Colistin Dosage without Loading Dose Is Efficacious when Treating Carbapenem-Resistant Acinetobacter baumannii Ventilator-Associated Pneumonia Caused by Strains with High Susceptibility to Colistin.

OBJECTIVES: This study aims to analyze the mortality and the length of ICU stay (LOS) of A. baumannii VAP compared to respiratory colonization in patients with mechanical ventilation (MV). METHODS: A prospective cohort study was performed in an ICU of adult patients (February 2010-June 2011). One hundred patients on MV with A. baumannii in lower respiratory airways were recruited, and classified as VAP or airways colonization according to CPIS criteria, with a punctuation ≥6. LOS, 30-days mortality, A. baumannii bacteremia, and clinical features including antibiotic therapy were recorded. Multivariate analysis (linear and Cox regression) and survival analysis (Kaplan-Meier curves) were performed. RESULTS: Fifty-seven VAP and 43 colonized A. baumannii patients were analyzed. Among the A. baumannii strains, 99% were non-susceptible to carbapenems and the MIC90 of colistin was 0.12 mg/l. Therapy was appropriate in 94.6% of VAP patients, most of them with colistin 6 MIU/day, although in 13 (23.6%) cases colistin was started 48 hours after the onset of VAP. Mortality was similar in both groups (VAP 24.6% vs. colonized 27.9%, p = 0.7). Bacteremia and acute kidney insufficiency were associated with decreased survival (p = 0.02 and p = 0.04, respectively) in VAP patients. LOS was 21.5 (11.5-42.75) vs. 9 (6-22) days for VAP and colonized patients (p = 0.004). VAP (p = 0.003) and age (p = 0.01) were independently related to a longer LOS. CONCLUSIONS: Multidrug-resistant A. baumannii VAP treated with colistin does not have a different mortality compared to lower airways colonization, among patients on mechanical-ventilation, in a setting of high susceptibility to colistin of A. baumannii.

Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality.

INTRODUCTION: Although early institution of adequate antimicrobial therapy is lifesaving in sepsis patients, optimal antimicrobial strategy has not been established. Moreover, the benefit of combination therapy over monotherapy remains to be determined. Our aims are to describe patterns of empiric antimicrobial therapy in severe sepsis, assessing the impact of combination therapy, including antimicrobials with different mechanisms of action, on mortality. METHODS: This is a Spanish national multicenter study, analyzing all patients admitted to ICUs who received antibiotics within the first 6 hours of diagnosis of severe sepsis or septic shock. Antibiotic-prescription patterns in community-acquired infections and nosocomial infections were analyzed separately and compared. We compared the impact on mortality of empiric antibiotic treatment, including antibiotics with different mechanisms of action, termed different-class combination therapy (DCCT), with that of monotherapy and any other combination therapy possibilities (non-DCCT). RESULTS: We included 1,372 patients, 1,022 (74.5%) of whom had community-acquired sepsis and 350 (25.5%) of whom had nosocomial sepsis. The most frequently prescribed antibiotic agents were ß-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to 388 patients (28.3%), whereas non-DCCT was administered to 984 (71.7%). The mortality rate was significantly lower in patients administered DCCTs than in those who were administered non-DCCTs (34% versus 40%; P = 0.042). The variables independently associated with mortality were age, male sex, APACHE II score, and community origin of the infection. DCCT was a protective factor against in-hospital mortality (odds ratio (OR), 0.699; 95% confidence interval (CI), 0.522 to 0.936; P = 0.016), as was urologic focus of infection (OR, 0.241; 95% CI, 0.102 to 0.569; P = 0.001). CONCLUSIONS: ß-Lactams, including carbapenems, are the most frequently prescribed antibiotics in empiric therapy in patients with severe sepsis and septic shock. Administering a combination of antimicrobials with different mechanisms of action is associated with decreased mortality.

