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Lack of rapid and comprehensive microbiological diagnosis in patients with community acquired pneumonia (CAP) hampers appropriate antimicrobial therapy. This study evaluates the real-world performance of the BioFire FilmArray Pneumonia panel plus (FAP plus ) and explores the feasibility of evaluation in a randomised controlled trial. Patients presenting to hospital with suspected CAP were recruited in a prospective feasibility study. An induced sputum or an endotracheal aspirate was obtained from all participants. The FAP plus turnaround time (TAT) and microbiological yield were compared with standard diagnostic methods (SDs). 96/104 (92%) enrolled patients had a respiratory tract infection (RTI); 72 CAP and 24 other RTIs. Median TAT was shorter for the FAP plus , compared with in-house PCR (2.6 vs 24.1 h, p < 0.001) and sputum cultures (2.6 vs 57.5 h, p < 0.001). The total microbiological yield by the FAP plus was higher compared to SDs (91% (162/179) vs 55% (99/179), p < 0.0001). Haemophilus influenzae , Streptococcus pneumoniae and influenza A virus were the most frequent pathogens. In conclusion, molecular panel testing in adults with CAP was associated with a significant reduction in time to actionable results and increased microbiological yield. The impact on antibiotic use and patient outcome should be assessed in randomised controlled trials.

In Latin America, community-acquired pneumonia remains a major cause of morbidity and mortality among children. Few studies have examined the etiology of pneumonia in Ecuador. This observational study was part of a randomized, double blind, placebo-controlled clinical trial conducted among children aged 2-59 months with severe pneumonia in Quito, Ecuador. Nasopharyngeal and blood samples were tested for bacterial and viral etiology by polymerase chain reaction. Risk factors for specific respiratory pathogens were also evaluated. Among 406 children tested, 159 (39.2%) had respiratory syncytial virus (RSV), 71 (17.5%) had human metapneumovirus (hMPV), and 62 (15.3%) had adenovirus. Streptococcus pneumoniae was identified in 37 (9.2%) samples and Mycoplasma pneumoniae in three (0.74%) samples. The yearly circulation pattern of RSV (P = 0.0003) overlapped with S. pneumoniae, (P = 0.03) with most cases occurring in the rainy season. In multivariable analysis, risk factors for RSV included younger age (adjusted odds ratio [aOR] = 1.9, P = 0.01) and being underweight (aOR = 1.8, P = 0.04). Maternal education (aOR = 0.82, P = 0.003), pulse oximetry (aOR = 0.93, P = 0.005), and rales (aOR = 0.25, P = 0.007) were associated with influenza A. Younger age (aOR = 3.5, P = 0.007) and elevated baseline respiratory rate were associated with HPIV-3 infection (aOR = 0.94, P = 0.03). These results indicate the importance of RSV and influenza, and potentially modifiable risk factors including undernutrition and future use of a RSV vaccine, when an effective vaccine becomes available. ClinicalTrials.gov NCT 00513929.

10 days after the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Netherlands (on Feb 27, 2020), 55 (4%) of 1497 health-care workers in nine hospitals located in the south of the Netherlands had tested positive for SARS-CoV-2 RNA. We aimed to gain insight in possible sources of infection in health-care workers. We did a cross-sectional study at three of the nine hospitals located in the south of the Netherlands. We screened health-care workers at the participating hospitals for SARS-CoV-2 infection, based on clinical symptoms (fever or mild respiratory symptoms) in the 10 days before screening. We obtained epidemiological data through structured interviews with health-care workers and combined this information with data from whole-genome sequencing of SARS-CoV-2 in clinical samples taken from health-care workers and patients. We did an in-depth analysis of sources and modes of transmission of SARS-CoV-2 in health-care workers and patients. Between March 2 and March 12, 2020, 1796 (15%) of 12 022 health-care workers were screened, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete and near-complete genome sequences from 50 health-care workers and ten patients. Most sequences were grouped in three clusters, with two clusters showing local circulation within the region. The noted patterns were consistent with multiple introductions into the hospitals through community-acquired infections and local amplification in the community. Although direct transmission in the hospitals cannot be ruled out, our data do not support widespread nosocomial transmission as the source of infection in patients or health-care workers. EU Horizon 2020 (RECoVer, VEO, and the European Joint Programme One Health METASTAVA), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Background. The frequent lack of a microbiological diagnosis in community-acquired pneumonia (CAP) impairs pathogen-directed antimicrobial therapy. This study assessed the use of comprehensive multibacterial, multiviral molecular testing, including quantification, in adults hospitalized with CAP. Methods. Clinical and laboratory data were collected for 323 adults with radiologically-confirmed CAP admitted to 2 UK tertiary care hospitals. Sputum (96%) or endotracheal aspirate (4%) specimens were cultured as per routine practice and also tested with fast multiplex real-time polymerase-chain reaction (PCR) assays for 26 respiratory bacteria and viruses. Bacterial loads were also calculated for 8 bacterial pathogens. Appropriate pathogen-directed therapy was retrospectively assessed using national guidelines adapted for local antimicrobial susceptibility patterns. Results. Comprehensive molecular testing of single lower respiratory tract (LRT) soecunebs achieved pathogen detection in 87% of CAP patients compared with 39% with culture-based methods. Haemophilus influenzae and Streptococcus pneumoniae were the main agents detected, along with a wide variety of typical and atypical pathogens. Viruses were present in 30% of cases; 82% of these were codetections with bacteria. Most (85%) patients had received antimicrobials in the 72 hours before admission. Of these, 78% had a bacterial pathogen detected by PCR but only 32% were culture-positive (P < .0001). Molecular testing had the potential to enable de-escalation in number and/or spectrum of antimicrobials in 77% of patients. Conclusions. Comprehensive molecular testing significantly improves pathogen detection in CAP, particularly in antimicrobial-exposed patients, and requires only a single LRT specimen. It also has the potential to enable early de-escalation from broad-spectrum empirical antimicrobials to pathogen-directed therapy.

Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). Clinical data on MERS-CoV infections are scarce. We report epidemiological, demographic, clinical, and laboratory characteristics of 47 cases of MERS-CoV infections, identify knowledge gaps, and define research priorities. We abstracted and analysed epidemiological, demographic, clinical, and laboratory data from confirmed cases of sporadic, household, community, and health-care-associated MERS-CoV infections reported from Saudi Arabia between Sept 1, 2012, and June 15, 2013. Cases were confirmed as having MERS-CoV by real-time RT-PCR. 47 individuals (46 adults, one child) with laboratory-confirmed MERS-CoV disease were identified; 36 (77%) were male (male:female ratio 3·3:1). 28 patients died, a 60% case-fatality rate. The case-fatality rate rose with increasing age. Only two of the 47 cases were previously healthy; most patients (45 [96%]) had underlying comorbid medical disorders, including diabetes (32 [68%]), hypertension (16 [34%]), chronic cardiac disease (13 [28%]), and chronic renal disease (23 [49%]). Common symptoms at presentation were fever (46 [98%]), fever with chills or rigors (41 [87%]), cough (39 [83%]), shortness of breath (34 [72%]), and myalgia (15 [32%]). Gastrointestinal symptoms were also frequent, including diarrhoea (12 [26%]), vomiting (ten [21%]), and abdominal pain (eight [17%]). All patients had abnormal findings on chest radiography, ranging from subtle to extensive unilateral and bilateral abnormalities. Laboratory analyses showed raised concentrations of lactate dehydrogenase (23 [49%]) and aspartate aminotransferase (seven [15%]) and thrombocytopenia (17 [36%]) and lymphopenia (16 [34%]). Disease caused by MERS-CoV presents with a wide range of clinical manifestations and is associated with substantial mortality in admitted patients who have medical comorbidities. Major gaps in our knowledge of the epidemiology, community prevalence, and clinical spectrum of infection and disease need urgent definition. None.

Background. Recent trials suggest procalcitonin-based guidelines can reduce antibiotic use for respiratory infections. However, the accuracy of procalcitonin to discriminate between viral and bacterial pneumonia requires further dissection. Methods. We evaluated the association between serum procalcitonin concentration at hospital admission with pathogens detected in a multicenter prospective surveillance study of adults hospitalized with community-acquired pneumonia. Systematic pathogen testing included cultures, serology, urine antigen tests, and molecular detection. Accuracy of procalcitonin to discriminate between viral and bacterial pathogens was calculated. Results. Among 1735 patients, pathogens were identified in 645 (37%), including 169 (10%) with typical bacteria, 67 (4%) with atypical bacteria, and 409 (24%) with viruses only. Median procalcitonin concentration was lower with viral pathogens (0.09 ng/mL; interquartile range [IQR], <0.05–0.54 ng/mL) than atypical bacteria (0.20 mg/mL; IQR, <0.05–0.87 ng/mL; P = .05), and typical bacteria (2.5 ng/mL; IQR, 0.29–12.2 ng/mL; P < .01). Procalcitonin discriminated bacterial pathogens, including typical and atypical bacteria, from viral pathogens with an area under the receiver operating characteristic (ROC) curve of 0.73 (95% confidence interval [CI], .69–.77). A procalcitonin threshold of 0.1 ng/mL resulted in 80.9% (95% CI, 75.3%–85.7%) sensitivity and 51.6% (95% CI, 46.6%–56.5%) specificity for identification of any bacterial pathogen. Procalcitonin discriminated between typical bacteria and the combined group of viruses and atypical bacteria with an area under the ROC curve of 0.79 (95% CI, .75–.82). Conclusions. No procalcitonin threshold perfectly discriminated between viral and bacterial pathogens, but higher procalcitonin strongly correlated with increased probability of bacterial pathogens, particularly typical bacteria.

