Procalcitonin and C-reactive protein to rule out early bacterial coinfection in COVID-19 critically ill patients.

PURPOSE: Although the prevalence of community-acquired respiratory bacterial coinfection upon hospital admission in patients with coronavirus disease 2019 (COVID-19) has been reported to be < 5%, almost three-quarters of patients received antibiotics. We aim to investigate whether procalcitonin (PCT) or C-reactive protein (CRP) upon admission could be helpful biomarkers to identify bacterial coinfection among patients with COVID-19 pneumonia. METHODS: We carried out a multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish intensive care units (ICUs). The primary outcome was to explore whether PCT or CRP serum levels upon hospital admission could predict bacterial coinfection among patients with COVID-19 pneumonia. The secondary outcome was the evaluation of their association with mortality. We also conducted subgroups analyses in higher risk profile populations. RESULTS: Between 5 February 2020 and 21 December 2021, 4076 patients were included, 133 (3%) of whom presented bacterial coinfection. PCT and CRP had low area under curve (AUC) scores at the receiver operating characteristic (ROC) curve analysis [0.57 (95% confidence interval (CI) 0.51-0.61) and 0.6 (95% CI, 0.55-0.64), respectively], but high negative predictive values (NPV) [97.5% (95% CI 96.5-98.5) and 98.2% (95% CI 97.5-98.9) for PCT and CRP, respectively]. CRP alone was associated with bacterial coinfection (OR 2, 95% CI 1.25-3.19; p = 0.004). The overall 15, 30 and 90 days mortality had a higher trend in the bacterial coinfection group, but without significant difference. PCT ≥ 0.12 ng/mL was associated with higher 90 days mortality. CONCLUSION: Our study suggests that measurements of PCT and CRP, alone and at a single time point, are not useful for ruling in or out bacterial coinfection in viral pneumonia by COVID-19.

Effects of Mechanical Insufflation-Exsufflation on Sputum Volume in Mechanically Ventilated Critically Ill Subjects.

BACKGROUND: Mechanical insufflation-exsufflation (MI-E) is a noninvasive technique performed to simulate cough and remove sputum from proximal airways. To date, the effects of MI-E on critically ill patients on invasive mechanical ventilation are not fully elucidated. In this randomized crossover trial, we evaluated the efficacy and safety of MI-E combined to expiratory rib cage compressions (ERCC). METHODS: Twenty-six consecutive subjects who were sedated, intubated, and on mechanical ventilation > 48 h were randomized to perform 2 sessions of ERCC with or without additional MI-E before tracheal suctioning in a 24-h period. The primary outcome was sputum volume following each procedure. Secondary end points included effects on respiratory mechanics, hemodynamics, and safety. RESULTS: In comparison to ERCC alone, median (interquartile range) sputum volume cleared was significantly higher during ERCC+MI-E (0.42 [0-1.39] mL vs 2.29 [1-4.67] mL, P < .001). The mean ± SD respiratory compliance improved in both groups immediately after the treatment, with the greater improvement in the ERCC+MI-E group (54.7 ± 24.1 mL/cm H2O vs 73.7 ± 35.8 mL/cm H2O, P < .001). Differences between the groups were not significant (P = .057). Heart rate increased significantly in both groups immediately after each intervention (P < .05). Additionally, a significant increase in oxygenation was observed from baseline to 1 h post-intervention in the ERCC+MI-E group (P < .05). Finally, several transitory hemodynamic variations occurred during both interventions, but these were nonsignificant and were considered clinically irrelevant. CONCLUSIONS: In mechanically ventilated subjects, MI-E combined with ERCC increased the sputum volume cleared without causing clinically important hemodynamic changes or adverse events. (ClinicalTrials.gov registration: NCT03316079.).

Aetiological diagnosis in new adult outpatients with bronchiectasis:role of predictors derived from real life experience.

