Search

Rationale: Coated devices may reduce biofilm formation and reduce the occurrence of device-related infections in critically ill patients. A bundle of coated devices (an endotracheal tube [ETT], central venous catheter [CVC], and urinary catheter [UC]) simultaneously inserted may optimize benefits of coated devices in patients with the most severe illness. Objectives: To assess the feasibility of a randomized controlled trial on simultaneous insertion of gold/silver/palladium-coated devices versus uncoated devices in severely ill patients, which required sequential insertion of all three devices (an ETT, CVC, and UC) for support in the intensive care unit (ICU). Methods: This was a multicenter randomized controlled pilot trial. Patients who required simultaneous insertion of an ETT, CVC, and UC were randomized to treatment with coated versus uncoated devices, which were used as necessary for up to 28 days. The primary endpoint was feasibility, defined as the trial being able to enroll enough participants to have the sample size necessary for its secondary primary endpoint (estimating sepsis incidence in this population) in less than 1 year and for estimating the number of admitted patients who require simultaneous insertion of all three devices. Secondary endpoints included the incidence of sepsis and device-associated infections (ventilator-associated pneumonia, catheter-related bloodstream infection, and catheter-related urinary-tract infection) within each group as well as the number of days alive and free of antibiotics during the ICU stay. All events were adjudicated. Results: One hundred and three patients (48 in the coated-device group and 55 in the uncoated-device group) were included in the perprotocol analysis. The inclusion period was 8 months. There were 13 septic events in each group (26 in total), with an approximate incidence of sepsis of 32.3 (95% credible interval [CrI], 22.4-44.9) per 100 patient-days. The overall incidences of ventilator-associated pneumonia, catheter-related urinary-tract infection, and catheterrelated bloodstream infection were 15.2 (95% CrI, 7.8-26.4), 6.3 (95% CrI, 2.4-13.7), and 7.9 (95% CrI, 3.6-15.1) per 1,000 patient-days, and incidence rates were not statistically different between groups. Patients in the coated-device group had more days alive and free of antibiotics in the ICU (28.97 d vs. 19.62 d per 100 patient-days; mean ratio, 1.48; 95% CrI, 1.16-1.89). Conclusions: Use of a bundle of coated devices as the initial treatment for of severely ill patients is feasible. Coated devices may be associated with more days alive and free of antibiotics. Clinical trial registered with www.clinicaltrials.gov (NCT 03868241).

Corticosteroids have been used for decades in the adjunctive treatment of severe infections in intensive care. The most frequent scenario in intensive care is in septic shock, where low doses of glucocorticoids appear to restore vascular responsiveness to norepinephrine. There is a strong body of evidence suggesting that hydrocortisone reduces time on vasopressor, and may modulate the immune response. In this review, we explore the current evidence supporting the use of corticosteroids in septic shock, its benefits, and potential harms. In addition to landmark clinical trials, we will also describe new frontiers for the use of corticosteroids in septic shock which should be explored in future studies.

Importance Intravenous fluids are used for almost all intensive care unit (ICU) patients. Clinical and laboratory studies have questioned whether specific fluid types result in improved outcomes, including mortality and acute kidney injury. Objective To determine the effect of a balanced solution vs saline solution (0.9% sodium chloride) on 90-day survival in critically ill patients. Design, Setting, and Participants Double-blind, factorial, randomized clinical trial conducted at 75 ICUs in Brazil. Patients who were admitted to the ICU with at least 1 risk factor for worse outcomes, who required at least 1 fluid expansion, and who were expected to remain in the ICU for more than 24 hours were randomized between May 29, 2017, and March 2, 2020; follow-up concluded on October 29, 2020. Patients were randomized to 2 different fluid types (a balanced solution vs saline solution reported in this article) and 2 different infusion rates (reported separately). Interventions Patients were randomly assigned 1:1 to receive either a balanced solution (n = 5522) or 0.9% saline solution (n = 5530) for all intravenous fluids. Main Outcomes and Measures The primary outcome was 90-day survival. Results Among 11 052 patients who were randomized, 10 520 (95.2%) were available for the analysis (mean age, 61.1 [SD, 17] years; 44.2% were women). There was no significant interaction between the 2 interventions (fluid type and infusion speed;P = .98). Planned surgical admissions represented 48.4% of all patients. Of all the patients, 60.6% had hypotension or vasopressor use and 44.3% required mechanical ventilation at enrollment. Patients in both groups received a median of 1.5 L of fluid during the first day after enrollment. By day 90, 1381 of 5230 patients (26.4%) assigned to a balanced solution died vs 1439 of 5290 patients (27.2%) assigned to saline solution (adjusted hazard ratio, 0.97 [95% CI, 0.90-1.05];P = .47). There were no unexpected treatment-related severe adverse events in either group. Conclusion and Relevance Among critically ill patients requiring fluid challenges, use of a balanced solution compared with 0.9% saline solution did not significantly reduce 90-day mortality. The findings do not support the use of this balanced solution. Trial Registration ClinicalTrials.gov Identifier:NCT02875873

Introduction Acinetobacter species treatment often represents a challenge. The main objective of this study is identify predictors of ICU mortality in patients submitted to mechanical ventilation (MV). Materials and methods Retrospective cohort study. Patients with MV > 48 h who developed a respiratory tract positive culture for Acinetobacter were included, and distinguished among colonized, ventilator-associated pneumonia (VAP) or ventilator-associated tracheobronchitis (VAT) patients. Primary outcome was ICU mortality. Results 153 patients were in MV and presented positive culture for Acinetobacter calcoaceticus-baumanii complex, 70 of them with VAP, 59 with VAT and 24 patients were colonized. The factors related to ICU mortality were VAP (OR 2.2, 95% CI 1.1–4.5) and shock at the time of diagnosis (OR 4.8, 95% CI 1.8–2.3). In multivariate analysis, only SOFA score at the time of diagnosis (OR 1.06, 95% CI 1.03–1.09) was related with ICU mortality. A paired-matched analysis was performed to assess effect of dual therapy on outcomes, and no effect was found in terms of clinical cure, ICU or hospital mortality or duration of antimicrobial therapy. Conclusions Previous comorbidities and degree of associated organic injury seem to be more important factors in the prognosis than double antibiotic therapy in patients with Acinetobacter-related respiratory infection.

