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Graphical abstract Fx1, Objetivo: Evaluar si el uso de corticoesteroides (Cs) se asocia con la mortalidad en la unidad de cuidados intensivos (UCI) en la población global y dentro de los fenotipos clínicos predeterminados Diseño: Análisis secundario de estudio multicéntrico observacional Ámbito: UCI Pacientes: Pacientes adultos con COVID-19 confirmado ingresados en 63 UCIs de España Intervención: Corticoides vs. no Corticoides Variables de interés principales: A partir del análisis no supervisado de grupos, 3 fenotipos clínicos fueron derivados y clasificados como: A: grave, B: critico and C: potencialmente mortal. Se efectuó un análisis multivariado después de un propensity optimal full matching (PS) y una regresión ponderada de Cox (HR) y análisis de Fine-Gray (sHR) para evaluar el impacto del tratamiento con Cs sobre la mortalidad en la población general y en cada fenotipo clínico. Resultados: Un total de 2.017 pacientes fueron analizados, 1.171(58%) con Cs. Después del PS, el uso de Cs no se relacionó significativamente con la mortalidad en UCI (OR:1.0,95%CI:0.98-1.15). Cs fueron administrados en 298/537(55.5%) pacientes del fenotipo “A” y no se observó asociación significativa con la mortalidad (HR=0.85[0.55-1.33]). Un total de 338/623(54.2%) pacientes del fenotipo “B” recibieron Cs sin efecto significativo sobre la mortalidad (HR=0.72[0.49-1.05]). Finalmente, 535/857(62.4%) pacientes del fenotipo “C” recibieron Cs. En este fenotipo, se evidenció un efecto protector de los Cs sobre la mortalidad HR (0.75[0.58-0.98]). Conclusión: Nuestros hallazgos alertan sobre el uso indiscriminado de Cs a dosis moderadas en todos los pacientes críticos con COVID-19. Solamente pacientes con elevado estado de inflamación podrían beneficiarse con el tratamiento con Cs.

Background More than 20% of hospitalized patients with COVID-19 demonstrate ARDS requiring ICU admission. The long-term respiratory sequelae in such patients remain unclear. Research Question What are the major long-term pulmonary sequelae in critical patients who survive COVID-19? Study Design and Methods Consecutive patients with COVID-19 requiring ICU admission were recruited and evaluated 3 months after hospitalization discharge. The follow-up comprised symptom and quality of life, anxiety and depression questionnaires, pulmonary function tests, exercise test (6-min walking test [6MWT]), and chest CT imaging. Results One hundred twenty-five patients admitted to the ICU with ARDS secondary to COVID-19 were recruited between March and June 2020. At the 3-month follow-up, 62 patients were available for pulmonary evaluation. The most frequent symptoms were dyspnea (46.7%) and cough (34.4%). Eighty-two percent of patients showed a lung diffusing capacity of less than 80%. The median distance in the 6MWT was 400 m (interquartile range, 362-440 m). CT scans showed abnormal results in 70.2% of patients, demonstrating reticular lesions in 49.1% and fibrotic patterns in 21.1%. Patients with more severe alterations on chest CT scan showed worse pulmonary function and presented more degrees of desaturation in the 6MWT. Factors associated with the severity of lung damage on chest CT scan were age and length of invasive mechanical ventilation during the ICU stay. Interpretation Three months after hospital discharge, pulmonary structural abnormalities and functional impairment are highly prevalent in patients with ARDS secondary to COVID-19 who required an ICU stay. Pulmonary evaluation should be considered for all critical COVID-19 survivors 3 months after discharge.

To compare the measurement of antimicrobial consumption by defined daily dose (DDD) versus by days of therapy (DOT).Retrospective analysis of clinical and administrative data from patients admitted to a polyvalent ICU.ICU at a University Hospital in Spain.All patients admitted to the ICU.None.For the DDD method, the World Health Organization (WHO)-assigned DDD was determined for the all the prescribed antimicrobials. For the DOT method, one DOT represented the administration of a single agent on a given day regardless of the number of doses administered. To express aggregate use, total DDDs and total DOTs were normalized to 100 patient-days.During the study period, 2393 adult patients were admitted to the ICU. Total median antimicrobial drugs measured by DDDs was 535.3 (IQR 319.8-845.5) vs. 344.0 (IQR 117.2-544.5) when measured by DOTs, p0.001. When antimicrobial consumption was normalized to 100 patient-days, median antimicrobial consumption was also higher when measured by DDDs [2.98/100 patient-days (IQR 1.76-5.25) vs. 1.89/100 patient-days (IQR 0.64-3.0) when measured by DOTs, p0.001].For most antibacterial and antifungal drugs used in critically ill patients, estimates of aggregate antibiotic use by DDDs per 100 patient-days and DOTs per 100 patient-days are discordant because the administered dose is dissimilar from the WHO-assigned DDD. DOT methods should be recommended to avoid the overestimation that occurs with DDDs in adult critically ill patients.

