Aminoglycosides in Immunocompromised Critically Ill Patients With Bacterial Pneumonia and Septic Shock: A Post-Hoc Analysis of a Prospective Multicenter Multinational Cohort.

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.

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016

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 wasdeveloped 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 subgroupsand 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.(AU)

A care bundle approach for prevention of ventilator-associated pneumonia.

Implementation of care bundles for prevention of ventilator-associated pneumonia (VAP) and its impact on patient outcomes requires validation with long-term follow-up. A collaborative multi-centre cohort study was conducted in five Spanish adult intensive-care units. A care bundle approach based on five measures was implemented after a 3-month baseline period, and compliance, VAP rates, intensive-care unit length of stay (ICU LOS) and duration of mechanical ventilation were prospectively recorded for 16 months. There were 149 patients in the baseline period and 885 after the intervention. Compliance with all measures after intervention was <30% (264/885). In spite of this, VAP incidence decreased from 15.5% (23/149) to 11.7% (104/885), after the intervention (p <0.05). This reduction was significantly associated with hand hygiene (OR = 0.35), intra-cuff pressure control (OR = 0.21), oral hygiene (OR = 0.23) and sedation control (OR = 0.51). Use of the care bundle was associated with an incidence risk ratio of VAP of 0.78 (95% CI 0.15-0.99). We documented a reduction of median ICU LOS (from 10 to 6 days) and duration of mechanical ventilation (from 8 to 4 days) for patients with full bundle compliance (intervention period). Efforts on VAP prevention and outcome improvement should focus on achieving higher compliance in hand and oral hygiene, sedation protocols and intracuff pressure control.

Severity assessment tools in ICU patients with 2009 influenza A (H1N1) pneumonia.

The aim of this study was to determine if severity assessment tools (general severity of illness and community-acquired pneumonia specific scores) can be used to guide decisions for patients admitted to the intensive care unit (ICU) due to pandemic influenza A pneumonia. A prospective, observational, multicentre study included 265 patients with a mean age of 42 (±16.1) years and an ICU mortality of 31.7%. On admission to the ICU, the mean pneumonia severity index (PSI) score was 103.2 ± 43.2 points, the CURB-65 score was 1.7 ± 1.1 points and the PIRO-CAP score was 3.2 ± 1.5 points. None of the scores had a good predictive ability: area under the ROC for PSI, 0.72 (95% CI, 0.65-0.78); CURB-65, 0.67 (95% CI, 0.59-0.74); and PIRO-CAP, 0.64 (95% CI, 0.56-0.71). The PSI score (OR, 1.022 (1.009-1.034), p 0.001) was independently associated with ICU mortality; however, none of the three scores, when used at ICU admission, were able to reliably detect a low-risk group of patients. Low risk for mortality was identified in 27.5% of patients using PIRO-CAP, but above 40% when using PSI (I-III) or CURB65 (<2). Observed mortality was 13.7%, 13.5% and 19.4%, respectively. Pneumonia-specific scores undervalued severity and should not be used as instruments to guide decisions in the ICU.

Determinants of prescription and choice of empirical therapy for hospital-acquired and ventilator-associated pneumonia.

The objectives of this study were to assess the determinants of empirical antibiotic choice, prescription patterns and outcomes in patients with hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in Europe. We performed a prospective, observational cohort study in 27 intensive care units (ICUs) from nine European countries. 100 consecutive patients on mechanical ventilation for HAP, on mechanical ventilation>48 h or with VAP were enrolled per ICU. Admission category, sickness severity and Acinetobacter spp. prevalence>10% in pneumonia episodes determined antibiotic empirical choice. Trauma patients were more often prescribed non-anti-Pseudomonas cephalosporins (OR 2.68, 95% CI 1.50-4.78). Surgical patients received less aminoglycosides (OR 0.26, 95% CI 0.14-0.49). A significant correlation (p<0.01) was found between Simplified Acute Physiology Score II score and carbapenem prescription. Basal Acinetobacter spp. prevalence>10% dramatically increased the prescription of carbapenems (OR 3.5, 95% CI 2.0-6.1) and colistin (OR 115.7, 95% CI 6.9-1,930.9). Appropriate empirical antibiotics decreased ICU length of stay by 6 days (26.3±19.8 days versus 32.8±29.4 days; p=0.04). The antibiotics that were prescribed most were carbapenems, piperacillin/tazobactam and quinolones. Median (interquartile range) duration of antibiotic therapy was 9 (6-12) days. Anti-methicillin-resistant Staphylococcus aureus agents were prescribed in 38.4% of VAP episodes. Admission category, sickness severity and basal Acinetobacter prevalence>10% in pneumonia episodes were the major determinants of antibiotic choice at the bedside. Across Europe, carbapenems were the antibiotic most prescribed for HAP/VAP.

