Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study.

BACKGROUND: Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required. OBJECTIVES: To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs). METHODS: A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity. RESULTS: One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival. CONCLUSIONS: Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.

Ghrelin alterations during experimental and human sepsis.

BACKGROUND: Ghrelin is a hormone mainly produced by cells of the gastric mucosa, which has been shown to possess anti-inflammatory and immunomodulatory properties. The objective of the study was to investigate ghrelin levels during sepsis, as well as in an experimental sepsis model. METHODS: All consecutive admissions to the ICU of a tertiary hospital in Athens, Greece were screened for eligibility during the study. Thirty four non-septic patients upon ICU admission who subsequently developed sepsis were enrolled. Clinical data and scores were recorded, and blood samples were obtained at baseline (upon ICU admission), and at sepsis development. Total and active ghrelin, leptin, and cytokines were measured. Moreover, lipopolysaccharide (LPS) was administered to mice in order to induce endotoxemia and at specified time points, blood and tissue samples were collected. RESULTS: In patients, serum total and active ghrelin concentrations were significantly elevated in sepsis compared to baseline (553.8 ±â€¯213.4 vs 193.5 ±â€¯123.2, p < 0.001; 254.3 ±â€¯70.6 vs 56.49 ±â€¯16.3, p < 0.001). Active ghrelin levels at the sepsis stage were inversely correlated with SOFA score and length of stay in the ICU (p = 0.023 and p = 0.027 respectively). In the mouse endotoxemia model ghrelin levels were elevated following LPS treatment, and the same trend was observed for leptin, TNFα and IL-6. Ghrelin administration managed to reduce IL-6 levels in mouse serum and in BALF. Pulmonary expression of ghrelin and its receptor GHSR1a was found decreased in LPS-treated mice. CONCLUSIONS: In a well-defined cohort of ICU patients, we have demonstrated that active and total ghrelin increase in sepsis. The same is true for the experimental sepsis model used in the study. The inverse correlation of active ghrelin levels with SOFA score and length of ICU stay among septic patients is indicative of a potential protective role of active ghrelin during the septic process.

-572 G/C single nucleotide polymorphism of interleukin-6 and sepsis predisposition in chronic renal disease.

Single nucleotide polymorphisms (SNPs) of interleukin (IL)-6 are associated with the development of chronic renal disease (CRD). Their impact for sepsis in the field of CRD was investigated. One control cohort of 115 patients with CRD without infection and another case cohort of 198 patients with CRD and sepsis were enrolled. Genotyping at the -174 (rs1800795) and -572 positions of IL-6 (rs1800796) was done by restriction fragment length polymorphism. Circulating IL-6 was measured by an enzyme immunoassay. The GG genotype of rs1800796 was more frequent among cases (78.3%) than controls (62.6%). No difference in the genotype frequencies of rs1800795 between cases and controls were found. Odds ratio for sepsis was 2.07 (95%CI 1.24-3.44, p = 0.005) with the GG genotype of rs1800796, which was confirmed by logistic regression analysis taking into consideration the presence of chronic comorbidities. All-cause mortality until day 28 was similar between patients with the GG genotype and the GC/CC genotypes of rs1800796, but death caused from cardiovascular events not-related with infection was more frequent with the GG genotype (14.6% vs 2.4%, p = 0.031). Circulating IL-6 was greater among patients of the GC/CC genotypes of rs1800796 and multiple organ dysfunction (p = 0.013). The GG genotype of rs1800796 predisposes to sepsis in CRD and to 28-day mortality by sepsis-unrelated cardiovascular phenomena.

Carbapenem-resistant versus carbapenem-susceptible Acinetobacter baumannii bacteremia in a Greek intensive care unit: risk factors, clinical features and outcomes.