International audience; Rationale: Early empirical antimicrobial treatment is frequently prescribed to critically ill patients with coronavirus disease (COVID-19) based on Surviving Sepsis Campaign guidelines.Objectives: We aimed to determine the prevalence of early bacterial identification in intubated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, as compared with influenza pneumonia, and to characterize its microbiology and impact on outcomes.Methods: A multicenter retrospective European cohort was performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation >48 hours were eligible if they had SARS-CoV-2 or influenza pneumonia at ICU admission. Bacterial identification was defined by a positive bacterial culture within 48 hours after intubation in endotracheal aspirates, BAL, blood cultures, or a positive pneumococcal or legionella urinary antigen test.Measurements and Main Results: A total of 1,050 patients were included (568 in SARS-CoV-2 and 482 in influenza groups). The prevalence of bacterial identification was significantly lower in patients with SARS-CoV-2 pneumonia compared with patients with influenza pneumonia (9.7 vs. 33.6%; unadjusted odds ratio, 0.21; 95% confidence interval [CI], 0.15-0.30; adjusted odds ratio, 0.23; 95% CI, 0.16-0.33; P < 0.0001). Gram-positive cocci were responsible for 58% and 72% of coinfection in patients with SARS-CoV-2 and influenza pneumonia, respectively. Bacterial identification was associated with increased adjusted hazard ratio for 28-day mortality in patients with SARS-CoV-2 pneumonia (1.57; 95% CI, 1.01-2.44; P = 0.043). However, no significant difference was found in the heterogeneity of outcomes related to bacterial identification between the two study groups, suggesting that the impact of coinfection on mortality was not different between patients with SARS-CoV-2 and influenza.Conclusions: Bacterial identification within 48 hours after intubation is significantly less frequent in patients with SARS-CoV-2 pneumonia than patients with influenza pneumonia.Clinical trial registered with www.clinicaltrials.gov (NCT04359693).

Purpose To evaluate the incidence and mortality of adult patients with community-acquired septic shock (CASS) and the influence of source control (SC) and other risk factors on the outcome. Material and methods The study included patients with CASS admitted to the ICU at a university hospital (2003–2016). Multivariate analyses were performed to identify risk factors of ICU mortality. Results A total of 625 patients were included. The incidence showed an average annual increase of 4.9% and the mortality an average annual decrease of 1.4%. The patients who required SC showed a lower mortality (20.4%) than patients who did not require SC (31.3%) (p = 0.002). However, the evolution in mortality was different: Mortality decreased in patients who did not require SC (from 56.3% to 20%; p = 0.02), but did not differ in those who required SC (from 21.4% to 27.6%; p = 0.43). In the multivariate analysis, severity at admission, age, alcoholism, cirrhosis, ARDS, neutropenia and thrombocytopenia were associated with worse outcome, whereas appropriate antibiotic treatment and adequate SC were independently associated with better survival. Conclusions The incidence of CASS increased and the ICU mortality decreased during the study period. The mortality was mainly due to a decrease in mortality in infections not requiring SC.

Background Continuous aspiration of subglottic secretions is effective in preventing ventilator-associated pneumonia, but it involves a risk of mucosal damage. The main objective of our study was to determine the incidence of airway complications related to continuous aspiration of subglottic secretions. Methods In consecutive adult patients with continuous aspiration of subglottic secretions, we prospectively recorded clinical airway complications during the period after extubation. A multidetector computed tomography of the neck was performed during the period of 5 days following extubation to classify subglottic and tracheal lesions as mucosal thickening, cartilage thickening or deep ulceration. Results In the 86 patients included in the study, 6 (6.9%) had transient dyspnea, 7 (8.1%) had upper airway obstruction and 18 (20.9%) had dysphonia at extubation. Univariate analysis identified more attempts required for intubation (2.3 ± 1.1 vs. 1.2 ± 0.5; p = 0.001), difficult intubation (71.4 vs. 10.1%, p = 0.001) and Cormack score III–IV (71.4 vs. 8.8%; p

Purpose of review The impact of multidrug-resistant organisms (MDROs) is rising and often underestimated. The epidemiology of MDROs is extremely complex and multifactorial. There is increasing antibiotic resistance, mainly related to antibiotic pressure and patients' characteristics. Recent findings Emphasis on MDRO epidemiology is needed to better understand current strategies of prevention and management. Among them, antibiotic stewardship has been one of the most successful strategies. It is important to note that there is a controversial issue when considering community and healthcare-related infections. In addition, different strategies have been determined to find the impact and optimal use of recently launched antibiotics for MDRO treatment. Summary Infections with MDROs can prolong hospital stay, promote antibiotic use and prolong duration of mechanical ventilation. Some points should be further explored in clinical research such as the heterogeneity of healthcare-associated pneumonia and the need of new drug development. Resistance to non fermentative Gram-negative bacilli, rising minimum inhibitory concentration in methicillin-resistant Staphylococcus aureus and spread of MDROs in patients without known risk factors suggest a review of guideline validation, taking into account ecology and severity of patient illness to provide timely and appropriate empiric therapy.

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.

