Forensic application of three interstitial pneumonia markers: search for new pneumonia markers in dead bodies.

In forensic cases, detailed identification of pneumonia is important. Our objective was to statistically determine the applicability of three interstitial lung disease (ILD) markers for forensic diagnosis using serum collected from dead bodies with various postmortem intervals (PMIs). We retrospectively analyzed the levels of postmortem serum Krebs von den Lungen-6 (KL-6) and pulmonary surfactant-associated proteins A and D (SP-A and SP-D) using 221 samples obtained during forensic autopsy at our facility from 2019 to 2023. We evaluated the diagnostic efficacy of ILD markers for various pneumonias against the pathological diagnosis, and examined the assessment of the severity of ILD. When comparing the ILD group with bacterial pneumonia (BP) versus the control group, there was a significant increase in KL-6 in the ILD group. When comparing the severe ILD (SILD) group with the mild ILD (MILD) group, there was a significant increase in KL-6 and SP-D in the SILD group. The optimal cutoff values for differentiating SILD were 607.0 U/mL for KL-6, 55.5 ng/mL for SP-A, and 160.0 ng/mL for SP-D, and the sensitivity/specificity (%) of KL-6, SP-A, and SP-D for SILD were 84.1/95.2, 55.6/85.7, and 66.7/74.6, respectively. This is the first study to examine KL-6 in postmortem serum in forensic medicine. By analyzing dead bodies with various PMIs, our results confirmed statistically that postmortem serum KL-6 specifically detects ILD, postmortem serum SP-A has high sensitivity to lung injury, and postmortem serum SP-D is potentially useful in assessing the severity of ILD.

Optimal cut-off value of serum procalcitonin in predicting bacterial infection induced acute exacerbation in chronic obstructive pulmonary disease: A prospective observational study.

OBJECTIVE: To explore the optimal cut-off value of serum procalcitonin (PCT) level in predicting bacterial infection in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: 204 hospitalized patients with AECOPD were enrolled in this study. Their diagnoses and treatments followed routine protocols in Fu-Xing Hospital affiliated to Capital Medical University, Beijing, China. Extra blood samples were taken for serum PCT level testing and the results were blinded to the treating physicians. On discharge, clinical data were collected and the treating physicians made comprehensive analyses to determine whether the AECOPD were triggered by respiratory tract bacterial infection or non-bacterial causes according to the "new diagnostic criteria" defined in this study. In the AECOPD patients with bacterial infection, treating physicians decided whether they had bacterial pneumonia based on imaging studies. Receiver operating characteristic curve (ROC) was used to analyze the accuracy of serum PCT level in predicting bacterial infection. RESULTS: In the 173 AECOPD patients who did not have pneumonia, 115 had evidences of bacterial infection while 58 did not. The median PCT levels were 0.1(0.08, 0.18) ng/ml and 0.07 (0.05, 0.08) ng/ml for each group, which were statistically different. The proposed optimal cut-off value of serum PCT level in predicting bacterial infection was 0.08 ng/mL according to this study, with a sensitivity of 81%, specificity of 67% and area under the ROC curve (AUC) of 0.794. There were 31 AECOPD patients diagnosed with pneumonia, their median PCT level was 0.23 ng/mL. CONCLUSIONS: The serum PCT levels slightly increased in the majority of hospitalized patients with AECOPD compared with reference range. When PCT level was ≥0.08 ng/mL, AECOPD was more likely to be caused by bacterial infection. A significantly elevated PCT levels may indicate combination of AECOPD and bacterial pneumonia.

Plasma Ferritin as Marker of Macrophage Activation-Like Syndrome in Critically Ill Patients With Community-Acquired Pneumonia.

