Albert Gabarrus

Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial.

IMPORTANCE In patients with severe community-acquired pneumonia, treatment failure is associated with excessive inflammatory response and worse outcomes. Corticosteroids may modulate cytokine release in these patients, but the benefit of this adjunctive therapy remains controversial. OBJECTIVE To assess the effect of corticosteroids in patients with severe community-acquired pneumonia and high associated inflammatory response. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, double-blind, placebo-controlled trial conducted in 3 Spanish teaching hospitals involving patients with both severe community-acquired pneumonia and a high inflammatory response, which was defined as a level of C-reactive protein greater than 150 mg/L at admission. Patients were recruited and followed up from June 2004 through February 2012. INTERVENTIONS Patients were randomized to receive either an intravenous bolus of 0.5 mg/kg per 12 hours of methylprednisolone (n = 61) or placebo (n = 59) for 5 days started within 36 hours of hospital admission. MAIN OUTCOMES AND MEASURES The primary outcome was treatment failure (composite outcome of early treatment failure defined as [1] clinical deterioration indicated by development of shock, [2] need for invasive mechanical ventilation not present at baseline, or [3] death within 72 hours of treatment; or composite outcome of late treatment failure defined as [1] radiographic progression, [2] persistence of severe respiratory failure, [3] development of shock, [4] need for invasive mechanical ventilation not present at baseline, or [5] death between 72 hours and 120 hours after treatment initiation; or both early and late treatment failure). In-hospital mortality was a secondary outcome and adverse events were assessed. RESULTS There was less treatment failure among patients from the methylprednisolone group (8 patients [13%]) compared with the placebo group (18 patients [31%]) (P = .02), with a difference between groups of 18% (95% CI, 3% to 32%). Corticosteroid treatment reduced the risk of treatment failure (odds ratio, 0.34 [95% CI, 0.14 to 0.87]; P = .02). In-hospital mortality did not differ between the 2 groups (6 patients [10%] in the methylprednisolone group vs 9 patients [15%] in the placebo group; P = .37); the difference between groups was 5% (95% CI, -6% to 17%). Hyperglycemia occurred in 11 patients (18%) in the methylprednisolone group and in 7 patients (12%) in the placebo group (P = .34). CONCLUSIONS AND RELEVANCE Among patients with severe community-acquired pneumonia and high initial inflammatory response, the acute use of methylprednisolone compared with placebo decreased treatment failure. If replicated, these findings would support the use of corticosteroids as adjunctive treatment in this clinical population. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00908713.

Microbial aetiology of community-acquired pneumonia and its relation to severity

Background The distribution of the microbial aetiology and mortality of community-acquired pneumonia (CAP) was investigated in relation to the clinical setting and severity scores (pneumonia severity index (PSI) and confusion, blood urea nitrogen, respiratory rate, blood pressure, age (CURB-65)). Methods 3523 patients with CAP were included (15% outpatients, 85% inpatients). The distribution of the microbial aetiology in relation to the clinical setting and severity scores (PSI, CURB-65) and the relative mortality of different aetiologies across the severity scores were analysed. Results The aetiology was established in 1463 patients (42%), of whom 257 died (7%). The ranking of aetiologies varied according to site of care, with increasing frequency of Streptococcus pneumoniae and mixed aetiologies and decreasing frequency of atypical pathogens in hospitalised patients and those in ICUs. The distribution of aetiologies according to severity scores showed corresponding patterns; however, the severity scores were more sensitive to Gram-negative enteric bacilli (GNEB) and Pseudomonas aeruginosa and less sensitive in identifying mixed aetiologies as moderate- and high-risk conditions. Mortality rates according to aetiology and severity scoring showed increasing mortality rates for all pathogens except atypical pathogens. S pneumoniae had the highest number of deaths while GNEB, P aeruginosa, Staphylococcus aureus and mixed aetiologies had the highest mortality rates. Legionella pneumophila was similarly distributed according to site of care and prognostic scores. Conclusions CAP due to atypical bacterial pathogens is recognised both clinically and by severity scoring as a low-risk condition. Severity scores are more sensitive in identifying patients with GNEB and P aeruginosa as moderate- and high-risk aetiologies whereas mixed aetiologies may be underestimated.