Importance Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients. Objective To determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19–associated ARDS. Design, Setting, and Participants Multicenter, randomized, open-label, clinical trial conducted in 41 intensive care units (ICUs) in Brazil. Patients with COVID-19 and moderate to severe ARDS, according to the Berlin definition, were enrolled from April 17 to June 23, 2020. Final follow-up was completed on July 21, 2020. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients. Interventions Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n =151) or standard care alone (n = 148). Main Outcomes and Measures The primary outcome was ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Secondary outcomes were all-cause mortality at 28 days, clinical status of patients at day 15 using a 6-point ordinal scale (ranging from 1, not hospitalized to 6, death), ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, and Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) at 48 hours, 72 hours, and 7 days. Results A total of 299 patients (mean [SD] age, 61 [14] years; 37% women) were enrolled and all completed follow-up. Patients randomized to the dexamethasone group had a mean 6.6 ventilator-free days (95% CI, 5.0-8.2) during the first 28 days vs 4.0 ventilator-free days (95% CI, 2.9-5.4) in the standard care group (difference, 2.26; 95% CI, 0.2-4.38;P = .04). At 7 days, patients in the dexamethasone group had a mean SOFA score of 6.1 (95% CI, 5.5-6.7) vs 7.5 (95% CI, 6.9-8.1) in the standard care group (difference, −1.16; 95% CI, −1.94 to −0.38;P= .004). There was no significant difference in the prespecified secondary outcomes of all-cause mortality at 28 days, ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, or the 6-point ordinal scale at 15 days. Thirty-three patients (21.9%) in the dexamethasone group vs 43 (29.1%) in the standard care group experienced secondary infections, 47 (31.1%) vs 42 (28.3%) needed insulin for glucose control, and 5 (3.3%) vs 9 (6.1%) experienced other serious adverse events. Conclusions and Relevance Among patients with COVID-19 and moderate or severe ARDS, use of intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days. Trial Registration ClinicalTrials.gov Identifier:NCT04327401

Submitted by DSpace Unilasalle (dspace@unilasalle.edu.br) on 2021-07-30T17:29:03Z No. of bitstreams: 1 Hydroxychloroquine with or without Azithromycin_NEJM.pdf: 657905 bytes, checksum: abd774ed0fca84d1bf82fc915cc48491 (MD5) Made available in DSpace on 2021-07-30T17:29:03Z (GMT). No. of bitstreams: 1 Hydroxychloroquine with or without Azithromycin_NEJM.pdf: 657905 bytes, checksum: abd774ed0fca84d1bf82fc915cc48491 (MD5) Previous issue date: 2020 BACKGROUND Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. METHODS We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. RESULTS A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P=1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P=1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. CONCLUSIONS Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.)

Submitted by DSpace Unilasalle (dspace@unilasalle.edu.br) on 2021-09-10T23:12:37Z No. of bitstreams: 1 The role of steroids in severe CAP.pdf: 232136 bytes, checksum: fc65c7581dcec5c29d337042cb681d4c (MD5) Made available in DSpace on 2021-09-10T23:12:37Z (GMT). No. of bitstreams: 1 The role of steroids in severe CAP.pdf: 232136 bytes, checksum: fc65c7581dcec5c29d337042cb681d4c (MD5) Previous issue date: 2020 Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality despite adequate antibiotic therapy. It is the single most common cause of infection-related mortality in the United States. An exaggerated host inflammatory response can potentially be harmful to both the lung and host, and has been associated with treatment failure and mortality. Modulation of inflammatory response may, therefore, be theoretically beneficial. The anti–inflammatory and immunosuppressive effects of steroids seem an attractive therapeutic option in severe CAP patients. Available datapoint to overall shorter time to clinical stability and decreased length-of-stay in CAP patients, with a potential mortality benefit in severe CAP. The level of evidence is, however, low to moderate regarding mortality due to high heterogeneity and insufficient power of data. Furthermore, steroids were deleterious in influenza pneumonia and in patients with pneumococcal pneumonia data suggest a lack of efficacy and potential harm. Both European and American guidelines recommend not using corticosteroids in CAP. Patients who might benefit and those that can be harmed from steroids remain to be clearly identified, as does the ideal steroid for CAP patients, based on pharmacokinetic and pharmacodynamic properties. It is essential for future studies to avoid the same methodological bias present in the available data so that high-quality evidence on the true role of steroids in CAP can be provided.

Rationale: Although proposed as a clinical prompt to sepsis based on predictive validity for mortality, the Quick Sepsis-related Organ Failure Assessment (qSOFA) score is often used as a screening tool, which requires high sensitivity.Objectives: To assess the predictive accuracy of qSOFA for mortality in Brazil, focusing on sensitivity.Methods: We prospectively collected data from two cohorts of emergency department and ward patients. Cohort 1 included patients with suspected infection but without organ dysfunction or sepsis (22 hospitals: 3 public and 19 private). Cohort 2 included patients with sepsis (54 hospitals: 24 public and 28 private). The primary outcome was in-hospital mortality. The predictive accuracy of qSOFA was examined considering only the worst values before the suspicion of infection or sepsis.Measurements and Main Results: Cohort 1 contained 5,460 patients (mortality rate, 14.0%; 95% confidence interval [CI], 13.1-15.0), among whom 78.3% had a qSOFA score less than or equal to 1 (mortality rate, 8.3%; 95% CI, 7.5-9.1). The sensitivity of a qSOFA score greater than or equal to 2 for predicting mortality was 53.9% and the 95% CI was 50.3 to 57.5. The sensitivity was higher for a qSOFA greater than or equal to 1 (84.9%; 95% CI, 82.1-87.3), a qSOFA score greater than or equal to 1 or lactate greater than 2 mmol/L (91.3%; 95% CI, 89.0-93.2), and systemic inflammatory response syndrome plus organ dysfunction (68.7%; 95% CI, 65.2-71.9). Cohort 2 contained 4,711 patients, among whom 62.3% had a qSOFA score less than or equal to 1 (mortality rate, 17.3%; 95% CI, 15.9-18.7), whereas in public hospitals the mortality rate was 39.3% (95% CI, 35.5-43.3).Conclusions: A qSOFA score greater than or equal to 2 has low sensitivity for predicting death in patients with suspected infection in a developing country. Using a qSOFA score greater than or equal to 2 as a screening tool for sepsis may miss patients who ultimately die. Using a qSOFA score greater than or equal to 1 or adding lactate to a qSOFA score greater than or equal to 1 may improve sensitivity.Clinical trial registered with www.clinicaltrials.gov (NCT03158493).

