Bacterial etiology of community-acquired pneumonia in immunocompetent hospitalized patients and appropriateness of empirical treatment recommendations: an international point-prevalence study.

An accurate knowledge of the epidemiology of community-acquired pneumonia (CAP) is key for selecting appropriate antimicrobial treatments. Very few etiological studies assessed the appropriateness of empiric guideline recommendations at a multinational level. This study aims at the following: (i) describing the bacterial etiologic distribution of CAP and (ii) assessing the appropriateness of the empirical treatment recommendations by clinical practice guidelines (CPGs) for CAP in light of the bacterial pathogens diagnosed as causative agents of CAP. Secondary analysis of the GLIMP, a point-prevalence international study which enrolled adults hospitalized with CAP in 2015. The analysis was limited to immunocompetent patients tested for bacterial CAP agents within 24 h of admission. The CAP CPGs evaluated included the following: the 2007 and 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA), the European Respiratory Society (ERS), and selected country-specific CPGs. Among 2564 patients enrolled, 35.3% had an identifiable pathogen. Streptococcus pneumoniae (8.2%) was the most frequently identified pathogen, followed by Pseudomonas aeruginosa (4.1%) and Klebsiella pneumoniae (3.4%). CPGs appropriately recommend covering more than 90% of all the potential pathogens causing CAP, with the exception of patients enrolled from Germany, Pakistan, and Croatia. The 2019 ATS/IDSA CPGs appropriately recommend covering 93.6% of the cases compared with 90.3% of the ERS CPGs (p < 0.01). S. pneumoniae remains the most common pathogen in patients hospitalized with CAP. Multinational CPG recommendations for patients with CAP seem to appropriately cover the most common pathogens and should be strongly encouraged for the management of CAP patients.

Relationship between acute kidney injury and serum procalcitonin (PCT) concentration in critically ill patients with influenza infection.

INTRODUCTION: Serum procalcitonin (PCT) concentration could be increased in patients with renal dysfunction in the absence of bacterial infection. OBJECTIVE: To determine the interactions among serum renal biomarkers of acute kidney injury (AKI) and serum PCT concentration, in patients admitted to the intensive care unit (ICU) due to lung influenza infection. DESIGN: Secondary analysis of a prospective multicentre observational study. SETTING: 148 Spanish ICUs. PATIENTS: ICU patients admitted with influenza infection without bacterial co-infection. Clinical, laboratory and hemodynamic variables were recorded. AKI was classified as AKI I or II based on creatinine (Cr) concentrations (≥1.60-2.50mg/dL and Cr≥2.51-3.99mg/dL, respectively). Patients with chronic renal disease, receiving renal replacement treatment or with Cr>4mg/dL were excluded. Spearman's correlation, simple and multiple linear regression analysis were performed. INTERVENTIONS: None. RESULTS: Out of 663 patients included in the study, 52 (8.2%) and 10 (1.6%) developed AKI I and II, respectively. Patients with AKI were significantly older, had more comorbid conditions and were more severally ill. PCT concentrations were higher in patients with AKI (2.62 [0.60-10.0]ng/mL vs. 0.40 [0.13-1.20]ng/mL, p=0.002). Weak correlations between Cr/PCT (rho=0.18) and Urea (U)/PCT (rho=0.19) were identified. Simple linear regression showed poor interaction between Cr/U and PCT concentrations (Cr R2=0.03 and U R2=0.018). Similar results were observed during multiple linear regression analysis (Cr R2=0.046 and U R2=0.013). CONCLUSIONS: Although PCT concentrations were slightly higher in patients with AKI, high PCT concentrations are not explained by AKI and could be warning sign of a potential bacterial infection.

Managing community acquired pneumonia in the elderly - the next generation of pharmacotherapy on the horizon.

