Atypical pathogens in hospitalized patients with community-acquired pneumonia: a worldwide perspective.
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ABSTRACT:
SUBMITTER: Gramegna A
PROVIDER: S-EPMC6299604 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
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Atypical pathogens in hospitalized patients with community-acquired pneumonia: a worldwide perspective.
Gramegna Andrea A Gramegna Andrea A Sotgiu Giovanni G Di Pasquale Marta M Radovanovic Dejan D Terraneo Silvia S Reyes Luis F LF Vendrell Ester E Neves Joao J Menzella Francesco F Blasi Francesco F Aliberti Stefano S Restrepo Marcos I MI
BMC infectious diseases 20181218 1
<h4>Background</h4>Empirical antibiotic coverage for atypical pathogens in community-acquired pneumonia (CAP) has long been debated, mainly because of a lack of epidemiological data. We aimed to assess both testing for atypical pathogens and their prevalence in hospitalized patients with CAP worldwide, especially in relation with disease severity.<h4>Methods</h4>A secondary analysis of the GLIMP database, an international, multicentre, point-prevalence study of adult patients admitted for CAP in ...[more]
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Project description:ObjectivesThis study aimed to investigate the etiology, clinical features, and outcomes of community-acquired pneumonia (CAP) in adults. Understanding the causative pathogens is essential for effective treatment and prevention.DesignBetween 2016-2018, 518 hospitalized adults with CAP and 241 controls without symptoms were prospectively enrolled. Urine samples were collected for pneumococcal urinary antigen tests and nasopharyngeal swabs for viral and bacterial analysis, combined with routine diagnostic care.ResultsAmong the included CAP patients, Streptococcus pneumoniae was the most common pathogen, detected in 28% of patients, followed by Haemophilus influenzae in 16%. Viruses were identified in 28%, and concurrent viruses and bacteria were detected in 15%. There was no difference in mortality, length of stay, or symptoms at hospitalization when comparing patients with bacterial, viral, or mixed etiologies. Among the control subjects without respiratory symptoms, S. pneumoniae, H. influenzae, or Moraxella catarrhalis were detected in 5-7%, and viruses in 7%.ConclusionStreptococcus pneumoniae emerged as the predominant cause of CAP, followed closely by viruses and H. influenzae. Intriguingly, symptoms and outcome were similar regardless of etiology. These findings highlight the complexity of this respiratory infection and emphasize the importance of comprehensive diagnostic and treatment strategies.Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT03606135].
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Project description:Severe sepsis, may be present on hospital arrival in approximately one-third of patients with community-acquired pneumonia (CAP).To determine the host characteristics and micro-organisms associated with severe sepsis in patients hospitalized with CAP.We performed a prospective multicenter cohort study in 13 Spanish hospital, on 4070 hospitalized CAP patients, 1529 of whom (37.6%) presented with severe sepsis. Severe sepsis CAP was independently associated with older age (>65 years), alcohol abuse (OR, 1.31; 95% CI, 1.07-1.61), chronic obstructive pulmonary disease (COPD) (OR, 1.75; 95% CI, 1.50-2.04) and renal disease (OR, 1.57; 95% CI, 1.21-2.03), whereas prior antibiotic treatment was a protective factor (OR, 0.62; 95% CI, 0.52-0.73). Bacteremia (OR, 1.37; 95% CI, 1.05-1.79), S pneumoniae (OR, 1.59; 95% CI, 1.31-1.95) and mixed microbial etiology (OR, 1.65; 95% CI, 1.10-2.49) were associated with severe sepsis CAP.CAP patients with COPD, renal disease and alcohol abuse, as well as those with CAP due to S pneumonia or mixed micro-organisms are more likely to present to the hospital with severe sepsis.
