Community-acquired pneumonia is the leading infectious cause of death in developed countries. Despite advances in antibiotic treatment, mortality among hospitalized patients with community-acquired pneumonia is still high, especially in those with severe pneumonia^1,2 and in those who experience treatment failure^3,4 (observed in 10%-20% of patients). In an earlier study conducted by the Neumofail Group,³ patients with treatment failure had higher mortality compared with those who did not experience treatment failure (25% vs 2%, respectively), and it was possible to use treatment failure as a surrogate parameter for mortality. In patients with community-acquired pneumonia, an excessive host inflammatory response is associated with treatment failure during intensive care unit (ICU) admission⁵ and mortality.⁶

There is a need for a clear definition of exacerbations used in clinical trials in patients with bronchiectasis. An expert conference was convened to develop a consensus definition of an exacerbation for use in clinical research.A systematic review of exacerbation definitions used in clinical trials from January 2000 until December 2015 and involving adults with bronchiectasis was conducted. A Delphi process followed by a round-table meeting involving bronchiectasis experts was organised to reach a consensus definition. These experts came from Europe (representing the European Multicentre Bronchiectasis Research Collaboration), North America (representing the US Bronchiectasis Research Registry/COPD Foundation), Australasia and South Africa.The definition was unanimously approved by the working group as: a person with bronchiectasis with a deterioration in three or more of the following key symptoms for at least 48 h: cough; sputum volume and/or consistency; sputum purulence; breathlessness and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND a clinician determines that a change in bronchiectasis treatment is required.The working group proposes the use of this consensus-based definition for bronchiectasis exacerbation in future clinical research involving adults with bronchiectasis.

Background: An inadequate response to initial empirical treatment of community acquired pneumonia (CAP) represents a challenge for clinicians and requires early identification and intervention. A study was undertaken to quantify the incidence of failure of empirical treatment in CAP, to identify risk factors for treatment failure, and to determine the implications of treatment failure on the outcome. Methods: A prospective multicentre cohort study was performed in 1424 hospitalised patients from 15 hospitals. Early treatment failure (<72 hours), late treatment failure, and in-hospital mortality were recorded. Results: Treatment failure occurred in 215 patients (15.1%): 134 early failure (62.3%) and 81 late failure (37.7%). The causes were infectious in 86 patients (40%), non-infectious in 34 (15.8%), and undetermined in 95. The independent risk factors associated with treatment failure in a stepwise logistic regression analysis were liver disease, pneumonia risk class, leucopenia, multilobar CAP, pleural effusion, and radiological signs of cavitation. Independent factors associated with a lower risk of treatment failure were influenza vaccination, initial treatment with fluoroquinolones, and chronic obstructive pulmonary disease (COPD). Mortality was significantly higher in patients with treatment failure (25% v 2%). Failure of empirical treatment increased the mortality of CAP 11-fold after adjustment for risk class. Conclusions: Although these findings need to be confirmed by randomised studies, they suggest possible interventions to decrease mortality due to CAP.

Introduction: Biofilm in endotracheal tubes (ETT) of ventilated patients has been suggested to play a role in the development of ventilator-associated pneumonia (VAP). Our purpose was to analyze the formation of ETT biofilm and its implication in the response and relapse of VAP. Methods: We performed a prospective, observational study in a medical intensive care unit. Patients mechanically ventilated for more than 24 hours were consecutively included. We obtained surveillance endotracheal aspirates (ETA) twice weekly and, at extubation, ETTs were processed for microbiological assessment and scanning electron microscopy. Results: Eighty-seven percent of the patients were colonized based on ETA cultures. Biofilm was found in 95% of the ETTs. In 56% of the cases, the same microorganism grew in ETA and biofilm. In both samples the most frequent bacteria isolated were Acinetobacter baumannii and Pseudomonas aeruginosa. Nineteen percent of the patients developed VAP (N = 14), and etiology was predicted by ETA in 100% of the cases. Despite appropriate antibiotic treatment, bacteria involved in VAP were found in biofilm (50%). In this situation, microbial persistence and impaired response to treatment (treatment failure and relapse) were more frequent (100% vs 29%, P = 0.021; 57% vs 14%, P = 0.133). Conclusions: Airway bacterial colonization and biofilm formation on ETTs are early and frequent events in ventilated patients. There is microbiological continuity between airway colonization, biofilm formation and VAP development. Biofilm stands as a pathogenic mechanism for microbial persistence, and impaired response to treatment in VAP.

Background: The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia. Methods: We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor. Results: At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non–community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001). Conclusions: Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses.