Enteral fluconazole is well absorbed in critically ill surgical patients

BACKGROUND: Enteral fluconazole, a triazole antifungal agent with an excellent oral bioavailability, has not been widely studied in critically ill surgical patients. METHODS: During a randomized placebo-controlled trial of enteral fluconazole (N = 130) versus placebo (N = 130) for the prevention of fungal infections in critically ill surgical patients, trough fluconazole levels were measured after the loading dose and 3 times weekly during intensive care unit stay. Minimum inhibitory concentrations (MICs) for fluconazole were measured on all infecting Candida isolates. RESULTS: Four hundred sixty-seven serum samples were assayed for fluconazole levels in 121 patients. The most common infecting fungal species was Candida albicans, isolated in 14 of 31 infections (45%). Other infecting species were C glabrata, C tropicalis, and C parapsilosis. Mean fluconazole levels were above the highest MIC for C albicans and C parapsilosis in all but 5 patients (4%). Mean fluconazole levels were below the median MIC for C glabrata in 93 of 121 patients (77%). No significant relationship was seen between fluconazole levels and risk for fungal infection. CONCLUSIONS: Serum fluconazole levels are above the MIC of most yeast species found in these patients. These levels may not be above the MIC of C glabrata, the second most common Candida isolate causing infection in this study.     

Effects of fluconazole administration in critically ill patients: analysis of bacterial and fungal resistance

HYPOTHESIS: The administration of fluconazole in intensive care unit (ICU) patients leads to the emergence of bacterial and fungal resistance. DESIGN: Retrospective analysis of 2 patient cohorts: (1) critically ill patients treated in surgical, trauma, and medical ICUs between June 1997 and January 1999 who did and did not receive fluconazole; and (2) ICU patients with fungal infections and sensitivity testing results from June 1994 to December 1998. SETTING: University-affiliated tertiary care hospital. PATIENTS: The first cohort included 99 ICU patients with documented microorganism culture(s) who were treated with (n = 50) or without (n = 49) fluconazole; the second cohort included 38 patients with Candida species infection, identification, and antifungal susceptibility testing. RESULTS: Mortality (40% vs 20%; P = .03) and hospital length of stay (33.8 vs 25.6 days; P = .04) were higher in the patients treated with fluconazole compared with patients not treated with fluconazole. The ICU length of stay was also higher in patients treated with fluconazole (23.7 vs 15.1 days; P = .009). An increase in bacterial resistance occurred in patients after fluconazole treatment as opposed to bacterial resistance of patients who were treated for bacterial microorganism(s) without fluconazole (16% vs 4%; P = .049). Comparison of patient populations with Candida species identification before and after December 1997 showed an increase in Candida species resistance to fluconazole (11% vs 36%; P = .16), respectively. Fungal strains were dominated by a combination of Candida albicans and Candida glabrata in both populations (60% [before 1998] vs 82% [after 1998]), with an emergence of Candida non-albicans species tolerant to fluconazole. The amount of fluconazole administered and the number of patients receiving fluconazole treatment in the ICUs has also increased when comparing both periods. CONCLUSIONS: Comparison of critically ill patient populations with and without fluconazole treatment found increased mortality and longer hospital and ICU lengths of stay in the fluconazole-treated group. This group also had higher bacterial pathogen resistance to antibiotics after fluconazole administration compared with bacterial resistance of patients without fluconazole treatment. Our results warrant concern regarding worsening bacterial infections, increased mortality, and an increase in Candida resistance to fluconazole from increased use in ICU patients, with a shift in yeast infection that is more difficult to treat.     

Randomized,prospective trial of antioxidant supplementation in critically ill surgical patients