Background The routine use of empiric combination therapy with aminoglycosides during critical illness is associated with uncertain benefit and increased risk of acute kidney injury. This study aimed to assess the benefits of aminoglycosides in immunocompromised patients with suspected bacterial pneumonia and sepsis. Methods Secondary analysis of a prospective multicenter study. Adult immunocompromised patients with suspected bacterial pneumonia and sepsis or septic shock were included. Primary outcome was hospital mortality. Secondary outcomes were needed for renal replacement therapy (RRT). Mortality was also assessed in neutropenic patients and in those with confirmed bacterial pneumonia. Results were further analyzed in a cohort matched on risk of receiving aminoglycosides combination. Results Five hundred thirty-five patients were included in this analysis, of whom 187 (35%) received aminoglycosides in addition to another antibiotic effective against gram-negative bacteria. Overall hospital mortality was 59.6% (58.3% vs. 60.3% in patients receiving and not receiving combination therapy; P = 0.71). Lack of association between mortality and aminoglycosides was confirmed after adjustment for confounders and center effect (adjusted OR 1.14 [0.69-1.89]) and in a propensity matched cohort (adjusted OR = 0.89 [0.49-1.61]). No association was found between aminoglycosides and need for RRT (adjusted OR = 0.83 [0.49-1.39], P = 0.477), nor between aminoglycoside use and outcome in neutropenic patients or in patients with confirmed bacterial pneumonia (adjusted OR 0.66 [0.23-1.85] and 1.25 [0.61-2.57], respectively). Conclusion Aminoglycoside combination therapy was not associated with hospital mortality or need for renal replacement therapy in immunocompromised patients with pulmonary sepsis.

Objective:To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.”Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for

Using biomarkers as a guide to tailor the duration of antibiotic treatment in respiratory infections is an attractive hypothesis assessed in several studies. Recent work aiming to summarize the evidence assessed the effect of a procalcitonin (PCT)-guided antibiotic treatment on outcomes in acute lower respiratory tract infections (LRTI), suggesting that significant reductions in antibiotic duration occur when using a PCT-guided algorithm. However, controversial evidence also suggested PCT-guided algorithms were associated with increased antibiotic duration and increased incidence of Clostridium difficile, without any impact on mortality, in real-world settings. So, although using PCT-guided antibiotic stewardship is promising, after more than a decade of randomized controlled trials on this topic the evidence in its favor is still less than compelling due to limitations in trial design, not taking into consideration fundamental aspects of PCT biology, and the absence of evidence-based antimicrobial duration in intervention and control groups. In this commentary we highlight some questions and limitations of primary PCT study data that might impact interpretation and clinical use of PCT at the bedside.

Ventilator-associated lower respiratory tract infection is one of the most frequent complications in mechanically ventilated patients. Ventilator-associated tracheobronchitis has been considered a disease that does not warrant antibiotic treatment by the medical community for many years. In the last decade, several studies have shown that tracheobronchitis could be considered an intermediate process that leads to ventilator-associated pneumonia. Furthermore, ventilator-associated tracheobronchitis has a limited impact on overall mortality but shows a significant association with increased patient costs, length of stay, antibiotic use, and duration of mechanical ventilation. Although we still need clear evidence, especially concerning treatment modalities, the present study on ventilator-associated tracheobronchitis highlights that there are important impacts of including this condition in clinical management and epidemiological and infection surveillance.As infecções do trato respiratório inferior associadas à ventilação mecânica são uma das complicações mais frequentes em pacientes em ventilação mecânica. Há muitos anos, a traqueobronquite associada à ventilação mecânica tem sido considerada uma doença que não demanda antibioticoterapia. Na última década, diversos estudos demonstraram que a traqueobronquite associada à ventilação mecânica deve ser considerada um processo intermediário que leva à pneumonia associada à ventilação mecânica, uma vez que apesar de ter impacto limitado sobre a mortalidade dos pacientes gravemente enfermos internados nas unidades de terapia intensiva, em contrapartida, demonstra associação significativa com o aumento dos custos hospitalares desses pacientes, assim como do tempo de internação na unidade de terapia intensiva e hospitalar, do uso de antibióticos, e da duração da ventilação mecânica. Embora ainda necessitemos de evidências científicas mais robustas, especialmente no que tange às modalidades terapêuticas, os dados atuais a respeito da traqueobronquite associada à ventilação mecânica salientam que há desfechos suficientemente importantes que exigem vigilância epidemiológica e controle clínico adequados.

Purpose The purpose of the study is to characterize the practices of Brazilian intensivists toward acute kidney injury (AKI) definition and management. Methods A cross-sectional survey was conducted among 36 Brazilian hospitals. Results Of 731 ICU physicians invited to participate, 310 (42%) responded to the survey. Nearly half of the intensive care unit (ICU) physicians (146/310) do not apply AKIN and/or RIFLE definitions to their ICU patients. Most of the respondents prescribe intravenous fluids as a first-line therapeutic intervention for AKI patients. Although 38% of the surveyed physicians considered worsening of respiratory parameters to be the main criterion for stopping fluid infusion, only 15% considered daily net fluid balance as a criterion. Most of the respondents believed in the benefits of early renal replacement therapy (RRT) and considered worsening acidosis the most important criteria for starting early RRT. The main reason for a nephrologist referral was an urgently needed RRT. Conclusions Despite recent advances in AKI definition and management, most of the surveyed ICU physicians in Brazil have not incorporated them in their clinical practice. Important differences in the management of AKI patients were observed among Brazilian ICU physicians, which is relevant for educational interventions and future research.

Submitted by DSpace Unilasalle (dspace@unilasalle.edu.br) on 2021-07-27T19:34:57Z No. of bitstreams: 1 Sepsis is an important healthcare_RBTI.pdf: 85062 bytes, checksum: 48d63f51802d17bed32b2431d29728bd (MD5) Made available in DSpace on 2021-07-27T19:34:57Z (GMT). No. of bitstreams: 1 Sepsis is an important healthcare_RBTI.pdf: 85062 bytes, checksum: 48d63f51802d17bed32b2431d29728bd (MD5) Previous issue date: 2018

We compared the discriminatory capacity of the sequential organ failure assessment (SOFA) versus the systemic inflammatory response syndrome (SIRS) score for predicting ICU mortality, need for and length of mechanical ventilation, ICU stay, and hospitalization in patients with suspected infection admitted to a mixed Brazilian ICU. We performed a retrospective analysis of a longitudinal ICU database from a tertiary hospital in Southern Brazil. Patients were categorized according to whether they met the criteria for sepsis according to SOFA (variation ≥2 points over the baseline clinical condition) and SIRS (SIRS score ≥2 points). From January 2008 to December 2014, 1487 patients were admitted to the ICU due to suspected infection. SOFA ≥2 identified more septic patients than SIRS ≥2 (79.0% [n = 1175] vs. 68.5% [n = 1020], p 7 days (AUROC = 0.65 vs. 0.63, p = 0.004), and length of hospitalization >10 days (AUROC = 0.61 vs. 0.59, p 7 days. Keywords: Sepsis, Intensive care unit, Organ dysfunction, Outcomes