BACKGROUND: In adult patients with bronchiectasis (BE) the identification of the underlying aetiology may be difficult. In a new patient with BE the performance of a panel of tests is recommended, even though this practice may be expensive and the level of evidence supporting is low. We aimed to identify a panel of variables able to predict the aetiological diagnosis of BE. METHODS: Our prospective study derived from our real-life experience on the management of adult stable BE outpatients. We recorded variables concerning clinical, radiological, microbiological and laboratory features. We identified five groups of aetiological diagnosis of BE (idiopathic, post-infective, COPD, asthma and non-common diseases [immunodeficiency or other rare conditions]). Multivariate models were used to identify predictors of each aetiological diagnosis. The suitability of performing a specific test for the diagnosis was also considered. RESULTS: We enrolled 354 patients with a new diagnosis of BE. Patients with different aetiological causes differed significantly with regard to age, sex, smoking habit, comorbidities, dyspnoea perception, airflow obstruction and severity scores. Various predictors were assessed, including sex, previous respiratory infections, diffuse localization of BE, risk scores, and laboratory variables (sodium and eosinophils). The levels of autoantibodies or immunoglobulins were reserved for the diagnosis of non-common disease. CONCLUSION: Our research confirms that some predictors are specific for the aetiological diagnosis of BE. The possibility of integrating this information may represent a useful tool for the diagnosis. The execution of certain specific tests should be reserved for patients with a non-common disease.

Association between physical activity and risk of hospitalisation in bronchiectasis.

BACKGROUND: Patients with bronchiectasis have a less active lifestyle than healthy peers, but the association with hospital admission has not been explored. The aim of this study was to investigate the association between 1) any physical activity variable; and 2) sedentary time, with hospitalisation due to exacerbation in adults with bronchiectasis. METHODS: In this prospective observational study, baseline lung function, quality of life, exercise tolerance, severity of bronchiectasis and physical activity were recorded. Physical activity was objectively assessed over a week using a SenseWear armband and the results were expressed in steps·day-1 and sedentary time. Number of hospitalisations due to a bronchiectasis exacerbation and time to first event were recorded after 1-year follow-up. RESULTS: Sixty-four patients with bronchiectasis were analysed, of whom 15 (23%) were hospitalised during the follow-up. Hospitalised patients showed poor baseline clinical and severity outcomes, fewer steps walked per day and more sedentary behaviour than the non-hospitalised group. Patients who walked ≤6290 steps·day-1 or spent ≥7.8 h·day-1 in sedentary behaviour had an increased risk of hospital admission due to bronchiectasis exacerbation at 1-year follow-up. Specifically, ≥7.8 h·day-1 of sedentary behaviour was associated with a 5.9-fold higher risk of hospital admission in the following year. CONCLUSIONS: Low levels of physical activity and high sedentary time at baseline were associated with a higher risk of hospitalisation due to bronchiectasis exacerbation. If these findings are validated in future studies, it might be appropriate to include physical activity and sedentary behaviour as an item in severity scores.

Mucoid Pseudomonas aeruginosa alters sputum viscoelasticity in patients with non-cystic fibrosis bronchiectasis.