BACKGROUND: There has been an increasing incidence of carbapenem-resistant Acinetobacter baumannii (CRAB) infections in recent years. The objective of this study was to determine specific risk factors for and outcome of bacteremia due to CRAB isolates among our ICU patients with A. baumannii bacteremia. PATIENTS AND METHODS: Among 96 patients with ICU-acquired A. baumannii bacteremia, 30 patients with CRAB were compared with the remaining 66 with carbapenem-susceptible A. baumannii (CSAB) isolates. RESULTS: Recent ventilator-associated pneumonia (VAP) due to CRAB (OR 16.74, 95% CI 3.16-88.79, p = 0.001) and a greater number of intravascular devices (OR 3.93, 95% CI 1.9-13.0, p = 0.025) were independently associated with CRAB bacteremia acquisition. Patients with CRAB bacteremia had a lower severity of illness on admission than those with CSAB. Although, by univariate analysis, patients with CRAB were more likely to have had exposure to colistin, carbapenems and linezolid, multivariate analysis did not revealed any significant association. The mortality was not different between patients with CRAB and CSAB bacteremia (43.3 vs. 46.9%, p = 0.740). Severity of organ failure (OR 1.42, 95% CI 1.20-1.67, p = 0.001), and increased white blood cell (WBC) count (OR 1.09, 95% CI 1.01-1.19, p = 0.036), at bacteremia onset were independently associated with mortality. CONCLUSION: VAP due to CRAB and excess use of intravascular devices are the most important risk factors for CRAB bacteremia in our ICU. Severity of organ failure and WBC count at A. baumannii bacteremia onset are independently associated with mortality.

Desferrioxamine attenuates minor lung injury following surgical acute liver failure.

Acute liver failure (ALF) can be complicated by lung dysfunction. The aim of this study was to test the hypothesis that inhibition of oxidative stress through iron chelation with desferrioxamine (DFX) attenuates pulmonary injury caused by ALF. 14 adult female domestic pigs were subjected to surgical devascularisation of the liver and were randomised to a study group (DFX group, n = 7), which received post-operative intravenous infusion of DFX (14.5 mg x kg(-1) x h(-1) for the first 6 h post-operatively and 2.4 mg x kg(-1) x h(-1) until completion of 24 h), and a control group (n = 7). Post-operative lung damage was evaluated by histological and bronchoalveolar lavage fluid (BALF) analysis. DFX resulted in reduced BALF protein levels and tissue phospholipase (PL)A(2) activity. Plasma malondialdehyde and BALF nitrate and nitrite concentrations were lower, while catalase activity in the lung was higher after DFX treatment. PLA(2), platelet-activating factor acetylhydrolase and total cell counts in BALF did not differ between groups. Histological examination revealed reduced alveolar collapse, pneumonocyte necrosis and total lung injury in the DFX-treated animals. DFX reduced systemic and pulmonary oxidative stress during ALF. The limited activity of PLA(2) and the attenuation of pneumonocyte necrosis could represent beneficial mechanisms by which DFX improves alveolar-capillary membrane permeability and prevents alveolar space collapse.

Predisposing factors for critical illness polyneuromyopathy in a multidisciplinary intensive care unit.

OBJECTIVE: To investigate risk factors of critical illness polyneuromyopathy (CIPM) in a general multidisciplinary intensive care unit (ICU). PATIENTS AND METHODS: Prospective observational study in a 28-bed university multidisciplinary ICU. Four hundred and seventy-four (323 M/151 F, age 55 +/- 19) consecutive patients were prospectively evaluated. All patients were assigned admission Acute Physiology and Chronic Health Evaluation (APACHE II; 15 +/- 7) and Sequential Organ Failure Assessment (SOFA; 6 +/- 3) scores and were subsequently evaluated for newly developed neuromuscular weakness. Other potential causes of new-onset weakness after ICU admission were excluded before CIPM was diagnosed. RESULTS: Forty-four (23.8%) of 185 patients developed generalized weakness that met the criteria for CIPM. Patients with CIPM had higher APACHE II (18.9 +/- 6.6 vs 15.6 +/- 6.4, P = 0.004) and SOFA scores (8.4 +/- 2.9 vs 7.1 +/- 2.9, P = 0.013). According to multivariate logistic regression analysis, the following risk factors were independently associated with the development of CIPM: severity of illness at the time of ICU admission, administration of aminoglycoside antibiotics and high blood glucose levels. Analysis according to severity of illness stratification revealed the emergence of Gram (-) bacteremia as the most important independent predisposing factor for CIPM development in less severely ill patients. CONCLUSIONS: CIPM has a high incidence in the ICU setting. Our study revealed the association of aminoglycosides, hyperglycemia and illness severity with CIPM development, as well as the association between Gram (-) bacteremia and development of CIPM in less severely ill patient population.