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Project description:BackgroundRhinoviruses (RVs) are ubiquitous respiratory pathogens that often cause mild or subclinical infections. Molecular detection of RVs from the upper respiratory tract can be prolonged, complicating etiologic association in persons with severe lower respiratory tract infections. Little is known about RV viremia and its value as a diagnostic indicator in persons hospitalized with community-acquired pneumonia (CAP).MethodsSera from RV-positive children and adults hospitalized with CAP were tested for RV by real-time reverse-transcription polymerase chain reaction. Rhinovirus species and type were determined by partial genome sequencing.ResultsOverall, 57 of 570 (10%) RV-positive patients were viremic, and all were children aged <10 years (n = 57/375; 15.2%). Although RV-A was the most common RV species detected from respiratory specimens (48.8%), almost all viremias were RV-C (98.2%). Viremic patients had fewer codetected pathogens and were more likely to have chest retractions, wheezing, and a history of underlying asthma/reactive airway disease than patients without viremia.ConclusionsMore than 1 out of 7 RV-infected children aged <10 years hospitalized with CAP were viremic. In contrast with other RV species, RV-C infections were highly associated with viremia and were usually the only respiratory pathogen identified, suggesting that RV-C viremia may be an important diagnostic indicator in pediatric pneumonia.
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Project description:National guidelines recommend obtaining blood cultures in children hospitalized with moderate or severe community-acquired pneumonia (CAP). The objectives of this study were to determine the prevalence of bacteremia in children, identify factors associated with bacteremia and quantify the influence of positive blood cultures on clinical management in children hospitalized with CAP.This multicenter retrospective study included children from 60 days to 18 years of age requiring hospitalization for CAP. Categories analyzed were bacteremia, culture negative and no culture.Blood cultures were performed in 369 (56%) of 658 children with CAP. The prevalence of bacteremia was 7% (4.7-10.1%) in patients with a blood culture obtained. Bacteremia occurred in 21% of patients with a pleural drainage procedure and 75% of patients with distant site of infection (eg, osteomyelitis). Patients with bacteremia had longer duration of fever before admission and higher C-reactive protein values compared with those with negative or no blood culture. However, differences in white blood cell count and erythrocyte sedimentation rate between those with bacteremia and those without were not significant. Contamination rates were low and similar across institutions, ranging from 1% to 3.8% (P = 0.63). Blood culture-directed changes in antibiotic management occurred in 33% of patients with a contaminated culture and 65% of bacteremic patients. Antibiotic therapy was narrowed in 26% of bacteremic patients at hospital discharge.The prevalence of bacteremia was higher than previously reported in children hospitalized with CAP and consistent across children's hospitals. Positive blood cultures should prompt change to narrow-spectrum antibiotic therapy.
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Project description:Lefamulin was the first systemic pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia based on two phase 3 trials (Lefamulin Evaluation Against Pneumonia [LEAP]-1 and LEAP-2). This pooled analysis evaluated lefamulin efficacy and safety in adults with community-acquired bacterial pneumonia caused by atypical pathogens (Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae). In LEAP-1, participants received intravenous lefamulin 150 mg every 12 h for 5-7 days or moxifloxacin 400 mg every 24 h for 7 days, with optional intravenous-to-oral switch. In LEAP-2, participants received oral lefamulin 600 mg every 12 h for 5 days or moxifloxacin 400 mg every 24 h for 7 days. Primary outcomes were early clinical response at 96 ± 24 h after first dose and investigator assessment of clinical response at test of cure (5-10 days after last dose). Atypical pathogens were identified in 25.0% (91/364) of lefamulin-treated patients and 25.2% (87/345) of moxifloxacin-treated patients; most were identified by ≥1 standard diagnostic modality (M. pneumoniae 71.2% [52/73]; L. pneumophila 96.9% [63/65]; C. pneumoniae 79.3% [46/58]); the most common standard diagnostic modality was serology. In terms of disease severity, more than 90% of patients had CURB-65 (confusion of new onset, blood urea nitrogen > 19 mg/dL, respiratory rate ≥ 30 breaths/min, blood pressure <90 mm Hg systolic or ≤60 mm Hg diastolic, and age ≥ 65 years) scores of 0-2; approximately 50% of patients had PORT (Pneumonia Outcomes Research Team) risk class of III, and the remaining patients were more likely to have PORT risk class of II or IV versus V. In patients with atypical pathogens, early clinical response (lefamulin 84.4-96.6%; moxifloxacin 90.3-96.8%) and investigator assessment of clinical response at test of cure (lefamulin 74.1-89.7%; moxifloxacin 74.2-97.1%) were high and similar between arms. Treatment-emergent adverse event rates were similar in the lefamulin (34.1% [31/91]) and moxifloxacin (32.2% [28/87]) groups. Limitations to this analysis include its post hoc nature, the small numbers of patients infected with atypical pathogens, the possibility of PCR-based diagnostic methods to identify non-etiologically relevant pathogens, and the possibility that these findings may not be generalizable to all patients. Lefamulin as short-course empiric monotherapy, including 5-day oral therapy, was well tolerated in adults with community-acquired bacterial pneumonia and demonstrated high clinical response rates against atypical pathogens.