Papel de daptomicina en el tratamiento empírico y dirigido de infecciones por cocos grampositivos del paciente crítico / Role of daptomycin in the empirical and directed therapy of infections caused by Grampositive bacteria in the critically ill patient

Las infecciones graves causadas por bacterias grampositivas son un problema grave y que se asocia a una elevada mortalidad. Entre ellas, hay que resaltar las causadas por Staphylococcus aureus resistente a meticilina siendo la bacteriemia primaria o asociada a catéter o a endocarditis las principales presentaciones. Vancomicina ha sido tradicionalmente el tratamiento de elección para estas infecciones pero su actividad no es satisfactoria especialmente en caso de SARM con concentración mínima inhibitoria (CMI) > 1mg/L. Daptomicina es un antibiótico lipopéptido cuyo espectro de acción son las bacterias grampositivas incluyendo SARM y Enterococcus spp resistente a glucopéptido. Destacar también que frente a S. aureus sensible a meticilina, daptomicina es rápidamente bactericida y más activo que vancomicina y al menos tan activo como las penicilinas isoxazólicas, En el presente artículo se discute el papel de este antibiótico en el tratamiento empírico y dirigido de las infecciones por bacterias grampositivas que afectan a los pacientes críticos(AU)

Infections caused by Gram-positive bacteria are a serious problem and is associated with high mortality. Among them, we should highlight those caused by methicillin-resistant Staphylococcus aureus (MRSA). Primary bacteremia, catheterrelated bloodstream infections and constitute the main presentations. Vancomycin has traditionally been the treatment of choice for these infections, but its activity is not satisfactory especially in cases of MRSA with minimum inhibitory concentration (MIC) > 1 mg/L. Daptomycin is a lipopeptide antibiotic active against Gram-positive bacteria including MRSA and glycopeptide-resistant Enterococcus spp. It is worth mentioning that daptomycin is rapidly bactericidal against methicillin-sensitive S. aureus, more potent than vancomycin and at least as active as isoxazole penicillins. This article discusses the role of this antibiotic in the empirical treatment of infections and directed by Gram-positive bacteria affecting critically ill patients(AU)

Uso prudente de antibióticos y propuestas de mejora desde la medicina hospitalaria / Prudent use of antibiotics and suggestions for improvement from hospital-based medicine

En el hospital, y dentro de él en las unidades de cuidados intensivos, se concentra la mayor densidad de consumo de antimicrobianos. La calidad del uso de antimicrobianos no es óptima, hasta el 50% de las prescripciones son innecesarias o inapropiadas. Las consecuencias del uso inapropiado son muy graves, incrementa la mortalidad y la morbilidad de los pacientes, y las resistencias microbianas. Y la razón fundamental del uso inapropiado es el conocimiento insuficiente de la cada vez más ingente y compleja información acerca del diagnóstico y el tratamiento de las enfermedades infecciosas. Hay acuerdo general en la necesidad de mejorar el uso de antimicrobianos en los hospitales, pero no en cómo hacerlo. El Hospital Universitario Virgen del Rocío (Sevilla) ha puesto en marcha el Programa Institucional para la Optimización del Tratamiento Antimicrobiano (PRIOAM), inspirado en las recomendaciones de la Sociedad Americana de Enfermedades Infecciosas, y adaptado a las características estructurales, funcionales y culturales del Hospital. El PRIOAM está coordinado por un equipo multidisciplinar elegido por la Comisión de Infecciones y Antimicrobianos y tiene 3 características básicas: es un programa institucional y con incentivos ligados a la consecución de objetivos; es un programa educativo, porque la formación y el conocimiento son la base para el buen uso de los antimicrobianos, y es un programa sujeto a resultados, en el que el objetivo principal es clínico, no económico, reducir la mortalidad y la morbilidad de los pacientes con infecciones y retrasar el desarrollo de resistencias