Impact of Age and Comorbidity on Cause and Outcome in Community-Acquired Pneumonia

BACKGROUND Prolonged life expectancy has currently increased the proportion of the very elderly among patients with community-acquired pneumonia (CAP). The aim of this study was to determine the influence of age and comorbidity on microbial patterns in patients over 65 years of age with CAP. METHODS This study was a prospective observational study of adult patients with CAP (excluding those in nursing homes) over a 12-year period. We compared patients aged 65 to 74 years, 75 to 84 years, and > 85 years for potential differences in clinical presentation, comorbidities, severity on admission, microbial investigations, causes, antimicrobial treatment, and outcomes. RESULTS We studied a total of 2,149 patients: 759 patients (35.3%) aged 65 to 74 years, 941 patients (43.7%) aged 75 to 84 years, and 449 patients (20.8%) aged > 85 years. At least one comorbidity was present in 1,710 patients (79.6%). Streptococcus pneumoniae was the most frequent pathogen in all age groups, regardless of comorbidity. Staphylococcus aureus, Enterobacteriaceae, and Pseudomonas aeruginosa accounted for 9.1% of isolates, and Haemophilus influenzae, 6.4%. All these pathogens were isolated only in patients with at least one comorbidity. Mortality increased with age (65-74 years, 6.9%; 75-84 years, 8.9%; > 85 years, 17.1%; P < .001) and was associated with increased comorbidities (neurologic; OR, 2.1; 95% CI, 1.5-2.1), Pneumonia Severity Index IV or V (OR, 3.2; 95% CI, 1.8-6.0), bacteremia (OR, 1.7; 95% CI, 1.1-2.7), the presence of a potential multidrug-resistant (MDR) pathogen (S. aureus, P. aeruginosa, Enterobacteriaceae; OR, 2.4; 95% CI, 1.3-4.3), and ICU admission (OR, 4.2; 95% CI, 2.9-6.1) on multivariate analysis. CONCLUSIONS Age does not influence microbial cause itself, whereas comorbidities are associated with specific causes such as H. influenzae and potential MDR pathogens. Mortality in the elderly is mainly driven by the presence of comorbidities and potential MDR pathogens.

Community-acquired polymicrobial pneumonia in the intensive care unit: aetiology and prognosis

IntroductionThe frequency and clinical significance of polymicrobial aetiology in community-acquired pneumonia (CAP) patients admitted to the ICU have been poorly studied. The aim of the present study was to describe the prevalence, clinical characteristics and outcomes of severe CAP of polymicrobial aetiology in patients admitted to the ICU.MethodsThe prospective observational study included 362 consecutive adult patients with CAP admitted to the ICU within 24 hours of presentation; 196 (54%) patients had an established aetiology.ResultsPolymicrobial infection was present in 39 (11%) cases (20% of those with defined aetiology): 33 cases with two pathogens, and six cases with three pathogens. The most frequently identified pathogens in polymicrobial infections were Streptococcus pneumoniae (n = 28, 72%), respiratory viruses (n = 15, 39%) and Pseudomonas aeruginosa (n = 8, 21%). Chronic respiratory disease and acute respiratory distress syndrome criteria were independent predictors of polymicrobial aetiology. Inappropriate initial antimicrobial treatment was more frequent in the polymicrobial aetiology group compared with the monomicrobial aetiology group (39% vs. 10%, P < 0.001), and was an independent predictor of hospital mortality (adjusted odds ratio = 10.79, 95% confidence interval = 3.97 to 29.30; P < 0.001). The trend for higher hospital mortality of the polymicrobial aetiology group compared with the monomicrobial aetiology group (n = 8, 21% versus n = 17, 11%), however, was not significantly different (P = 0.10).ConclusionsPolymicrobial pneumonia occurs frequently in patients admitted to the ICU. This is a risk factor for inappropriate initial antimicrobial treatment, which in turn independently predicts hospital mortality.