Describe the patterns of C-reactive protein relative changes in response to antibiotic therapy in critically ill cancer patients with healthcare-associated pneumonia (HCAP) and its ability to predict outcome.Secondary analysis of a prospective cohort of critically ill cancer patients with HCAP. CRP was sampled every other day from D0 to D6 of antibiotic therapy. Patients were classified according to an individual pattern of CRP-ratio response: fast - CRP at D4 of therapy was0.4 of D0 CRP; slow - a continuous but slow decrease of CRP; non - CRP remained ≥0.8 of D0 CRP; biphasic - initial CRP decrease to levels0.8 of the D0 CRP followed by a secondary rise ≥0.8.129 patients were included and septic shock was present in 74% and invasive mechanical ventilation was used in 73%. Intensive care unit (ICU) and hospital mortality rates were 47% and 64%, respectively. By D4, both CRP and CRP-ratio of survivors were significantly lower than in nonsurvivors (p0.001 and p=0.004, respectively). Both time-dependent analysis of CRP-ratio of the four previously defined patterns (p0.001) as ICU mortality were consistently different [fast 12.9%, slow 43.2%, biphasic 66.7% and non 71.8% (p0.001)].CRP-ratio was useful in the early prediction of poor outcomes in cancer patients with HCAP.

Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods: The panel consisted of five sections: hemodynamics infection adjunctive therapies metabolic and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. Results: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Conclusions: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality. © 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Purpose: The purpose of this study is to characterize the practices of pulmonary, internal medicine, and critical care physicians toward the management of patients with severe community-acquired pneumonia (CAP). Materials and methods: A cross-sectional international anonymous survey was conducted among a convenience sample of critical care, pulmonary, emergency, and internal medicine physicians from Portugal, Spain, and South America between October and December 2008. The electronic survey evaluated physicians’ attitudes toward diagnosis, risk assessment, and therapeutic interventions for patients with severe CAP. Results: Four hundred sixty-eight physicians responded being 84.6% from 4 countries (Brazil, Portugal, Spain, and Argentina) whom 66.9% had more than 10 years experience. Risk assessment of severe CAP was very heterogeneous being clinical evaluation the most frequent. Although blood cultures were recognized as presenting a poor diagnostic performance, they were performed by 77.1%. In opposition, the presence of urinary pneumococcal and Legionella antigen was asked by less than one-third of physicians. The great majority (95%) prescribes antibiotics according to a guideline being the combination of β-lactam plus macrolide the most frequent choice. Conclusions: Despite the recent advances of knowledge reflected in the present study in the management of severe CAP, several of themare still incompletely translated into clinical practice. Significant variation in practice is observedamong physicians and represents a potential target for future research and educational interventions.

Lower respiratory tract infections in mechanically ventilated patients are a frequent cause of antibiotic treatment in intensive-care units. These infections present as severe sepsis or septic shock with respiratory dysfunction in intubated patients. Purulent respiratory secretions are needed for diagnosis, but distinguishing between pneumonia and tracheobronchitis is not easy. Both presentations are associated with longlasting mechanical ventilation and extended intensive-care unit stay, providing a rationale for antibiotic treatment initiation. Differentiation of colonisers from true pathogens is difficult, and microbiological data show Staphylococcus aureus and Pseudomonas aeruginosa to be of great concern because of clinical outcomes and therapeutic challenges. Key management issues include identification of the pathogen, choice of initial empirical antibiotic, and decisions with regard to the resolution pattern.

Hand hygiene is the most important measure to reduce health care-related infections and colonization with multiresistant micro-organisms. We sought to determine the rate and seasonality of handwashing compliance in a university-affiliated hospital.In January 2006 (baseline period), handwashing observation was first made in an intensive care unit. From March to May 2006, there was an intervention period; and, from June 2006 to August 2009, we followed hand hygiene compliance. Seasonality curves for handwashing compliance were made during follow-up period.During baseline period, a total of 166 observations was made. During follow-up, 17,664 opportunities for hand hygiene were observed. Compliance improved from 30.0% to a mean of 56.7% after the intervention (P.001). The highest mean rate of compliance was 77.9% for nurses, compared with 52.6% for technicians (P.001) and 44.6% for physicians (P.001). Compliance was lower during summer days (first trimester of the year) and increased after March and April and slowly decreased through the end of the year.One of the reasons for the lower handwashing compliance in the first 3 months of the year is that, in Brazil, this is the summer vacation time; and, because of that, the staff's workload and the number of less well-trained personnel are higher. We emphasize the importance of continuously monitoring hand hygiene to determine the seasonal aspects of compliance.

Influenza pneumonia is associated with high number of severe cases requiring hospital and intensive care unit (ICU) admissions with high mortality. Systemic steroids are proposed as a valid therapeutic option even though its effects are still controversial. Heterogeneity of published data regarding study design, population demographics, severity of illness, dosing, type and timing of corticosteroids administered constitute an important limitation for drawing robust conclusions. However, it is reasonable to admit that, as it was not found any advantage of corticosteroid therapy in so diverse conditions, such beneficial effects do not exist at all. Its administration is likely to increase overall mortality and such trend is consistent regardless of the quality as well as the sample size of studies. Moreover it was shown that corticosteroids might be associated with higher incidence of hospital-acquired pneumonia and longer duration of mechanical ventilation and ICU stay. Finally, it is reasonable to conclude that corticosteroids failed to demonstrate any beneficial effects in the treatment of patients with severe influenza infection. Thus its current use in severe influenza pneumonia should be restricted to very selected cases and in the setting of clinical trials.

Purpose The purposes of this study were to evaluate the clinical course and to identify independent predictors of mortality in patients with cancer with sepsis. Materials and Methods This is a secondary analysis of a prospective cohort study conducted at an oncological medical-surgical intensive care unit. Logistic regression was used to identify predictors of hospital mortality. Results A total of 563 patients (77% solid tumor, 23% hematologic malignancies) were included over a 55-month period. The most frequent sites of infection were the lung, abdomen, and urinary tract; 91% patients had severe sepsis/septic shock. Gram-negative bacteria were responsible for more than half of the episodes of infection; 38% of patients had polymicrobial infections. Intensive care unit, hospital, and 6-month mortality rates were 51%, 65%, and 72%, respectively. In multivariate analyses, sepsis in the context of medical complications; active disease; compromised performance status; presence of 3 to 4 systemic inflammatory response syndrome criteria; and the presence of respiratory, renal, and cardiovascular failures were associated with increased mortality. Adjusting for other covariates, patients with non–urinary tract infections, mostly represented by patients with pneumonia and abdominal infections, had worse outcomes. Conclusions Sepsis remains a frequent complication in patients with cancer and associated with high mortality. Our results can be of help to assist intensivists in clinical decisions and to improve characterization and risk stratification in these patients.