Validation of the new Sepsis-3 definitions: proposal for improvement in early risk identification.

OBJECTIVES: Sepsis-3 definitions generated controversies regarding their general applicability. The Sepsis-3 Task Force outlined the need for validation with emphasis on the quick Sequential Organ Failure Assessment (qSOFA) score. This was done in a prospective cohort from a different healthcare setting. METHODS: Patients with infections and at least two signs of systemic inflammatory response syndrome (SIRS) were analysed. Sepsis was defined as total SOFA ≥2 outside the intensive care unit (ICU) or as an increase of ICU admission SOFA ≥2. The primary endpoints were the sensitivity of qSOFA outside the ICU and sepsis definition both outside and within the ICU to predict mortality. RESULTS: In all, 3346 infections outside the ICU and 1058 infections in the ICU were analysed. Outside the ICU, respective mortality with ≥2 SIRS and qSOFA ≥2 was 25.3% and 41.2% (p <0.0001); the sensitivities of qSOFA and of sepsis definition to predict death were 60.8% and 87.2%, respectively. This was 95.9% for sepsis definition in the ICU. The sensitivity of qSOFA and of ≥3 SIRS criteria for organ dysfunction outside the ICU was 48.7% and 72.5%, respectively (p <0.0001). Misclassification outside the ICU with the 1991 and Sepsis-3 definitions into stages of lower severity was 21.4% and 3.7%, respectively (p <0.0001) and 14.9% and 3.7%, respectively, in the ICU (p <0.0001). Adding arterial pH ≤7.30 to qSOFA increased sensitivity for prediction of death to 67.5% (p 0.004). CONCLUSIONS: Our analysis positively validated the use of SOFA score to predict unfavourable outcome and to limit misclassification into lower severity. However, qSOFA score had inadequate sensitivity for early risk assessment.

Left ventricular diastolic dysfunction--an independent risk factor for weaning failure from mechanical ventilation.

The objective of this study was to investigate the contribution of left ventricular (LV) diastolic dysfunction to weaning failure, along with the levels of the currently used cardiac biomarkers. Forty-two mechanically ventilated patients, who fulfilled criteria for weaning from mechanical ventilation (MV), underwent a two-hour spontaneous breathing trial (SBT). Transthoracic echocardiography (TTE) was performed before the start of the SBT. The grade of LV diastolic dysfunction was assessed by pulsed-wave Doppler and tissue Doppler imaging at the level of the mitral valve. Haemodynamic and respiratory parameters were recorded. Blood levels of B-type natriuretic peptide (BNP), troponin I, creatine kinase-MB, and myoglobin were measured on MV and at the end of the SBT. Weaning success was defined as the patient's ability to tolerate spontaneous breathing for more than 48 hours. Fifteen patients failed to wean. LV diastolic dysfunction was significantly associated with weaning failure (P<0.001). The grade of diastolic dysfunction was significantly correlated with BNP levels both on MV and at the end of the SBT (P<0.001, r=0.703 and P<0.001, r=0.709, respectively). BNP levels on MV were lower in patients who successfully weaned compared to those who did not (361±523 ng/l versus 643±382 ng/l respectively, P=0.008). The presence of diastolic dysfunction was independently associated with weaning failure (odds ratio [OR] 11.23, confidence interval [CI] 1.16-109.1, P=0.037) followed by respiratory frequency/tidal volume (OR 1.05, CI 1.00-1.10, P=0.048). Therefore, assessment of LV diastolic function before the start of weaning could be useful to identify patients at risk of weaning failure.

Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins.