Community-acquired pneumonia in outpatients: aetiology and outcomes

The purpose of this study was to establish the microbial aetiology and outcomes of patients with community-acquired pneumonia (CAP) treated as outpatients after presenting to a hospital emergency care unit. A prospective observational study was carried out in the Hospital Clinic of Barcelona (Barcelona, Spain). All consecutive cases of CAP treated as outpatients were included. 568 adult outpatients with CAP were studied (mean±sd age 47.2±17.6 yrs; 110 (19.4%) were aged ≥65 yrs). Aetiological diagnoses were established in 188 (33.1%) cases. Streptococcus pneumoniae was the most frequent pathogen followed by Mycoplasma pneumoniae and respiratory viruses. Legionella was detected in 13 (2.3%) cases. More than one causative agent was found in 17 (9.0%) patients. Mortality was low (three (0.5%) patients died) and other adverse events were rare (30 (5.2%) patients had complications, 13 (2.3%) were re-admitted and treatment failed in 13 (2.3%)). Complications were mostly related to pleural effusion and empyema, and re-admissions and treatment failures to comorbidities. Outpatients with CAP have a characteristic microbial pattern. Regular antipneumococcal coverage remains mandatory. Treatment failures and re-admissions are rare and may be reduced by increased attention to patients requiring short-term observation in the emergency care unit and in the presence of pleural effusion and comorbidities.

The Effect of Macrolide Resistance on the Presentation and Outcome of Patients Hospitalized for Streptococcus pneumoniae Pneumonia.

RATIONALE There are conflicting reports describing the effect of macrolide resistance on the presentation and outcomes of patients with Streptococcus pneumoniae pneumonia. OBJECTIVES We aimed to determine the effect of macrolide resistance on the presentation and outcomes of patients with pneumococcal pneumonia. METHODS We conducted a retrospective, observational study in the Hospital Clinic of Barcelona of all adult patients hospitalized with pneumonia who had positive cultures for S. pneumoniae from January 1, 2000 to December 31, 2013. Outcomes examined included bacteremia, pulmonary complications, acute renal failure, shock, intensive care unit admission, need for mechanical ventilation, length of hospital stay, and 30-day mortality. MEASUREMENTS AND MAIN RESULTS Of 643 patients hospitalized for S. pneumoniae pneumonia, 139 (22%) were macrolide resistant. Patients with macrolide-resistant organisms were less likely to have bacteremia, pulmonary complications, and shock, and were less likely to require noninvasive mechanical ventilation. We found no increase in the incidence of acute renal failure, the frequency of intensive care unit admission, the need for invasive ventilatory support, the length of hospital stay, or the 30-day mortality in patients with (invasive or noninvasive) macrolide-resistant S. pneumoniae pneumonia, and no effect on outcomes as a function of whether treatment regimens did or did not comply with current guidelines. CONCLUSIONS We found no evidence suggesting that patients hospitalized for macrolide-resistant S. pneumoniae pneumonia were more severely ill on presentation or had worse clinical outcomes if they were treated with guideline-compliant versus noncompliant regimens.

Community-acquired lung respiratory infections in HIV-infected patients: microbial aetiology and outcome