Background. Influenza virus infections are associated with a wide spectrum of disease. However, few studies have investigated in detail the epidemiological and virological characteristics of asymptomatic and mild illness with influenza virus infections. Methods. In a community-based study in Hong Kong from 2008 to 2014, we followed up initially healthy individuals who were household contacts of symptomatic persons with laboratory-confirmed influenza, to identify secondary infections. Information from daily symptom diaries was used to classify infections as symptomatic (≥2 signs/symptoms, including fever ≥37.8°C, headache, myalgia, cough, sore throat, runny nose and sputum), paucisymptomatic (1 symptom only), or asymptomatic (none of these symptoms). We compared the patterns of influenza viral shedding between these groups. Results. We identified 235 virologically confirmed secondary cases of influenza virus infection in the household setting, including 31 (13%) paucisymptomatic and 25 (11%) asymptomatic cases. The duration of viral RNA shedding was shorter and declined more rapidly in paucisymptomatic and asymptomatic than in symptomatic cases. The mean levels of influenza viral RNA shedding in asymptomatic and paucisymptomatic cases were approximately 1–2 log10 copies lower than in symptomatic cases. Conclusions. The presence of influenza viral shedding in patients with influenza who have very few or no symptoms reflects their potential for transmitting the virus to close contacts. These findings suggest that further research is needed to investigate the contribution of persons with asymptomatic or clinically mild influenza virus infections to influenza virus transmission in household, institutional, and community settings.

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.

To update recommendations of the 4th European Conference on Infections in Leukaemia (ECIL-4) on community-acquired respiratory virus (CARV) infections published in 2013, we reviewed publications from between Jan 1, 2014, and June 30, 2024 on adenovirus, bocavirus, coronavirus, influenzavirus, metapneumovirus, parainfluenzavirus, respiratory syncytial virus (RSV), and rhinovirus in patients with haematological malignancies or undergoing haematopoietic cell transplantation (HCT), or both. In the current ECIL recommendations (ECIL-10), we outline a common approach to infection control, laboratory testing, and diagnosis for all CARVs (including SARS-CoV-2) and specific management and deferral strategies for CARVs other than SARS-CoV-2. For influenzavirus, seasonal inactivated-vaccines and early antivirals are recommended, whereas routine antiviral prophylaxis is discouraged for immunocompromised patients. For RSV, licensed vaccines can be considered according to local approval, despite scarce evidence for patients with haematological malignancies and those undergoing HCT. Passive immunisation with palivizumab or nirsevimab is recommended for children younger than 2 years, but data are insufficient for pre-exposure or post-exposure prophylaxis, or treatment of older children and adults. Oral ribavirin or intravenous immunoglobulins, or a combination of the two, are recommended for patients undergoing HCT with severe immunodeficiency scores. For other CARVs, recommendations include only supportive care, improving immune functions, correcting hypogammaglobulinaemia, and judicious lowering of corticosteroids. We highlight unmet needs in immunisation and antivirals for reducing CARV-associated morbidity and mortality in patients with haematological malignancies and those undergoing HCT.

On February 27, 2020, the first patient with coronavirus disease 2019 (COVID-19) was reported in the Netherlands. During the following weeks, at 2 Dutch teaching hospitals, 9 health care workers (HCWs) received a diagnosis of COVID-19, 8 of whom had no history of travel to China or northern Italy, raising the question of whether undetected community circulation was occurring. To determine the prevalence and clinical presentation of COVID-19 among HCWs with self-reported fever or respiratory symptoms. This cross-sectional study was performed in 2 teaching hospitals in the southern part of the Netherlands in March 2020, during the early phase of the COVID-19 pandemic. Health care workers employed in the participating hospitals who experienced fever or respiratory symptoms were asked to voluntarily participate in a screening for infection with the severe acute respiratory syndrome coronavirus 2. Data analysis was performed in March 2020. The prevalence of severe acute respiratory syndrome coronavirus 2 infection was determined by semiquantitative real-time reverse transcriptase-polymerase chain reaction on oropharyngeal samples. Structured interviews were conducted to document symptoms for all HCWs with confirmed COVID-19. Of 9705 HCWs employed (1722 male [18%]), 1353 (14%) reported fever or respiratory symptoms and were tested. Of those, 86 HCWs (6%) were infected with severe acute respiratory syndrome coronavirus 2 (median age, 49 years [range, 22-66 years]; 15 [17%] male), representing 1% of all HCWs employed. Most HCWs experienced mild disease, and only 46 (53%) reported fever. Eighty HCWs (93%) met a case definition of fever and/or coughing and/or shortness of breath. Only 3 (3%) of the HCWs identified through the screening had a history of travel to China or northern Italy, and 3 (3%) reported having been exposed to an inpatient with a known diagnosis of COVID-19 before the onset of symptoms. Within 2 weeks after the first Dutch case was detected, a substantial proportion of HCWs with self-reported fever or respiratory symptoms were infected with severe acute respiratory syndrome coronavirus 2, likely as a result of acquisition of the virus in the community during the early phase of local spread. The high prevalence of mild clinical presentations, frequently not including fever, suggests that the currently recommended case definition for suspected COVID-19 should be used less stringently.