Use of early corticosteroid therapy on ICU admission in patients affected by severe pandemic (H1N1)v influenza A infection.

INTRODUCTION: Early use of corticosteroids in patients affected by pandemic (H1N1)v influenza A infection, although relatively common, remains controversial. METHODS: Prospective, observational, multicenter study from 23 June 2009 through 11 February 2010, reported in the European Society of Intensive Care Medicine (ESICM) H1N1 registry. RESULTS: Two hundred twenty patients admitted to an intensive care unit (ICU) with completed outcome data were analyzed. Invasive mechanical ventilation was used in 155 (70.5%). Sixty-seven (30.5%) of the patients died in ICU and 75 (34.1%) whilst in hospital. One hundred twenty-six (57.3%) patients received corticosteroid therapy on admission to ICU. Patients who received corticosteroids were significantly older and were more likely to have coexisting asthma, chronic obstructive pulmonary disease (COPD), and chronic steroid use. These patients receiving corticosteroids had increased likelihood of developing hospital-acquired pneumonia (HAP) [26.2% versus 13.8%, p < 0.05; odds ratio (OR) 2.2, confidence interval (CI) 1.1-4.5]. Patients who received corticosteroids had significantly higher ICU mortality than patients who did not (46.0% versus 18.1%, p < 0.01; OR 3.8, CI 2.1-7.2). Cox regression analysis adjusted for severity and potential confounding factors identified that early use of corticosteroids was not significantly associated with mortality [hazard ratio (HR) 1.3, 95% CI 0.7-2.4, p = 0.4] but was still associated with an increased rate of HAP (OR 2.2, 95% CI 1.0-4.8, p < 0.05). When only patients developing acute respiratory distress syndrome (ARDS) were analyzed, similar results were observed. CONCLUSIONS: Early use of corticosteroids in patients affected by pandemic (H1N1)v influenza A infection did not result in better outcomes and was associated with increased risk of superinfections.

Rabbit model of uncontrolled hemorrhagic shock and hypotensive resuscitation

Clinically relevant animal models capable of simulating traumatic hemorrhagic shock are needed. We developed a hemorrhagic shock model with male New Zealand rabbits (2200-2800 g, 60-70 days old) that simulates the pre-hospital and acute care of a penetrating trauma victim in an urban scenario using current resuscitation strategies. A laparotomy was performed to reproduce tissue trauma and an aortic injury was created using a standardized single puncture to the left side of the infrarenal aorta to induce hemorrhagic shock similar to a penetrating mechanism. A 15-min interval was used to simulate the arrival of pre-hospital care. Fluid resuscitation was then applied using two regimens: normotensive resuscitation to achieve baseline mean arterial blood pressure (MAP, 10 animals) and hypotensive resuscitation at 60 percent of baseline MAP (10 animals). Another 10 animals were sham operated. The total time of the experiment was 85 min, reproducing scene, transport and emergency room times. Intra-abdominal blood loss was significantly greater in animals that underwent normotensive resuscitation compared to hypotensive resuscitation (17.1 ± 2.0 vs 8.0 ± 1.5 mL/kg). Antithrombin levels decreased significantly in normotensive resuscitated animals compared to baseline (102 ± 2.0 vs 59 ± 4.1 percent), sham (95 ± 2.8 vs 59 ± 4.1 percent), and hypotensive resuscitated animals (98 ± 7.8 vs 59 ± 4.1 percent). Evidence of re-bleeding was also noted in the normotensive resuscitation group. A hypotensive resuscitation regimen resulted in decreased blood loss in a clinically relevant small animal model capable of reproducing hemorrhagic shock caused by a penetrating mechanism.

Rabbit model of uncontrolled hemorrhagic shock and hypotensive resuscitation.

