (CAP). On admission, all patients had elevated CRP levels (> 10 mg/l), but only 60 patients (54%) had elevated PCT levels (> 0.1 microgram/l). The severity of disease measured by APACHE II score was strongly associated with admission levels of PCT (p = 0.006), but not with CRP. Eight of nine patients with pneumonia caused by atypical agents had PCT levels < 0.5 microgram/l compared with 6/27 patients with pneumonia caused by classic bacterial pathogens, mainly Streptococcus pneumoniae (p = 0.03). No such correlation between CRP levels and etiology was found. Our data indicate that in patients admitted to the hospital with CAP, measurement of PCT gives information about the severity of the disease, and may aid the physician to differentiate typical bacterial etiology from atypical etiology, and thereby to choose appropriate initial antibiotic treatment.
Article
Atypical pathogens such as Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae are an important cause of community-acquired pneumonia. The available detection methods (culture and serology) either lack sensitivity or give only a retrospective diagnosis. In order to improve their detection and quantification in respiratory samples, a real-time multiplex PCR, performed in two separate reactions, was developed for these three pathogens. The comparison of multiplex real-time and conventional PCR assay on 73 respiratory specimens showed an overall agreement of 98.3%, corresponding to 95.8%, 100% and 100% agreement for C. pneumoniae, L. pneumophila and M. pneumoniae, respectively. Clinical application of this multiplex real-time PCR was done on 40 respiratory samples from 38 patients with respiratory tract infections. Of 19 serology-positive patients, 14 were confirmed by the multiplex real-time PCR to be infected by either one of the three pathogens. All samples from serology-negative patients were negative with the multiplex real-time PCR.
Article
A meta-analysis was performed to evaluate the accuracy of determination of procalcitonin (PCT) and C-reactive protein (CRP) levels for the diagnosis of bacterial infection. The analysis included published studies that evaluated these markers for the diagnosis of bacterial infections in hospitalized patients. PCT level was more sensitive (88% [95% confidence interval {CI}, 80%–93%] vs. 75% [95% CI, 62%–84%]) and more specific (81% [95% CI, 67%–90%] vs. 67% [95% CI, 56%–77%]) than CRP level for differentiating bacterial from noninfective causes of inflammation. The Q value for PCT markers was higher (0.82 vs. 0.73). The sensitivity for differentiating bacterial from viral infections was also higher for PCT markers (92% [95% CI, 86%–95%] vs. 86% [95% CI, 65%–95%]); the specificities were comparable (73% [95% CI, 42%–91%] vs. 70% [95% CI, 19%–96%]). The Q value was higher for PCT markers (0.89 vs. 0.83). PCT markers also had a higher positive likelihood ratio and lower negative likelihood ratio than did CRP markers in both groups. On the basis of this analysis, the diagnostic accuracy of PCT markers was higher than that of CRP markers among patients hospitalized for suspected bacterial infections.
Article
The host response to microbial invasion in the lung must be sufficiently vigorous to allow for microbial eradication but appropriately controlled to prevent spillover of the response into the systemic circulation. Although inflammatory responses in pneumonia are generally compartmentalized, microbial and host factors can promote disordered systemic responses to lung infection. Assessment of the magnitude of the systemic inflammatory response in pneumonia is of limited clinical value, and attempts to suppress this response have failed to improve clinical outcomes. The systemic inflammatory response that occurs in sepsis and other critical illnesses can substantially impair lung innate and acquired immunity. Mechanisms of critical illness-induced immunoparalysis have been incompletely characterized and are the focus of ongoing clinical and basic investigations.
Article
To evaluate the usefulness of procalcitonin serum levels as a predictor of etiology and prognosis in adult patients with community-acquired pneumonia (CAP) when they are stratified according to severity. One-year, population-based, prospective study. University teaching hospital. All adult patients who received a diagnosis of CAP throughout the study period. Interventions and measurements: An extensive noninvasive microbiological workup was performed. In patients who gave informed consent, a blood sample was collected at the time the diagnosis of CAP was established to measure biological markers. Procalcitonin levels were measured by a commercially available monoclonal immunoluminometric assay (limit of detection, 0.1 microg/L). Patients were classified according to microbial diagnosis, Patients Outcome Research Team pneumonia severity index (PSI), and outcome measures, and procalcitonin levels were compared among groups. Of 240 patients who received a diagnosis of CAP during the study period, procalcitonin concentrations were measured in 185 patients (77.1%). Levels were higher in patients with high-severity risk classes (PSI classes III-V) [p = 0.01] and in those with complications (p = 0.03) or death (p < 0.0001). Among patients classified into PSI low-severity risk classes (classes I-II), levels tended to be higher in those with bacterial etiology (p = 0.08); in this group, a serum procalcitonin level > or = 0.15 microg/L was more frequently found in patients with bacterial pneumonia than in those with nonbacterial pneumonia (p = 0.03). In patients with higher-severity risk classes, no significant differences were observed in procalcitonin levels among etiologic groups, but higher concentrations were associated with development of complications (p = 0.01) and death (p < 0.0001). Procalcitonin contribution to the evaluation of CAP varies according to severity. While procalcitonin may have a role to predict the microbial etiology in patients with a low PSI score, in patients classified within high PSI risk classes, it is a prognostic marker rather than a predictor of etiology.
