Community-acquired pneumonia.

The European Organization for Research and Treatment of Cancer (EORTC) was founded in 1962 by research workers in the main cancer research institutes of the Common Market countries and Switzerland. This small group of cancer specialists comprising clinicians and basic science researchers decided to form an association to promote cancer research in Europe through the joint efforts of the clinical and basic research groups of several countries. Among them, were Henri TAGNON from Brussels (Belgium), Silvio GARATTINI, Director of the Institute for pharmacological Research in Milan (Italy), D. VAN BEKKUM, Director of the Radiobiological Institute TN0 at Rijswijk (Netherlands), K. BREUR, Director of the Amsterdam Cancer Institute (Netherlands), G. MATHE, D. SCHWARTZ, and M. TUBIANA from Villejuif (France). Initially the organization was called the “Groupe Europeen de Chimiotherapie anticancereuse” (GECA), 1 year later it became the EORTC and has been known all over the world under this appellation. G. MATHE was its first President from 1962 to 1965. The creation of the EORTC was immediately greeted both by the governments of the various EEC countries and by the medical and scientific circles. From the outset its two main goals were first to develop and coordinate clinical research in Europe and indeed it has organized several hundreds of cooperative multi-center controlled clinical trials and second to promote that area of basic research, which is closed, to providing significant results for diagnosis or therapy. During the past 25 years the EORTC has progressively become the largest organization for therapeutic cancer research in Europe. In 1972, the NC1 in Washington stated that its creation has been “the most important development in therapeutic research on cancer in Europe.” PRESENT STRUCTURES

The European organization for research and treatment of cancer (EORTC)

Globally, pneumonia is a serious public health concern and a major cause of mortality and morbidity. Despite advances in antimicrobial therapies, microbiological diagnostic tests and prevention measures, pneumonia remains the main cause of death from infectious disease in the world. An important reason for the increased global mortality is the impact of pneumonia on chronic diseases, along with the increasing age of the population and the virulence factors of the causative microorganism. The increasing number of multidrug-resistant bacteria, difficult-to-treat microorganisms, and the emergence of new pathogens are a major problem for clinicians when deciding antimicrobial therapy. A key factor for managing and effectively guiding appropriate antimicrobial therapy is an understanding of the role of the different causative microorganisms in the etiology of pneumonia, since it has been shown that the adequacy of initial antimicrobial therapy is a key factor for prognosis in pneumonia. Furthermore, broad-spectrum antibiotic therapies are sometimes given until microbiological results are available and de-escalation cannot be performed quickly. This review provides an overview of microbial etiology, resistance patterns, epidemiology and microbial diagnosis of pneumonia.

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Microbial Etiology of Pneumonia: Epidemiology, Diagnosis and Resistance Patterns.

Extended-spectrum β-lactamase (ESBL)-producing Gram-negative pathogens are a major cause of resistance to expanded-spectrum β-lactam antibiotics. Since their discovery in the early 1980s, they have spread worldwide and an are now endemic in Enterobacterales isolated from both hospital-associated and community-acquired infections. As a result, they are a global public health concern. In the past, TEM- and SHV-type ESBLs were the predominant families of ESBLs. Today CTX-M-type enzymes are the most commonly found ESBL type with the CTX-M-15 variant dominating worldwide, followed in prevalence by CTX-M-14, and CTX-M-27 is emerging in certain parts of the world. The genes encoding ESBLs are often found on plasmids and harboured within transposons or insertion sequences, which has enabled their spread. In addition, the population of ESBL-producing Escherichia coli is dominated globally by a highly virulent and successful clone belonging to ST131. Today, there are many diagnostic tools available to the clinical microbiology laboratory and include both phenotypic and genotypic tests to detect β-lactamases. Unfortunately, when ESBLs are not identified in a timely manner, appropriate antimicrobial therapy is frequently delayed, resulting in poor clinical outcomes. Several analyses of clinical trials have shown mixed results with regards to whether a carbapenem must be used to treat serious infections caused by ESBLs or whether some of the older β-lactam-β-lactamase combinations such as piperacillin/tazobactam are appropriate. Some of the newer combinations such as ceftazidime/avibactam have demonstrated efficacy in patients. ESBL-producing Gram-negative pathogens will continue to be major contributor to antimicrobial resistance worldwide. It is essential that we remain vigilant about identifying them both in patient isolates and through surveillance studies.