OBJECTIVES: Plasma ferritin levels above 4,420 ng/mL have been proposed as a diagnostic marker for macrophage activation-like syndrome in sepsis and used for selection of sepsis patients for anti-inflammatory therapy. We here sought to determine the frequency, presentation, outcome, and host response aberrations of macrophage activation-like syndrome, as defined by admission ferritin levels above 4,420 ng/mL, in critically ill patients with community-acquired pneumonia. DESIGN: A prospective observational cohort study. SETTING: ICUs in two tertiary hospitals in the Netherlands. PATIENTS: One hundred fifty-three patients admitted with community-acquired pneumonia. MEASUREMENTS AND MAIN RESULTS: Patients were stratified in community-acquired pneumonia-macrophage activation-like syndrome (n = 15; 9.8%) and community-acquired pneumonia-control groups (n = 138; 90.2%) based on an admission plasma ferritin level above or below 4,420 ng/mL, respectively. Community-acquired pneumonia-macrophage activation-like syndrome patients presented with a higher disease severity and had a higher ICU mortality (46.7% vs 12.3% in community-acquired pneumonia-controls; p = 0.002). Twenty-three plasma biomarkers indicative of dysregulation of key host response pathways implicated in sepsis pathogenesis (systemic inflammation, cytokine responses, endothelial cell activation, and barrier function, coagulation activation) were more disturbed in community-acquired pneumonia-macrophage activation-like syndrome patients. Hematologic malignancies were overrepresented in community-acquired pneumonia-macrophage activation-like syndrome patients (33.3% vs 5.1% in community-acquired pneumonia-controls; p = 0.001). In a subgroup analysis excluding patients with hematologic malignancies (n = 141), differences in mortality were not present anymore, but the exaggerated host response abnormalities in community-acquired pneumonia-macrophage activation-like syndrome patients remained. CONCLUSIONS: Macrophage activation-like syndrome in critically ill patients with community-acquired pneumonia occurs more often in patients with hematologic malignancies and is associated with deregulation of multiple host response pathways.

Chronic infection with Chlamydia pneumoniae in asthma: a type-2 low infection related phenotype.

BACKGROUND: Chlamydia pneumoniae and Mycoplasma pneumoniae have been implicated in the pathogenesis of asthma and are responsible for chronic inflammation when host immune system fails to eradicate the bacteria. METHOD: We performed a prospective study on 410 patients who underwent a visit at the asthma clinic of CHU of Liege between June 2016 and June 2018 with serology testing for C. pneumoniae and M. pneumoniae. RESULTS: 65% of our asthmatic population had serum IgA and/or IgG towards C. pneumoniae, while only 12.6% had IgM and/or IgG against M. pneumoniae. Compared to seronegative asthmatics, asthmatics with IgA+ and IgG+ against C. pneumoniae were more often male and older with a higher proportion of patients with smoking history. They received higher doses of inhaled corticosteroids (ICS) and displayed lower FEV1/FVC ratio, higher RV/TLC ratio and lower conductance. They had higher levels of fibrinogen, though in the normal range and had lower sputum eosinophil counts. Patients with IgA- and IgG+ against C. pneumoniae were older and had higher blood monocyte counts and alpha-1-antitrypsin levels as compared to seronegative patients. Patients with IgM and/or IgG towards M. pneumoniae were more often males than seronegative asthmatics. In a subpopulation of 14 neutrophilic asthmatics with Chlamydia pneumoniae IgA + /IgG + treated with macrolides, we found a significant decrease in blood neutrophils and normalization of sputum neutrophil count but no effect on asthma quality of life and exacerbations. CONCLUSION: Positive Chlamydia serologic test is more common than positive Mycoplasma serology. Asthmatics with IgA and IgG against C. pneumoniae have more severe disease with increased airway obstruction, higher doses of ICS, more signs of air trapping and less type-2 inflammation.

Utilization of serum procalcitonin as a biomarker in the diagnosis and treatment of children with bacterial hospital-acquired pneumonia.

Hospital-acquired pneumonia (HAP) is one of the common infections in hospitalized patients. Early and prompt diagnosis of HAP is important because it aids in the appropriate selection of antibiotics and decreases the mortality and morbidity of patients. The investigation on serum procalcitonin (PCT) levels in pediatric patients is limited. Herein we aimed to evaluate the role of PCT in the early diagnosis of children with bacterial HAP. The study enrolled 264 children (< 14 years old) who were radiographically detected by pulmonary condensation chest X-rays. The HAP patients were stratified by patterns of microbiological detection of pathogens. Baseline white blood cell (WBC) count, neutrophil proportion, PCT, and C-reactive protein (CRP) were measured on admission. The laboratory findings and microbiological findings were analyzed and compared among groups. The median PCT concentration of patients with typical bacterial pathogens (3.95 ± 3.75 ng/mL) was significantly higher than the one of the patients with other pathogen types (median lower than 1.20 ng/mL). Correlation analysis indicated a significant correlation between PCT concentrations and the main inflammation makers including WBC count, neutrophil proportion, and CRP. PCT level was significantly decreased to 0.86 ± 1.46 ng/mL in post-treatment patients (p < 0.001). This cohort study with 264 pediatric HAP patients demonstrated the reliability of PCT level as a biomarker in patients with typical bacterial pathogens. Specifically, PCT cutoffs of 2 ng/mL accurately identified HAP children with typical bacterial pathogens. This finding suggested that PCT may serve as a reliable biomarker for the early diagnosis and treatment indicator of children with HAP.

