A Systematic Review of the Pulmonary Microbiome in Patients with Acute Exacerbation COPD Requiring ICU Admission.

Background: Chronic obstructive pulmonary disease (COPD) is a major health concern. Acute exacerbations (AECOPD) may require intensive care unit (ICU) admission and mechanical ventilation. Acute infections and chronic colonization of the respiratory system are known to precipitate AECOPD. Detailed knowledge of the respiratory microbiome could lead to effective treatment and prevention of exacerbations. Objective: The aim of this review is to summarize the available evidence on the respiratory microbiome of patients with a severe AECOPD requiring mechanical ventilation and intensive care admission. Methods: A systematic literature search was conducted to identify the published papers until January 2023. The collected data were then subjected to qualitative analysis. After the first analysis, a secondary focused review of the most recent publications studying the relationship between microbiome and mortality in AECOPD was performed. Results: Out of 120 screened articles six articles were included in this review. Potentially pathogenic microorganisms (PPMs) were identified in 30% to 72% of the patients with community-acquired bacteria, gram-negative enteric bacilli, Stenotrophomonas and Pseudomonas being the most frequently isolated. During hospitalization, 21% of patients experienced colonization by PPMs. Adequate antimicrobial therapy resulted in the eradication of 77% of the identified PPMs. However, 24% of the bacteria displayed multi-drug resistance leading to prolonged or failure of eradication. Conclusion: PPMs are prevalent in a significant proportion of patients experiencing an AECOPD. The most identified PPMs include community-acquired pathogens and gram-negative enteric bacilli. Notably, no differences in mortality or duration of ventilation were observed between patients with and without isolated PPMs. However, the included studies did not investigate the virome of the patients, which may influence the microbiome and the outcome of infection. Therefore, further research is essential to comprehensively investigate the complete microbial and viral composition of the lower respiratory system in COPD patients admitted to the ICU.

Increased incidence of Mycoplasma pneumoniae infections and hospital admissions in the Netherlands, November to December 2023.

Mycoplasma pneumoniae is an important cause of pneumonia and extra-pulmonary manifestations. We observed a rise in admissions due to M. pneumoniae infections starting October 2023 in a regional hospital in the Netherlands and an increased incidence in national surveillance data. The incidence in the Netherlands has not been that high since 2011. The patients had a lower median age compared with 2019 and 2020 (28 vs 40 years). M. pneumoniae should be considered in patients with respiratory symptoms, especially children.

Outcomes of community-acquired pneumonia using the Pneumonia Severity Index versus the CURB-65 in routine practice of emergency departments.

Background: The Pneumonia Severity Index (PSI) and the CURB-65 score assess disease severity in patients with community-acquired pneumonia (CAP). We compared the clinical performance of both prognostic scores according to clinical outcomes and admission rates. Methods: A nationwide retrospective cohort study was conducted using claims data from adult CAP patients presenting to the emergency department (ED) in 2018 and 2019. Dutch hospitals were divided into three categories: "CURB-65 hospitals" (n=25), "PSI hospitals" (n=19) and hospitals using both ("no-consensus hospitals", n=15). Main outcomes were hospital admission rates, intensive care unit admissions, length of hospital stay, delayed admissions, readmissions and all-cause 30-day mortality. Multilevel logistic and Poisson regression analysis were used to adjust for potential confounders. Findings: Of 50 984 included CAP patients, 21 157 were treated in CURB-65 hospitals, 17 279 in PSI hospitals and 12 548 in no-consensus hospitals. The 30-day mortality was significantly lower in CURB-65 hospitals versus PSI hospitals (8.6% and 9.7%, adjusted odds ratio (aOR) 0.89, 95% CI: 0.83-0.96, p=0.003). Other clinical outcomes were similar between CURB-65 hospitals and PSI hospitals. No-consensus hospitals had higher admission rates compared to the CURB-65 and PSI hospitals combined (78.4% and 81.5%, aOR 0.78, 95% CI: 0.62-0.99). Interpretation: In this study, using the CURB-65 in CAP patients at the ED is associated with similar and possibly even better clinical outcomes compared to using the PSI. After confirmation in prospective studies, the CURB-65 may be recommended over the use of the PSI since it is associated with lower 30-day mortality and is more user-friendly.