Extended-spectrum β-lactamases: an update on their characteristics, epidemiology and detection

Pneumonia remains a worldwide health problem with a high rate of morbidity and mortality. Identification of microbial pathogens which cause pneumonia is an important area for optimum clinical management of pneumonia patients and is a big challenge for conventional microbiological methods. The development and implementation of molecular diagnostic tests for pneumonia has been a major advance in the microbiological diagnosis of respiratory pathogens in recent years. However, with new knowledge regarding the microbiome, together with the recognition that the lungs are a dynamic microbiological ecosystem, our current concept of pneumonia is not totally realistic as this new concept of pneumonia involves a dysbiosis or alteration of the lung microbiome. A new challenge for microbiologists and clinicians has therefore arisen. There is much to learn regarding the information provided by this new diagnostic technology, which will lead to improvements in the time to antibiotic therapy, targeted antibiotic selection and more effective de-escalation and improved stewardship for pneumonia patients. This article provides an overview of current methods of laboratory diagnosis of pneumonia in the molecular age.

https://erj.ersjournals.com/content/erj/48/6/1764.full.pdf

Laboratory diagnosis of pneumonia in the molecular age.

Severe pneumonia remains an important cause of morbidity and mortality. Polymerase chain reaction (PCR) has been shown to be more sensitive than current standard microbiological methods – particularly in patients with prior antibiotic treatment – and therefore, may improve the accuracy of microbiological diagnosis for hospitalized patients with pneumonia. Conventional detection techniques and multiplex PCR for 14 typical bacterial pneumonia-associated pathogens were performed on respiratory samples collected from adult hospitalized patients enrolled in a prospective multi-center study. Patients were enrolled from March until September 2012. A total of 739 fresh, native samples were eligible for analysis, of which 75 were sputa, 421 aspirates, and 234 bronchial lavages. 276 pathogens were detected by microbiology for which a valid PCR result was generated (positive or negative detection result by Curetis prototype system). Among these, 120 were identified by the prototype assay, 50 pathogens were not detected. Overall performance of the prototype for pathogen identification was 70.6% sensitivity (95% confidence interval (CI) lower bound: 63.3%, upper bound: 76.9%) and 95.2% specificity (95% CI lower bound: 94.6%, upper bound: 95.7%). Based on the study results, device cut-off settings were adjusted for future series production. The overall performance with the settings of the CE series production devices was 78.7% sensitivity (95% CI lower bound: 72.1%) and 96.6% specificity (95% CI lower bound: 96.1%). Time to result was 5.2 hours (median) for the prototype test and 43.5 h for standard-of-care. The Pneumonia Application provides a rapid and moderately sensitive assay for the detection of pneumonia-causing pathogens with minimal hands-on time.

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Detection of pneumonia associated pathogens using a prototype multiplexed pneumonia test in hospitalized patients with severe pneumonia

Bronchoalveolar lavage (BAL) culture is a standard, though time-consuming, approach for identifying microorganisms in patients with severe lower respiratory tract (LRT) infections. The sensitivity of BAL culture is relatively low, and prior antimicrobial therapy decreases the sensitivity further, leading to overuse of empirical antibiotics. The Unyvero LRT BAL Application (Curetis GmbH, Germany) is a multiplex molecular panel that detects 19 bacteria, 10 antibiotic resistance markers, and a fungus, Pneumocystis jirovecii, in BAL fluid in ∼4.5 h. Its performance was evaluated using 1,016 prospectively collected and 392 archived specimens from 11 clinical trial sites in the United States. Overall positive and negative percent agreements with culture results for identification of bacteria that grow in routine cultures were 93.4% and 98.3%, respectively, with additional potential pathogens identified by Unyvero in 21.7% of prospectively collected specimens. For detection of P. jirovecii, the positive percent agreement with standard testing was 87.5%. Antibiotic resistance marker results were compared to standard antibiotic susceptibility test results to determine positive predictive values (PPVs). PPVs ranged from 80 to 100%, based on the microorganism and specific resistance marker(s). The Unyvero LRT BAL Application provides accurate detection of common agents of bacterial pneumonia and of P. jirovecii. The sensitivity and rapidity of this panel suggest significant clinical value for choosing appropriate antibiotics and for antibiotic stewardship.

Sandra Barth

Papers

Detection of pneumonia associated pathogens using a prototype multiplexed pneumonia test in hospitalized patients with severe pneumonia

Multicenter Evaluation of the Unyvero Platform for Testing Bronchoalveolar Lavage Fluid.