O tétano acidental, a despeito de ser uma doença prevenível por imunização, ainda é frequente nos países subdesenvolvidos e em desenvolvimento. Sua letalidade ainda é elevada e os estudos sobre a melhor forma de tratamento são escassos. Tendo em vista esta escassez e a importância clínica dessa doença, um grupo de especialistas reunidos pela Associação de Medicina Intensiva Brasileira (AMIB), desenvolveu recomendações baseadas na melhor evidencia disponível para o manejo do tétano no paciente necessitando cuidados intensivos. As recomendações incluem aspectos relativos à admissão do paciente tetânico na unidade de terapia intensiva, tratamento com imunoglobulinas, tratamento antibiótico, manejo da analgossedação e bloqueio neuromuscular, manejo da disautonomia e especificidades na ventilação mecânica e fisioterapia nesta população especial. Although tetanus can be prevented by appropriate immunization, accidental tetanus continues to occur frequently in underdeveloped and developing countries. Tetanus mortality rates remain high in these areas, and studies regarding the best therapy for tetanus are scarce. Because of the paucity of data on accidental tetanus and the clinical relevance of this condition, the Associação de Medicina Intensiva Brasileira (AMIB) organized a group of experts to develop these guidelines, which are based on the best available evidence for the management of tetanus in patients requiring admission to the intensive care unit. The guidelines discuss the management of tetanus patients in the intensive care unit, including the use of immunoglobulin therapy, antibiotic therapy, management of analgesics, sedation and neuromuscular blockade, management of dysautonomia and specific issues related to mechanical ventilation and physiotherapy in this population.

Peripheral muscle tissue oxygenation determined noninvasively using near-infrared spectroscopy may help to identify tissue hypoperfusion in septic patients. The aim of this study was to investigate regional oxygen saturation index (rSO2) in the brachioradialis (forearm) muscle by comparing measurements in healthy subjects and in intensive care unit (ICU) septic shock patients, and determine whether brachioradialis muscle rSO2 is associated with poor outcome in ICU septic shock patients. We conducted a prospective observational study in healthy volunteers (n = 50) and ICU septic shock patients (n = 19). Brachioradialis (forearm) rSO2 measurements in healthy volunteers at rest and in ICU septic shock patients were compared. Pulmonary artery catheter monitoring was used in ICU patients. Significant differences in rSO2 were observed between healthy volunteers and ICU septic shock patients at ICU admission (68.7 ± 4.9 vs. 55.0 ± 13.0; p < 0.001). When comparing septic shock survivors and nonsurvivors, significant differences were observed in rSO2 at baseline (64.5 ± 8.9 vs. 47.5 ± 10.7; p < 0.01), 12 hours (67.3 ± 9.6 vs. 45.0 ± 14.9; p < 0.01), and 24 hours (65.7 ± 7.0 vs. 50.1 ± 10.3; p < 0.01). Lactate concentration was lower in survivors than nonsurvivors at 24 hours (12.0 ± 7.5 mmol/L vs. 23.2 ± 12.5 mmol/L; p < 0.04). Cardiac index was greater in nonsurvivors than survivors at baseline (4.6 + 1.9 L/min/m2 vs. 3.0 + 0.9 L/min/m2; p < 0.05) and 12 h (3.9 + 0.5 L/min/m2 vs. 3.1 + 0.3 L/min/m2; p < 0.05). We observed that septic shock patients with forearm skeletal muscle rSO2 ≤60% throughout first 24 hours after ICU admission had significantly greater mortality rate than patients with forearm skeletal muscle rSO2 >60% throughout this critical time.

The incidence of pleural infection continues to rise worldwide. Identifying the causative organism(s) is important to guide antimicrobial therapy. The bacteriology of pleural infection is complex and has changed over time. Recent data suggest that the bacterial causes of empyema are significantly different between adult and paediatric patients, between community-acquired and nosocomial empyemas and can vary among geographical regions of the world. Since the introduction of pneumococcal vaccines, a change has been observed in the distribution of the serotypes of Streptococcus pneumoniae in empyema. These observations have implications on therapy and vaccine strategies. Clinicians need to be aware of the local bacteriology of empyema in order to guide antibiotic treatment.

Background A cohort of patients with bacteremic Streptococcus pneumoniae pneumonia was reviewed to assess why mortality is higher in health-care-associated pneumonia (HCAP) than in community-acquired pneumonia (CAP). Methods A prospective cohort of all adult patients with bacteremic pneumococcal pneumonia attended at the ED was used. Results One hundred eighty-four cases were classified as CAP and 44 (19%) as HCAP. Fifty-two (23%) were admitted to the ICU. Three (1.5%) isolates were resistant to β-lactams, and only two patients received inappropriate therapy. The CAP cohort was significantly younger (median age 68 years, interquartile range [IQR] 42–78 vs 77 years, IQR 67–82, P P 30/min, Pao 2 /Fio 2 P P = .17) and vasopressor use (9% vs 18.4%, P = .17) were documented. More patients in the HCAP cohort presented with a pneumonia severity index score > 90 (class IV-V, 95% vs 65%, P P Conclusions Pneumococcal HCAP presents excess mortality, which is independent of bacterial susceptibility. Differences in outcomes were probably due to differences in age, comorbidities, and criteria for ICU admission rather than to therapeutic decisions.

A sepsis staging system focused on predisposition, insult, host response and organ failure may provide a useful basis for risk stratification. Knowledge on interactions among predisposing factors, insult characteristics and host response might help us to improve our understanding on sepsis pathophysiology and allow more individual therapeutic approach. Recent clinical studies documented the clinical importance of PIRO approach for severity stratification in septic patients in intensive care unit, and also for specific conditions such as community acquired pneumonia and ventilator associated pneumonia , with a good performance for outcome prediction. In this review we describe how this new concept can be used in clinical practice and provide some insights on its usefulness to facilitate the stratification and potential for enrollment in clinical trials of sepsis therapies.

The influence of infecting serotype group on outcome in bacteraemic pneumococcal pneumonia remains unclear. We performed a prospective, 10-yr observational study in an 800-bed teaching hospital. 299 adults diagnosed with pneumonia whose blood cultures showed growth of Streptococcus pneumoniae were included in the study. High invasive disease potential (H) serotypes included serotypes 1, 5 and 7F, which served as a reference category, were compared with low invasive disease potential (L) serotypes (3, 6A, 6B, 8, 19F, and 23F) and other (O) serotypes (non-H, non-L). The influence on outcome was determined for each group of serotypes after adjusting for underlying conditions and severity of illness at admission. Overall, 30-day mortality was 11%. H serotypes (n = 93) infected primarily younger people and presented a higher risk of complicated parapneumonic effusion or empyema (17.2 versus 5.1%; p = 0.01), with lower mortality (3.2%). The isolation of L serotypes (n = 78) was an independent risk factor for 30-day mortality (OR 7.02, 95% CI 1.72–28.61), as were Charlson score (OR 1.30, 95% CI 1.08–1.58), alcohol abuse (OR 3.99, 95% CI 1.39–11.39) and severity of illness measured by American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) criteria (OR 4.80, 95% CI 1.89–12.13). A vaccination strategy including serotypes 3, 6A, 6B, 8, 19F and 23F may improve survival in adults.