Little is known about the impact of community-acquired respiratory coinfection in patients with pandemic 2009 influenza A(H1N1) virus infection.This was a prospective, observational, multicenter study conducted in 148 Spanish ICUs.Severe respiratory syndrome was present in 645 ICU patients. Coinfection occurred in 113 (17.5%) of patients. Streptococcus pneumoniae (in 62 patients [54.8%]) was identified as the most prevalent bacteria. Patients with coinfection at ICU admission were older (47.5±15.7 vs 43.8±14.2 years, P.05) and presented a higher APACHE (Acute Physiology and Chronic Health Evaluation) II score (16.1±7.3 vs 13.3±7.1, P.05) and Sequential Organ Failure Assessment (SOFA) score (7.0±3.8 vs 5.2±3.5, P.05). No differences in comorbidities were observed. Patients who had coinfection required vasopressors (63.7% vs 39.3%, P.05) and invasive mechanical ventilation (69% vs 58.5%, P.05) more frequently. ICU length of stay was 3 days longer in patients who had coinfection than in patients who did not (11 [interquartile range, 5-23] vs 8 [interquartile range 4-17], P=.01). Coinfection was associated with increased ICU mortality (26.2% vs 15.5%; OR, 1.94; 95% CI, 1.21-3.09), but Cox regression analysis adjusted by potential confounders did not confirm a significant association between coinfection and ICU mortality.During the 2009 pandemics, the role played by bacterial coinfection in bringing patients to the ICU was not clear, S pneumoniae being the most common pathogen. This work provides clear evidence that bacterial coinfection is a contributor to increased consumption of health resources by critical patients infected with the virus and is the virus that causes critical illness in the vast majority of cases.

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.

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.

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.

To explore the type and frequency of oral care practices in European ICUs and the attitudes, beliefs, and knowledge of health care workers.An anonymous questionnaire was distributed to representatives of European ICUs. Results were obtained from 59 ICUs (one questionnaire per ICU) in seven countries 91% of respondents were registered nurses.Of the respondents 77% reported that they had received adequate training on providing oral care; most (93%) also expressed the desire to learn more about oral care. Oral care was perceived to be high priority in mechanically ventilated patients (88%). Cleaning the oral cavity was considered difficult by 68%, and unpleasant as well as difficult by 32%. In 37% of cases respondents felt that despite their efforts oral health worsens over time in intubated patients. Oral care practices are carried out once daily (20%), twice (31%) or three times (37%). Oral care consists principally of mouth washes (88%), mostly performed with chlorhexidine (61%). Foam swabs (22%) and moisture agents (42%) are used less frequently as well as manual toothbrushes (41%) although the literature indicates that these are more effective for thorough cleaning of the oral cavity. Electric toothbrushes were never used.In European ICUs oral care is considered very important. It is experienced as a task that is difficult to perform, and that does not necessarily succeed in ensuring oral health in patients with prolonged intubation. Oral care consists primarily of mouth washes. The use of toothbrushes should be given more attention.

To assess the feasibility and safety of the respiratory infection control (RIC) device, a silver-coated endotracheal tube, and its effect on bacterial burden in the airways.Prospective, randomized, single-blind, multiple-center study.Three hospitals in Spain and one in the United States.Patients were eligible adults who required mechanical ventilation foror =24 hrs and did not have respiratory infections. One hundred forty-nine patients were intubated and analyzed for safety; 121 were intubatedor =24 hrs and analyzed for tube colonization; 67 had negative baseline quantitative endotracheal aspirates and were analyzed for quantitative endotracheal aspirates colonization.Intubation with the RIC device or a control endotracheal tube.The RIC device was associated with delayed colonization on the tube compared with the control device at the threshold of ++, +++, oror =10(4) colony-forming units/mL (p = .02, log-rank test; p = .10, Wilcoxon's test) and in quantitative endotracheal aspirates ator =10(6) colony-forming units/mL (p = .08, log-rank test; p = .05, Wilcoxon's test). The RIC device was associated with reduced colonization rate by days on the tube (p = .04, Wilcoxon's test) and in quantitative endotracheal aspirates (p = .05, Wilcoxon's test) at the same thresholds. The RIC device was associated with lower maximal bacterial burden in tracheal aspirates for 7 days (mean log-transformed burden, 4.2 +/- 2.3 vs. 5.5 +/- 1.7 log colony-forming units/mL; p = .02, Wilcoxon's test). Other between-group differences favored the RIC device but were not significant. Five adverse events were considered device related, including three events in the RIC group and two events in the control group.In this prospectively planned, preliminary analysis, the RIC device was feasible and well tolerated. Larger studies are needed to determine whether delayed colonization, reduced colonization rate, and decreased bacterial burden will decrease the incidence of ventilator-associated pneumonia.

To determine whether ventilator-associated pneumonia caused by oxacillin-resistant Staphylococcus aureus (VAP-ORSA) treated with glycopeptides is associated with an increased mortality rate.Retrospective matched cohort study.Four intensive care units in teaching hospitals.Seventy-five patients were matched to 75 controls.None.All adult intensive care unit patients with microbiologically documented VAP-ORSA were matched to intubated controls who did not develop VAP-ORSA, based on disease severity (Acute Physiology and Chronic Health Evaluation II score) at admission (+/-3 points), diagnostic category, and length of stay before pneumonia onset. Population characteristics and intensive care unit mortality rates of patients with VAP-ORSA and their controls without pneumonia were compared. Attributable mortality was determined by subtracting the crude mortality rate of controls from the crude mortality rate of VAP-ORSA patients. Thirty-six of the 75 matched VAP-ORSA patients died, representing a crude mortality rate of 48%, whereas 19 of the 75 controls died, a crude mortality rate of 25.3% (p.01). Excess mortality was estimated to be 22.7% (95% confidence interval, 2.4-42.9%). Median length of intensive care unit stay in the surviving pairs was 33 days (interquartile range, 25-75%: 25-45 days) for VAP-ORSA patients and 21 days (interquartile range, 25-75%: 15-34.75 days) days for controls (p = .054).Despite appropriate glycopeptide therapy, there is an increased attributable mortality for pneumonia by ORSA, after careful adjustment for disease severity and diagnostic category.