OBJECTIVE: To determine the effectiveness of early, routine antioxidant supplementation using alpha-tocopherol and ascorbic acid in reducing the rate of pulmonary morbidity and organ dysfunction in critically ill surgical patients. SUMMARY BACKGROUND DATA: Oxidative stress has been associated with the development of the acute respiratory distress syndrome (ARDS) and organ failure through direct tissue injury and activation of genes integral to the inflammatory response. In addition, depletion of endogenous antioxidants has been associated with an increased risk of nosocomial infections. The authors postulated that antioxidant supplementation in critically ill surgical patients may reduce the incidence of ARDS, pneumonia, and organ dysfunction. METHODS: This randomized, prospective study was conducted to compare outcomes in patients receiving antioxidant supplementation (alpha-tocopherol and ascorbate) versus those receiving standard care. The primary endpoint for analysis was pulmonary morbidity (a composite measure of ARDS and nosocomial pneumonia). Secondary endpoints included the development of multiple organ failure, duration of mechanical ventilation, length of ICU stay, and mortality. RESULTS: Five hundred ninety-five patients were enrolled and analyzed, 91% of whom were victims of trauma. The relative risk of pulmonary morbidity was 0.81 (95% confidence interval 0.60-1.1) in patients receiving antioxidant supplementation. Multiple organ failure was significantly less likely to occur in patients receiving antioxidants than in patients receiving standard care, with a relative risk of 0.43 (95% confidence interval 0.19-0.96). Patients randomized to antioxidant supplementation also had a shorter duration of mechanical ventilation and length of ICU stay. CONCLUSIONS: The early administration of antioxidant supplementation using alpha-tocopherol and ascorbic acid reduces the incidence of organ failure and shortens ICU length of stay in this cohort of critically ill surgical patients.     

Increased resource use associated with catheter-related bloodstream infection in the surgical intensive care unit

HYPOTHESIS: Catheter-related bloodstream infection (CRBSI) in critically ill surgical patients with prolonged intensive care unit (ICU) stays is associated with a significant increase in health care resource use. DESIGN: Prospective cohort study. SETTING: Surgical ICU at a large tertiary care center. PATIENTS: Critically ill surgical patients (N = 260) with projected surgical ICU length of stay greater than 3 days. INTERVENTIONS: Central venous catheters were cultured for clinical suspicion of infection. MAIN OUTCOME MEASURES: Increases in total hospital cost, ICU cost, hospital days, and ICU days attributable to CRBSI were estimated using multiple linear regression after adjusting for demographic factors and severity of illness (APACHE III [Apache Physiology and Chronic Health Evaluation III] score). RESULTS: The incidence of CRBSI per 1000 catheter-days was 3.6 episodes (95% confidence interval [CI], 2.1-5.8 episodes). Microbiologic isolates were Gram-positive bacteria in 75%, Gram-negative bacteria in 20%, and yeast in 5%. After adjusting for demographic factors and severity of disease, CRBSI was associated with an increase of $56 167 (95% CI, $11 523-$165 735; P =.001) (in 1998 dollars) in total hospital cost, an increase of $71 443 (95% CI, $11 960-$195 628; P<.001) in ICU cost, a 22-day increase in hospital length of stay, and a 20-day increase in ICU length of stay. CONCLUSIONS: For critically ill surgical patients, CRBSI is associated with a profound increase in resource use. Prevention, early diagnosis, and intervention for CRBSI might result in cost savings in this high-risk population.     

Infection in the critically ill surgical patient

After surgery, critically ill patients in the intensive care unit (ICU) may acquire infections which differ from those acquired elsewhere with regard to the anatomical site involved and the causative micro-organisms. Specific risk factors for infection in the ICU have been shown to be associated with exposure to invasive devices and the use of broad-spectrum antibiotic treatment. Control of infection depends on the timely suspicion of its presence and the identification of the potential anatomical source of infection. Furthermore, the collection of adequate fluid samples for cultures before any anti-microbial treatment is introduced is paramount in order to identify responsible microbes correctly and to re-adjust therapy subsequently. It should be stressed that, when empirical anti-microbial therapy is started before micro-organism identification, the initial treatment will be appropriate only in half of the cases. Gram-negative bacteria of the Pseudomonas aeruginosa and Enterobacter cloaca strains remain the leading cause of nosocomial infection in the ICU. Other pathogens which have caused concern in ICU patients over the past decade are Staphylococcus aureus and fungal infection mainly of theCandida spp.This chapter reviews the more common infections encountered in the high-risk surgical patients in the ICU according to the anatomical localization of the infection, i.e. respiratory, abdominal, urinary, wound and bloodstream infections.     

Fungal infections

Systemic fungal infections are a rapidly increasing problem in critically ill patients and rates have increased significantly in the past 20 years. They represent a major cause of morbidity and mortality in a variety of hospitalized patients including those in neonatal and intensive care units. This trend concerns not only severely compromised hosts such as transplant recipients, neutropenic and HIV-positive patients, but also and non-compromised patients, on intensive care units (ICU) with specific risk factors for infection.     