Effects of long-term tobramycin inhalation solution (TIS) once daily on exacerbation rate in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: Use of long-term tobramycin inhalation solution (TIS) has been shown beneficial in cystic fibrosis (CF) and earlier findings also suggest a benefit in non-CF bronchiectasis. We investigated the efficacy and safety of maintenance TIS once daily (OD) in frequent exacerbating bronchiectasis patients chronically infected by different pathogens sensitive for tobramycin. OBJECTIVE: The primary outcome was the frequency of exacerbations during the 12-month study period. Secondary outcomes were time to first exacerbation, change in lung function and quality of life (QoL), bacterial analysis and safety. MATERIALS/PATIENTS: IN THIS MULTICENTER RCT PATIENTS AGED ≥ 18-YEAR-OLD WERE INCLUDED WITH CONFIRMED BRONCHIECTASIS AND ≥ 2 EXACERBATIONS IN THE PRECEDING YEAR. PATIENTS WERE ASSIGNED (1:1) TO RECEIVE TIS OR PLACEBO OD FOR 1-YEAR.: RESULTS: 58 patients were included of which 52 were analyzed in the mITT analysis. TIS reduced exacerbation frequency with a RR of 0.74 (95% CI 0.49-1.14) (p = 0.15). Within the TIS population a decrease in number of exacerbations was found (2; p = 0.00), which was also seen in the placebo-treated patients (1.5; p = 0.00). In the TIS-treated patients the QoL improved (LRTI-VAS p = 0.02 Leicester Cough p = 0.02) without additional safety concerns. No differences were found for the other secondary outcomes. CONCLUSION: Long-term TIS OD is a safe treatment modality and showed a non-significant reduced exacerbation frequency of 0.74 as compared to placebo in bronchiectasis patients chronically infected by tobramycin sensitive pathogens. TIS OD may be a potential therapeutic strategy in selected patients with bronchiectasis suffering from a high burden of disease. TRAIL REGISTRATION NUMBER: The BATTLE study was registered at Clinical trials.gov number: NCT02657473 . Date: 13 august 2016.

Initial Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load Is Associated With Disease Severity: A Retrospective Cohort Study.

Background: We assessed the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and hospital admission, intensive care unit (ICU) admission, and in-hospital mortality. Methods: All SARS-CoV-2-positive persons with a combined nasopharyngeal and oropharyngeal swab that was collected between 17 March 2020 and 31 March 2021 in public health testing facilities were included. Results: From 20 207 SARS-CoV-2-positive persons, 310 (1.5%) were hospitalized within 30 days. High viral loads (crossing point [Cp] <25) were associated with an increased risk of hospitalization as compared to low viral loads (Cp >30), adjusted for age and sex (adjusted odds ratio [aOR], 1.57 [95% confidence interval {CI}, 1.11-2.26]). The same association was seen for ICU admission (aOR, 7.06 [95% CI, 2.15-43.57]). The median [interquartile range] Cp value of the 17 patients who died in hospital was significantly lower compared to the 226 survivors (22.7 [3.4] vs 25.0 [5.2]). Conclusions: Higher initial SARS-CoV-2 viral load is associated with an increased risk of hospital admission, ICU admission, and in-hospital mortality. Our findings emphasize the added value of reporting SARS-CoV-2 viral load or cycle threshold/Cp values to identify persons who are at the highest risk of adverse outcomes such as hospital or ICU admission and who therefore may benefit from more intensive monitoring or early initiation of antiviral therapy.

Validating a clinical prediction score for Legionella-related community acquired pneumonia.