We describe the aetiology of community-acquired pneumonia (CAP) in HIV-infected patients, risk factors for bacterial or Pneumocystis jirovecii CAP and prognostic factors of 30-day mortality. This was a prospective observational study of 331 consecutive adult CAP cases in HIV-infected patients (January 2007 to July 2012). 128 (39%) patients had CD4+ cell counts <200 per mm3 and 99 (43%) ha HIV RNA levels <200 copies per mL on antiretroviral therapy. Streptococcus pneumoniae was the most frequent microorganism in the group with CD4+ cell counts ≥200 per mm3; P. jirovecii was the most frequent microorganism in the group with CD4+ cell counts <200 per mm3 and in patients with HIV RNA ≥200 copies per mL. Predictors of bacterial CAP were: time with symptoms ≤5 days (OR 2.6, 95% CI 1.5–4.4), C-reactive protein level ≥22 mg·dL−1 (OR 4.3, 95% CI 2.3–8.2) and hepatitis C virus co-infection (OR 2.3, 95% CI 1.4–3.9). White blood cell count ≤4×1012 per L (OR 3.7, 95% CI 1.2–11.5), lactate dehydrogenase (LDH) level ≥598 U·L−1 (OR 12.9, 95% CI 4.2–39.7) and multilobar infiltration (OR 5.8, 95% CI 1.9–19.5) were predictors of P. jirovecii. Overall 30-day mortality was 7%. Appropriate antibiotic treatment (OR 0.1, 95% CI 0.03–0.4), LDH ≥598 U·L−1 (OR 6.2, 95% CI 1.8–21.8) and mechanical ventilation (OR 22.0, 95% CI 6.2–78.6) were the variables independently associated with 30-day mortality. The described predictors may help clinicians to distinguish between bacterial and P. jirovecii pneumonia in patients with suspected or confirmed HIV infection. Clinical risk factors in HIV patients to distinguish between bacterial and Pneumocystis jirovecii pneumonia http://ow.ly/sV2hf

New Sepsis Definition (Sepsis-3) and Community-acquired Pneumonia Mortality. A Validation and Clinical Decision-Making Study

Rationale: The Sepsis‐3 Task Force updated the clinical criteria for sepsis, excluding the need for systemic inflammatory response syndrome (SIRS) criteria. The clinical implications of the proposed flowchart including the quick Sequential (Sepsis‐related) Organ Failure Assessment (qSOFA) and SOFA scores are unknown. Objectives: To perform a clinical decision‐making analysis of Sepsis‐3 in patients with community‐acquired pneumonia. Methods: This was a cohort study including adult patients with community‐acquired pneumonia from two Spanish university hospitals. SIRS, qSOFA, the Confusion, Respiratory Rate and Blood Pressure (CRB) score, modified SOFA (mSOFA), the Confusion, Urea, Respiratory Rate, Blood Pressure and Age (CURB‐65) score, and Pneumonia Severity Index (PSI) were calculated with data from the emergency department. We used decision‐curve analysis to evaluate the clinical usefulness of each score and the primary outcome was in‐hospital mortality. Measurements and Main Results: Of 6,874 patients, 442 (6.4%) died in‐hospital. SIRS presented the worst discrimination, followed by qSOFA, CRB, mSOFA, CURB‐65, and PSI. Overall, overestimation of in‐hospital mortality and miscalibration was more evident for qSOFA and mSOFA. SIRS had lower net benefit than qSOFA and CRB, significantly increasing the risk of over‐treatment and being comparable with the “treat‐all” strategy. PSI had higher net benefit than mSOFA and CURB‐65 for mortality, whereas mSOFA seemed more applicable when considering mortality/intensive care unit admission. Sepsis‐3 flowchart resulted in better identification of patients at high risk of mortality. Conclusions: qSOFA and CRB outperformed SIRS and presented better clinical usefulness as prompt tools for patients with community‐acquired pneumonia in the emergency department. Among the tools for a comprehensive patient assessment, PSI had the best decision‐aid tool profile.

Effects of duty cycle and positive end-expiratory pressure on mucus clearance during mechanical ventilation*.