The largest consumption of antimicrobials is concentrated in hospitals and within them, the intensive care units. The quality of antimicrobial use is not optimal, with up to 50% of prescriptions being unnecessary or inappropriate. Inappropiate antibiotic use leads to severe consequences, such as increased patient mortality and morbidity and bacterial resistance. The primary reason for inappropriate use is the insufficient knowledge of the increasingly vast and complex information about the diagnosis and treatment of infectious diseases. There is general agreement on the need to improve the use of antimicrobials in hospitals but not on how to improve it. University Hospital Virgen del Rocío (Seville) has launched the Institutional Programme for the Optimisation of Antimicrobial Treatment (PRIOAM), inspired by the recommendations of the Infectious Diseases Society of America and adapted to the structural, functional and cultural characteristics of the hospital. PRIOAM is coordinated by a multidisciplinary team chosen by the Committee on Infections and Antimicrobials and has three basic characteristics: it is an institutional programme that has incentives linked to achieving goals; it is an educational programme in which training and knowledge are the basis for the proper use of antimicrobials; and it is a programme subject to results, in which the main objectives are clinical, not economic, to reduce mortality and morbidity in patients with infections and to delay the development of resistance

Risk factors for fluconazole-resistant candidemia.

Previous studies have sought to determine the risk factors associated with candidemia caused by non-albicans Candida spp. or with potentially fluconazole-resistant Candida spp. (C. glabrata and C. krusei). Non-albicans Candida strains are a heterogeneous group that includes species with different levels of virulence, and only a limited number of C. glabrata isolates are resistant to fluconazole. We set out to identify the risk factors associated with microbiologically proven fluconazole-resistant candidemia. A prospective study including adult patients with candidemia was performed. Data were collected on patient demographics; underlying diseases; exposure to corticosteroids, antibiotics, or fluconazole; and invasive procedures. Risk factors associated either with non-albicans Candida spp. or potentially fluconazole-resistant Candida spp. (C. glabrata or C. krusei) or with Candida spp. with microbiologically confirmed fluconazole resistance were assessed using logistic regressions. We included 226 candidemia episodes. Non-albicans Candida isolates accounted for 53.1% of the fungal isolates, but only 18.2% of the cases were caused by potentially fluconazole-resistant organisms. Thirty isolates exhibited microbiologically confirmed fluconazole resistance. The multivariate analysis revealed that independent predictors associated with fluconazole-resistant Candida spp. were neutropenia (odds ratio [OR]=4.94; 95% confidence interval [CI]=1.50 to 16.20; P=0.008), chronic renal disease (OR=4.82; 95% CI=1.47 to 15.88; P=0.01), and previous fluconazole exposure (OR=5.09; 95% CI=1.66 to 15.6; P=0.004). Independently significant variables associated with non-albicans Candida bloodstream infection or with potentially fluconazole-resistant Candida spp. did not include previous fluconazole exposure. We concluded that prior fluconazole treatment is an independent risk factor only for candidemia caused by microbiologically confirmed fluconazole resistant species. Our findings may be of value for selecting empirical antifungal therapy.

[Prudent use of antibiotics and suggestions for improvement from hospital-based medicine]. / Uso prudente de antibióticos y propuestas de mejora desde la medicina hospitalaria.

The largest consumption of antimicrobials is concentrated in hospitals and within them, the intensive care units. The quality of antimicrobial use is not optimal, with up to 50% of prescriptions being unnecessary or inappropriate. Inappropriate antibiotic use leads to severe consequences, such as increased patient mortality and morbidity and bacterial resistance. The primary reason for inappropriate use is the insufficient knowledge of the increasingly vast and complex information about the diagnosis and treatment of infectious diseases. There is general agreement on the need to improve the use of antimicrobials in hospitals but not on how to improve it. University Hospital Virgen del Rocío (Seville) has launched the Institutional Programme for the Optimisation of Antimicrobial Treatment (PRIOAM), inspired by the recommendations of the Infectious Diseases Society of America and adapted to the structural, functional and cultural characteristics of the hospital. PRIOAM is coordinated by a multidisciplinary team chosen by the Committee on Infections and Antimicrobials and has three basic characteristics: it is an institutional programme that has incentives linked to achieving goals; it is an educational programme in which training and knowledge are the basis for the proper use of antimicrobials; and it is a programme subject to results, in which the main objectives are clinical, not economic, to reduce mortality and morbidity in patients with infections and to delay the development of resistance.