To evaluate de-escalation of antibiotic therapy in patients with ventilator-associated pneumonia.Prospective observational study during a 43-month period.Medical-surgical intensive care unit.One hundred and fifteen patients admitted to the intensive care unit with clinical diagnosis of ventilator-associated pneumonia. All the episodes of ventilator-associated pneumonia received initial broad-spectrum coverage followed by reevaluation according to clinical response and microbiology. Quantitative cultures obtained by bronchoscopic examination or tracheal aspirates were used to modify therapy.: None.One hundred and twenty-one episodes of ventilator-associated pneumonia were diagnosed. Change of therapy was documented in 56.2%, including de-escalation (the most frequent cause) in 31.4% (increasing to 38% if isolates were sensitive). Overall intensive care unit mortality rate was 32.2%. Inappropriate antibiotic therapy was identified in 9% of cases and was associated with 14.4% excess intensive care unit mortality. Quantitative tracheal aspirates and bronchoscopic samples (58 protected specimen brush and three bronchoalveolar lavage) were associated with 32.7% and 29.5% intensive care unit mortality and 29.3% and 34.4% de-escalation rate. De-escalation was lower (p.05) in the presence of nonfermenting Gram-negative bacillus (2.7% vs. 49.3%) and in the presence of late-onset pneumonia (12.5% vs. 40.7%). When the pathogen remained unknown, half of the patients died and de-escalation was not performed.De-escalation was the most important cause of antibiotic modification, being more feasible in early-onset pneumonia and less frequent in the presence of nonfermenting Gram-negative bacillus. The impact of quantitative tracheal aspirates or bronchoscopic techniques was comparable in terms of mortality.

To review barriers to nursing adherence to nonpharmacologic evidence-based guidelines for preventing ventilator-associated pneumonia.Descriptive study.Intensive care units.Subjects were 110 nurses approached at two critical care nursing meetings.A questionnaire was administered to nurses to assess their adherence to 19 nonpharmacologic prevention strategies and to identify barriers to adherence to evidence-based guidelines.Fifty-one nurses responded, and overall nonadherence was 22.3%. Significant differences of adherence were identified when compared with the rates previously reported by physicians in nine of the 19 strategies investigated. The most important reasons for nonadherence were unavailability of resources (37.0%), patient discomfort (8.2%), disagreement with reported trial results (7.8%), fear of potential adverse effects (5.8%), and costs (3.4%). Nurses were more likely (p.05) to identify patient discomfort (odds ratio, 4.8) and fear of adverse events (odds ratio, 3.3), whereas physicians were more likely to report costs (odds ratio, 5.4) and disagreement with interpretation of trials (odds ratio, 3.7) as reasons for nonadherence.Nurses had different levels of adherence than physicians for many nonpharmacologic strategies. The most important barriers to implementation were environment-related. Other reasons for nonadherence show significant variability between nurse and physician opinion leaders, patient-related barriers being significantly more important for nurses. Our findings suggest the need for development of multinational guidelines to reduce variability and the need to include the nursing point of view in these guidelines.

To update the state-of-the-art on pneumonia in adult patients in the intensive care unit (ICU), with special emphasis on new developments in management.We searched MEDLINE, using the following keywords: hospital-acquired pneumonia, ventilator-associated pneumonia and healthcare-associated pneumonia, diagnosis, therapy, prevention.Interventions to prevent pneumonia in the ICU should combine multiple measures targeting the invasive devices, microorganisms, and protection of the patient. Once pneumonia develops, the appropriateness of the initial antibiotic regimen is a vital determinant of outcome. Three questions should be formulated: a) Is the patient at risk of methicillin-resistant Staphylococcus aureus?; b) Is Acinetobacter baumannii a problem in the institution?; and c) is the patient at risk of Pseudomonas aeruginosa? Antibiotic therapy should be started immediately and must circumvent pathogen-resistance mechanisms developed after previous antibiotic exposure. Therefore, antibiotic choice should be institution specific and patient oriented. Microbiologic investigation is useful on evaluating the quality of the respiratory sample and permits early modification of the regimen in light of the microbiologic findings.A decision tree outlining an approach to the evaluation and management of ventilator-associated pneumonia is provided.

Resumen Fundamento Con el objetivo de mejorar a medio plazo su posicion competitiva, la Sociedad Catalana de Medicina Intensiva y Critica (SOCMIC), por mandato asambleario, decidio la elaboracion de un plan estrategico (PE). Metodos Siguiendo una metodologia clasica y de forma ampliamente participativa, se elabora un plan estrategico que incluye: el diagnostico de situacion de la SOCMIC, la definicion de las politicas generales, la declaracion de mision, el analisis de los puntos fuertes y debiles, asi como las amenazas y oportunidades; y finalmente, la identificacion, el desarrollo y la priorizacion de las lineas de accion estrategicas. Resultados La elaboracion del plan estrategico ha permitido identificar y desarrollar ocho lineas de accion estrategicas, la mayoria de ellas relacionadas con una estrategia de marketing externo y con la gestion del conocimiento y las competencias esenciales propias de los miembros de la SOCMIC. La linea estrategica “posicionar a la SOCMIC como punto de referencia en la toma de decisiones de la atencion al enfermo critico” ha sido la linea de accion mas valorada. Conclusiones Importante por si mismo, el nivel de participacion ha sido alto, lo que ha sido basico para establecer, por ejemplo, la mision de la SOCMIC. La elaboracion del plan estrategico de la SOCMIC permite priorizar lineas de accion que se espera favorezcan su posicion competitiva, y ha de permitir la implantacion del plan en la medida que se desee.