INTRODUCTION: Community acquired pneumonia (CAP) is associated with high rates of morbidity and mortality, especially among the elderly. Antibiotic treatment for CAP in the elderly is particularly challenging for many reasons, including compliance issues, immunosuppression, polypharmacy and antimicrobial resistance. There are few available antibiotics that are able to address these concerns. Areas covered: After a systematic review of the current literature, we describe seven novel antibiotics that are currently in advanced stages of development (phase 3 and beyond) and show promise for the treatment of CAP in those over the age of 65. These antibiotics are: Solithromycin, Pristinamycin, Nemonaxacin, Lefamulin, Omadacycline, Ceftobiprole and Delafloxacin. Using a novel conceptual framework designed by the present authors, known as the 'San Antonio NIPS model', we evaluate their strengths and weaknesses based on their ability to address the unique challenges that face the elderly. Expert opinion: All seven antibiotics have potential value for effective utilization in the elderly, but to varying degrees based on their NIPS model score. The goal of this model is to reorganize a clinician's focus on antibiotic choices in the elderly and bring attention to a seldom discussed topic that may potentially become a health-care crisis in the next decade.

Bacteremic pneumococcal pneumonia: clinical outcomes and preliminary results of inflammatory response.

PURPOSE: Further examination of clinical outcomes and inflammatory response of bacteremic pneumococcal community-acquired pneumonia (CAP) is of great interest to enhance the care of patients with pneumococcal CAP. METHODS: This is a secondary analysis of the Community Acquired Pneumonia Organization (CAPO) to compare the time to clinical stability (TCS), length of hospital stay (LOS), and in-hospital mortality of hospitalized pneumococcal CAP patients with and without bacteremia. To measure the effect of bacteremia in pneumococcal CAP patients on outcomes, we modeled all-cause in-hospital mortality using a Poisson regression model, and TCS and LOS using Cox proportional hazards models. Adjusted multivariate regression models were also used to predict the probability of occurrence of each of the study outcomes. To investigate the inflammatory response, we measured the plasma levels of pro- and anti-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1rα, IL-6, IL-8, IL-10], inflammatory biomarkers [C-reactive protein (CRP), pro-calcitonin (PCT), and B-type natriuretic peptide (BNP)], and peripheral blood neutrophil responses in 10 patients, 4 bacteremic and 6 non-bacteremic pneumococcal CAP, upon admission and every other day during the first 6 days of hospitalization. Functional data were presented as median and standard error of the median (SEM); due to small number of samples no statistical comparisons were performed between groups. RESULTS: From 833 pneumococcal CAP patients, 394 patients (47 %) were bacteremic. Bacteremic pneumococcal CAP were less likely to reach TCS with an adjusted hazard ratio (AHR) of 0.82 (95 % CI 0.69-0.97; p = 0.02) and had higher in-hospital mortality with an AHR of 1.63 (95 % CI 1.06-2.50, p = 0.026). Bacteremic pneumococcal CAP patients had a longer LOS than non-bacteremic pneumococcal CAP (p < 0.003). Higher plasma levels of CRP, PCT, and BNP were found in bacteremic than in non-bacteremic patients. The bacteremic group had consistently higher plasma levels of both pro- and anti-inflammatory cytokines. The blood neutrophil functional responses were similar in both groups of patients. CONCLUSIONS: Bacteremic pneumococcal CAP patients were significantly associated with higher in-hospital mortality, lower TCS, and longer LOS. HIV-infected patients showed a greater mortality which was not statistically significant. Bacteremic pneumococcal CAP patients had higher levels of biomarkers and systemic cytokines.

Desenlace de los enfermos traqueotomizados después de la reintubación / Outcome of tracheotomized patients following reintubation