Risk factors and prognosis of catheter-related bloodstream infection in critically ill patients: a multicenter study.

OBJECTIVE: To assess the risk factors associated with CR-BSI development in critically ill patients with non-tunneled, non-cuffed central venous catheters (CVC) and the prognosis of the episodes of CR-BSI. Design and setting; prospective, observational, multicenter study in nine Spanish Hospitals. PATIENTS: All subjects admitted to the participating ICUs from October 2004 to June 2005 with a CVC. INTERVENTIONS: None. MEASUREMENT AND RESULTS: Overall, 1,366 patients were enrolled and 2,101 catheters were analyzed. Sixty-six episodes of CR-BSI were diagnosed. The incidence of CR-BSI was significantly higher in CVC compared with peripherically inserted central venous catheters (PICVC) without significant differences among the three locations of CVC. In the multivariate analysis, duration of catheterization and change over a guidewire were the independent variables associated with the development of CR-BSI whereas the use of a PICVC was a protective factor. Excluding PICVC, 1,598 conventional CVC were analyzed. In this subset, duration of catheterization, tracheostomy and change over a guidewire were independent risk factors for CR-BSI. A multivariate analysis of predictors for mortality among 66 patients with CRSI showed that early removal of the catheter was a protective factor and APACHE II score at the admission was a strong determinant of in-hospital mortality. CONCLUSIONS: Peripherically inserted central venous catheters is associated with a lower incidence of CR-BSI in critically ill patients. Exchange over a guidewire of CVC and duration of catheterization are strong contributors to CR-BSI. Our results reinforce the importance of early catheter removal in critically ill patients with CR-BSI.

Mortality and morbidity attributable to inadequate empirical antimicrobial therapy in patients admitted to the ICU with sepsis: a matched cohort study.

OBJECTIVES: To determine the attributable mortality and excess length of stay (LOS) associated with the use of inadequate empirical antimicrobial therapy in patients with sepsis at admission to the intensive care unit (ICU). METHODS: A retrospective matched cohort study was performed using a prospectively collected database at a 40 bed general ICU at a university public hospital. Patients who received inadequate antimicrobial therapy at admission to the ICU (exposed) were matched with controls (unexposed) on the basis of origin of sepsis, inflammatory response at admission, surgical or medical status, hospital- or community-acquired sepsis, APACHE II score (+/-2 points) and age (+/-10 years). Clinical outcome was assessed by in-hospital mortality, and this analysis was also performed in those pairs without nosocomial infection in the ICU. RESULTS: Eighty-seven pairs were successfully matched. Fifty-nine exposed patients died [67.8% mortality (95% CI, 58.0-77.6%)] and 25 unexposed controls died [28.7% mortality (95% CI, 19.2-38.2%)] (P < 0.001). Excess in-hospital mortality was estimated to be 39.1%. The rate of nosocomial infection was significantly higher in patients with inadequate empirical therapy (16.1%) than in those treated empirically with adequate antibiotics (3.4%) (P = 0.013). Excess in-hospital mortality was 31.4% after excluding those 17 pairs that developed a nosocomial infection in the ICU. Inadequate antimicrobial therapy was associated with a significant increment in duration of hospitalization (15 days in surviving pairs). CONCLUSIONS: Inadequate antimicrobial therapy at admission to the ICU with sepsis is associated with excess mortality and increases LOS.

Timing of adequate antibiotic therapy is a greater determinant of outcome than are TNF and IL-10 polymorphisms in patients with sepsis.