BACKGROUND: Legionella-related community acquired pneumonia (CAP) is a disease with an increasing incidence and a high mortality rate, especially if empirical antibiotic therapy is inadequate. Antibiotic treatment highly relies on clinical symptoms, although proven non-specific, because currently available diagnostic techniques provide insufficient accuracy for detecting Legionella CAP on admission. This study validates a diagnostic scoring system for detection of Legionella-related CAP, based on six items on admission (Legionella prediction score). METHODS: We included patients with Legionella-related CAP admitted to five large Dutch hospitals between 2006 and 2016. Controls were non-Legionella-related CAP patients. The following six conditions were rewarded one point if present: fever > 39.4 °C; dry cough; hyponatremia (sodium) < 133 mmol/L; lactate dehydrogenase (LDH) > 225 mmol/L; C-reactive protein (CRP) > 187 mg/L and platelet count < 171 × 109/L. The accuracy of the prediction score was assessed by calculating the area under the curve (AUC) through logistic regression analysis. RESULTS: We included 131 cases and 160 controls. A score of 0 occurred in non-Legionella-related CAP patients only, a score of 5 and 6 in Legionella-related CAP patients only. A cut-off ≥ 4 resulted in a sensitivity of 58.8% and a specificity of 93.1%. The AUC was 0.89 (95% CI 0.86-0.93). The strongest predictors were elevated LDH, elevated CRP and hyponatremia. CONCLUSIONS: This multi-centre study validates the Legionella prediction score, an easily applicable diagnostic scoring system, in a large group of patients and finds high diagnostic accuracy. The score shows promise for future prospective validation and could contribute to targeted antibiotic treatment of suspected Legionella CAP.

The Effect of Varying Interval Definitions on the Prevalence of SARS-CoV-2 Reinfections: A Retrospective Cross-Sectional Cohort Study.

BACKGROUND: We assessed the SARS-CoV-2 reinfection rate in a large patient cohort, and evaluated the effect of varying time intervals between two positive tests on assumed reinfection rates using viral load data. METHODS: All positive SARS-CoV-2 samples collected between 1 March 2020 and 1 August 2021 from a laboratory in the region Kennemerland, the Netherlands, were included. The reinfection rate was analyzed using different time intervals between two positive tests varying between 2 and 16 weeks. SARS-CoV-2 PCR crossing point (Cp) values were used to estimate viral loads. RESULTS: In total, 679,513 samples were analyzed, of which 53,366 tests (7.9%) were SARS-CoV-2 positive. The number of reinfections varied between 260 (0.52%) for an interval of 2 weeks, 89 (0.19%) for 4 weeks, 52 (0.11%) for 8 weeks, and 37 (0.09%) for a minimum interval of 16 weeks between positive tests. The median Cp-value (IQR) in the second positive samples decreased when a longer interval was chosen, but stabilized from week 8 onwards. CONCLUSIONS: Although the calculated reinfection prevalence was relatively low (0.11% for the 8-week time interval), choosing a different minimum interval between two positive tests resulted in major differences in reinfection rates. As reinfection Cp-values stabilized after 8 weeks, we hypothesize this interval to best reflect novel infection rather than persistent shedding.

SARS-CoV-2 viral-load distribution reveals that viral loads increase with age: a retrospective cross-sectional cohort study.

BACKGROUND: Describing the SARS-CoV-2 viral-load distribution in different patient groups and age categories. METHODS: All results from first nasopharyngeal (NP) and oropharyngeal (OP) swabs from unique patients tested via SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) collected between 1 January and 1 December 2020 predominantly in the Public Health Services regions Kennemerland and Hollands Noorden, province of North Holland, the Netherlands, were included in this study. SARS-CoV-2 PCR crossing-point (Cp)-values were used to estimate viral loads. RESULTS: In total, 278 455 unique patients were tested, of whom 9.1% (n = 25.374) were SARS-CoV-2-positive. PCRs performed by Public Health Services (n = 211 914), in which sampling and inclusion were uniform, revealed a clear relation between age and SARS-CoV-2 viral load, with especially children aged <12 years showing lower viral loads than adults (ß: -0.03, 95% confidence interval: -0.03 to -0.02, p < 0.001), independently of sex and/or symptom duration. Interestingly, the median Cp-values between the >79- and <12-year-old populations differed by more than four PCR cycles, suggesting an ∼16-fold difference in viral load. In addition, the proportion of children aged <12 years with a low load (Cp-value >30) was higher compared with other patients (31.1% vs 17.2%, p-value < 0.001). CONCLUSIONS: In patients tested by Public Health Services, SARS-CoV-2 viral load increases with age. Further studies should elucidate whether the lower viral load in children is indeed related to their suggested limited role in SARS-CoV-2 transmission. Moreover, as rapid antigen tests are less sensitive than PCR, these results suggest that SARS-CoV-2 antigen tests have lower sensitivity in children than in adults.