Longitudinal outcomes of intra-abdominal infection complicated by critical illness

BACKGROUND: Critically ill surgical patients remain at high risk of adverse outcomes as a result of intra-abdominal infections, including prolonged length of stay, organ dysfunction, and death despite advances in critical care and innovations in management of the peritoneal cavity. We evaluated the causes and consequences of intra-abdominal infections among critically ill surgical patients in a single tertiary-care intensive care unit (ICU) over a decade. METHODS: Prospective study of 465 critically ill surgical patients with hollow viscus perforation and peritonitis or abscess from 1991-2002. Data collected were age, gender, admission APACHE III score, multiple organ dysfunction score, ICU and hospital length of stay, abscess (yes/no), site and type of perforation (colon vs. other), de novo vs. nosocomial origin, and mortality. Statistical analysis was by univariate ANOVA for coordinate data, Fisher exact test for continuous data, and logistic regression analysis. RESULTS: The incidence of intra-abdominal infection was 5.75%, 73.7% of the patients developed organ dysfunction, and mortality was 22.6%. Females comprised 46.8% of the patients. De novo infection represented 71.8% of cases, whereas nosocomial infection comprised 28.2% of cases. Perforations were of the colon (including the appendix) 49.9% of the time. An abscess formed in 22.3% of patients; the remainder had peritonitis but no abscess. Patients in the cohort with peritonitis were older (p = 0.0157), sicker on admission (p = 0.0411) and developed more organ dysfunction (p = 0.0072), but had the same rate of mortality. Despite steadily increasing acuity since 1991 (r(2) = .71, p < 0.0001), the magnitude of organ dysfunction (r(2) = 0.11) and the mortality rate remained constant (r(2) = .01). By logistic regression, abscess correlated with less severe organ dysfunction (score > or = 5 [odds ratio 0.54, 95% CI 0.33-0.90] and > or =9 points [odds ratio 0.38, 95% CI 0.20-0.74]), and increasing magnitude of organ dysfunction was associated with mortality (each point [odds ratio 1.46, 95% CI 1.32-1.61]). CONCLUSIONS: Although outcomes are improving, generalized peritonitis still causes high organ dysfunction-related mortality among critically ill surgical patients. Further improvements in resuscitation, surgical technique, and pharmacotherapy of severe intra-abdominal infections are needed.     

Incidence of fungal infections in a solid organ recipients dedicated intensive care unit

Invasive fungal infections are a significant cause of morbidity and mortality for patients undergoing solid organ transplantation. Our aim was to evaluate the incidence of invasive fungal infections in solid organ recipients within a dedicated intensive care unit (ICU). MATERIALS AND METHODS: From May 2002 to May 2005, 278 patients undergoing solid organ transplantation (105 liver, 142 kidney, 20 lung, 2 combined liver-kidney, 9 combined pancreas-kidney) were admitted to our posttransplant intensive care unit. We retrospectively analyzed data obtained from the ICU stay. Fungal infection was defined by positivity of normally sterile biological samples and by elevated positivity of normally non sterile biological samples. We did not consider superficial fungal infections and asymptomatic colonizations. RESULTS: Forty-six patients (16.5%) developed a fungal infection; at least one mycotic agent was isolated from each patient. Candida albicans was the most common pathogen, isolated from 71 % of infected patients (33 of 46). Infected patients showed a mortality rate of 35%, while that for non infected recipients was 3.5%. Total length of ICU stay was the most significant risk factor among infected patients (30.26 days vs 5.04 days P < .0001). Mean time between transplantation and first positive samples was 6.17 days (SD 8.88). CONCLUSION: Fungal infections in solid organ transplant patients are a major issue because of their associated morbidity and mortality. Candida albicans was the most common pathogen and total length of ICU stay was the most important risk factor.     