El diagnostico y el tratamiento en las unidades de cuidados intensivos (UCI) resulta dificil, debido, en parte, a la naturaleza compleja de la enfermedad y tambien a la imposibilidad, en algunas ocasiones, de comunicacion con el paciente. Los recientes avances tecnologicos y la secuenciacion del genoma humano ofrecen una oportunidad interesante para incrementar el conocimiento en la enfermedad aguda El objetivo de este trabajo es revisar el concepto de polimorfismo genetico en el paciente critico, para lo que se ha realizado una revision de la bibliografia (Medline) de 1995 a 2002 En la pasada decada, con el avance de la medicina molecular, el conocimiento de los mecanismos fisiopatologicos ha aumentado exponencialmente; ademas, es incuestionable la contribucion de la genetica al existir enfermedades monogenicas y poligenicas. La respuesta del sistema inmunitario a la agresion se produce a traves de repuestas celulares y humorales primarias, secundarias y terciarias. En este contexto, el papel del sustrato genetico en la respuesta inflamatoria determina una gran variabilidad individual en el comportamiento de los mediadores La informacion genetica individual puede utilizarse para identificar a grupos de pacientes con un riesgo elevado de desarrollar sepsis o disfuncion multiorganica y determinar a los pacientes que pueden beneficiarse de una terapeutica basada en el bloqueo de mediadores

En el primer manuscrito se describieron los trabajos mas importantes en relacion con el polimorfismo genetico en el paciente critico respecto a la inflamacion y la sepsis. En la presente Revision se discute la importancia de los aspectos geneticos enrelacion con la coagulacion y el sindrome de distres respiratorio agudo (SDRA). Ademas, se hace notar como la variabilidad genetica individual puede influir en pacientes traumaticos y grandes cirugias, como la cirugia cardiaca, participando en fenomenos fisiopatologicos que rodean a este tipo de intervenciones. Finalmente, se analiza el potencial papel de los genes como tratamiento: farmacogenetica y terapia genica A la luz de los datos disponibles, sera posible la utilizacion de marcadores geneticos que ayudaran a estratificar a los pacientes por grados de riesgo y a identificar a aquellos con un peor pronostico. Ademas, la identificacion de las variaciones geneticas individuales que participan en enfermedades complejas ha permitido que aumente el interes por la terapia genica

Objective Adherence to clinical practice guidelines is highly variable. Our objective was to review barriers to physicians' adherence to evidence-based guidelines (EBGs) for preventing ventilator-associated pneumonia (VAP). Methods A questionnaire was administered to 110 opinion leaders on VAP from 22 countries to indicate whether 33 pharmacologic and nonpharmacologic practices that had been listed in a recent publication had been implemented in their ICUs. If these prevention strategies were not used, the respondents were asked to indicate one of seven reasons for nonadherence, with the objective of identifying barriers to adherence to EBGs. Results The overall nonadherence rate was 37.0%. The nonadherence rate was 25.2% for strategies recommended for clinical use, compared with 45.6% for strategies with less effectiveness (odds ratio [OR], 1.80). Pharmacologic strategies had a higher degree of nonadherence than nonpharmacologic strategies (OR, 2.92). Nonadherence to recommendations graded A, B, C, D, and U based on an objective assessment of the consistency of the supporting evidence was 41.3%, 35.7%, 16.0%, 45.7%, and 20.8%, respectively. The most common reasons for nonadherence were the following: disagreement with interpretation of clinical trials (35%); unavailability of resources (31.3%); and costs (16.9%). Conclusion We conclude that nonadherence to EBGs for preventing VAP was common and largely uninfluenced by the degree of evidence. A rational approach toward improving VAP guideline adherence should take into account the heterogeneous factors that influence physician adherence to them.

Introduction. The aim of the study was to examine different antibiotic choices and their relation to outcomes. Methods. We reviewed patients with severe community-acquired pneumonia (SCAP) from two multicenter studies. Empirical antimicrobial regimens were classified as: macrolides alone (group M); macrolides plus betalactams (group MB); macrolides plus betalactam/betalactamase inhibitor (group MBI); every regimen including aminoglycosides (group A); non-pseudomonal third-generation cephalosporins alone (group C); another betalactam alone (first- and second-generation cephalosporins, or betalactam/betalactamase inhibitor) (group B); fluoroquinolones (group F); and other regimens (group Misc). Results. Initial distribution of regimens was: group MB: 261 patients; group A: 65 patients; group C: 31 patients; group B: 23 patients; group M: 18 patients; group MBI: 13 patients; group F: 11 patients; group Misc: 38 patients. The lowest overall mortality was associated with initial treatment with a macrolide plus other agent (or alone). No deaths were documented among the 13 patients receiving amoxicillin/clavulanate plus a macrolide. The excess mortality for initial treatment with group A was significantly higher (14.2%; CI 95% 27.3–1.1) than the overall mortality rate between patients receiving a macrolide plus other agents. No significant differences were documented when mortality was adjusted for intubated patients. Conclusion. Clinicians select the empirical antibiotic regimen after classifying patients according to likely pathogens and prognosis. The inclusion of a macrolide as part of the initial therapeutic regimen for SCAP appears to be as safe and effective as alternative options. Addition of a macrolide agent to a betalactam/betalactamase inhibitor or using a macrolide alone was a marker for less severe disease.