Article
Procalcitonin (PCT) kinetics is a good prognosis marker in infectious diseases, but few studies of community-acquired pneumonia (CAP) have been performed in intensive care units (ICU). We analyzed the relationship between PCT kinetics and outcome in ICU patients with severe CAP. Prospective observational study in a 16-bed university hospital ICU. 100 critically ill patients with community-acquired pneumonia. Median PCT was 5.2 ng/ml on day 1 and 2.9 ng/ml on day 3. It increased from day 1 to day 3 in nonsurvivors but decreased in survivors. In multivariate analysis four variables were associated with death: invasive ventilation (odds ratio 10-), multilobar involvement (5.6-), LOD score (6.9-), and PCT increase from day 1 to day 3 (4.5-). In intubated patients with a PCT level below 0.95 ng/ml on day 3 the survival rate was 95%. Increased PCT from day 1 to day 3 in severe CAP is a poor prognosis factor. A PCT level less than 0.95 ng/ml on day 3 in intubated patients is associated with a favorable outcome.
Article
The limitation of polymerase chain reaction (PCR) in diagnosis of lower respiratory tract infections (LRTIs) caused by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis has been a distinguishing colonization from infection. We assess here the usefulness of real-time quantitative PCR (RQ-PCR) performed on lower respiratory tract samples to overcome this problem. Consecutive respiratory tract samples from patients with and without signs of infection (n = 203) were subjected to RQ-PCR, targeting the genes pneumolysin (S. pneumoniae), fumarate reductase (H. influenzae), and outer membrane protein B (M . catarrhalis). DNA from positive controls with predefined colony forming units (CFUs) per milliliter were included to allow estimation of CFU per milliliter for the test samples. In parallel, assessment of quantitative cultures from all samples was performed. In the group of patients with LRTI, significant pathogens (>/=10(5) CFU/mL) were found in 32/135 samples (23.7%) with culture, in 51/135 (37.7%) with RQ-PCR, and in 59/135 (43.7%) when combining the methods.
Article
We assessed the clinical usefulness of a real-time quantitative polymerase chain reaction (RQ-PCR) method applied on sputum samples to identify Streptococcus pneumoniae in 184 consecutive patients admitted to hospital with community-acquired pneumonia. Induced sputum samples were analyzed by culture and RQ-PCR. In total, 70/184 patients (38%) were diagnosed with S. pneumoniae. Cultures from blood and nasopharyngeal secretions were positive in 27/179 (15%) and 42/158 (27%) cases, respectively. Pneumococcal antigen was detected in 33/169 (20%) urine specimens. In sputum samples, culture was significantly positive in 19/128 (15%), whereas a significant concentration of DNA was found by RQ-PCR in 34/127 (27%) cases (P < 0.001). In 28/34 (82%) patients with RQ-PCR-positive sputum samples, S. pneumoniae was also detected with other methods. In the 34 RQ-PCR-positive sputum samples, 17 were negative by sputum culture, out of which 14 were obtained from patients treated with antibiotics prior to sampling. S. pneumoniae may be rapidly diagnosed by analyzing induced sputum samples by RQ-PCR and may be particularly valuable in patients in whom antibiotic therapy has been initiated.
Article
Acute lower respiratory tract infections are a major cause of death and disability, yet the mechanisms that make such infections so virulent are not entirely understood. This review emphasizes the roles of inflammation and the response of the innate immune system and explains how these two processes interact to rid the lung of microbes but also how they can bring the elimination of infection in the lung to a perilous climax.
BTS guidelines for the management of community acquired pneumonia in adults: update 2009 Acute lower respiratory tract infection
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