The emergence of infections by multidrug-resistant (MDR) Gram-negative bacteria, which is accompanied by considerable mortality due to inappropriate therapy, led to the investigation of whether adjunctive treatment with one polyclonal IgM-enriched immunoglobulin preparation (IgGAM) would improve outcomes. One hundred patients in Greece with microbiologically confirmed severe infections by MDR Gram-negative bacteria acquired after admission to the Intensive Care Unit and treated with IgGAM were retrospectively analysed from a large prospective multicentre cohort. A similar number of patient comparators well-matched for stage of sepsis, source of infection, appropriateness of antimicrobials and co-morbidities coming from the same cohort were selected. All-cause 28-day mortality was the primary end point; mortality by extensively drug-resistant (XDR) pathogens and time to breakthrough bacteraemia were the secondary end points. Fifty-eight of the comparators and 39 of the IgGAM-treated cases died by day 28 (p 0.011). The OR for death under IgGAM treatment was 0.46 (95% CI 0.26-0.85). Stepwise regression analysis revealed that IgGAM was associated with favourable outcome whereas acute coagulopathy, cardiovascular failure, chronic obstructive pulmonary disease and chronic renal disease were associated with unfavourable outcome. Thirty-nine of 62 comparators (62.9%) were infected by XDR Gram-negative bacteria and died by day 28 compared with 25 of 65 cases treated with IgGAM (38.5%) (p 0.008). Median times to breakthrough bacteraemia were 4 days and 10 days, respectively (p <0.0001). Results favour the use of IgGAM as an adjunct to antimicrobial treatment for the management of septic shock caused by MDR Gram-negative bacteria. A prospective randomized trial is warranted.

Early response roles for prolactin cortisol and circulating and cellular levels of heat shock proteins 72 and 90α in severe sepsis and SIRS.

OBJECTIVE: To evaluate the early heat shock protein (HSP) and hormonal stress response of intensive care unit (ICU) patients with severe sepsis/septic shock (SS) or systemic inflammatory response syndrome (SIRS) compared to healthy subjects (H). METHODS: Patients with early (first 48 hrs) SS (n = 29) or SIRS (n = 29) admitted to a university ICU and 16 H were enrolled in the study. Serum prolactin, cortisol, and plasma ACTH were determined using immunoassay analyzers. ELISA was used to evaluate extracellular HSPs (eHSP90α, eHSP72) and interleukins. Mean fluorescence intensity (MFI) values for intracellular HSPs (iHSP72, iHSP90α) were measured using 4-colour flow-cytometry. RESULTS: Prolactin, cortisol, and eHSP90α levels were significantly increased in SS patients compared to SIRS and H (P < 0.003). ACTH and eHSP72 were significantly higher in SS and SIRS compared to H (P < 0.005). SS monocytes expressed lower iHSP72 MFI levels compared to H (P = 0.03). Prolactin was related with SAPS III and APACHE II scores and cortisol with eHSP90α, IL-6, and lactate (P < 0.05). In SS and SIRS eHSP90α was related with eHSP72, IL-6, and IL-10. CONCLUSION: Prolactin, apart from cortisol, may have a role in the acute stress response in severe sepsis. In this early-onset inflammatory process, cortisol relates to eHSP90α, monocytes suppress iHSP72, and plasma eHSP72 increases.

Changes in thenar muscle tissue oxygen saturation assessed by near-infrared spectroscopy during weaning from mechanical ventilation.

BACKGROUND: Tissue oxygen saturation (StO2) measured by near-infrared spectroscopy (NIRS) has been used to provide information on local tissue oxygenation in different clinical settings. This study aims to determine the effect of weaning from mechanical ventilation on thenar muscle StO2. METHODS: In consecutive critically ill mechanically ventilated patients, StO2 at the thenar eminence, along with a vascular occlusion test (VOT), were measured by NIRS, on mechanical ventilation and during a 2-hour T-piece spontaneous breathing trial (SBT). Hemodynamic, gas exchange and respiratory variables were recorded. RESULTS: Forty-four patients were included in this study, 25 tolerated the SBT and 19 failed. On mechanical ventilation, no differences in any measured variable were observed between patients who succeeded or failed. Two minutes after SBT start, StO2 was decreased in patients who failed whereas it did not change in patients who succeeded (P<0.001). For all data, 2 minutes after the start of SBT, StO2 significantly correlated with SaO2 (r=0.32, P=0.037) and with the respiratory frequency/tidal volume (f/VT) index (r=-0.34, P=0.023). VOT-derived StO2 downslope and StO2 upslope did not change significantly along the SBT test. The maximum StO2 value, its ratio to minimum StO2, and the post-VOT StO2 value decreased significantly in patients who failed whereas no change was found in those who succeeded the SBT (P=0.003, P=0.025 and P<0.001 respectively). StO2 and f/VT at the second minute of SBT yielded a receiver operator characteristics curve area value of 0.77 and 0.80, P=0.002, respectively, in detecting the SBT outcome. CONCLUSION: SBT failure was associated with a significant impairment of thenar muscle StO2. A decrease of StO2 at 2 minutes after disconnection from the ventilator was associated with SBT failure. Further validation is warranted.