INTRODUCTION: Genetic variations may influence clinical outcomes in patients with sepsis. The present study was conducted to evaluate the impact on mortality of three polymorphisms after adjusting for confounding variables, and to assess the factors involved in progression of the inflammatory response in septic patients. METHOD: The inception cohort study included all Caucasian adults admitted to the hospital with sepsis. Sepsis severity, microbiological information and clinical variables were recorded. Three polymorphisms were identified in all patients by PCR: the tumour necrosis factor (TNF)-alpha 308 promoter polymorphism; the polymorphism in the first intron of the TNF-beta gene; and the IL-10-1082 promoter polymorphism. Patients included in the study were followed up for 90 days after hospital admission. RESULTS: A group of 224 patients was enrolled in the present study. We did not find a significant association among any of the three polymorphisms and mortality or worsening inflammatory response. By multivariate logistic regression analysis, only two factors were independently associated with mortality, namely Acute Physiology and Chronic Health Evaluation (APACHE) II score and delayed initiation of adequate antibiotic therapy. In septic shock patients (n = 114), the delay in initiation of adequate antibiotic therapy was the only independent predictor of mortality. Risk factors for impairment in inflammatory response were APACHE II score, positive blood culture and delayed initiation of adequate antibiotic therapy. CONCLUSION: This study emphasizes that prompt and adequate antibiotic therapy is the cornerstone of therapy in sepsis. The three polymorphisms evaluated in the present study appear not to influence the outcome of patients admitted to the hospital with sepsis.

Isolation of Aspergillus spp. from the respiratory tract in critically ill patients: risk factors, clinical presentation and outcome.

INTRODUCTION: Our aims were to assess risk factors, clinical features, management and outcomes in critically ill patients in whom Aspergillus spp. were isolated from respiratory secretions, using a database from a study designed to assess fungal infections. METHODS: A multicentre prospective study was conducted over a 9-month period in 73 intensive care units (ICUs) and included patients with an ICU stay longer than 7 days. Tracheal aspirate and urine samples, and oropharyngeal and gastric swabs were collected and cultured each week. On admission to the ICU and at the initiation of antifungal therapy, the severity of illness was evaluated using the Acute Physiology and Chronic Health Evaluation II score. Retrospectively, isolation of Aspergillus spp. was considered to reflect colonization if the patient did not fulfil criteria for pneumonia, and infection if the patient met criteria for pulmonary infection and if the clinician in charge considered the isolation to be clinically valuable. Risk factors, antifungal use and duration of therapy were noted. RESULTS: Out of a total of 1756 patients, Aspergillus spp. were recovered in 36. Treatment with steroids (odds ratio = 4.5) and chronic obstructive pulmonary disease (odds ratio = 2.9) were significantly associated with Aspergillus spp. isolation in multivariate analysis. In 14 patients isolation of Aspergillus spp. was interpreted as colonization, in 20 it was interpreted as invasive aspergillosis, and two cases were not classified. The mortality rates were 50% in the colonization group and 80% in the invasive infection group. Autopsy was performed in five patients with clinically suspected infection and confirmed the diagnosis in all of these cases. CONCLUSION: In critically ill patients, treatment should be considered if features of pulmonary infection are present and Aspergillus spp. are isolated from respiratory secretions.

Effect of critical illness polyneuropathy on the withdrawal from mechanical ventilation and the length of stay in septic patients.