Clinically relevant animal models capable of simulating traumatic hemorrhagic shock are needed. We developed a hemorrhagic shock model with male New Zealand rabbits (2200-2800 g, 60-70 days old) that simulates the pre-hospital and acute care of a penetrating trauma victim in an urban scenario using current resuscitation strategies. A laparotomy was performed to reproduce tissue trauma and an aortic injury was created using a standardized single puncture to the left side of the infrarenal aorta to induce hemorrhagic shock similar to a penetrating mechanism. A 15-min interval was used to simulate the arrival of pre-hospital care. Fluid resuscitation was then applied using two regimens: normotensive resuscitation to achieve baseline mean arterial blood pressure (MAP, 10 animals) and hypotensive resuscitation at 60% of baseline MAP (10 animals). Another 10 animals were sham operated. The total time of the experiment was 85 min, reproducing scene, transport and emergency room times. Intra-abdominal blood loss was significantly greater in animals that underwent normotensive resuscitation compared to hypotensive resuscitation (17.1 ± 2.0 vs 8.0 ± 1.5 mL/kg). Antithrombin levels decreased significantly in normotensive resuscitated animals compared to baseline (102 ± 2.0 vs 59 ± 4.1%), sham (95 ± 2.8 vs 59 ± 4.1%), and hypotensive resuscitated animals (98 ± 7.8 vs 59 ± 4.1%). Evidence of re-bleeding was also noted in the normotensive resuscitation group. A hypotensive resuscitation regimen resulted in decreased blood loss in a clinically relevant small animal model capable of reproducing hemorrhagic shock caused by a penetrating mechanism.

Ventilator-associated pneumonia in trauma patients is associated with lower mortality: results from EU-VAP study.

BACKGROUND: Differences in trauma patients developing ventilator-associated pneumonia (VAP) are described regarding etiology and risk factors associated. We aim to describe the differences in outcomes in trauma and nontrauma patients with VAP. METHODS: A prospective, observational study conducted in 27 intensive care units from nine European countries. We included patients requiring invasive mechanical ventilation for >48 hours who developed VAP. Logistic regression model was used to assess the factors independently associated with mortality in trauma patients with VAP. RESULTS: A total of 2,436 patients were evaluated; 465 developed VAP and of these 128 (27.5%) were trauma patients. Trauma patients were younger than nontrauma (45.3 ± 19.4 vs. 61.1 ± 16.7, p < 0.0001). Nontrauma had higher simplified acute physiology score II compared with trauma patients (45.5 ± 16.3 vs. 41.1 ± 15.2, p = 0.009). Most prevalent pathogens in trauma patients with early VAP were Enterobacteriaceae spp. (46.9% vs. 27.8%, p = 0.06) followed by methicillin-susceptible Staphylococcus aureus (30.6% vs. 13%, p = 0.03) and then Haemophilus influenzae (14.3% vs. 1.9%, p = 0.02), and the most prevalent pathogen in late VAP was Acinetobacter baumannii (12.2% vs. 44.4%, p < 0.0001). Mortality was higher in nontrauma patients than in trauma patients (42.6% vs. 17.2%, p < 0.001, odds ratio [OR] = 3.55, 95%CI = 2.14-5.88). A logistic regression model adjusted for sex, age, severity of illness at intensive care unit admission, and sepsis-related organ failure assessment score at the day of VAP diagnosis confirmed that trauma was associated with a lower mortality compared with nontrauma patients (odds ratio [OR] = 0.37, 95%CI = 0.21-0.65). CONCLUSIONS: Trauma patients developing VAP had different demographic characteristics and episodes of etiology. After adjustment for potential confounders, VAP episodes in trauma patients are associated with lower mortality when compared with nontrauma patients.

Gripe A pandémica en una unidad de cuidados intensivos: experiencia en España y Latinoamérica (Grupo Español de Trabajo de Gripe A Grave/Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias) / Pandemic Influenza A in the ICU: Experience in Spain and Latin America GETGAG/SEMICYUC/(Spanish Work Group on Severe Pandemic Influenza A/SEMICYUC)

Introducción: La pandemia de gripe A (H1N1)v es la primera pandemia en la que las unidades de cuidados intensivos (UCI) desempeñan un papel fundamental. Su evolución ha sido muy rápida desde los primeros casos diagnosticados en México y la afectación posterior de países del cono sur hasta su llegada a Europa durante la época estival. Objetivo: Comparar las características clínicas y de evolución de los pacientes críticos ingresados hasta el 31 de julio de 2009 en España con algunas series de Latinoamérica. Material y método: Se consideraron 6 series de pacientes ingresados en la UCI. Se realizaron comparaciones de las características clínicas, complicaciones y evolución entre las series. Resultados: Los datos evidencian una población joven (35-45 años) con predominio de ingresos por neumonía viral con grave insuficiencia respiratoria y una elevada necesidad de ventilación mecánica (60-100%). Si bien algunas determinadas poblaciones, como los obesos, las embarazadas y los pacientes con enfermedad pulmonar crónica, parecen estar expuestas a un riesgo más elevado, la ausencia de comorbilidades alcanza un porcentaje considerable en casi todas las series (40-50%). La mortalidad superior en Latinoamérica osciló entre el 25 y el 50%, y demostró el particular potencial patogénico del nuevo virus. El uso del tratamiento antiviral es tardío (entre 3 y 6 días) y poco generalizado, con mayor retraso en Latinoamérica respecto de España. Conclusiones: Estos datos indican que una estrategia de tratamiento más intensivo con un acceso más precoz y fácil al antiviral podría reducir el número de pacientes que requieren UCI y su mortalidad (AU)