INTRODUCTION AND AIM: Pseudomonas aeruginosa could acquire a mucoid phenotype due to mutations in mucA (mucoid Pseudomonas aeruginosa - mPA) that is a hallmark of poor prognosis in patients with bronchiectasis. Despite the higher prevalence of Pseudomonas aeruginosa in bronchiectasis, how mPA and non-mucoid Pseudomonas aeruginosa (non-mPA) phenotypes could affect viscoelastic properties of sputum is unknown. Our aim was to determine the relationship between Pseudomonas aeruginosa phenotypes isolation, the viscoelastic properties of sputum and the clinical outcomes in patients with bronchiectasis. METHODS: A cross-sectional study was conducted of sputum samples obtained by spontaneous expectoration and sent for microbiology and rheology analysis. Elasticity and viscosity were measured at two oscillatory frequencies (1 and 100 rad/s). Socio-demographic and clinical data were recorded. RESULTS: We analyzed 17 patients with mPA, 14 with non-mPA and 17 with no organism reported (NOR). Compared with the NOR group, the mPA group showed higher elasticity (median 10.30 vs. 5.70, p = 0.023), viscosity (2.40 vs. 1.50, p = 0.039), and stiffness (10.70 vs. 6.00, p = 0.024). Values in the mPA group tended to be higher compared with non-mPA. Clinically, the mPA group showed greater hospitalizations during the previous year and greater affected lobes than the non-mPA and NOR groups. CONCLUSIONS: The mPA phenotype is associated with increased elasticity, viscosity and stiffness of bronchiectatic sputum. Viscoelastic properties could be used as a marker of poor mucociliary clearance in mPA, with potentially important clinical implications.

Twenty-year trend in mortality among hospitalized patients with pneumococcal community-acquired pneumonia.

BACKGROUND: There is only limited information on mortality over extended periods in hospitalized patients with pneumococcal community-acquired pneumonia (CAP). We aimed to evaluate the 30-day mortality and whether is changed over a 20-year period among immunocompetent adults hospitalized with pneumococcal CAP. METHODS: We conducted a retrospective observational study of data that were prospectively collected at the Hospital Clinic of Barcelona of all adult patients hospitalized with diagnosis of pneumococcal CAP over a 20-year period. To aid analysis, results were divided into four periods of 5 years each (1997-2001, 2002-2006, 2007-2011, 2012-2016). The primary outcome was 30-day mortality, but secondary outcomes included intensive care unit (ICU) admission, lengths of hospital and ICU-stays, ICU-mortality, and need of mechanical ventilation. RESULTS: From a cohort of 6,403 patients with CAP, we analyzed the data for 1,120 (17%) adults with a diagnosis of pneumococcal CAP. Over time, we observed decreases in the rates of alcohol consumption, smoking, influenza vaccination, and older patients (age ≥65 years), but increases in admissions to ICU and the need for non-invasive mechanical ventilation. The overall 30-day mortality rate was 8% (95% confidence interval, 6%-9%; 84 of 1,120 patients) and did not change significantly between periods (p = 0.33). Although, we observed a decrease in ICU-mortality comparing the first period (26%) to the second one (10%), statistical differences disappeared with adjustment (p0.38). CONCLUSION: Over time, 30-day mortality of hospitalized pneumococcal CAP did not change significantly. Nor did it change in the propensity-adjusted multivariable analysis. Since mortality in pneumococcal pneumonia has remained unaltered for many years despite the availability of antimicrobial agents with proven in vitro activity, other non-antibiotic strategies should be investigated.

Impact of bronchiectasis on outcomes of hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease: A propensity matched analysis.

The coexistence of both Chronic Obstructive Pulmonary Disease (COPD) and bronchiectasis (BE) define an emerging phenotype with a worse prognosis; however, data about these patients do not consider baseline characteristics as confounders. We evaluate the impact of BE on outcomes of hospitalized patients with acute exacerbation of COPD (AECOPD). We prospectively considered AECOPD patients, analysed using a propensity score matching (PSM) method. The outcomes included length of hospital stay, use of non-invasive and invasive mechanical ventilation, intensive care unit admission, and mortality up to 3-years. Out of the 449 patients enrolled, 160 had associated BE. AECOPD with BE were older, had lower body mass index and greater functional impairment and severity of symptoms than AECOPD without BE. After PSM, 91 patients were considered for each group and no significant differences were found for all baseline characteristics. In full cohort, the cumulative mortality rate, the survival time, the Kaplan-Meier survival curves and the risk of death were worse in AECOPD with BE in the follow-up of 6-months, 1-year and 3-years. After PSM, data on mortality were similar between AECOPD with and without BE. In conclusion, in AECOPD patients the presence of BE does not influence mortality in a long-term follow-up.