OBJECTIVES: No previous study has demonstrated whether critical illness polyneuropathy itself lengthens mechanical ventilation or whether this prolonged duration of ventilatory support is explained by concomitant risk factors for weaning failure. Our objectives were to evaluate the impact of critical illness polyneuropathy on the length of mechanical ventilation after controlling for coexisting risk factors for weaning failure and to assess the impact of critical illness polyneuropathy on the length of the stay in a cohort of septic patients. DESIGN: Prospective cohort study. SETTING: Intensive care unit of a tertiary hospital. PATIENTS: All patients with severe sepsis or septic shock who required mechanical ventilation for > or =7 days who were considered ready to discontinue mechanical ventilation. INTERVENTIONS: Patients underwent a neurophysiologic evaluation at onset of weaning from mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Sixty-four critically ill septic patients were enrolled, and 34 developed critical illness polyneuropathy (53.1%; 95% confidence interval, 40.2-65.7%). Length of mechanical ventilation was significantly higher in patients who had developed critical illness polyneuropathy (median 34 days vs. 14 days, p < .001). The duration of the weaning period was also significantly greater in patients with critical illness polyneuropathy (median 15 days vs. 2 days, p < .001) even though factors suspected to influence the weaning process did not differ between these two groups. Multiple logistic regression analysis indicated that critical illness polyneuropathy was the only risk factor independently associated with weaning failure (odds ratio, 15.4; 95% confidence interval, 4.55, 52.3; p < .001). Lengths of intensive care unit and hospital stays were significantly higher in patients with critical illness polyneuropathy. CONCLUSIONS: In critically ill septic patients, critical illness polyneuropathy significantly increases the duration of mechanical ventilation and prolongs the lengths of intensive care unit and hospital stays.

Steroid-induced myopathy in patients intubated due to exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE: To determine incidence, risk factors and impact on various outcome parameters of the development of acute quadriplegic myopathy in a selected population of critically ill patients. SETTING: A prospective cohort study carried out in the intensive care unit of a tertiary-level university hospital. PATIENTS: All patients admitted due to acute exacerbation of chronic obstructive pulmonary disease who required intubation and mechanical ventilation, and received high doses of intravenous corticosteroids. INTERVENTIONS: A neurophysiological study was performed in all cases at the onset of weaning. Muscular biopsy was taken when the neurophysiological study revealed a myopathic pattern. MEASUREMENTS AND RESULTS: Twenty-six patients were enrolled in the study. Nine patients (34.6%) developed myopathy. Only seven patients were treated with muscle relaxants. Histology confirmed the diagnosis in the three patients who underwent muscle biopsy. APACHE II score at admission, the rate of sepsis and the total doses of corticosteroids were significantly higher in patients with myopathy compared with those patients that did not develop it. Myopathy is associated with an increase in the duration of mechanical ventilation [15.4 (9.2) versus 5.7 (3.9) days; p<0.006], the length of ICU stay [23.6 (10.7) versus 11.4 (7.05) days; p<0.003] and hospital stay [33.3 (19.2) versus 21.2 (16.1) days; p<0.034)]. Myopathy was not associated with increased mortality. CONCLUSIONS: In the population under study, severity of illness at admission, the development of sepsis and the total dose of corticosteroids are factors associated with the occurrence of myopathy after the administration of corticosteroids. Myopathy was associated with prolonged mechanical ventilation and in-hospital stay.

Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis.