Blood cultures and blood microbiota analysis as surrogates for bronchoalveolar lavage fluid analysis in dogs with bacterial pneumonia.

BACKGROUND: Diagnosis of canine bacterial pneumonia relies on airway lavage to confirm septic, suppurative inflammation, and a positive bacterial culture. Considering risks of bronchoalveolar lavage fluid (BALF) collection, minimally invasive methods like culture or next generation sequencing of blood would be appealing. In dogs with bacterial pneumonia, our study aims included (1): determining proportion of agreement between cultivable bacteria in BALF and blood (2); characterizing BALF, blood, and oropharyngeal (OP) microbiota and determining if bacteria cultured from BALF were present in these communities; and (3) comparing relatedness of microbial community composition at all three sites. Bacterial cultures were performed on BALF and blood. After DNA extraction of BALF, blood and OP, 16S rRNA amplicon libraries were generated, sequenced, and compared to a bacterial gene sequence database. RESULTS: Disregarding one false positive, blood cultures were positive in 2/9 dogs (5 total isolates), all 5 isolates were present in BALF cultures (16 total isolates). Based on sequencing data, all sites had rich and diverse microbial communities. Comparing cultured BALF bacterial genera with sequenced taxa, all dogs had ≥1 cultured isolate present in their microbiota: cultured BALF isolates were found in microbiota of BALF (12/16), blood (7/16), and OP (6/11; only 7 dogs had OP swabs). Of 394 distinct taxa detected in BALF, these were present in 75% OP and 45% blood samples. BALF community composition was significantly different than OP (p = 0.0059) and blood (p = 0.0009). CONCLUSIONS: Blood cultures are insensitive but specific for cultured BALF bacteria in canine bacterial pneumonia. Cultivable BALF bacteria were present in BALF, blood and OP microbiota to differing degrees.

Procalcitonin and lung ultrasound algorithm to diagnose severe pneumonia in critical paediatric patients (PROLUSP study). A randomised clinical trial.

BACKGROUND: Lung ultrasound (LUS) in combination with a biomarker has not yet been studied. We propose a clinical trial where the primary aims are: 1. To assess whether an algorithm with LUS and procalcitonin (PCT) may be useful for diagnosing bacterial pneumonia; 2. To analyse the sensitivity and specificity of LUS vs chest X-ray (CXR). METHODS/DESIGN: A 3-year clinical trial. INCLUSION CRITERIA: children younger than 18 years old with suspected pneumonia in a Paediatric Intensive Care Unit. Patients will be randomised into two groups: Experimental Group: LUS will be performed as first lung image. CONTROL GROUP: CXR will be performed as first pulmonary image. Patients will be classified according to the image and the PCT: a) PCT < 1 ng/mL and LUS/CXR are not suggestive of bacterial pneumonia (BN), no antibiotic will be prescribed; b) LUS/CXR are suggestive of BN, regardless of the PCT, antibiotic therapy is recommended; c) LUS/CXR is not suggestive of BN and PCT > 1 ng/mL, antibiotic therapy is recommended. CONCLUSION: This algorithm will help us to diagnose bacterial pneumonia and to prescribe the correct antibiotic treatment. A reduction of antibiotics per patient, of the treatment length, and of the exposure to ionizing radiation and in costs is expected. TRIAL REGISTRATION: NCT04217980 .

Diagnosis of severe community-acquired pneumonia caused by Acinetobacter baumannii through next-generation sequencing: a case report.

BACKGROUND: Acinetobacter baumannii is a gram-negative aerobic bacillus that is commonly causes of hospital-acquired infections. Community-acquired pneumonia caused by Acinetobacter baumannii (CAP-Ab) is rare but fatal if diagnosis and treatment are delayed. Conventional culture of clinical specimens is the main method for clinical diagnosis of A. baumannii infections which may suffer from limited positive rate and is time consuming. Timely and precise diagnosis of CAP-Ab remains challenging. CASE PRESENTATION: A 66-year-old man with 24 h history of acute fever and dyspnea was admitted to our hospital. He was diagnosed as severe community acquired pneumonia (CAP), septic shock, respiratory failure and acute kidney injury. Next-generation sequencing (NGS) was performed on the patient's sputum and blood, which identified numerous A. baumannii nucleotide sequences in the sample of sputum and led to the rapid diagnosis and treatment of community acquired pneumonia caused by A. baumannii. This result was confirmed by subsequent sputum culture. CONCLUSIONS: This case described that the successful application of the next generation sequencing assisting the speedy diagnosis of A. baumannii infection provides a new idea for the timely diagnosis of CAP-Ab and highlights that NGS is a promising tool in rapid etiological diagnosis of acute and severe infectious diseases.

Characteristics and Outcomes of Patients With and Without Type 2 Diabetes Mellitus and Pulmonary Sepsis.

PURPOSE: To date, studies have provided conflicting results regarding the impact of type 2 diabetes mellitus (DM) on sepsis-related outcomes. Our objective is to understand the impact of type 2 DM in bacterial pneumonia and sepsis-related intensive care unit (ICU) outcomes. METHODS: Retrospective study using Multiparameter Intelligent Monitoring in Intensive Care III database. We included 1698 unique patients admitted with sepsis secondary to bacterial pneumonia to the ICU within the time period of 2001 to 2012. RESULTS: The type 2 DM group had an increased incidence of acute kidney injury (67.9% vs 58.1%, P < .01) and need for dialysis compared to the non-DM group. There was no difference in mortality, microbiology, other organ failure, or hospital length of stay between the type 2 DM and non-DM group. Lower admission blood glucose was associated with increased mortality in patients with type 2 DM (49% at ≤120 mg/dL, 35.1% at 121-180 mg/dL, and 32.1% at >180 mg/dL) but not in non-DM patients. Conversely, higher mean glucose during the hospital stay was associated with increased mortality in non-DM patients (24.7% at ≤120 mg/dL, 45.1% at 121-180 mg/dL, and 73.0% at >180 mg/dL) but not in patients with type 2 DM. CONCLUSIONS: Our findings demonstrated that type 2 DM does not increase the overall mortality. Our findings of increased mortality in both type 2 DM patients with lower admission glucose, and non-DM patients with higher mean glucose during the hospital stay needs to be further evaluated. Future studies in regards to this could lead to personalized glucose treatment goals for patients.

Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis.

In the recent outbreak of novel coronavirus infection worldwide, the risk of thrombosis and bleeding should be concerned. We aimed to observe the dynamic changes of D-dimer levels during disease progression to evaluate their value for thrombosis. In this study, we report the clinical and laboratory results of 57 patients with confirmed COVID-19 pneumonia and 46 patients with confirmed community-acquired bacterial pneumonia (CAP). And their concentrations of D-dimer, infection-related biomarkers, and conventional coagulation were retrospectively analyzed. The Padua prediction score is used to identify patients at high risk for venous thromboembolism (VTE). The results found that, on admission, both in COVID-19 patients and CAP patients, D-dimer levels were significantly increased, and compared with CAP patients, D-dimer levels were higher in COVID-19 patients (P < 0.05). Besides, we found that in COVID-19 patients, D-dimer were related with markers of inflammation, especially with hsCRP (R = 0.426, P < 0.05). However, there was low correlation between VTE score and D-dimer levels (Spearman's R = 0.264, P > 0.05) weakened the role of D-dimer in the prediction of thrombosis. After treatments, D-dimer levels decreased which was synchronous with hsCRP levels in patients with good clinical prognosis, but there were still some patients with anomalous increasing D-dimer levels after therapy. In conclusion, elevated baseline D-dimer levels are associated with inflammation but not with VTE score in COVID-19 patients, suggesting that it is unreasonable to judge whether anticoagulation is needed only according to D-dimer levels. However, the abnormal changes of D-dimer and inflammatory factors suggest that anticoagulant therapy might be needed.

Interleukin-5, interleukin-6, interferon induced protein-10, procalcitonin and C-reactive protein among mechanically ventilated severe community-acquired viral and bacterial pneumonia patients.

