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Antibiotic therapy (AT) is the cornerstone of the management of severe community-acquired pneumonia (CAP). However, the best treatment strategy is far from being established. To evaluate the impact of different aspects of AT on the outcome of critically ill patients with CAP, we performed a post hoc analysis of all CAP patients enrolled in a prospective, observational, multicentre study. Of the 502 patients included, 76% received combination therapy, mainly a β-lactam with a macrolide (80%). AT was inappropriate in 16% of all microbiologically documented CAP (n=177). Hospital and 6months mortality were 34% and 35%. In adjusted multivariate logistic regression analysis, combination AT with a macrolide was independently associated with a reduction in hospital (OR 0.17, 95%CI 0.06-0.51) and 6months (OR 0.21, 95%CI 0.07-0.57) mortality. Prolonged AT (>7days) was associated with a longer ICU (14 vs. 7days; p7days had no survival benefit and was associated with a longer LOS. info:eu-repo/semantics/publishedVersion

Purpose To identify a single/panel of biomarkers and to provide a point score that, after 48 h of treatment, could early predict treatment failure at fifth day of Intensive Care Unit (ICU) stay in severe community-acquired pneumonia (SCAP) patients. Materials and methods Single-center, prospective cohort study of 107 ICU patients with SCAP. Primary outcome included death or absence of improvement in Sequential Organ Failure Assessment score by ≥2 points within 5 days of treatment. Biomarkers were evaluated within 12 h of first antibiotic dose (D1) and 48 h after the first assessment (D3). Results A model based on Charlson's score and a panel of biomarkers (procalcitonin on D1 and D3, B-natriuretic peptide on D1, D-dimer and lactate on D3) had good discrimination for primary outcome in both derivation (AUC 0.82) and validation (AUC 0.76) samples and was well calibrated (X2 = 0.98; df = 1; p = .32). A point score system (PRoFeSs score) built on the estimates of regression coefficients presented good discrimination (AUC 0.81; 95% Confidence Interval 0.72–0.89) for primary outcome. Conclusions In SCAP, a combination of biomarkers measured at admission and 48 h later may early predict treatment failure. PRoFeSs score may recognize patients with poor short-term prognosis.

Purpose This study aimed to evaluate the role of biomarkers as markers of pneumococcal bacteremia in severe community-acquired pneumonia (SCAP). Materials and Methods A prospective, single-center, observational cohort study of 108 patients with SCAP admitted to the intensive care department of a university hospital in Portugal was conducted. Leucocytes, C-reactive protein (CRP), lactate, procalcitonin (PCT), d-dimer, brain natriuretic peptide (BNP), and cortisol were measured within 12 hours after the first antibiotic dose. Results Fifteen patients (14%) had bacteremic pneumococcal pneumonia (BPP). They had significantly higher levels of median CRP (301 [interquartile range, or IQR], 230-350] mg/L vs 201 [IQR, 103-299] mg/L; P = .023), PCT (40 [IQR, 25-102] ng/mL vs 8 [IQR, 2-26] ng/mL; P P = .027), and lactate (5.5 [IQR, 4.5-9.8] mmol/L vs 3.1 [IQR, 1.9-6.2] mmol/L; P = .009) than did patients without BPP. The discriminatory power evaluated by the area under the receiver operating characteristic curve (aROC) for PCT (aROC, 0.79) was superior to lactate (aROC, 0.71), BNP (aROC, 0.67), and CRP (aROC, 0.70). At a cutoff point of 17 ng/mL, PCT showed a sensitivity of 87%, a specificity of 67%, a positive predictive value of 30% and a negative predictive value of 97%, as a marker of pneumococcal bacteremia. Conclusions In this cohort, significantly higher PCT, BNP, lactate, and CRP levels were found in BPP, and PCT presented the best ability to identify pneumococcal bacteremia. A PCT serum level lower than 17 ng/mL could identify patients with SCAP unlikely to have pneumococcal bacteremia.

Background Technological advances improved the practice of “modern” extracorporeal membrane oxygenation (ECMO). In the present report, we describe the experience of a referral ECMO center using portable miniaturized ECMO systems for H1N1-related severe acute respiratory distress syndrome (ARDS). Methods An observational study of all patients with H1N1-associated ARDS treated with ECMO in Hospital S. Joao (Porto, Portugal) between November 2009 and April 2011 was performed. Extracorporeal membrane oxygenation support was established using either ELS or Cardiohelp systems (Maquet-Cardiopulmonary-AG, Hirrlingen, Germany). Results Ten adult patients with severe ARDS secondary to H1N1 infection (Pa o 2/fraction of inspired oxygen, 69 mm Hg [56-84]; Murray score, 3.5 [3.5-3.8]) were included, and 60% survived to hospital discharge. Five patients were uneventfully transferred on ECMO from referring hospitals to our center by ambulance. Six patients were treated during the first postpandemic influenza season. All patients were treated with oseltamivir, and 1 received in addition zanamivir. Four patients received corticosteroids. Nosocomial infection was the most common complication (40%). Of the 4 deaths, 2 were caused by hemorrhagic shock; 1, by irreversible multiple organ failure; and 1, by refractory septic shock. Conclusion In our experience, ECMO support was a valuable therapeutic option for H1N1-related severe ARDS. The use of portable miniaturized systems allowed urgent rescue of patients from referring hospitals and safe interhospital and intrahospital transport during ECMO support.

Considerable evidence has shown that adequate antibiotic therapy is of utmost importance in the critically ill septic patient. However, antibiotic concentration may be insufficient early in infection course. We propose the concept of dose modulation, meaning front-line variability of antibiotic dose, according to patient and microorganism characteristics, followed by its reduction after clinical response and patient recovery. Therefore, dose modulation means concentrating the largest weight of antibiotics at the front-end, when the microbial load is higher and the pharmacokinetic changes poses the highest risk of underdosing and nibbling off antibiotic dose, when the sepsis syndrome is improving, guided by pharmacokinetic and pharmacodynamic data.