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).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.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, P0.05) and presented a higher score on the simplified Acute Physiology Score II at admission (45.6 +/- 15.4 vs. 50.8 +/- 17.5, P0.05). 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).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.

Despite recent advances in diagnosis and care of critically ill patients sepsis related mortality rate remains unacceptably high. Therefore, new methods of evaluation are necessary to provide an earlier and more accurate characterization of septic patients. Based on the (oncologic) TNM system, the PIRO concept was introduced as a new staging system for sepsis in order to assess risk and predict prognosis, with potential to assist in inclusion of patients in clinical studies and estimate the probability of response of patients to specific therapeutic interventions.

Background There is a clinical need for more objective methods of identifying patients at risk for septic shock and poorer outcomes among those with community-acquired pneumonia (CAP). As viral load is useful in viral infections, we hypothesized that bacterial load may be associated with outcomes in patients with pneumococcal pneumonia. Methods Quantification of Streptococcus pneumoniae DNA level by real-time polymerase chain reaction (rt-PCR) was prospectively conducted on whole-blood samples from a cohort of 353 patients who were displaying CAP symptoms upon their admission to the ED. Results CAP caused by S pneumoniae was documented in 93 patients (36.5% with positive blood culture findings). A positive S pneumoniae rt-PCR assay finding was associated with a statistically significant higher mortality (odds ratio [OR], 7.08), risk for shock (OR, 6.29), and the need for mechanical ventilation (MV) [OR, 7.96]. Logistic regression, adjusted for age, sex, comorbidities, and pneumonia severity index class, revealed bacterial load as independently associated with septic shock (adjusted odds ratio [aOR], 2.42; 95% CI, 1.10 to 5.80) and the need for MV (aOR, 2.71; 95% CI, 1.17 to 6.27). An S pneumoniae bacterial load of ≥ 10 3 copies per milliliter occurred in 29.0% of patients (27 of 93 patients; 95% CI, 20.8 to 38.9%) being associated with a statistically significant higher risk for septic shock (OR, 8.00), the need for MV (OR, 10.50), and hospital mortality (OR, 5.43). Conclusion In patients with pneumococcal pneumonia, bacterial load is associated with the likelihood of death, the risk of septic shock, and the need for MV. High genomic bacterial load for S pneumoniae may be a useful tool for severity assessment.

Information on clinical practice regarding the diagnosis of pneumonia in European intensive care units is limited. The aim of this study was to describe the spectrum of actual diagnostic practices in a large sample of European intensive care units.Prospective, observational, multicenter study.Twenty-seven intensive care units of nine European countries.Consecutive patients requiring invasive mechanical ventilation for an admission diagnosis of pneumonia or receiving mechanical ventilation for48 hrs irrespective of admission diagnosis.None.A total of 2,436 patients were evaluated; 827 were admitted with or developed nosocomial pneumonia (hospital-acquired pneumonia [HAP], 27.1%; ventilator-associated pneumonia [VAP], 56.2%; very early onset VAP, 16.7%). Mean age was 59.4 +/- 18.1 yrs, 65.0% were men, and mean admission Simplified Acute Physiology Score II was 46.7 +/- 17.1. Worsening oxygenation (76.8%), purulent/changing respiratory secretions (72.1%), and new temperature elevation (69.2%) were the most frequent clinical signs of nosocomial pneumonia. Etiological diagnosis was based on noninvasive respiratory specimens in 74.8% of episodes. Bronchoscopy was performed in 23.3% of episodes. Bronchoscopy performance, after adjustment by severity of illness, age, and type of hospital, were predicted by worsening oxygenation (odds ratio 2.03; 95% confidence interval, 1.27-3.24) and male sex (odds ratio 1.77; 95% confidence interval, 1.19-2.65). Definite cause was documented in 69.5% of nosocomial pneumonia cases. The most common isolates were Staphylococcus aureus (16.3% methicillin-sensitive S. aureus and 16.0% methicillin-resistant S. aureus), Pseudomonas aeruginosa (23.1%), and Acinetobacter baumannii (19.1%). Presence of nosocomial pneumonia significantly prolonged mean length of mechanical ventilation (10.3 days, p.05) and mean intensive care unit length of stay (12.2 days, p.05) in intensive care unit survivors. Mortality rate was 37.7% for nosocomial pneumonia vs. 31.6% for patients without pneumonia (p.05).Etiological diagnosis of nosocomial pneumonia in a large sample of European intensive care units was based mainly on noninvasive techniques. However, there was high variability in bronchoscopy use between the participating intensive care units.

Background Poor oral hygiene is associated with respiratory pathogen colonization and secondary lung infection. The impact of adding electric toothbrushing to oral care in order to reduce ventilator-associated pneumonia (VAP) incidence is unknown. Methods The study design was a prospective, simple-blind, randomized trial of adult patients intubated for > 48 h. Controlling for exposure to antibiotic treatment, patients were randomized to oral care every 8 h with 0.12% chlorhexidine digluconate (standard group) or standard oral care plus electric toothbrushing (toothbrush group). VAP was documented by quantitative respiratory cultures. Mechanical ventilation (MV) duration, hospital ICU length of stay (LOS), antibiotic use, and hospital ICU mortality were secondary end points. Results The study was terminated after randomizing 147 patients (74 toothbrush group) in a scheduled interim analysis. The two groups were comparable at baseline. The toothbrush group and standard group had similar rates of suspected VAP (20.3% vs 24.7%; p=0.55). After adjustment for severity of illness and admission diagnosis, the incidence of microbiologically documented VAP was also similar in the two groups (hazard ratio, 0.84; 95% confidence interval, 0.41 to 1.73). The groups did not differ significantly in mortality, antibiotic-free days, duration of MV, or hospital ICU LOS. Conclusions Our findings suggest that the addition of electric toothbrushing to standard oral care with 0.12% chlorhexidine digluconate is not effective for the prevention of VAP. Trial registration ClinicalTrials.gov Identifier: NCT00842478

Obesity is a serious public health problem worldwide and is a major contributor to the global burden of chronic disease and disability. It is a complex condition, with serious social and psychological dimensions, affecting virtually all ages and socioeconomic groups. When faced with critically ill obese patients, the assistance of multiple allied health specialists with thorough understanding of the pathophysiologic effects of obesity on the various organ systems is needed to achieve a satisfactory outcome. In this article we review the literature on obesity-related derangements in cardiopulmonary and metabolic function and the potential complications associated with managing these patients in the intensive care unit. We also discuss the possible opportunities for research, based on an integrative physiological approach of obesity and its potential interactions with sepsis and inflammatory states frequently found in critically ill patients.