BACKGROUND: The serum cytokine levels among 45 mechanically ventilated, intensive care unit (ICU)-treated severe community-acquired pneumonia (SCAP) patients with known microbial etiology in three different etiology groups were assessed. METHODS: Blood samples for C-reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-5, IL-6, IL-10, human interferon gamma induced protein (IP)-10, and TNF-α (tumor necrosis factor alpha) were collected at time points 0, 12, 24, 48, 72 and 96 h after study inclusion. RESULTS: There were 21 (43%) pure bacterial infections (bacterial group, BG), 5 (10%) pure viral infections (viral group, VG), and 19 (39%) mixed bacterial-viral infections (mixed group, MG) among 45 mechanically ventilated SCAP patients. CRP and PCT levels were significantly higher in the MG and values decreased with time in all groups. PCT differed also in time and group analysis (P = 0.001), the highest being in the MG. IL-5 levels were significantly higher in the VG compared to others (Ptime = 0.001, Pgroup = 0.051 and Ptimexgroup = 0.016). IL-6 and IP-10 levels decreased over time (Ptime = 0.003 and Ptime = 0.021), but there were no differences between groups. CONCLUSION: SCAP patients with viral etiology have higher IL-5 levels. Patients with mixed viral and bacterial group have higher PCT compared to other etiologies.

Investigating the role of circulating CXCR5-expressing CD8+ T-cells as a biomarker for bacterial infection in subjects with pneumonia.

BACKGROUND: Recently, lymphoid follicle-confined and circulating CD8+ T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) were described, which was involved in anti-virus immune response. However, the dynamics and role of circulating CXCR5-expressing CD8+ T-cells during bacterial infection is unknown. So, we asked whether CXCR5+ CD8+ T cells were also generated during bacterial infections in lower respiratory tract. METHODS: The clinical data of 65 pneumonia patients were analyzed. The patients were divided into groups as tuberculosis, bronchiectasis and community or hospital acquired pneumonia (CAP, HAP). The sputum/bronchial secretion or bronchoalveolar lavage fluid (BALF) samples were taken for microbiological examination. The procalcitonin (PCT) was used to evaluate disease severity of these groups and compared among patients. We characterized the number and phenotype (PD-1 and CD103) of CXCR5 + CD8+ T cells in the peripheral circulation by flow cytometry in all individuals and analyzed their association with the serum PCT level and disease severity. RESULTS: Patients were mainly infected with Escherichia coli, Acinetobacter baumannii, Klebsiella pneumonia (K.p), Pseudomonas aeruginosa, and Staphylococcus aureus. Of note is the finding that PCT was weakly correlated with severity of respiratory infections. Furthermore, it was revealed an increase of CXCR5-expressing CD8+ T cells in peripheral blood of un-controlled CAP and progressive HAP compared controlled CAP and HAP, respectively (P < 0.05). Strikingly, the circulating CXCR5-expressing CD8+ T-cells in K.p-infected group was higher than that non-K.p-infected group (P < 0.05). Meanwhile, the ratio of CXCR5 + CD8+/CD8 was positively correlated with PCT level (P < 0.05). In clinic, the determination of CXCR5-expressing CD8+ T-cells showed better results compared to PCT and can be useful for the prediction of exacerbation of CAP or HAP. Phenotypically, CXCR5+ CD8 + T cell expressed comparable level of inhibitory molecules PD-1 and lower CD103 compared to their CXCR5- counterparts. CONCLUSION: The circulating CXCR5-expressing CD8+ T-cell has diagnostic value for current pneumonia severity, and could act as a biomarker for identifying a bacteria-associated exacerbation. These cells may provide novel insight for the pathogenesis of pneumonia.

Nbeal2 Deficiency Increases Organ Damage but Does Not Affect Host Defense During Gram-Negative Pneumonia-Derived Sepsis.

Objective- Nbeal2-/- mice, a model of human gray platelet syndrome, have reduced neutrophil granularity and impaired host defense against systemic Staphylococcus aureus infection. We here aimed to study the role of Nbeal2 deficiency in both leukocytes and platelets during gram-negative pneumonia and sepsis. Approach and Results- We studied the role of Nbeal2 in platelets and leukocytes during murine pneumonia and sepsis by Klebsiella pneumoniae. Apart from platelet α-granule deficiency and reduced neutrophil granularity, also monocyte granularity was reduced in Nbeal2-/- mice, whereas plasma levels of MPO (myeloperoxidase), elastase, NGAL (neutrophil gelatinase-associated lipocalin), and MMP-9 (matrix metalloproteinase 9), and leukocyte CD11b expression were increased. Nbeal2-/- leukocytes showed unaltered in vitro antibacterial response and phagocytosis capacity against Klebsiella, and unchanged reactive nitrogen species and cytokine production. Also during Klebsiella pneumonia and sepsis, Nbeal2-/- mice had similar bacterial growth in lung and distant body sites, with enhanced leukocyte migration to the bronchoalveolar space. Despite similar infection-induced inflammation, organ damage was increased in Nbeal2-/- mice, which was also seen during endotoxemia. Platelet-specific Nbeal2 deficiency did not influence leukocyte functions, indicating that Nbeal2 directly modifies leukocytes. Transfusion of Nbeal2-/- but not of Nbeal2+/+ platelets into thrombocytopenic mice was associated with bleeding in the lung but similar host defense, pointing at a role for platelet α-granules in maintaining vascular integrity but not host defense during Klebsiella pneumosepsis. Conclusions- These data show that Nbeal2 deficiency-resulting in gray platelet syndrome-affects platelets, neutrophils, and monocytes, with intact host defense but increased organ damage during gram-negative pneumosepsis.