外科重症患者早期肠内营养误吸状况及影响因素研究

目的探讨重症患者早期肠内营养误吸发生现况及影响因素,为临床护理干预提供参考。方法采用便利抽样法,选取实施早期肠内营养的外科重症患者,动态监测并记录患者从实施肠内营养开始7 d内误吸情况,采用Logistic回归分析误吸发生的影响因素。结果共纳入126例患者,发生误吸30例(23.81%)。误吸组第7天目标热量达标率显著低于无误吸组,住院时间、住院费用显著高于无误吸组(均P<0.01)。APACHEⅡ评分、意识状况、营养风险、鼻饲管置入长度是外科重症患者误吸的危险因素(P<0.05,P<0.01)。结论重症患者早期肠内营养误吸发生率较高,与患者意识、营养状态、疾病程度和鼻饲管置入长度相关。应针对误吸危险因素采取针对性措施防范重症患者肠内营养误吸。     

Surveillance strategies and impact of vancomycin-resistant enterococcal colonization and infection in critically ill patients

OBJECTIVE: To determine the optimal site and frequency for vancomycin-resistant enterococci (VRE) surveillance to minimize the number of days of VRE colonization before identification and subsequent isolation. SUMMARY BACKGROUND DATA: The increasing prevalence of VRE and the limited therapeutic options for its treatment demand early identification of colonization to prevent transmission. METHODS: The authors conducted a 3-month prospective observational study in medical and surgical intensive care unit (ICU) patients with a stay of 3 days or more. Oropharyngeal and rectal swabs, tracheal and gastric aspirates, and urine specimens were cultured for VRE on admission to the ICU and twice weekly until discharge. RESULTS: Of 117 evaluable patients, 23 (20%) were colonized by VRE. Twelve patients (10%) had VRE infection. Of nine patients who developed infections after ICU admission, eight were colonized before infection. The rectum was the first site of colonization in 92% of patients, and positive rectal cultures preceded 89% of infections acquired in the ICU. This was supported by strain delineations using pulsed-field gel electrophoresis. Twice-weekly rectal surveillance alone identified 93% of the maximal estimated VRE-related patient-days; weekly or admission-only surveillance was less effective. As a test for future VRE infection, rectal surveillance culture twice weekly had a negative predictive value of 99%, a positive predictive value of 44%, and a relative risk for infection of 34. CONCLUSIONS: Twice-weekly rectal VRE surveillance of critically ill patients is an effective strategy for early identification of colonized patients at increased risk for VRE transmission, infection, and death.     

Higher body mass index predicts need for insulin but not hyperglycemia, nosocomial infection, or death in critically ill surgical patients

BACKGROUND: Strict glycemic control in critically ill patients has been an important advance in surgical critical care, as hyperglycemia is associated with a higher likelihood of death, complications, and nosocomial infections. Insulin resistance is particularly common in obese patients, but the impact of body mass index (BMI) on insulin requirements, ability to achieve euglycemia, and infectious outcomes in critically ill surgical patients has not been studied. We hypothesized that obese patients would not incur a higher likelihood of infection if euglycemia was maintained. METHODS: Admissions to the surgical intensive care unit (ICU) from October 1, 2004, to October 31, 2006, were identified. Necessary data were available for 946 patients. The main predictor variable was BMI, which was analyzed as both a continuous and a five-level categorical variable. Data on insulin requirements as well as glycemic control were captured. The main outcome variable was the occurrence of at least one nosocomial infection. Additional outcomes were dysfunction of at least one organ system at any time during surgical ICU admission, quantified using the Multiple Organ Dysfunction Score, as well as the ICU length of stay and death. All statistical analyses were performing using SPSS version 11 for Macintosh. RESULTS: Both the need for insulin infusion (p = 0.0001) and the mean insulin units/day among patients receiving infusions (p = 0.03) increased significantly with increasing BMI. However, periods of euglycemia were similar among BMI groups. A total of 152 patients (16.1%) incurred at least one nosocomial infection, for a total of 169 infections. The majority (n = 107; 63.3%) were ventilator-associated pneumonias. Neither infection (p = 0.99), organ dysfunction (p = 0.14), ICU length of stay (p = 0.22), nor mortality rate (p = 0.09) differed significantly by BMI group. The need for an insulin infusion was associated significantly with nosocomial infection (p = 0.0001). Additional predictors of infection were a higher Acute Physiology and Chronic Health Evaluation (APACHE) III score (p < 0.0001), age-adjusted APACHE III score (p < 0.0001), and emergency admission (0.001). After controlling for the need for an insulin infusion, BMI was not associated with infection. CONCLUSIONS: Increasing BMI was associated significantly with insulin resistance. Despite insulin resistance, however, obese patients did not incur longer periods of hyperglycemia. Outcomes that have been associated consistently with glycemic control, such as nosocomial infection and mortality rate, did not differ according to BMI. These data suggest that BMI is not associated with infection during critical illness, and that this absence of an association may be influenced at least partially by the ability to maintain similar glycemic control in obese and non-obese patients.     