Community-Acquired Legionella Pneumonia in Human Immunodeficiency Virus-Infected Adult Patients: A Matched Case-Control Study.

We investigate whether the clinical presentations and outcomes of Legionella pneumonia in human immunodeficiency virus (HIV)-infected patients were comparable to those seen in non-HIV-infected patients (case-control design). HIV-infected individuals presented neither a more severe disease nor a worse clinical outcome than matched HIV-negative control patients.

Comparison of two prognostic scores (BSI and FACED) in a Spanish cohort of adult patients with bronchiectasis and improvement of the FACED predictive capacity for exacerbations.

Bronchiectasis (BE) is a chronic and heterogeneous respiratory disease that requires a multidimensional scoring system to properly assess severity. The aim of this study was to compare the severity stratification by 2 validated scores (BSI and FACED) in a BE cohort and to determine their predictive capacity for exacerbations and hospitalizations. Moreover, we proposed a modified version of FACED which was created to better predict the risk of exacerbations in clinical practice. We performed a prospective cohort study including BE patients >18 years old with a follow-up period of 1-year. One-hundred eighty-two patients (40% males; mean age 68) were studied. Patients were stratified according to the number of exacerbations during the follow-up, and according to BSI and FACED scores. BSI classified most of our patients as severe 99 (54.4%) or moderate 47 (25.8%), while FACED mainly classified as mild 108 (59.3%) or moderate 61 (33.5%). BSI and FACED showed an area under ROC curve (AUC) for exacerbations of 0.808 and 0.734; and for hospitalizations (due to BE exacerbations) of 0.893 and 0.809, respectively. Subsequently, we modified FACED by adding previous exacerbations (Exa-FACED) and this new score classified patients as mild 48.4%, moderate 34.6% and severe 17.0%, with an improved AUC for exacerbations (0.760) and hospitalizations (0.820). Despite previous validations of BSI and FACED, they classified our patients very differently. As expected, FACED showed poor prognostic capacity for exacerbations. We support the Exa-FACED score to predict the risk future exacerbations for been easy to use in clinical practice.

Intensive care unit-acquired pneumonia due to Pseudomonas aeruginosa with and without multidrug resistance.

OBJECTIVE: Pseudomonas aeruginosa often presents multi-drug resistance (MDR) in intensive care unit (ICU)-acquired pneumonia (ICUAP), possibly resulting in inappropriate empiric treatment and worse outcomes. We aimed to identify patients with ICUAP at risk for these pathogens in order to improve treatment selection and outcomes. METHODS: We prospectively assessed 222 consecutive immunocompetent ICUAP patients confirmed microbiologically. We determined the characteristics, risk factors, systemic inflammatory response and outcomes of P. aeruginosa pneumonia (Pa-ICUAP), compared to other aetiologies. We also compared patients with MDR vs. non-MDR Pa-ICUAP. RESULTS: Pseudomonas aeruginosa was the most frequent aetiology (64, 29%); 22 (34%) cases had MDR. Independent predictors for Pa-ICUAP were prior airway colonization by P. aeruginosa, previous antibiotic treatment, solid cancer and shock; alcohol abuse and pleural effusion were independently associated to lower risk for Pa-ICUAP. Chronic liver disease independently predicted MDR among Pa-ICUAP. The inflammatory biomarkers were similar between all groups. Patients with Pa-ICUAP had lower unadjusted 90-day survival (p = 0.049). However, the 90-day survival adjusted for confounding factors using a propensity score did not differ between all groups. CONCLUSION: Pseudomonas aeruginosa remains the most frequent aetiology of ICUAP, with high prevalence of MDR. These risk factors should be taken into account to avoid inappropriate empiric antibiotics for Pa-ICUAP. Pseudomonas aeruginosa, regardless multidrug resistance, was not associated with different propensity-adjusted survival.