The Role of Neutrophil to Lymphocyte Count Ratio in the Differential Diagnosis of Pulmonary Tuberculosis and Bacterial Community-Acquired Pneumonia: a Cross-Sectional Study at Ayder and Mekelle Hospitals, Ethiopia.

BACKGROUND: The differential diagnosis of pulmonary tuberculosis and bacterial community-acquired pneumonia is often a challenging phenomenon. The neutrophil to lymphocyte count ratio, a suitable indicator of inflammation, has been demonstrated to be a useful biomarker for predicting bacteremia. The main aim this study is to evaluate the role of neutrophil to lymphocyte count ratio in the differential diagnosis of pulmonary tuberculosis and bacterial Community-Acquired Pneumonia at Ayder and Mekelle hospitals, Mekelle, Ethiopia. METHODS: A hospital based cross-sectional study was conducted from February to May 2017 on a total of 146 patients at Ayder and Mekelle hospitals. After taking written informed consent, study participants were interviewed for a detailed history and 5 mL of blood was collected for hematological analysis. Pulmonary tuberculosis was diagnosed by using Ziehl-Neelsen and Gene X-pert. Community acquired pneumonia was diagnosed using sputum culture. Student's t-test, Pearson's chi-square test, and receiver operating characteristics curve analysis were used. A p-value < 0.05 was considered statistically significant. RESULTS: The neutrophil to lymphocyte count ratio and eythrocyte sedimentation rate were significantly higher in pulmonary tuberculosis patients than bacterial community-acquired pneumonia patients. Neutrophil to lymphocyte count ratio and eythrocyte sedimentation rate with cutoff values of ≥ 2.72 and ≥ 39, respectively, showed the highest area under the curve (AUC = 0.69; 95% CI: 0.62, 0.77). CONCLUSIONS: Neutrophil to lymphocyte count ratio and eythrocyte sedimentation rate together at a time with their respective cutoff values gave a 69% accuracy in differentiating pulmonary tuberculosis from bacterial community-acquired pneumonia. Therefore, neutrophil to lymphocyte count ratio and erythrocyte sedimentation rate can be used in differentiating pulmonary tuberculosis from PTB patients from bacterial Community-acquired pneumonia, especially in resource-limited settings.

Combination of clinical symptoms and blood biomarkers can improve discrimination between bacterial or viral community-acquired pneumonia in children.

BACKGROUND: Differentiating bacterial from viral pneumonia is important for guiding targeted management and judicious use of antibiotics. We assessed if clinical characteristics and blood inflammatory biomarkers could be used to distinguish bacterial from viral pneumonia. METHODS: Western Australian children (≤17 years) hospitalized with radiologically-confirmed community-acquired pneumonia were recruited and clinical symptoms and management data were collected. C-reactive protein (CRP), white cell counts (WCC) and absolute neutrophil counts (ANC) were measured as part of routine care. Clinical characteristics and biomarker levels were compared between cases with definite bacterial pneumonia (clinical empyema and/or bacteria detected in blood or pleural fluid), presumed viral pneumonia (presence of ≥1 virus in nasopharyngeal swab without criteria for definite bacterial pneumonia), and other pneumonia cases (pneumonia in the absence of criteria for either definite bacterial or presumed viral pneumonia). The area-under-curve (AUC) of the receiver operating characteristic (ROC) curve for varying biomarker levels were used to characterise their utility for discriminating definite bacterial from presumed viral pneumonia. For biomarkers with AUC > 0.8 (fair discriminator), Youden index was measured to determine the optimal cut-off threshold, and sensitivity, specificity, predictive values (positive and negative) were calculated. We investigated whether better discrimination could be achieved by combining biomarker values with the presence/absence of symptoms. RESULTS: From May 2015 to October 2017, 230 pneumonia cases were enrolled: 30 with definite bacterial pneumonia, 118 with presumed viral pneumonia and 82 other pneumonia cases. Differences in clinical signs and symptoms across the groups were noted; more definite bacterial pneumonia cases required intravenous fluid and oxygen supplementation than presumed viral or other pneumonia cases. CRP, WCC and ANC were substantially higher in definite bacterial cases. For a CRP threshold of 72 mg/L, the AUC of ROC was 0.82 for discriminating definite bacterial pneumonia from presumed viral pneumonia. Combining the CRP with either the presence of fever (≥38οC) or the absence of rhinorrhea improved the discrimination. CONCLUSIONS: Combining elevated CRP with the presence or absence of clinical signs/ symptoms differentiates definite bacterial from presumed viral pneumonia better than CRP alone. Further studies are required to explore combination of biomarkers and symptoms for use as definitive diagnostic tool.

Protective effects of ethyl acetate extracts of Rimulus Cinnamon on systemic inflammation and lung injury in endotoxin-poisoned mice.

Rimulus cinnamon is the dried twig of Cinnamomum cassia Presl. It is widely used in China for the treatment of inflammatory processes, amenorrhea, and other diseases. We aimed to study the protective effects of ethyl acetate extracts of R. cinnamon (EAE) on systemic inflammation and lung injury in endotoxin-poisoned mice. EAE was administered 5 d prior to lipopolysaccharide (LPS) challenge with 15 mg/kg LPS. The administration of EAE increased the levels of interferon-γ (IFN-γ) and decreased the levels of interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) in the serum. Additionally, EAE relieved the pathological changes in the tissues of the lungs and spleen, and significantly reduced the number of neutrophils in the lung tissues. In addition, treatment with EAE decreased the mRNA expression of the NLR family, pyrin domain-containing protein 3 (NLRP3), caspase-1, and interleukin-1ß (IL-1ß) in the lungs, as well as the expression of NLRP3, caspase-1 (p20), and pro-IL-1ß proteins. These results demonstrated the promising anti-inflammatory effects of EAE in endotoxin-poisoned mice. Furthermore, EAE could alleviate the lung injury of endotoxin-poisoned mice by antagonizing the activation of the NLRP3 inflammasome.

Colistin Use in Patients with Chronic Kidney Disease: Are We Underdosing Patients?

Colistin is administered as its inactive prodrug colistimethate (CMS). Selection of an individualized CMS dose for each patient is difficult due to its narrow therapeutic window, especially in patients with chronic kidney disease (CKD). Our aim was to analyze CMS use in patients with CKD. Secondary objectives were to assess the safety and efficacy of CMS in this special population. In this prospective observational cohort study of CMS-treated CKD patients, CKD was defined as the presence of a glomerular filtration rate (GFR) < 60 mL/min/m² for more than 3 months. The administered doses of CMS were compared with those recently published in the literature. Worsened CKD at the end of treatment (EOT) was evaluated with the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Colistin plasma concentrations (Css) were measured using high-performance liquid chromatography. Fifty-nine patients were included. Thirty-six (61.2%) were male. The median age was 76 (45⁻95) years and baseline GFR was 36.6 ± 13.6. The daily mean CMS dosage used was compared with recently recommended doses (3.36 vs. 6.07; p < 0.001). Mean Css was 0.9 (0.2⁻2.9) mg/L, and Css was <2 mg/L in 50 patients (83.3%). Clinical cure was achieved in 43 (72.9%) patients. Worsened renal function at EOT was present in 20 (33.9%) patients and was reversible in 10 (52.6%). The CMS dosages used in this cohort were almost half those currently recommended. The mean achieved Css were under the recommended target of 2 mg/dL. Despite this, clinical cure rate was high. In this patient cohort, the incidence of nephrotoxicity was similar to those found in other recent studies performed in the general population and was reversible in 52.6%. These results suggest that CMS is safe and effective in patients with CKD and may encourage physicians to adjust dosage regimens to recent recommendations in order to optimize CMS treatments.

Clinical outcome of granulocyte transfusion therapy for the treatment of refractory infection in neutropenic patients with hematological diseases.