[Adjuvant treatment with corticosteroids: what is the benefit in patients with community-acquired pneumonia?] / Adjuvante behandeling met corticosteroïden.

Community-acquired pneumonia (CAP) is frequently seen in the general population and has high morbidity and a substantial mortality. Several studies investigated the role of short course of corticosteroids (CS) as adjuvant treatment next to antibiotics. In patients with severe CAP admitted to the ICU, CS seems to be effective with a reduction of length of stay (LOS) and a reduction in mortality. However, these studies are of moderate quality. In patients with CAP admitted to a general ward CS may result in a more rapid clinical stability and reduction of LOS with one day. The disadvantage of adjuvant CS are an increased risk for CAP related rehospitalisation and hyperglycaemia. Further research with CS is needed, especially in those patients with a hyperinflammation state.

Performance- and cost-benefit analysis of an influenza point-of-care test compared to laboratory-based multiplex RT-PCR in the emergency department.

INTRODUCTION: Influenza poses a heavy burden on emergency departments (ED) and hospital wards. Fast and reliable bedside tests are invaluable in obtaining indications for (cohort) droplet isolation precautions and improving patient flow. We performed a cost-benefit analysis comparing influenza point-of-care testing (POCT) to laboratory-based multiplex ligation-dependent probe amplification. METHODS: Data of 275 ED presentations between January-April 2019 were analyzed. Patients received both POCT and MLPA to calculate POCT sensitivity and specificity. Costs were calculated for both a POCT and MLPA scenario, including costs for testing, admission, droplet isolation precautions and cleaning. RESULTS: In our study population, 34 patients (12%) were identified with influenza A. No cases of influenza B were identified. Mean age of the influenza positive patients was 75(18) years and 56% were male. The most common symptoms upon presentation were cough, malaise and fever, with 74%, 56% and 50%, respectively. Compared to MLPA, POCT yielded a sensitivity of 94%, a specificity of 98% and a negative predictive value of 99% for influenza A. Using POCT yielded a cost reduction of €93,26 per patient. CONCLUSIONS: Influenza POCT is an accurate and cost-beneficial method to differentiate between admission with or without droplet isolation precautions. It can be useful in clinical decision making and reducing pressure on ED and hospital beds in an influenza peak season, by enabling fast patient flow and cohort isolation.

QTc Prolongation in COVID-19 Patients Using Chloroquine.

Chloroquine is used in the treatment of patients with COVID-19 infection, although there is no substantial evidence for a beneficial effect. Chloroquine is known to prolong the QRS and QTc interval on the ECG. To assess the effect of chloroquine on QRS and QTc intervals in COVID-19 patients, we included all inpatients treated with chloroquine for COVID-19 in the Spaarne Gasthuis (Haarlem/Hoofddorp, the Netherlands) and had an ECG performed both in the 72 h before and during or at least 48 h after treatment. We analyzed the (change in) QRS and QTc interval using the one-sample t-test. Of the 106 patients treated with chloroquine, 70 met the inclusion criteria. The average change in QRS interval was 6.0 ms (95% CI 3.3-8.7) and the average change in QTc interval was 32.6 ms (95% CI 24.9-40.2) corrected with the Bazett's formula and 38.1 ms (95% CI 30.4-45.9) corrected with the Fridericia's formula. In 19 of the 70 patients (27%), the QTc interval was above 500 ms after start of chloroquine treatment or the change in QTc interval was more than 60 ms. A heart rate above 90 bpm, renal dysfunction, and a QTc interval below 450 ms were risk factors for QTc interval prolongation. Chloroquine prolongs the QTc interval in a substantial number of patients, potentially causing rhythm disturbances. Since there is no substantial evidence for a beneficial effect of chloroquine, these results discourage its use in COVID-19 patients.