Two hundred fifty intubated patients were followed during the first 48 h after intubation in order to identify potential risk factors for developing pneumonia within this period. Thirty-two developed pneumonia during this time. Univariate analysis established that large volume aspiration, presence of sedation, intubation caused by respiratory/cardiac arrest or decrease in the level of consciousness, emergency procedure, cardiopulmonary resuscitation (CPR), and Glasgow coma score < 9 were significantly associated with pneumonia. In contrast, prior infection and prior antimicrobial use were associated with a protective effect. Presence of subglottic secretion drainage and 15 other variables had no significant effect. Multivariate analysis selected CPR (odds ratio [OR] = 5.13, 95% confidence intervals [CI] = 2.14, 12.26) and continuous sedation (OR = 4.40, 95% CI = 1.83, 10.59) as significant risk factors for pneumonia, while antibiotic use (OR = 0.29, 95% CI = 0.12, 0.69) showed a protective effect. Our findings emphasize that risk factors for pneumonia change during the intubation period, and preventing pneumonia requires a combined approach.

Study objectives To determine the clinical significance of Candida sp isolated from bronchoscopic samples in patients with suspected pneumonia. Design A retrospective chart review was performed in all nonneutropenic adult patients with Candida sp isolates from respiratory secretions obtained by bronchoscopy over a 5-year period (1991 to 1995). Potential risk factors, therapeutic decisions, and outcome were recorded. Microbiological findings, chest radiograph reports, and pathologic material were reviewed. Isolates were classified as definite, probable, or indeterminate contamination, or as definite pulmonary candidiasis, on the basis of histologic findings, therapeutic decisions, and outcome. Setting A 600-bed teaching hospital with 16 beds in a medical-surgical ICU. Patients Thirty-seven consecutive patients with positive cultures for Candida sp from respiratory samples obtained by bronchoscopy were evaluated. Thirty-two of these 37 patients (86.5%) received antibiotic therapy prior to sampling, and 23 (62.2%) were intubated. Results Contamination was classified as definite in 3 patients (8.1%) and probable in 30 others (81.0%). Contamination was indeterminate in two cases (5.4%). Two additional patients (5.4%) received antifungal agents for systemic candidiasis. No cases of pulmonary candidiasis could be demonstrated, although 24 of 28 patients showed protected specimen brush cultures ≥10 3 cfu/mL. Conclusions Nonneutropenic patients with isolation of Candida sp from bronchoscopic samples, even in high concentrations, are unlikely to have invasive candidiasis. Indication for initiation of antifungal therapy should be based on histologic evidence or identification from sterile specimens.

Objective: Inhalation of nitric oxide (NO) can improve oxygenation and decrease mean pulmonary artery pressure (MPAP) in patients with the acute respiratory distress syndrome (ARDS). It is not known whether inhaled NO exerts a similar effect in hypoxemic patients with chronic obstructive pulmonary disease (COPD). Design: Prospective clinical study. Setting: General intensive care unit in Sabadell, Spain. Patients: Nine mechanically ventilated COPD patients (mean age 72±2 years; forced expiratory volume in 1 s 0.91±0.11 l) and nine ARDS patients (mean age 57±6 years; mean lung injury score 2.8±0.1) Measurements and results: We measured hemodynamic and gas exchange parameters before NO inhalation (basal 1), during inhalation of 10 ppm NO (NO-10), and 20 min after NO was discontinued (in basal 2) in the ARDS group. In the COPD group, these parameters were measured before NO inhalation (basal 1), during different doses of inhaled NO (10, 20, and 30 ppm), and 20 min after NO was discontinued (basal 2). A positive response to NO was defined as a 20% increment in basal arterial partial pressure of oxygen (PaO2). MPAP and pulmonary vascular resistance (PVR) decreased significantly, while other hemodynamic parameters remained unchanged after NO-10 in both groups. Basal oxygenation was higher in the COPD group (PaO2/FIO2 (fractional inspired oxygen) 190±18 mmHg) than in the ARDS group (PaO2/FIO2 98±12 mmHg), (p

Purpose Information about healthcare-associated pneumonia (HCAP) in critically ill patients is scarce. Methods This prospective study compared clinical presentation, outcomes, microbial etiology, and treatment of HCAP, community-acquired pneumonia (CAP), and immunocompromised patients (ICP) with severe pneumonia admitted to 34 Spanish ICUs. Results A total of 726 patients with pneumonia (449 CAP, 133 HCAP, and 144 ICP) were recruited during 1 year from April 2011. HCAP patients had more comorbidities and worse clinical status (Barthel score). HCAP and ICP patients needed mechanical ventilation and tracheotomy more frequently than CAP patients. Streptococcus pneumoniae was the most frequent pathogen in all three groups (CAP, 34.2 %; HCAP, 19.5 %; ICP, 23.4 %; p = 0.001). The overall incidence of Gram-negative pathogens, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa was low, but higher in HCAP and ICP patients than CAP. Empirical treatment was in line with CAP guidelines in 73.5 % of patients with CAP, in 45.5 % of those with HCAP, and in 40 % of those with ICP. The incidence of inappropriate empirical antibiotic therapy was 6.5 % in CAP, 14.4 % in HCAP, and 21.8 % in ICP (p