Risk factors for and influence of bloodstream infections on mortality: a 1-year prospective study in a Greek intensive-care unit.

To determine the incidence, risk factors for, and the influence of bloodstream infections (BSIs) on mortality of patients in intensive-care units (ICUs), prospectively collected data from all patients with a stay in an ICU >48 h, during a 1-year period, were analysed. Of 572 patients, 148 developed a total of 232 BSI episodes (incidence 16.3 episodes/1000 patient-days). Gram-negative organisms with high level of resistance to antibiotics were the most frequently isolated pathogens (157 strains, 67.8%). The severity of illness on admission, as estimated by APACHE II score (OR 1.07, 95% CI 1.04-1.1, P<0.001), the presence of acute respiratory distress syndrome (OR 3.57, 95% CI 1.92-6.64, P<0.001), and a history of diabetes mellitus (OR 2.37, 95% CI 1.36-4.11, P=0.002) were risk factors for the occurrence of BSI whereas the development of an ICU-acquired BSI was an independent risk factor for death (OR 1.76, 95% CI 1.11-2.78, P=0.015). Finally, the severity of organ dysfunction on the day of the first BSI episode, as estimated by SOFA score, and the level of serum albumin, independently affected the outcome (OR 1.44, 95% CI 1.22-1.7, P<0.001 and OR 0.47, 95% CI 0.23-0.97, P=0.04 respectively).

Non-invasive assessment of the microcirculation in critically ill patients.

Sepsis is associated with abnormalities of muscle tissue oxygenation and of microvascular function. We investigated whether the technique of near-infrared spectroscopy can evaluate such abnormalities in critically ill patients and compared near-infrared spectroscopy-derived indices of critically ill patients with those of healthy volunteers. We studied 41 patients (mean age 58 +/- 22 years) and 15 healthy volunteers (mean age 49 +/- 13 years). Patients were classified into one of three groups: systemic inflammatory response syndrome (SIRS) (n = 21), severe sepsis (n = 8) and septic shock (n = 12). Near-infrared spectroscopy was used to continuously measure thenar muscle oxygen saturation before, during and after a three-minute occlusion of the brachial artery via pneumatic cuff. Oxygen saturation was significantly lower in patients with SIRS, severe sepsis or septic shock than in healthy volunteers. Oxygen consumption rate during stagnant ischaemia was significantly lower in patients with SIRS (23.9 +/- 7.7%/minute, P < 0.001), severe sepsis (16.9 +/- 3.4%/minute, P < 0.001) or septic shock (14.8 +/- 6%/minute, P < 0.001) than in healthy volunteers (35.5 +/- 10.6%/minute). Furthermore, oxygen consumption rate was significantly lower in patients with septic shock than patients with SIRS. Reperfusion rate was significantly lower in patients with SIRS (336 +/- 141%/minute, P < 0.001), severe sepsis (257 +/- 150%/minute, P < 0.001) or septic shock (146 +/- 101%/minute, P < 0.001) than in healthy volunteers (713 +/- 223%/minute) and significantly lower in the septic shock than in the SIRS group. Near-infrared spectroscopy can detect tissue oxygenation deficits and impaired microvascular reactivity in critically ill patients, as well as discriminate among groups with different disease severity.