Hyperglycemia in the intensive care unit: no longer just a marker of illness severity

BACKGROUND: Hyperglycemia is a common occurrence in critically ill patients. Recent evidence has demonstrated improved survival in patients in surgical intensive care units (SICUs) receiving "tight glycemic control." The mechanisms of this survival advantage are not well understood. METHODS: A review of the English language literature pertaining to potential mechanisms affecting outcome in critically ill patients receiving insulin therapy, including recently published human trials evaluating mortality outcomes. RESULTS: This review discusses the results of clinical trials of "tight glycemic control," considers mechanisms of hyperglycemia in critical illness, and reviews potential mechanisms of improved outcome related in the critically ill patient. CONCLUSIONS: A number of human studies have demonstrated improved outcomes in critically ill patient populations receiving insulin therapy with a target of euglycemia, suggesting at least part of the benefit of this therapy is normal blood sugar and not the effects of insulin. An important population not studied to date is patients in the medical ICU. However, aggressive control of hyperglycemia now remains an important component of care for all surgical patients in the ICU.     

Does enteral glutamine supplementation decrease infectious morbidity?

BACKGROUND: Although some studies have demonstrated lower infectious morbidity in patients receiving supplemental glutamine, there remains no consensus on the utility of such treatment. This study was designed to investigate the effects of supplemental enteral glutamine on the rate and outcomes of infection in critically ill surgical patients. METHODS: All 185 surgical and trauma patients admitted to a single university surgical trauma intensive care unit (STICU) over an approximately three-year period who were to receive enteral nutrition support were assigned sequentially to one of three diets: standard 1-kCal/mL feedings with added protein (Group 1), standard feedings with glutamine 0.6 g/kg per day (Group 2), or immune-modulated feedings with a similar amount of glutamine (Group 3). Group compositions and patient characteristics were similar at baseline. Data were collected prospectively on infections acquired during hospitalization. RESULTS: A total of 119 patients had at least one infection: 59% of the patients in Group 1, 64% of Group 2, and 69% of Group 3 (p = NS). There were no differences among the groups in the mean number of infections. The most common sites in all groups were the lungs, blood, and urine; and the frequencies of these infections did not differ between groups. Minor differences were found between groups in the organisms isolated. Antibiotic usage did not differ. CONCLUSION: Supplemental enteral glutamine in the dose studied does not appear to influence the acquisition or characteristics of infection in patients admitted to a mixed STICU.     

Daily evaluation of macroaspiration in the critically ill post-trauma patient

BACKGROUND: Although critically ill trauma patients represent a high-risk population for macroaspiration, studies of trauma patients have not been explored. The study aims were to quantify rate and associated risks of macroaspiration and explore the pattern of antibiotic use and incidence of aspiration pneumonia within this patient group. METHODS: Consecutive trauma patients admitted to the intensive care unit (ICU) were prospectively observed for development of macroaspiration and subsequent aspiration pneumonia. Daily monitoring included chart review, laboratory and radiography results, and nurse inquiries for witnessed macroaspiration events. RESULTS: Seven of 60 patients included experienced a clinically confirmed macroaspiration event (11.7%). The incidence of pneumonia was similar, regardless of macroaspiration occurrence (28.6%: macroaspiration cases vs 17.0%: controls, p > or = 0.05). Patients with macroaspiration required a longer duration of mechanical ventilation (15 vs 9.5 days, p = 0.021) and intensive care unit stay (28 vs 7 days, p = 0.015). Paralytic agent utilization was associated with an increased risk for aspiration (p = 0.045). CONCLUSIONS: The incidence of macroaspiration within a critically ill trauma population may be less frequent compared with studies performed in other patient populations. Although macroaspiration was associated with a longer duration of mechanical ventilation and intensive care unit stay, this condition may not be associated with an increased rate of pulmonary infection.     

The other fungi: it's not just Candida albicans anymore

Background: Candida albicans continues to be the fungus most often causing disease in surgical patients, but with the treatment of an increasing number of critically ill and immunosuppressed patients, other candidal and non-candidal fungal pathogens are becoming more common. Methods: Review of current practice and guidelines. Results: The presentation and management of non-C. albicans fungal infections differs depending on the genus and species. The availability of newer anti-fungal agents has in many cases improved outcomes or decreased toxicities associated with these diseases. Conclusions: Although such infections are still relatively uncommon, a working knowledge of infections with non-C. albicans fungi may be beneficial for surgeons, who are likely to encounter such patients both primarily and in consultation. Prompt recognition and treatment of these diseases should improve outcomes.     