Dapagliflozin for prednisone-induced hyperglycaemia in acute exacerbation of chronic obstructive pulmonary disease.

The aim of the present study was to compare the effectiveness and safety of add-on treatment with dapagliflozin to placebo in patients with prednisone-induced hyperglycaemia during treatment for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We enrolled 46 patients hospitalized for an AECOPD in a multicentre double-blind randomized controlled study in which add-on treatment with dapagliflozin 10 mg was compared with placebo. Glycaemic control and incidence of hypoglycaemia were measured through a blinded subcutaneous continuous glucose monitoring device. Participants in the dapagliflozin group spent 54 ± 27.7% of the time in target range (3.9-10 mmol/L) and participants in the placebo group spent 53.6 ± 23.4% of the time in target range (P = .96). The mean glucose concentration was 10.1 mmol/L in the dapagliflozin group and 10.4 mmol/L in the placebo group (P = .66). One participant using dapagliflozin and 2 participants using placebo experienced symptomatic hypoglycaemia. Treatment with dapagliflozin was safe and there was no difference in risk of hypoglycaemia compared with placebo. Dapagliflozin did not result in better glycaemic control compared with placebo in participants with prednisone-induced hyperglycaemia during AECOPD.

Corticosteroids in Patients Hospitalized With Community-Acquired Pneumonia: Systematic Review and Individual Patient Data Metaanalysis.

Background: Our aim was to evaluate the benefits and harms of adjunctive corticosteroids in adults hospitalized with community-acquired pneumonia (CAP) using individual patient data from randomized, placebo-controlled trials and to explore subgroup differences. Methods: We systematically searched Medline, Embase, Cochrane Central, and trial registers (all through July 2017). Data from 1506 individual patients in 6 trials were analyzed using uniform outcome definitions. We investigated prespecified effect modifiers using multivariable hierarchical regression, adjusting for pneumonia severity, age, and clustering effects. Results: Within 30 days of randomization, 37 of 748 patients (5.0%) assigned to corticosteroids and 45 of 758 patients (5.9%) assigned to placebo died (adjusted odds ratio [aOR], 0.75; 95% confidence interval [CI], .46 to 1.21; P = .24). Time to clinical stability and length of hospital stay were reduced by approximately 1 day with corticosteroids (-1.03 days; 95% CI, -1.62 to -.43; P = .001 and -1.15 days; 95% CI, -1.75 to -.55; P < .001, respectively). More patients with corticosteroids had hyperglycemia (160 [22.1%] vs 88 [12.0%]; aOR, 2.15; 95% CI, 1.60 to 2.90; P < .001) and CAP-related rehospitalization (33 [5.0%] vs 18 [2.7%]; aOR, 1.85; 95% CI, 1.03 to 3.32; P = .04). We did not find significant effect modification by CAP severity or degree of inflammation. Conclusions: Adjunct corticosteroids for patients hospitalized with CAP reduce time to clinical stability and length of hospital stay by approximately 1 day without a significant effect on overall mortality but with an increased risk for CAP-related rehospitalization and hyperglycemia.

Pneumococcal urinary antigen test: diagnostic yield and impact on antibiotic treatment.

BACKGROUND: The pneumococcal urinary antigen test (PUAT) is commonly used for the etiological diagnosis of community-acquired pneumonia (CAP) and can be useful for targeting pathogen-directed therapy. OBJECTIVES: The aim of our study was to evaluate the diagnostic yield of the PUAT and the impact of a positive PUAT result on antibiotic treatment in patients with CAP in a clinical non-research setting. METHODS: Adults hospitalized with CAP between January 2005 and November 2007 were studied retrospectively. All patients were tested by PUAT. The sensitivity of the PUAT was determined and changes in antibiotic therapy were assessed. RESULTS: A total of 681 patients with CAP were included. The microorganism most frequently identified was Streptococcus pneumoniae. It was found in 95 (14.0%) patients, and the PUAT increased the diagnostic yield to a total of 184 (27.0%) patients. The S. pneumoniae antigen was detected in 37 of 55 patients with definitive pneumococcal pneumonia (67.3%). Pneumococcal urinary antigen was positive in 56 of 95 pneumococcal cases (definite and probable), resulting in an overall test sensitivity of 59.0%. Positive results of the PUAT led physicians to narrow the spectrum of antibiotic treatment in 69 (45.1%) patients. CONCLUSIONS: The PUAT is a useful method for early detection of S. pneumoniae in patients with CAP, but the test was less sensitive in this clinical setting than prospective studies indicated. The PUAT results led physicians to narrow the spectrum of antibiotic treatment in approximately half of the relevant cases, which limited the impact of a positive PUAT.