The second most important infectious complication in hospitalized patients is pneumonia, this occupying the first place in the Intensive Care Units (ICU). Approximately 80% of the episodes of nosocomial pneumonia occur in patients with an artificial airway, which is called ventilation-associated pneumonia (VAP). VAP is the most frequent cause of mortality among nosocomial infections in the ICU, mainly if they are caused by Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA). It also increases days of mechanical ventilation and length of stay in the ICU and hospital. In spite of the available diagnostic procedures, the diagnosis of VAP continues to be a clinical one. The presence of X-ray infiltrates and purulent endotracheal secretions are the essential conditions for the diagnosis. We should also evaluate the patient's condition and the risk factors for difficult-to-treat pathogens. If the VAP is early and there are no risk factors, most of the empiric antibiotic strategies will provide correct coverage of the flora found. However, if the diagnosis of VAP is made in a patient who has been receiving mechanical ventilation for more than one week, under antibiotic use, with risk factors for multi-resistant pathogens, we should individualize the empiric antibiotic treatment.

Antibiotic exposure and timing of pneumonia onset influence ventilator-associated pneumonia (VAP) isolates. The first goal of this investigation was to evaluate whether trauma also influences prevalence of microorganisms. A retrospective, single-center, observational cohort study. Multidisciplinary teaching ICU. Adult patients requiring mechanical ventilation identified as having VAP. Retrospective evaluation of a prospective manual database. VAP isolates in a multidisciplinary ICU documented by quantitative respiratory cultures and recorded in a 42-month database were compared, based on the presence or absence of trauma. Causative microorganisms were classified in four groups, based on mechanical ventilation duration (> 5 days), and previous antibiotic exposure. One hundred eighty-three patients developed 196 episodes of VAP (98 trauma). Methicillin-sensitive Staphylococcus aureus (MSSA) was more frequent (34.5% vs. 11.5%, p

To determine the pattern of resolution of classic infectious and respiratory variables in patients with ventilator-associated pneumonia (VAP) and appropriate empirical therapy, depending on the presence of acute respiratory distress syndrome (ARDS). A secondary objective was to identify clinical variables that might be useful for monitoring response to therapy.Prospective, observational cohort study.Medical-surgical intensive care unit.Seventy-five episodes of VAP without ARDS were identified and compared with 20 episodes with ARDS at VAP onset. Six episodes were excluded due to in vitro resistance to the initial antibiotic choice and six due to death in the first 72 hrs.None.Resolution of fever, Pao2/Fio2250 mm Hg, and white blood cell count in episodes of VAP were present in 73.3%, 74.7%, and 53.3% of patients after 3 days of therapy. Indeed,50% of episodes with the absence of ARDS presented resolution of fever and Pao2/Fio2250 within the first day of therapy. In contrast, resolution of radiologic opacities and clearance of secretions (median of 14 and 6 days of resolution) were late events. In patients with ARDS, resolution of fever remained the earliest variable. However, similar to Pao2/Fio2 250 and white blood cell count, fever showed a significantly worse pattern after 3 days of therapy: 45%, 15% and 25%, respectively. Radiologic resolution was an extremely poor indicator, being present in only 10% of ARDS patients after 15 days of follow-up. Failure to improve after 48 hrs of therapy was documented in 65% of ARDS patients and 14.7% of controls (p.05).Measures of oxygenation and core temperature can help physicians to individualize and shorten the duration of antibiotic therapy in VAP episodes. ARDS patients with VAP take twice as long to resolve fever, whereas hypoxemia should be ignored in defining resolution in this subset.

Objective To determine the epidemiology of pneumonia in patients with tracheotomy receiving short-term mechanical ventilation. Design Observational prospective study. Setting A 14-bed medical-surgical ICU. Subjects Ninety-nine critically ill acute patients requiring percutaneous dilatational tracheotomy for mechanical ventilation. Interventions Tracheal aspirate obtained 48 h before tracheotomy. Measurements and main results Eighteen patients (18.1%) acquired pneumonia (median of 7 days after tracheotomy). Pseudomonas aeruginosa was the most frequently identified pathogen, found in eight of the episodes (four not documented by prior tracheal colonization), followed by other Gram-negative bacilli. The development of ventilator-associated pneumonia (VAP) was not anticipated by any clinical variable. A positive tracheal aspirate (TA) culture result obtained before tracheotomy was associated with a risk of acquiring pneumonia of 19.7%, whereas sterile TA cultures were associated with a risk of 14.3% (p > 0.20). VAP prolonged ICU stay or the ventilation period for a median of 19 days and 15 days, respectively. Overall mortality was 34.3%, but the presence of VAP did not increase the mortality rate. Conclusions Percutaneous tracheotomy in patients receiving short-term mechanical ventilation predisposes to pneumonia. Pneumonia was associated with prolonged ventilation and ICU stay, but was not associated with increased mortality. Pseudomonas is a common pathogen after tracheotomy, and this observation should be considered in selecting an antibiotic regimen, because TA obtained prior to the tracheotomy often failed to identify this pathogen.