Nosocomial infections and outcome of critically ill elderly patients after surgery

BACKGROUND: The relation between older age and nosocomial infection and mortality in the intensive care unit (ICU) is still a controversial issue. METHODS: The authors prospectively studied 406 patients admitted to a surgical ICU, 106 of whom were more than 75 yr old. Information concerning ICU-acquired nosocomial infections, severity of illness, therapeutic activity, and hospital outcome was collected. A Cox proportional hazard analysis was used to evaluate potential risk factors for ICU-acquired nosocomial infections, ICU, and hospital death. RESULTS: During their ICU stay, 23 elderly patients experienced 40 nosocomial infections, 28 "young" patients (< 60 yr) experienced 54 nosocomial infections, and 52 "intermediate age" patients (60-75 yr) experienced 98 nosocomial infections. Incidence density of nosocomial infections was 4.9% patient days for elderly patients, 4.7% for young patients, and 6.0% for intermediate age patients (no significance). The frequency distribution of the various microorganisms isolated was similar between the three groups. Compared with younger patients, elderly patients had a higher Acute Physiology and Chronic Health Evaluation II score and a higher ICU and hospital mortality rate. Despite a higher level of severity of illness, elderly patients had a reduction of therapeutic activity. However, Cox proportional hazard analysis showed that age more than 75 yr was not a risk factor for ICU-acquired nosocomial infection, ICU, or hospital death. CONCLUSIONS: In patients referred to a surgical ICU after a surgical procedure, age more than 75 yr by itself does not appear to be a significant predictor of ICU-acquired nosocomial infection or mortality rate during the ICU stay. However, it appears that patients more than 60 yr have a higher incidence of nosocomial infection in ICU.     

Prophylactic fluconazole in liver transplant recipients: A randomized,double-blind,placebo-controlled trial

Background:Among persons who receive solid organ 0842 transplants, liver transplant recipients have the highest incidence of invasive fungal infection; however, no antifungal prophylaxis has been proven to be effective.Objective:To evaluate the efficacy and safety of prophylactic0842 fluconazole in liver transplant recipients.Design:Randomized, double-blind, placebo-controlled trial. 0842Setting:University-affiliated transplantation center.0842Patients:212 liver transplant recipients who received fluconazole0842 (400 mg/d) or placebo until 10 weeks after transplantation.Measurements:Fungal colonization, proven superficial 0842 or invasive fungal infection, drug-related side effects, and death.Results:Fungal colonization increased in 0842 patients who received placebo (from 60% to 90%) but decreased in patients who received fluconazole (from 70% to 28%). Proven fungal infection occurred in 45 of 104 placebo recipients (43%) but in only 10 of 108 fluconazole recipients (9%) (P < 0.001). Fluconazole prevented both superficial infection (29 of 104 placebo recipients became infected [28%] compared with 4 of 108 fluconazole recipients [4%]; P < 0.001) and invasive infection (24 of 104 placebo recipients became infected [23%] compared with 6 of 108 fluconazole recipients [6%]; P < 0.001). Fluconazole prevented infection by most Candida species, except C. glabrata. However, infection and colonization by organisms intrinsically resistant to fluconazole did not seem to increase. Fluconazole was not associated with any hepatotoxicity. Patients receiving fluconazole had higher serum cyclosporine levels and more adverse neurologic events (headaches, tremors, or seizures in 13 fluconazole recipients compared with 3 placebo recipients; P = 0.01). Although the overall mortality rate was similar in both groups (12 of 108 [11%] in the fluconazole group compared with 15 of 104 [14%] in the placebo group; P > 0.2), fewer deaths related to invasive fungal infection were seen in the fluconazole group (2 of 108 patients [2%]) than in the placebo group (13 of 104 patients [13%]) (P = 0.003).Conclusions:Prophylactic 0842 fluconazole after liver transplantation decreases fungal colonization, prevents superficial and invasive fungal infections, and has no appreciable hepatotoxicity. Although fluconazole prophylaxis is associated with fewer deaths from fungal infection, it does not improve overall survival. Patients receiving prophylactic fluconazole require close monitoring of serum cyclosporine levels to avoid neurologic toxicity.     