Objetivo Evaluar el desenlace de pacientes que fueron traqueotomizados tras una reintubación. Diseño Análisis secundario de un estudio de cohorte prospectivo. Ámbito Treinta y seis unidades de cuidados intensivos de 8 países.Pacientes180 pacientes con ventilación mecánica durante más de 48 horas extubados y que requirieron reintubación en las primeras 48 horas. Intervenciones Ninguna. Variables de interés principal Mortalidad en la Unidad de Cuidados Intensivos, días de estancia en la unidad de cuidados intensivos, fracaso de órganos. Resultados Cincuenta y dos pacientes (29%) fueron traqueotomizados inicialmente después de reintubación. La mediana de tiempo desde la reintubación a la traqueotomía fue de 2,5 días (rango inter-cuartil: 1, 8). La duración de la estancia en la UCI fue significativamente mayor en el grupo de traqueotomía, en comparación con el grupo inicialmente sin traqueotomía [mediana de 25 días (rango inter-cuartil: 17, 43) versus 16,5 días (rango inter-cuartil: 11, 25); p <0,001]. En el grupo de traqueotomía no se observó una menor mortalidad (31% frente al 27%; p=0,57).Conclusiones En nuestra cohorte, la traqueotomía después de reintubación es un procedimiento común pero no ofrece ninguna ventaja significativa (AU)

Objective To evaluate the outcome of tracheotomized patients after reintubation. Method Secondary analysis from a prospective, multicenter and observational study including 36 Intensive Care Units (ICUs) from 8 countries. Patients A total of 180 patients under mechanical ventilation for more than 48hours, extubated and reintubated within 48hours.InterventionsNone.OutcomesICU mortality, length of ICU stay, organ failure. Results Fifty-two patients (29%) underwent tracheotomy after reintubation. The median time from reintubation to tracheotomy was 2.5 days (interquartile range (IQR) 1-8 days). The length of ICU stay was significantly longer in the tracheotomy group compared with the group without tracheotomy (median time 25 days, IQR 17-43 versus 16.5 days (IQR 11-25); p<0.001). ICU mortality in the tracheotomy group was not significantly different (31% versus 27%; p 0.57).Conclusions In our cohort of reintubated patients, tracheotomy is a common procedure in the ICU. Patients with tracheotomy had an outcome similar to those without tracheotomy (AU)

Outcome of tracheotomized patients following reintubation.

OBJECTIVE: To evaluate the outcome of tracheotomized patients after reintubation. METHOD: Secondary analysis from a prospective, multicenter and observational study including 36 Intensive Care Units (ICUs) from 8 countries. PATIENTS: A total of 180 patients under mechanical ventilation for more than 48 hours, extubated and reintubated within 48 hours. INTERVENTIONS: None. OUTCOMES: ICU mortality, length of ICU stay, organ failure. RESULTS: Fifty-two patients (29%) underwent tracheotomy after reintubation. The median time from reintubation to tracheotomy was 2.5 days (interquartile range (IQR) 1-8 days). The length of ICU stay was significantly longer in the tracheotomy group compared with the group without tracheotomy (median time 25 days, IQR 17-43 versus 16.5 days (IQR 11-25); p<0.001). ICU mortality in the tracheotomy group was not significantly different (31% versus 27%; p 0.57). CONCLUSIONS: In our cohort of reintubated patients, tracheotomy is a common procedure in the ICU. Patients with tracheotomy had an outcome similar to those without tracheotomy.

Differences in hospital- and ventilator-associated pneumonia due to Staphylococcus aureus (methicillin-susceptible and methicillin-resistant) between Europe and Latin America: a comparison of the EUVAP and LATINVAP study cohorts.

PURPOSE: A comparison is made of epidemiological variables (demographic and clinical characteristics) and outcomes in patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) caused by methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) in the Latin American VAP (LATINVAP) vs. the European Union VAP (EUVAP) cohorts of patients admitted to intensive care units (ICUs). METHODS: The EUVAP project was a prospective, multicenter observational study reporting 827 patients with HAP/VAP in 27 ICUs from 9 European countries. The LATINVAP project was a multicenter prospective observational study, with an identical design, performed in 17 ICUs from 4 Latin American countries involving 99 patients who developed HAP/VAP. Episodes of VAP/HAP caused by S. aureus, MSSA, and MRSA were compared in both cohorts. RESULTS: Forty-five patients had S. aureus HAP/VAP in the EUVAP cohort vs. 11 patients in the LATINVAP cohort. More patients had MRSA in the LATINVAP study than in the EUVAP (45% vs. 33%). ICU mortality among patients with MSSA HAP/VAP in EUVAP was 10% vs. 50% for LATINVAP (OR=9.75, p=0.01). Fifteen patients in the EUVAP cohort developed MRSA HAP/VAP as opposed to 5 in LATINVAP. In the EUVAP study there was an ICU mortality rate of 33.3%. In the LATINVAP cohort, the ICU mortality rate was 60% (OR for death=3.0; 95%CI 0.24-44.7). CONCLUSION: MRSA pneumonia was associated with poorer outcomes in comparison with MSSA. Our study suggests significant variability among European and Latin American ICU practices that may influence clinical outcomes. Furthermore, patients with pneumonia in Latin America have different outcomes.

[Antifungal prophylaxis in the postoperative period of lung transplant surgery in Spain]. / Profilaxis antifúngica en el postoperatorio de trasplante de pulmón en España.

OBJECTIVES: To examine the type and duration of antifungal prophylaxis provided during the postoperative period of lung transplant recipients, together with the most frequent complications during admission to Intensive Care Units in Spain. PATIENTS AND METHODS: A questionnaire was developed including demographic data on each transplant center, the type of antifungal prophylaxis used, its duration, and the most frequent complications. The questionnaire was distributed among the 7 Spanish national lung transplant centers, followed by analysis of the results obtained. RESULTS: All 7 centers completed the questionnaire. All of them provided universal prophylaxis in lung transplant patients. Monotherapy was the most widely used protocol (5/7; 71.4%), with amphotericin B in liposomal or conventional form being the most frequent drug, administered via the inhalatory route. In the case of combination therapy, a great diversity of drugs was observed. The most frequently administered second choice drug was anidulafungin (3/7; 43%), followed by voriconazole (2/7; 28.5%). Antifungal therapy was maintained on an indefinite basis by 43% of the centers. Invasive fungal infection (IFI) in the postoperative period of transplantation during admission to the Intensive Care Unit was suspected in 5-10% of the cases but was confirmed in less than 5%. Among other complications registered in these patients in the Intensive Care Unit, the most frequent problems were respiratory infections (5/7; 71.5%). CONCLUSIONS: Antifungal prophylaxis during the postoperative period of lung transplantation is provided on a universal basis, though consensus is lacking as to the drug of choice, the administration route and the duration of such treatment.

Guideline-concordant therapy and outcomes in healthcare-associated pneumonia.

Healthcare-associated pneumonia (HCAP) guidelines were first proposed in 2005 but have not yet been validated. The objective of this study was to compare 30-day mortality in HCAP patients treated with either guideline-concordant (GC)-HCAP therapy or GC community-acquired pneumonia (CAP) therapy. We performed a population-based cohort study of >150 hospitals in the US Veterans Health Administration. Patients were included if they had one or more HCAP risk factors and received antibiotic therapy within 48 h of admission. Critically ill patients were excluded. Independent risk factors for 30-day mortality were determined in a generalised linear mixed-effect model, with admitting hospital as a random effect. Propensity scores for the probability of receiving GC-HCAP therapy were calculated and incorporated into a second logistic regression model. A total of 15,071 patients met study criteria and received GC-HCAP therapy (8.0%), GC-CAP therapy (75.7%) or non-GC therapy (16.3%). The strongest predictors of 30-day mortality were recent hospital admission (OR 2.49, 95% CI 2.12-2.94) and GC-HCAP therapy (OR 2.18, 95% CI 1.86-2.55). GC-HCAP therapy remained an independent risk factor for 30-day mortality (OR 2.12, 95% CI 1.82-2.48) in the propensity score analysis. In nonsevere HCAP patients, GC-HCAP therapy is not associated with improved survival compared with GC-CAP therapy.

Inhaled corticosteroid use is associated with lower mortality for subjects with COPD and hospitalised with pneumonia.