Disseminated Mycobacterium chelonae infection in a patient with T-cell lymphoma.

Infections with rapidly growing mycobacteria are rare and most often seen in immunocompromised patients. We herein present the case of a 69-year-old man with a T-cell lymphoma treated by chemotherapy and mogamulizumab with a 6-month history of febrile episodes and subcutaneous nodules in both arms and arthritis of metacarpophalangeal joints. Blood cultures and DNA sequencing results demonstrated the growth of Mycobacterium chelonae. The patient was successfully treated with clarithromycin, moxifloxacin, and tobramycin, but died shortly after due to lymphoma progression.

Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques.

BACKGROUND: Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay. METHODS AND FINDINGS: We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® S. pneumoniae urine antigen test (UAT) with blood and/or sputum culture) in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8% (95% CI: 21.3%, 28.9%). The estimated proportion of CAP attributable to pneumococcus was 27.3% (95% CI: 23.9%, 31.1%). The Binax UAT diagnosed an additional 11.4% (95% CI: 9.6, 13.6%) of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults. CONCLUSIONS: Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia, we estimate that there are at least 3 additional cases of non-bacteremic pneumococcal pneumonia.

Diagnostic accuracy of a serotype-specific antigen test in community-acquired pneumonia.

Our aim was to evaluate the diagnostic accuracy and clinical utility of a serotype-specific urinary antigen detection multiplex assay for identification of 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) in urine of patients with community-acquired pneumonia. Adult patients with clinical suspicion of community-acquired pneumonia were included. In addition to standard diagnostic procedures, a urine sample was collected to perform the urinary antigen detection test. Demographic, clinical, radiological and microbiological data were collected. Among 1095 community-acquired pneumonia patients Streptococcus pneumoniae was identified as causative pathogen in 257 (23%), when using conventional diagnostic methods and in 357 (33%) when urinary antigen detection was added. Of the 49 bacteraemic episodes caused by one of the 13 serotypes covered by the urinary antigen detection, 48 were detected by the urinary antigen detection, indicating a sensitivity of 98%. Of the 77 community-acquired pneumonia episodes with a "non-urinary antigen detection" causative pathogen, none had a positive urinary antigen detection result, indicating a specificity of 100%. Addition of the urinary antigen detection test to conventional diagnostic methods increased the prevalence of S. pneumoniae community-acquired pneumonia by 39%. Using bacteraemic episodes as reference sensitivity and specificity of the urinary antigen detection was 98% and 100%, respectively.

Transient impairment of reticulocyte hemoglobin content and hepcidin-25 induction in patients with community-acquired pneumonia.