Neutropenic patients with hematological diseases are prone to severe infections. Granulocyte transfusion therapy (GTX) is considered as a logical therapeutic approach for these problems. However, the efficacy and complications of GTX have not been well identified. We retrospectively analyzed the clinical outcomes of GTX therapy in our hospital from 2009 to 2015. After 117 granulocyte transfusions for 47 patients, 72.3% of these patients' infections were effectively improved, and the overall survival rates at 30 and 120 days were 66.0 and 57.5%, respectively. The patients who experienced neutrophil recovery within 10 days after their therapy initiation had a better response and long-term survival period (14/15, 93.3%, vs 20/32, 62.5%, P = 0.037). Higher-dose granulocytes (> 2.55 × 108/kg) might improve the effective rate of infection in the patients who had more than 10 days neutrophil recovery time (17/23, 73.9%, vs 3/9, 33.3%, P = 0.049). In addition, GTX benefited the patients who suffered from pulmonary bacterial infections (16/20, 80%) compared with the bloodstream infection group (7/12, 58.3%) and skin or mucous infection group (1/5, 20%). The primary data showed that GTX did not affect the incidence of graft-versus-host disease (GVHD) and cytomegalovirus viremia when patients received further HSCT treatment. Collectively, GTX was an adjunct treatment modality for severely neutropenic patients who were likely to experience hematopoietic recovery. More randomized trials are needed to verify the efficacy and complications of GTX therapy.

Continuous hypoxia reduces the concentration of streptomycin in the blood.

BACKGROUND: A high incidence and mortality of plague in the past two decades occurred in the Qinghai-Tibet Plateau, China. High dose streptomycin (6-8 g/d) remained the first practical strategy for controlling the progressive, vicious clinical circumstances for patients with pneumonic plague in the Plateau, as opposed to the routine dosage recommended by the World Health Organization. To investigate whether patients with pneumonic plague truly required a large dosage of streptomycin in the hypoxic environment of the Tibetan Plateau, we investigated the hypothesis that hypoxic environment would change the pharmacokinetics of streptomycin in vivo. METHODS: (1) We retrospectively analyzed the data of pneumonic plague patients administered streptomycin from January 1, 2000 to December 31, 2012 in these areas, which came from the database of the Qinghai Center for Disease Control; and (2) We used a persistent hypoxia chamber to simulate the plateau hypoxic environment and fed Sprague Dawley rats in the chambers for one month. Then, we continuously administered hypoxic rats a single loading dose (200 mg/kg) of streptomycin and analyzed its concentrations by high performance liquid chromatography. The pharmacokinetic profiles were analyzed using a non-compartmental method in the Phoenix WinNonlin program. RESULTS: (1) There were 32 cases of patients with pneumonic plague in the past two decades totally and 9 of them died (all-cause mortality 28.125%, 9/32), including 7 cases died of delayed diagnosis without treatment of streptomycin, and the only 2 patients received normal dose of streptomycin. (2) The pharmacokinetic behaviors of streptomycin were different between the hypoxic and normal rats. Administration in a hypoxic state resulted in 74.81% and 29.28% decreases in maximum plasma concentration and area under the concentration-time curve from time zero to infinity compared with those values under normal condition for streptomycin. CONCLUSIONS: These results indicated that hypoxic condition could significantly decrease the absorption rate and extent of streptomycin. Therefore, patients with pneumonic plague require higher doses of streptomycin to maintain effective drug concentrations in Qing Hai and the Tibetan Plateau.

Significance of blood cultures in nursing home-acquired pneumonia.

The significance of blood cultures in nursing home-acquired pneumonia (NHAP) is incompletely understood. We retrospectively analyzed the clinical and laboratory features of 515 patients with NHAP admitted to our hospital over an 11-year period. Blood cultures were obtained from 336 patients (65.2%). We compared 13 and 323 patients with positive and negative blood cultures, respectively. The former showed lower systolic blood pressure and higher blood urea nitrogen (BUN), creatinine, C-reactive protein (CRP), and A-DROP scores than the latter. With regard to A-DROP parameters, patients with positive blood cultures showed significantly higher rates of dehydration (BUN ≥ 21 mg/dL) and low blood pressure (systolic blood pressure ≤ 90 mmHg). Multivariate analysis identified CRP values and low blood pressure as independent predictors of bacteremia: CRP (odds ratio [OR] 1.11; 95% confidence interval [CI] 1.04-1.19, P = 0.003) and low blood pressure (OR 6.03; 95% CI 1.06-34.25, P = 0.04). A receiver operating characteristic curve indicated that CRP was of moderate accuracy (area under the curve = 0.75), and its diagnostic accuracy was optimal at a cut-off point of 19.2 mg/dL (sensitivity 69%, specificity 87%). Since the probability of true bacteremia is very low in NHAP, obtaining blood cultures from all patients with NHAP is unnecessary. However, our results suggest blood cultures are warranted from patients with high CRP values (≥20 mg/dL) or low blood pressure.