Predicting In-Hospital Treatment Failure (≤ 7 days) in Patients with COPD Exacerbation Using Antibiotics and Systemic Steroids.

Although pharmacological treatment of COPD exacerbation (COPDE) includes antibiotics and systemic steroids, a proportion of patients show worsening of symptoms during hospitalization that characterize treatment failure. The aim of our study was to determine in-hospital predictors of treatment failure (≤ 7 days). Prospective data on 110 hospitalized COPDE patients, all treated with antibiotics and systemic steroids, were collected; on the seventh day of hospitalization, patients were divided into treatment failure (n = 16) or success (n = 94). Measures of inflammatory serum biomarkers were recorded at admission and at day 3; data on clinical, laboratory, microbiological, and severity, as well data on mortality and readmission, were also recorded. Patients with treatment failure had a worse lung function, with higher serum levels of C-reactive protein (CRP), procalcitonin (PCT), tumour necrosis factor-alpha (TNF-α), interleukin (IL) 8, and IL-10 at admission, and CRP and IL-8 at day 3. Longer length of hospital stay and duration of antibiotic therapy, higher total doses of steroids and prevalence of deaths and readmitted were found in the treatment failure group. In the multivariate analysis, +1 mg/dL of CRP at admission (OR, 1.07; 95% CI, 1.01 to 1.13) and use of penicillins or cephalosporins (OR, 5.63; 95% CI, 1.26 to 25.07) were independent variables increasing risk of treatment failure, whereas cough at admission (OR, 0.20; 95% CI, 0.05 to 0.75) reduces risk of failure. In hospitalized COPDE patients CRP at admission and use of specific class of antibiotics predict in-hospital treatment failure, while presence of cough has a protective role.

Microbiology and outcomes of community acquired pneumonia in non cystic-fibrosis bronchiectasis patients.

BACKGROUND: It is general belief that Non-cystic fibrosis bronchiectasis (NCFB) is characterized by frequent community-acquired pneumonia. Nonetheless, the knowledge on clinical characteristics of CAP in NCFBE is poor and no specific recommendations are available. We aim to investigate clinical and microbiological characteristics of NCFBE patients with CAP. METHODS: Prospective observational study of 3495 CAP patients (2000-2011). RESULTS: We found 90 (2.0%) NCFBE-CAP that in comparison with non-bronchiectatic CAP (n, 3405) showed older age (mean ± [SD], NCFBE-CAP 73 ± 14 vs. CAP 65 ± 19yrs), more vaccinations (pneumococcal: 35% vs. 14%; influenza: 60% vs. 42%), comorbidities (n ≥ 2: 43% vs. 25%), previous antibiotics (38% vs. 22%), and inhaled steroids (53% vs. 16%) (p < 0.05 each). Streptococcus pneumoniae was the most frequent isolate in both groups (NCFBE-CAP 44.4% vs. CAP 42.7%; p = 0.821) followed by respiratory virus, mixed infections and atypical bacteria. Considering overall frequencies of the main pathogens (including monomicrobial and mixed infections) Pseudomonas aeruginosa (15.5% vs. 2.9%; p < 0.001) and Enterobacteriaceae (8.8% vs. 2.4%; p = 0.025) were more prevalent in NCFBE-CAP patients than in CAP. Despite these clinical and microbiological differences, NCFBE-CAP showed similar outcomes to CAP patients (mortality, length of hospital stay, etc.). CONCLUSIONS: NCFBE-CAP patients are usually older and have more comorbidities but similar outcomes than general CAP population. Usual CAP pathogens, such as S. pneumoniae, are also involved in NCFBE-CAP but P. aeruginosa and other Enterobacteriaceae were globally more frequent than in CAP. Therefore, a wide microbiological investigation should be recommended in all NCFBE-CAP cases as well as routine pneumococcal vaccination for prevention of pneumonia.