Background Clinical resolution of ventilator-associated pneumonia (VAP) determines the duration of treatment and mechanical ventilation. The aim of this study was to evaluate the influence of organisms and their susceptibility to treatment on outcomes. Methods Prospective observational study in three teaching ICUs. Sixty episodes of VAP with appropriate therapy ( Haemophilus influenzae , 15 episodes; methicillin-sensitive Staphylococcus aureus [MSSA], 15 episodes; Pseudomonas aeruginosa , 15 episodes; and methicillin-resistant S aureus [MRSA], 15 episodes), and 30 episodes with initial inappropriate therapy, all due to P aeruginosa , were compared. The main outcome measures were clinical resolution variables and, in survivors, length of mechanical ventilation after VAP onset. Results A significant delay in the resolution of hypoxemia was observed in VAP episodes due to MRSA and P aeruginosa with inappropriate antibiotic therapy (IAT) (median time to resolution, 10 and 8 days, respectively) when compared with the remaining pathogens (median time to resolution, 2 days). A multiple regression model, adjusted for disease severity, confirmed the delayed clinical resolution for MRSA and P aeruginosa with IAT. Similar associations were documented for defervescence. Among survivors, the median duration of mechanical ventilation after VAP onset was significantly longer for MRSA (17 days) and P aeruginosa IAT (11 days) when compared with episodes due to H influenzae or MSSA (6 days). Multiple regression analysis, adjusted for disease severity, confirmed that MRSA required significantly ( R 2 = 0.132; p Conclusions When treated promptly, the resolution of VAP due to MSSA, H influenzae , and P aeruginosa was comparable. The resolution of MRSA VAP, regardless of the appropriateness of initial antibiotic therapy, was associated with longer respiratory support.

OBJECTIVE: Appropriateness of antibiotic therapy is associated with reduction of bacterial load in ventilator-associated pneumonia. C-reactive protein is a valid biochemical surrogate. The objective was to determine the correlation of bacterial load, measured by quantitative tracheal aspirate (QTA), with serum C-reactive protein as an indicator of inflammatory response in episodes of ventilator-associated pneumonia and association of its variation with antibiotic appropriateness. DESIGN: Prospective, observational cohort study. SETTING: Two medical-surgical intensive care units at large urban hospitals affiliated with teaching institutions. PATIENTS: Sixty-eight intubated patients with monomicrobial ventilator-associated pneumonia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: QTA and serum C-reactive protein were measured in patients with suspected ventilator-associated pneumonia on diagnosis (baseline) and 96 hrs afterward (follow-up). Its logarithm value (logQTA) was calculated. LogQTA correlated positively with serum C-reactive protein (rho = 0.46, p < .05), temperature (rho = 0.20, p = .05), and white blood cell count (rho = 0.22, p < .05). LogQTA decreased significantly more from baseline to follow-up in patients receiving appropriate empirical antibiotic therapy compared with those with inappropriate treatment (logQTA ratio 0.77 +/- 0.22 vs. 1.02 +/- 0.27, p < .05). Mean serum C-reactive protein levels showed a similar pattern, decreasing from baseline to follow-up in patients receiving appropriate empirical antibiotic treatment but not in episodes with inappropriate treatment (C-reactive protein ratio 0.58 +/- 0.32 vs. 1.36 +/- 1.11, p < .05). There was a positive correlation between serum C-reactive protein and logQTA variations (r2 = .59, p < .05). Adjusted mean serum C-reactive protein levels by analysis of covariance on follow-up were significantly lower in patients with appropriate antibiotic treatment than in those with inappropriate empirical treatment (103 +/- 10 mg/L vs. 192 +/- 14 mg/L, p < .05). A C-reactive protein ratio of 0.8 at 96 hrs was a useful indicator of appropriateness of antibiotic therapy (sensitivity 77%; specificity 87%; area under the receiver operating characteristic curve 0.86 [0.75-0.96]). CONCLUSIONS: C-reactive protein is a useful biochemical surrogate of bacterial burden in patients with ventilator-associated pneumonia. Follow-up measurements of serum C-reactive protein anticipate the appropriateness of antibiotic therapy.

To assess whether bacteremic ventilator-associated pneumonia (B-VAP) differs in terms of risk factors, organisms, and outcomes from nonbacteremic VAP (NB-VAP).A retrospective, single-center, observational, cohort study.Multidisciplinary teaching intensive care unit.Adult patients requiring mechanical ventilation, identified as having VAP in a 44-month prospective surveillance database.Each B-VAP patient was matched with two controls with VAP and negative blood cultures based on the microbial etiology responsible for VAP, Acute Physiology and Chronic Health Evaluation II score on admission (+/-3 points), diagnostic category, and length of stay before pneumonia onset.B-VAP was documented in 35 (17.6%) of 199 microbiologically confirmed VAP episodes. B-VAP developed later (median 8 vs. 5 days, p = .03) and was more frequent in previously hospitalized patients (34.3% vs. 11.0%, p.01) and in older patients (57.4 +/- 15.2 vs. 49.5 +/- 19.3 yrs, p = .02). B-VAP was more often caused by methicillin-resistant Staphylococcus aureus (12 [20.7%] vs. 13 [5.1%] episodes, p.01), whereas Haemophilus influenzae was associated with NB-VAP (52 [20.4%] vs. 0, p.01). Multivariate analysis confirmed an association between B-VAP and both methicillin-resistant S. aureus (odds ratio 3.18; 95% confidence interval 1.15-8.76, p.01) and prior hospitalization (odds ratio 2.56; 95% confidence interval 1.01-6.54, p = .05). After adjustment for potential confounders, B-VAP (hazard ratio for death 2.55; 95% confidence interval 1.25-5.23, p = .01) and vasopressor use (hazard ratio 2.43; 95% confidence interval 1.23-4.82, p = .01) remained associated with mortality. The estimated relative risk of death for bacteremic cases was 2.86 (95% confidence interval 1.09-7.51), since mortality for cases and matched NB-VAP controls was 40.6% (13 of 32) and 19.3% (11 of 57), respectively.B-VAP occurs later during intensive care unit stay, is more frequent in previously hospitalized patients, is more often caused by methicillin-resistant S. aureus, and is independently associated with increased intensive care unit mortality.