Objectives:During mechanical ventilation, air flows may play a role in mucus transport via two-phase gas liquid flow. The aim of this study was to evaluate effects of duty cycles and positive end-expiratory pressure on mucus clearance in pigs using mechanical ventilation, and to assess their safety. Design:Prospective randomized animal study. Setting:Animal research facility, University of Barcelona, Spain. Subjects:Eight healthy pigs. Interventions:Pigs were intubated and on volume-control mechanical ventilation for up to 84 hrs. After 4, 24, 48, and 72 hrs of mechanical ventilation, six levels of duty cycle (0.26, 0.33, 0.41, 0.50, 0.60, and 0.75) with no associated positive end-expiratory pressure or 5 cm H2O of positive end-expiratory pressure were randomly applied. Surgical bed was oriented 30 degrees in the reverse Trendelenburg position, as in the semirecumbent position. Measurement and Main Results:Inspiratory and expiratory flows and hemodynamics were measured after each 30-min ventilation period. Mucus movement was assessed through fluoroscopy tracking of radio-opaque markers. Mucus velocity was described by a positive vector (toward the glottis) or negative vector (toward the lungs). No effect of positive end-expiratory pressure was found; however, as duty cycle was increasingly prolonged, a trend toward reduced velocity of mucus moving toward the lungs and increased outward mucus velocity was found (p = .064). Two clusters of mucus velocities were identified as duty cycle was prolonged beyond 0.41. Thus, duty cycle >0.41 increased mean expiratory–inspiratory flow bias from −4.1 ± 4.6 to 7.9 ± 5.9 L/min (p < .0001) and promoted outward mucus velocity from −0.22 ± 1.71 mm/min (range, −5.78 to 2.42) to 0.53 ± 1.06 mm/min (−1.91 to 3.88; p = .0048). Duty cycle of 0.75 resulted in intrinsic positive end-expiratory pressure (2.1 ± 1.1 cm H2O [p < .0001] vs. duty cycle 0.26–0.5), with no hemodynamic compromise. Conclusions:In the semirecumbent position, mucus clearance is improved with prolongation of the duty cycle. However, in clinical practice, positive findings must be balanced against the potentially adverse hemodynamic and respiratory effects.

Bacteraemia and antibiotic-resistant pathogens in community acquired pneumonia: risk and prognosis

The sensitivity of blood cultures in the diagnosis of bacteraemia for community-acquired pneumonia is low. Recommendations, by guidelines, to perform blood cultures are discordant. We aimed to determine the incidence, microbial aetiology, risk factors and outcomes of bacteraemic patients with community-acquired pneumonia, including cases with antibiotic-resistant pathogens (ARP). A prospective, observational study was undertaken on consecutive adult patients admitted to the Hospital Clinic of Barcelona (Barcelona, Spain) with community-acquired pneumonia and blood cultures were obtained. Of the 2892 patients included, bacteraemia was present in 297 (10%) patients; 30 (10%) of whom had ARP (multidrug-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and an extended spectrum of beta-lactamase producing Enterobacteriaceae). In multivariate analyses, pleuritic pain, C-reactive protein ≥21.6 mg·dL−1 and intensive care unit admissions were independently associated with bacteraemia, while prior antibiotic treatment and pneumococcal vaccine were protective factors. The risk factors for ARP bacteraemia were previous antibiotics and C-reactive protein <22.2 mg·dL−1, while pleuritic pain was the only protective factor in the multivariate analysis. Bacteraemia (excluding ARP), appropriate empiric treatment, neurological disease, arterial oxygen tension/inspiratory oxygen fraction <250, pneumonia severity index risk classes IV and V, and intensive care unit admission were independently associated with a 30-day hospital mortality in the multivariate analysis. Inappropriate therapy was more frequent in ARP bacteraemia, compared with other bacteraemias (27% versus 3%, respectively, p<0.001). Antibiotic therapy protected against bacteraemia, but increased specifically the risk of bacteraemia from ARP due to the inappropriate coverage of these pathogens. Identifying patients at risk of ARP bacteraemia would help in deciding appropriate empiric antimicrobial therapy. The results from this study provide evidence concerning community-acquired pneumonia patients in whom blood cultures should not be performed. Understand risk factors for ARP bacteraemia and the importance of identifying patients who may have these organisms http://ow.ly/EUs8d