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Project description:BackgroundThe epidemiology of Mycoplasma pneumoniae (Mp) among US children (<18 years) hospitalized with community-acquired pneumonia (CAP) is poorly understood.MethodsIn the Etiology of Pneumonia in the Community study, we prospectively enrolled 2254 children hospitalized with radiographically confirmed pneumonia from January 2010-June 2012 and tested nasopharyngeal/oropharyngeal swabs for Mp using real-time polymerase chain reaction (PCR). Clinical and epidemiological features of Mp PCR-positive and -negative children were compared using logistic regression. Macrolide susceptibility was assessed by genotyping isolates.ResultsOne hundred and eighty two (8%) children were Mp PCR-positive (median age, 7 years); 12% required intensive care and 26% had pleural effusion. No in-hospital deaths occurred. Macrolide resistance was found in 4% (6/169) isolates. Of 178 (98%) Mp PCR-positive children tested for copathogens, 50 (28%) had ≥1 copathogen detected. Variables significantly associated with higher odds of Mp detection included age (10-17 years: adjusted odds ratio [aOR], 10.7 [95% confidence interval {CI}, 5.4-21.1] and 5-9 years: aOR, 6.4 [95% CI, 3.4-12.1] vs 2-4 years), outpatient antibiotics ≤5 days preadmission (aOR, 2.3 [95% CI, 1.5-3.5]), and copathogen detection (aOR, 2.1 [95% CI, 1.3-3.3]). Clinical characteristics were non-specific.ConclusionsUsually considered as a mild respiratory infection, Mp was the most commonly detected bacteria among children aged ≥5 years hospitalized with CAP, one-quarter of whom had codetections. Although associated with clinically nonspecific symptoms, there was a need for intensive care in some cases. Mycoplasma pneumoniae should be included in the differential diagnosis for school-aged children hospitalized with CAP.
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Project description:BackgroundCommunity acquired pneumonia (CAP) is a high incidence disease resulting in about 260,000 hospital admissions per year in Germany, more than myocardial infarction or stroke. Worldwide, CAP is the most frequent infectious disease with high lethality ranging from 1.2 % in those 20-29 years old to over 10 % in patients older than 70 years, even in industrial nations. CAP poses numerous medical challenges, which the PROGRESS (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis) network aims to tackle: Operationalization of disease severity throughout the course of disease, outcome prediction for hospitalized patients and prediction of transitions from uncomplicated CAP to severe CAP, and finally, to CAP with sepsis and organ failure as a life-threatening condition. It is a major aim of PROGRESS to understand and predict patient heterogeneity regarding outcome in the hospital and to develop novel treatment concepts.MethodsPROGRESS was designed as a clinical, observational, multi-center study of patients with CAP requiring hospitalization. More than 1600 patients selected for low burden of co-morbidities have been enrolled, aiming at a total of 3000. Course of disease, along with therapy, was closely monitored by daily assessments and long-term follow-up. Daily blood samples allow in depth molecular-genetic characterization of patients. We established a well-organized workflow for sample logistics and a comprehensive data management system to collect and manage data from more than 50 study centers in Germany and Austria. Samples are stored in a central biobank and clinical data are stored in a central data base which also integrates all data from molecular assessments.DiscussionWith the PROGRESS study, we established a comprehensive data base of high quality clinical and molecular data allowing investigation of pressing research questions regarding CAP. In-depth molecular characterization will contribute to the discovery of disease mechanisms and establishment of diagnostic and predictive biomarkers. A strength of PROGRESS is the focus on younger patients with low burden of co-morbidities, allowing a more direct look at host biology with less confounding. As a resulting limitation, insights from PROGRESS will require validation in representative patient cohorts to assess clinical utility.Trial registrationThe PROGRESS study was retrospectively registered on May 24(th), 2016 with ClinicalTrials.gov: NCT02782013.