INTRODUCTION: Patients with community-acquired pneumonia (CAP) often exhibit a declining hemoglobin (Hb) concentration. During inflammation pro-inflammatory cytokines and cells of the reticuloendothelial system induce disturbances in iron homeostasis. In this study inflammation markers and hepcidin-25 concentrations were monitored together with short-term alterations in reticulocyte hemoglobinization (RET-He). METHODS: A total of 25 patients with CAP participated in the study. The assay for serum hepcidin-25 is based on a combination of weak cation exchange chromatography and time-of-flight mass spectrometry. RESULTS: At hospital admission serum hepcidin-25 concentrations (14.6 ± 6.9 nMol/L, mean ± SD) were established in the upper level of the reference range (0.5-13.9 nMol/L). Results for C-reactive protein (CRP) and Interleukin-6 (IL-6) were obviously increased compared to the reference ranges. From admission until day 14 hepcidin-25, CRP and IL-6 steadily decreased towards the reference ranges. Hb concentrations declined from admission until day 4 from 8.1 ± 1.0 mMol/L to 7.4 ± 0.9 mMol/L. At admission Ret-He results were within the lower region of the reference range (1900-2300aMol) and results demonstrated a decline during admission from 1931 ± 241 aMol until 1845 ± 199 aMol (NS) at day 4. From a minimum Ret-He value at day 4 results increased towards 2129 ± 136 aMol at day14. CONCLUSION: A transient increase of cytokine-stimulated serum hepcidin-25 in combination with a temporary decrease of Hb and Ret-He is demonstrated in patients with CAP. Our results support the hypothesis that hepcidin-25 induces transient impairment of reticulocyte hemoglobin content (Ret-He).

D-dimer levels in assessing severity and clinical outcome in patients with community-acquired pneumonia. A secondary analysis of a randomised clinical trial.

BACKGROUND: D-dimer levels are in several studies elevated in patients with CAP. In this study we assess the use of D-dimer levels and its association with severity assessment and clinical outcome in patients hospitalised with community-acquired pneumonia. METHODS: In a subset of randomised trial patients with community-acquired pneumonia serial D-dimer levels was analysed. CURB-65 scores were calculated at admission. RESULTS: A total of 147 patients were included. D-dimer levels at admission were higher in patients with severe CAP (2166 ± 1258 versus 1630 ± 1197 µg/l, p=0.03), with clinical failure at day 30 (2228 ± 1512 versus 1594 ± 1078 µg/l, p=0.02) and with early failure (2499 ± 1817 µg/l versus 1669 ± 1121 µg/l, p=0.01). Non-survivors had higher D-dimer levels (3025 ± 2105 versus 1680 ± 1128 µg/l, p=0.05). None of the 16 patients with D-dimer levels<500 µg/l died. In multivariate analysis D-dimer levels were not associated with clinical outcome. D-dimer levels have poor accuracy for predicting clinical outcome at day 30 (AUC 0.62, 95% CI 0.51-0.73) or 30 day mortality (AUC 0.71 (95% CI 0.51-0.91)). Addition of D-dimer levels to CURB-65 did not increase accuracy. No differences were observed in serial D-dimer levels between patients with clinical success or failure at day 30. CONCLUSION: D-dimer levels are elevated in patients with CAP. Significantly higher D-dimer levels are found in patients with clinical failure and with severe CAP. D-dimer levels as single biomarker or as addition to the CURB-65 have no added value for predicting clinical outcome or mortality. D-dimer levels<500 µg/l may identify candidates at low risk for complications.

Evaluation of a new procalcitonin assay for the Siemens ADVIA Centaur with the established method on the B.R.A.H.M.S Kryptor.

BACKGROUND: In this study, we compared the B.R.A.H.M.S Kryptor procalcitonin (PCT) assay with the newly developed ADVIA Centaur B.R.A.H.M-S PCT assay. Furthermore, the long-term stability of PCT at - 20 degrees C was assessed. METHODS: Samples from 97 patients with lower respiratory tract infections were retested on both systems and compared with Passing-Bablok regression over two clinically relevant cutoff ranges for PCT, 0 - 2.0 microg/L and > 2.0 microg/L. RESULTS: After storage for 2.5 to 4 years, PCT levels in patient sera declined only 3.7%. Passing-Bablok regression analysis of the total sample range (n = 97) showed that both methods correlated well (r = 0.9944), although with a deviation from the line of identity (y = 0.880x - 0.025 microg/L). Comparison of both methods within the clinically important interval of 0 - 2.0 microg/L showed acceptable correlation (y = 0.943x + 0.010 microg/L). CONCLUSIONS: The ADVIA Centaur B.R.A.H.M.S PCT assay showed good correlation with the established Kryptor method. Therefore, this new technique can be used in clinical routine with the same clinical interpretation.