Recent studies suggest that use of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) may be associated with a higher incidence of pneumonia. However, it is unclear whether COPD subjects on ICS who develop pneumonia have worse outcomes. Therefore, our aim was to examine the association of prior outpatient ICS therapy with mortality in hospitalised COPD subjects with pneumonia. We included subjects ≥64 yrs of age, hospitalised with pneumonia in US Veterans Affairs hospitals, and assessed the association of ICS exposure with mortality for hospitalised COPD subjects with pneumonia in a covariate-adjusted regression model. We identified 6,353 subjects with a diagnosis of pneumonia and prior COPD, of whom 38% were on ICS. Mortality was 9% at 30 days and 16% at 90 days. In regression analyses, outpatient ICS therapy was associated with lower mortality at both 30 days (OR 0.76, 95% CI 0.70-0.83), and 90 days (OR 0.80, 95% CI 0.75-0.86). Outpatient therapy with ICS was associated with a significantly lower 30- and 90-day mortality in hospitalised COPD patients with pneumonia.

Combination antibiotic therapy with macrolides improves survival in intubated patients with community-acquired pneumonia.

OBJECTIVE: To assess the effect on survival of macrolides or fluoroquinolones in intubated patients admitted to the intensive care unit (ICU) with severe community-acquired pneumonia (severe CAP). METHODS: Prospective, observational cohort, multicenter study conducted in 27 ICUs of 9 European countries. Two hundred eighteen consecutive patients requiring invasive mechanical ventilation for an admission diagnosis of CAP were recruited. RESULTS: Severe sepsis and septic shock were present in 165 (75.7%) patients. Microbiological documentation was obtained in 102 (46.8%) patients. ICU mortality was 37.6% (n = 82). Non-survivors were older (58.6 +/- 16.1 vs. 63.4 +/- 16.7 years, P < 0.05) and presented a higher score on the simplified Acute Physiology Score II at admission (45.6 +/- 15.4 vs. 50.8 +/- 17.5, P < 0.05). Monotherapy was given in 43 (19.7%) and combination therapy in 175 (80.3%) patients. Empirical antibiotic therapy was in accordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) guidelines in 100 (45.9%) patients (macrolides in 46 patients and fluoroquinolones in 54). In this cohort, a Cox regression analysis adjusted by severity identified that macrolide use was associated with lower ICU mortality (hazard ratio, HR 0.48, confidence intervals, 95% CI 0.23-0.97, P = 0.04) when compared to the use of fluoroquinolones. When more severe patients presenting severe sepsis and septic shock were analyzed (n = 92), similar results were obtained (HR 0.44, 95% CI 0.20-0.95, P = 0.03). CONCLUSIONS: Patients with severe community-acquired pneumonia had a low adherence with the 2007 IDSA/ATS guidelines. Combination therapy with macrolides should be preferred in intubated patients with severe CAP.

Antifungal prophylaxis with voriconazole or itraconazole in lung transplant recipients: hepatotoxicity and effectiveness.

Invasive fungal infections (IFI) are common after lung transplantation and there are limited data for the use of antifungal prophylaxis in these patients. Our aim was to compare the safety and describe the effectiveness of universal prophylaxis with two azole regimens in lung transplant recipients. This is a retrospective study in lung transplant recipients from July 2003 to July 2006 who received antifungal prophylaxis with itraconazole or voriconazole plus inhaled amphotericin B to compare the incidence of hepatotoxicity. Secondary outcomes include describing the incidence of IFI, clinical outcomes after IFI and mortality. Sixty-seven consecutive lung transplants received antifungal prophylaxis, 32 itraconazole and 35 voriconazole and inhaled amphotericin B. There were no significant differences between groups in the acute physiology and chronic health evaluation (APACHE) score at the time of transplantation, demographic characteristics, comorbidities and concomitant use of hepatotoxic medications. Hepatotoxicity occurred in 12 patients receiving voriconazole and inhaled amphotericin B and in no patients receiving itraconazole (p < 0.001). There was no significant difference between groups with regard to the percentage of transplants with IFI, but one case of zygomycosis occurred in a transplant treated with voriconazole. Voriconazole prophylaxis after lung transplantation was associated with a higher incidence of hepatotoxicity and similar clinical effectiveness when compared to itraconazole.