To determine whether ventilator-associated pneumonia caused by Acinetobacter baumannii (VAPAB) is associated with increased mortality rate.A retrospective matched case-control study in which all intensive care unit adult patients with microbiologically documented VAPAB were defined as cases.Four intensive care units from teaching hospitals.Sixty patients were matched to sixty controls.Controls were matched based on stay before pneumonia onset, disease severity (Acute Physiology and Chronic Health Evaluation II) at admission, and diagnostic category. Population characteristics and intensive care unit mortality rates of patients with VAPAB and their controls were compared. Attributable mortality was determined by subtracting the crude mortality rate of the controls from the crude mortality rate of the case patients. Twenty-four of the 60 case patients died, representing a crude mortality rate of 40%, whereas 17 of the 60 controls died, a crude mortality rate of 28.3% (p =.17). Crude intensive care unit mortality was the same (12 of 35, 34.2%) in patients with VAPAB caused by strains sensitive to imipenem and in their matched controls. It was 44% for the 25 patients with imipenem-resistant strains with an estimated attributable mortality rate of 20.0% (95% confidence interval, -5.6% to 45.7%). Mean intensive care unit stay of patients and controls was 35.3 and 36.6 days, respectively (p = nonsignificant).In intubated patients, pneumonia by A. baumannii is not significantly associated with attributable mortality rate or an increased length of intensive care unit stay.

The study documents the impact of microbiological investigations on therapeutic decisions and outcome in patients with severe community-acquired pneumonia (SCAP).Retrospective analysis of prospectively collected data.ICUs in two teaching Spanish hospitals.Two hundred four consecutive patients admitted to intensive care with SCAP.None.One hundred six patients required intubation, while 98 other patients did not (81 of these patients were managed with noninvasive mechanical ventilation). The microbiologic diagnosis was established in 57.3% of patients. The most common pathogens were Streptococcus pneumoniae, Legionella pneumophila, and Haemophilus influenzae. Pseudomonas (6.6.% vs 1.0%, p0.05) and Legionella (15.1% vs 7.1%, p0.05) were more frequently documented in intubated patients. Overall mortality was 23.5% (44.3% in intubated patients), with S pneumoniae (n = 7), Pseudomonas aeruginosa (n = 7), and L pneumophila (n = 5) being the most common lethal pathogens. Bacteriological investigation led to changes in antibiotic prescription in 41.6% of patients, including 11 patients (5%) in whom initial treatment was ineffective against the microbial isolates. The most frequent reason for changes was simplification of therapy in 65 episodes (31.8%).We conclude that microbiological testing is fully justified in patients with SCAP, because identifying the causative agent and adjusting treatment both impact on patient outcome. Our findings suggest that intubated patients should be empirically treated for Pseudomonas and Legionella while awaiting bacteriology results.

Ventilator-associated pneumonia (VAP) is an important health problem that still generates great controversy. A consensus conference attended by 12 researchers from Europe and Latin America was held to discuss strategies for the diagnosis and treatment of VAP. Commonly asked questions concerning VAP management were selected for discussion by the participating researchers. Possible answers to the questions were presented to the researchers, who then recorded their preferences anonymously. This was followed by open discussion when the results were known. In general, peers thought that early microbiological examinations are warranted and contribute to improving the use of antibiotherapy. Nevertheless, no consensus was reached regarding choices of antimicrobial agents or the optimal duration of therapy. Piperacillin/tazobactam was the preferred choice for empiric therapy, followed by a cephalosporin with antipseudomonal activity and a carbapenem. All the peers agreed that the pathogens causing VAP and multiresistance patterns in their ICUs were substantially different from those reported in studies in the United States. Pathogens and multiresistance patterns also varied from researcher to researcher inside the group. Consensus was reached on the importance of local epidemiology surveillance programs and on the need for customized empiric antimicrobial choices to respond to local patterns of pathogens and susceptibilities.

Therapy of ventilator-associated pneumonia should be a patient-based approach focusing on some key features are listed here: early initial therapy should be based on broad-spectrum antibiotics. Empirical treatment may be targeted after direct staining and should be modified according to good-quality quantitative microbiological findings, but should never be withdrawn in presence of negative direct staining or delayed until microbiological results are available. Courses of therapy should be given at high doses according to pharmacodynamic and tissue penetration properties. Prolonging antibiotic treatment does not prevent recurrences. Methicillin-sensitive Staphylococcus aureus should be expected in comatose patients. Methicillin-resistant Staphylococcus aureus should not be expected in patients without previous antibiotic coverage. Pseudomonas aeruginosa should be covered with combination therapy. Antifungal therapy, even when Candida spp is isolated in significant concentrations, is not recommended for intubated nonneutropenic patients. Vancomycin, given at the standard doses and route of administration for the treatment of VAP caused by Gram-positive pathogens, is associated with poor outcomes. The choice of initial antibiotic should be based on the patient's previous antibiotic exposure and comorbidities, and local antibiotic susceptibility patterns, which should be updated regularly.