OBJECTIVES: Our primary goal was to evaluate the impact on in-hospital mortality rate of adequate empirical antibiotic therapy, after controlling for confounding variables, in a cohort of patients admitted to the intensive care unit (ICU) with sepsis. The impact of adequate empirical antibiotic therapy on early (<3 days), 28-day, and 60-day mortality rates also was assessed. We determined the risk factors for inadequate empirical antibiotic therapy. DESIGN Prospective cohort study. SETTING: ICU of a tertiary hospital. PATIENTS: All the patients meeting criteria for sepsis at admission to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four hundred and six patients were included. Microbiological documentation of sepsis was obtained in 67% of the patients. At ICU admission, sepsis was present in 105 patients (25.9%), severe sepsis in 116 (28.6%), and septic shock in 185 (45.6%). By multivariate analysis, predictors of in-hospital mortality were Sepsis-related Organ Failure Assessment (SOFA) score at ICU admission (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.19-1.40), the increase in SOFA score over the first 3 days in the ICU (OR, 1.40; 95% CI, 1.19-1.65), respiratory failure within the first 24 hrs in the ICU (OR, 3.12; 95% CI, 1.54-6.33), and inadequate empirical antimicrobial therapy in patients with "nonsurgical sepsis" (OR, 8.14; 95% CI, 1.98-33.5), whereas adequate empirical antimicrobial therapy in "surgical sepsis" (OR, 0.37; 95% CI, 0.18-0.77) and urologic sepsis (OR, 0.14; 95% CI, 0.05-0.41) was a protective factor. Regarding early mortality (<3 days), factors associated with fatality were immunosuppression (OR, 4.57; 95% CI, 1.69-13.87), chronic cardiac failure (OR, 9.83; 95% CI, 1.98-48.69) renal failure within the first 24 hrs in the unit (OR, 8.63; 95% CI, 3.31-22.46), and respiratory failure within the first 24 hrs in the ICU (OR, 12.35; 95% CI, 4.50-33.85). Fungal infection (OR, 47.32; 95% CI, 5.56-200.97) and previous antibiotic therapy within the last month (OR, 2.23; 95% CI, 1.1-5.45) were independent variables related to administration of inadequate antibiotic therapy. CONCLUSIONS: In patients admitted to the ICU for sepsis, the adequacy of initial empirical antimicrobial treatment is crucial in terms of outcome, although early mortality rate was unaffected by the appropriateness of empirical antibiotic therapy.

Immunonutrition in the intensive care unit. A systematic review and consensus statement.

OBJECTIVE: To systematically review the effects of enteral nutrition with pharmaconutrients-enriched diets in critically ill patients and to establish recommendations for their use. DATA SOURCES: Computerized bibliographic search of published research and citation review of relevant articles. STUDY SELECTION: Randomized clinical trials of critically ill patients treated with enteral nutrition comparing diets enriched with pharmaconutrients vs not enriched diets were included. Infectious complications and outcome variables (days on mechanical ventilation, ICU and hospital length of stay and mortality) were evaluated. Studies were classified in four subgroups according to the patient's primary diagnosis: surgical, trauma, burned or medical. DATA EXTRACTION: A group of experts in methodology performed data extraction and statistical processes. A global analysis of the studies was done and also a separate study for each subgroup. Results of the meta-analysis were discussed within a 'clinical group' of clinicians with experience in the nutritional support of ICU patients, in order to find agreement about recommendations for the use of pharmaconutrients-enriched diets in critically ill patients. RESULTS: Independent review of 267 articles identified 26 relevant primary studies. Global results indicate that there was a reduction in infection rate in the pharmaconutrition group, considering the appreciated lower incidence in abdominal abscesses (OR: 0.26, CI: 0.12-0.55) (P=0.005), nosocomial pneumonia (OR: 0.54, CI: 0.35-0.84) (P=0.007) and bacteremia (OR: 0.45, CI: 0.35-0.84) (P=0.0002). Also, patients treated with pharmaconutrition diets have a reduction in time on mechanical ventilation (mean 2.25 days, CI: 0.5-3.9) (P=0.009), ICU length of stay (mean reduction of 1.6 days, CI: 1.9-1.2) (P<0.0001) and hospital length of stay (mean reduction of 3.4 days, CI: 4.0-2.7) (P<0.0001). No effects were appreciated on mortality (OR: 1.10, CI: 0.85-1.42) (P=0.5). Nevertheless, the separate analysis for each subgroup showed that the reported beneficial effects were not the same for each patient population. Also, the clinician panel of experts identifies several problems in the published data about enteral pharmaconutrition in critically ill patients. In spite of the subgroup differences and of the problems detected, the clinician group considered that the appreciated results could support a Grade B recommendation for the use of these formulas in ICU patients. CONCLUSIONS: Considering the beneficial effects and the absence of detrimental ones, the use of diets enriched with pharmaconutrients could be recommended in ICU patients requiring enteral feeding. Nevertheless, more investigation is needed in this field in order to find the more appropriate population of patients that can benefit from this nutritional therapy.