Patients with cancer are at increased risk for sepsis as a consequence of immunosuppression. The hospital mortality remains elevated and it could be attributed to antibiotic failure because of the presence of multiresistant pathogens. Once the patient is critically ill, the use of the American Thoracic Society/Infectious Diseases Society of America classification does not seem very useful in the assessment of outcomes and the choice of antimicrobials. In critically ill patients, the characteristics of clinical response to antibiotics are usually inaccurate and occur late in the course of disease. So, the sequential evaluation of C-reactive protein-ratio is useful in the early identification of patients with antibiotic failure. To achieve safe and efficient antimicrobial therapy, we proposed an algorithm that may aid clinicians in their decision-making process.

PURPOSE OF REVIEW: The present article reviews recent data on the de-escalation of empirical antibiotic treatment on pneumonia, with special attention to newer strategies aimed at increasing adequacy and minimizing resistance emergence risks in ventilator-associated pneumonia. RECENT FINDINGS: A de-escalation strategy is feasible in a large proportion of patients with pneumonia, and at least two reports have associated de-escalation with a significantly better survival. Combined with other strategies, such as using biomarkers (e.g. C-reactive protein or procalcitonin), antibiotic heterogeneity, adherence to local microbiological flora, objective clinical criteria of non-response and of clinical ventilator-associated pneumonia resolution, they contribute to rationalizing and individualizing antimicrobial therapy. SUMMARY: A patient-based approach with prompt adequate empirical therapy, using broad-spectrum antibiotics based on reliable local microbiological data with streamlining as soon as microbiological data become available, allow outcomes to be improved and the emergence of resistance to be minimized.

OBJECTIVE: Studies suggest an association between vitamin D deficiency and morbidity/mortality in critically ill patients. Several issues remain unexplained, including which vitamin D levels are related to morbidity and mortality and the relevance of vitamin D kinetics to clinical outcomes. We conducted this study to address the association of baseline vitamin D levels and vitamin D kinetics with morbidity and mortality in critically ill patients. METHOD: In 135 intensive care unit (ICU) patients, vitamin D was prospectively measured on admission and weekly until discharge from the ICU. The following outcomes of interest were analyzed: 28-day mortality, mechanical ventilation, length of stay, infection rate, and culture positivity. RESULTS: Mortality rates were higher among patients with vitamin D levels 12 ng/mL) (32.2% vs. 13.2%), with an adjusted relative risk of 2.2 (95% CI 1.07-4.54; p< 0.05). There were no differences in the length of stay, ventilation requirements, infection rate, or culture positivity. CONCLUSIONS: This study suggests that low vitamin D levels on ICU admission are an independent risk factor for mortality in critically ill patients. Low vitamin D levels at ICU admission may have a causal relationship with mortality and may serve as an indicator for vitamin D replacement among critically ill patients.

This article describes a patient presenting with dyspnea and platypnea and whose only clinical finding was presence of patent foramen ovale with a right to left shunt, without pulmonary hypertension, characteristic of the rare Platypnea-Orthodeoxya Syndrome, with very interesting pathophysiological findings and with therapeutic alternatives not yet defined.

Such variability comes mainly from two aspects: the presence of case-mix differences among the different units evaluated in the literature and the lack of accurate diagnostic criteria that allow for an accurate functional diagnosis, making subjectivity an important aspect of definitive diagnosis and treatment decisions.

Vancomycin is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections; however, treatment failure is not uncommon, even when the minimum inhibitory concentration (MIC) of the MRSA strain is within the susceptible range for vancomycin.To describe the relationship between molecular markers such as the mecA and agrII genes, serum vancomycin levels and vancomycin MICs, and the 30-day mortality rate of patients with nosocomial MRSA pneumonia in an intensive care unit (ICU).The present study was a prospective cohort study including all patients with MRSA hospital-acquired pneumonia or ventilator-associated pneumonia who were admitted to the ICU of a tertiary care hospital between June 2009 and December 2011. The MIC for vancomycin was determined using the E-test and broth microdilution methods. Variables analyzed included age, sex, comorbid conditions, serum vancomycin trough concentration, the Acute Physiology and Chronic Health Evaluation II (APACHE) score and the presence of the agrII gene. The primary outcome was mortality at 30 days.Thirty-six (42.4%) patients died within 30 days of the index MRSA culture. A multiple regression analysis that included the variables of MIC (determined using the E-test or broth microdilution methods), APACHE II score, serum vancomycin level and the presence of agrII revealed that only the APACHE II score was related to the 30-day mortality rate (P=0.03). Seven patients (9.0%) with isolates exhibiting an MIC ≥1.5 μg/mL according to the E-test method died, and nine patients (11.6%) survived (P=0.76). Of the patients for whom MICs were determined using the broth microdilution method, 11 (14.1%) patients with MICs of 1.0 μg/mL died, and 16 (20.5%) survived (P=0.92). The median APACHE II score of survivors was 22.5, and the median score of nonsurvivors was 25.0 (P=0.03). The presence of the agrII gene was not related to the 30-day mortality rate.Patients with severe hospital-acquired pneumonia presented with MRSA isolates with low to intermediate vancomycin MICs in the ICU setting. At the Hospital de Clínicas de Porto Alegre (Porto Alegre, Brazil), the 30-day mortality rate was high, and was similar among patients with severe hospital-acquired pneumonia infected with MRSA isolates that exhibited MICs of ≤1.5 μg/mL determined using the E-test method and ≤1.0 μg/mL determined using the broth microdilution method in those who achieved optimal serum vancomycin levels. The APACHE II scores which provides an overall estimate of ICU mortality were independently associated with mortality in the present study, regardless of the MICs determined. Molecular markers, such as the agrII gene, were not associated with higher mortality in the present study.La vancomycine est le traitement de première intention des infections par leDécrire le lien entre les marqueurs moléculaires comme les gènesLa présente étude prospective de cohorte incluait tous les patients ayant une pneumonie à SARM d’origine nosocomiale ou d’une pneumonie acquise sous ventilation mécanique qui ont été hospitalisés à l’USI d’un hôpital de soins tertiaires entre juin 2009 et décembre 2011. Les chercheurs ont déterminé la CMI de la vancomycine au moyen des méthodes d’E-test et de microdilution en bouillon. Les variables qu’ils ont analysées sont l’âge, le sexe, les états comorbides, la concentration minimale de vancomycine sérique, le score APACHE (évaluation de physiologie aiguë et de maladie chronique II) et la présence du gèneTrente-six patients (42,4 %)sont décédés dans les 30 jours suivant la culture de référence du SARM. Une analyse de régression multiple qui incluait les variables de la CMI (déterminée au moyen des méthodes d’E-test ou de microdilution en bouillon, le score APACHE II, le taux de vancomycine sérique et la présence du gène fLes patients ayant une grave pneumonie d’origine nosocomiale présentaient des isolats de SARM à la CMI faible à intermédiaire à la vancomycine à l’USI. Au