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Project description:The use of corticosteroids as adjunctive therapy might be effective in patients with community-acquired pneumonia (CAP). Oral administration of dexamethasone is a practical and safer alternative to the intravenous route. Since patients hospitalized with pneumonia might have delayed gastric emptying, this study explored systemic exposure in terms of area under the concentration-time curve (AUC) of oral dexamethasone in patients hospitalized with CAP.In this randomized, open label study, 30 patients admitted with CAP were randomized to receive either 4?mg intravenous or 6?mg oral dexamethasone for 4?consecutive days. Serial blood samples were obtained before and after drug administration.Median AUC to infinity was 626??g?l(-1) ?h (IQR 401-1161) for the intravenous group and 774??g?l(-1) ?h (IQR 618-1146) for the oral group. The AUC ratio of 6?mg oral and 4?mg intravenous dexamethasone was 1.22 (95% confidence interval (CI) 0.81, 1.82), which represents a bioavailability of 81% (95% CI 54, 121) after correction for differences in dexamethasone dose.Bioavailability of oral dexamethasone in patients hospitalized with pneumonia is sufficient. This makes oral dexamethasone an appropriate alternative for intravenous administration in these patients.
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Project description:ObjectiveViruses are more common than bacteria in patients hospitalized with community-acquired pneumonia. Little is known, however, about the frequency of respiratory viral testing and its associations with antimicrobial utilization.DesignRetrospective cohort study.SettingThe study included 179 US hospitals.PatientsAdults admitted with pneumonia between July 2010 and June 2015.MethodsWe assessed the frequency of respiratory virus testing and compared antimicrobial utilization, mortality, length of stay, and costs between tested versus untested patients, and between virus-positive versus virus-negative patients.ResultsAmong 166,273 patients with pneumonia on admission, 40,787 patients (24.5%) were tested for respiratory viruses, 94.8% were tested for influenza, and 20.7% were tested for other viruses. Viral assays were positive in 5,133 of 40,787 tested patients (12.6%), typically for influenza and rhinovirus. Tested patients were younger and had fewer comorbidities than untested patients, but patients with positive viral assays were older and had more comorbidities than those with negative assays. Blood cultures were positive for bacterial pathogens in 2.7% of patients with positive viral assays versus 5.3% of patients with negative viral tests (P < .001). Antibacterial courses were shorter for virus-positive versus -negative patients overall (mean 5.5 vs 6.4 days; P < .001) but varied by bacterial testing: 8.1 versus 8.0 days (P = .60) if bacterial tests were positive; 5.3 versus 6.1 days (P < .001) if bacterial tests were negative; and 3.3 versus 5.2 days (P < .001) if bacterial tests were not obtained (interaction P < .001).ConclusionsA minority of patients hospitalized with pneumonia were tested for respiratory viruses; only a fraction of potential viral pathogens were assayed; and patients with positive viral tests often received long antibacterial courses.
| S-EPMC8665830 | biostudies-literature