Introduction: Pandemic Influenza A (H1N1)v infection is the first pandemic in which intensive care units (ICU) play a fundamental role. It has spread very rapidly since the first cases were diagnosed in Mexico with the subsequent spread of the virus throughout the Southern Cone and Europe during the summer season. Objective: This study has aimed to compare the clinical presentation and outcome among the critical patients admitted to the ICU until July 31, 2009 in Spain with some series from Latin America. Material and method: Six series of critically ill patients admitted to the ICU were considered. Clinical characteristics, complications and outcome were compared between series. Results: Young patients (35-45 years) with viral pneumonia as a predominant ICU admission cause with severe respiratory failure and a high need of mechanical ventilation (60-100%) were affected. Obesity, pregnancy and chronic lung disease were risk factors associated with a worse outcome, however there was a high number of patients without comorbidities (40-50%). Mortality rate was between 25-50% and higher in the Latin America series, demonstrating the specific potential pathogenesis of the new virus. The use of antiviral treatment was delayed (between 3 and 6 days) and not generalized, with greater delay in Latin America in regards to Spain. Conclusions: These data suggest that a more aggressive treatment strategy, with earlier and easier access to the antiviral treatment might reduce the number of ICU admissions and mortality (AU)

Influence of pneumococcal serotype group on outcome in adults with bacteraemic pneumonia.

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.

[Pandemic influenza A in the ICU: experience in Spain and Latin America. GETGAG/SEMICYUC/(Spanish Working Group on Severe Pandemic Influenza A/SEMICYUC)]. / Gripe A pandémica en una unidad de cuidados intensivos: experiencia en España y Latinoamérica (Grupo Español de Trabajo de Gripe A Grave/Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias).

INTRODUCTION: Pandemic Influenza A (H1N1)v infection is the first pandemic in which intensive care units (ICU) play a fundamental role. It has spread very rapidly since the first cases were diagnosed in Mexico with the subsequent spread of the virus throughout the Southern Cone and Europe during the summer season. OBJECTIVE: This study has aimed to compare the clinical presentation and outcome among the critical patients admitted to the ICU until July 31, 2009 in Spain with some series from Latin America. MATERIAL AND METHOD: Six series of critically ill patients admitted to the ICU were considered. Clinical characteristics, complications and outcome were compared between series. RESULTS: Young patients (35-45 years) with viral pneumonia as a predominant ICU admission cause with severe respiratory failure and a high need of mechanical ventilation (60-100%) were affected. Obesity, pregnancy and chronic lung disease were risk factors associated with a worse outcome, however there was a high number of patients without comorbidities (40-50%). Mortality rate was between 25-50% and higher in the Latin America series, demonstrating the specific potential pathogenesis of the new virus. The use of antiviral treatment was delayed (between 3 and 6 days) and not generalized, with greater delay in Latin America in regards to Spain. CONCLUSIONS: These data suggest that a more aggressive treatment strategy, with earlier and easier access to the antiviral treatment might reduce the number of ICU admissions and mortality.

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.

[Prevention of nosocomial infections: strategies to improve the safety of the patients in the Intensive Care Unit]. / Prevención de infecciones nosocomiales: estrategias para mejorar la seguridad de los pacientes en la Unidad de Cuidados Intensivos.

Infection prevention is an intervention opportunity to promote patient safety. The strategies to obtain the full implementation of available prevention measures is the main challenge in clinical practice. Using care bundles, continuing education and feedback on adherence to the measures proposed are key points to improve the safety of patients in the Intensive Care Unit.

Mucormycosis in an immunocompetent patient: follow-up of 1 year after treatment.

Mucormycosis is a rare acute fatal fungal infection. It is typically observed in diabetic or immunocompromised patients but not in systemically healthy individuals. Here, we describe an unusual mucormycosis case in an immunocompetent patient who had clinical signs of a maxillary sinusitis and associated osteomyelitis at the first examination. He was treated by surgery and removal of the necrotic bone and amphotericin B medication. At 1-year follow-up he shows complete recovery.