Benefits of a Synbiotic Formula (Synbiotic 2000Forte<Superscript>®</Superscript>) in Critically Ill Trauma Patients: Early Results of a Randomized Controlled Trial

Background Since probiotics are considered to exert beneficial health effects by enhancing the host’s immune response, we investigated the benefits of a synbiotics treatment on the rate of infections, systemic inflammatory response syndrome (SIRS), severe sepsis, and mortality in critically ill, mechanically ventilated, multiple trauma patients. Length of stay in the intensive care unit (ICU) and number of days under mechanical ventilation were also evaluated. Method Sixty-five patients were randomized to receive once daily for 15 days a synbiotic formula (Synbiotic 2000Forte, Medipharm, Sweden) or maltodextrin as placebo. The synbiotic preparation consisted of a combination of four probiotics (10¹¹ CFU each): Pediococcus pentosaceus 5–33:3, Leuconostoc mesenteroides 32–77:1, L. paracasei ssp. paracasei 19; and L. plantarum 2,362; and inulin, oat bran, pectin, and resistant starch as prebiotics. Infections, septic complications, mortality, days under ventilatory support, and days of stay in ICU were recorded. Results Synbiotic-treated patients exhibited a significantly reduced rate of infections (P = 0.01), SIRS, severe sepsis (P = 0.02), and mortality. Days of stay in the ICU (P = 0.01) and days under mechanical ventilation were also significantly reduced in relation to placebo (P = 0.001). Conclusion The administration of this synbiotic formula in critically ill, mechanically ventilated, multiple trauma patients seems to exert beneficial effects in respect to infection and sepsis rates and to improve the patient’s response, thus reducing the duration of ventilatory support and intensive care treatment.     

Long-term functional outcome and performance status after intensive care unit re-admission: a prospective survey

BACKGROUND: Intensive care unit (ICU) re-admission identifies a high-risk group in terms of hospital mortality, length of stay, and resource utilization. Only hospital and ICU mortality are well described in the literature on critically ill patients needing re-admission. METHODS: With ethical committee approval, from a prospectively collected database of all admissions to a combined medical and surgical ICU from January 1 to December 31, 2004, we identified all ICU re-admissions from within the hospital and analysed the factors associated with increased incidence of re-admission. At 2-3 yr after discharge, we evaluated the functional outcome of the surviving re-admitted patients as Glasgow Outcome Score (GOS) and Karnofsky index and identified determinants of both mortality and good functional outcome. RESULTS: Seventy-three (7.4%) of the 1061 patients who survived their first ICU stay were re-admitted during the study period. Of the 73 re-admitted patients, 14 died in ICU, 17 died later in the same hospital stay, and 10 died in the interim. Thus, 32 (43.8%) were alive 2-3 yr after discharge. The median [IQR] GOS of the survivors was 4 (see Mackle and colleagues in One year outcome of intensive care patients with decompensated alcoholic liver disease. CONCLUSIONS: Although the ICU, hospital, and subsequent mortalities are high in patients after ICU re-admission, most survivors at 2-3 yr had by then made a good functional recovery and were independent.     

Ketoconazole prevents Candida sepsis in critically ill surgical patients

We conducted a prospective, randomized, double-blind, placebo-controlled study to determine whether or not ketoconazole could prevent yeast colonization or invasion in critically ill adult surgical patients. Fifty-seven patients in a surgical intensive care unit (SICU) with three or more clinical risk factors for Candida infection were randomized to receive ketoconazole, 200 mg via the gastrointestinal tract daily (27 patients), or placebo (30 patients). Patients with hepatic dysfunction were excluded. The study was continued for 21 days or until one week after discharge from the SICU, whichever was longer. Stool cultures were obtained every three days and other cultures as indicated clinically. Patients were observed for yeast colonization (sputum, urine, stool, or wound) and invasion (fungemia or deep tissue focus). The incidence of Candida colonization was significantly lower in the ketoconazole group than the placebo group. Invasive yeast sepsis developed in five (17%) of the placebo-treated patients and in no patient in the ketoconazole group, a significant difference. Length of stay in the SICU was significantly lower in the ketoconazole group, as were the basic SICU patient charges. Sixty percent of the patients with invasive fungal sepsis died.