Application of the sequential organ failure assessment (SOFA) score to bacteremic ICU patients.

BACKGROUND: Patients admitted to intensive care units (ICUs) are at a high risk of acquiring blood stream infections. We examined whether SOFA score on ICU admission and on the day of bacteremia can predict the occurrence of bacteremia and the outcome of bacteremic ICU patients. PATIENTS AND METHODS: All patients admitted to a multidisciplinary ICU for more than 48 h from January 1, 2002 to December 31, 2004, were prospectively studied. Demographic, clinical and laboratory data were recorded on admission for all patients and additionally, on the day of the first bacteremic episode for those patients who developed bacteremia. Accordingly, APACHE II and SOFA scores were calculated on the same day. RESULTS: A total of 185 patients developed one or more episodes of bacteremia, giving an incidence of 9.6 per 1,000 ICU days. The ICU mortality rate was 43.9% for bacteremic and 25.8% for the remaining patients (p < 0.001). Admission SOFA score was independently associated with the occurrence of bacteremia (OR = 1.20, 95% CI: 1.11-1.26, p < 0.001). Among bacteremic patients, SOFA score on the day of bacteremia was the only independent prognostic factor for outcome (OR = 1.44, 95% CI: 1.21-1.71, p < 0.001). When all patients were included in the multivariate analysis, admission SOFA (OR = 1.3, CI: 1.16-1.38, p < 0.001), APACHE II (OR = 1.1, CI: 1.02-1.11, p = 0.003) score and the presence of bacteremia (OR = 1.8, CI: 1.1-2.9, p = 0.023) were independently associated with the outcome. CONCLUSION: Admission SOFA score is independently associated with the occurrence of ICU-acquired bacteremia, whereas it is not sufficient to predict the outcome of patients who subsequently will develop this complication. However, SOFA score on the first day of bacteremia is an independent prognostic factor for outcome in these patients.

Does soluble triggering receptor expressed on myeloid cells-1 play any role in the pathogenesis of septic shock?

In order to define the significance of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) upon progression from sepsis or severe sepsis to septic shock a prospective study was designed with 90 enrolled patients with septic syndrome due to ventilator-associated pneumonia. Blood was sampled on seven consecutive days upon initiation of symptoms and concentrations of tumour necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), IL-8 and sTREM-1 were estimated in serum by an enzymeimmunoassay. No differences in concentrations of TNFalpha, IL-6 and IL-8 were found between patients with sepsis, severe sepsis and septic shock on the first day of presentation of symptoms. Patients presenting with septic shock had concentrations of sTREM-1 significantly higher than both patients with sepsis and severe sepsis on the first day; no difference was found between patients with sepsis and severe sepsis. A positive correlation was detected between sTREM-1 and the white blood cell count. Serum levels of sTREM-1 were significantly lower in patients where VAP resolved compared to those where VAP did not resolve; similar findings were noted between patients who eventually survived and those who died. IL-6 followed the kinetics of sTREM-1 in correlation to patients's prognosis; levels of TNFalpha and IL-8 were unrelated to prognosis. It is concluded that sTREM-1 is particularly increased upon evolution from sepsis or severe sepsis to septic shock. Its sustained increase is an indication of poor outcome. The underlined pathophysiological role of sTREM-1 for the transition from sepsis or severe sepsis to septic shock might constitute a novel target for immunomodulatory therapy.

A comparative study of the Reaction Level Scale (RLS85) with Glasgow Coma Scale (GCS) and Edinburgh-2 Coma Scale (modified) (E2CS(M)).

In this work a new coma scale for the assessment of responsiveness in acute brain disorders, constructed near the year 1985 by Scandinavian investigators, the Reaction Level Scale (RLS85), is compared with two other coma scales namely: (i) the Glasgow Coma Scale: (GCS); (ii) the Edinburgh-2 Coma Scale, after modification: (E2CS(M)). The study proceeded in the form of a statistical analysis of assessments made on 46 patients according to RLS85 and GCS (i.e., when comparison was with GCS) and on 28 patients according to RLS85 and E2CS(M). In all 74 cases two physicians participating as "observers" carried out the assessments. They were both contacting the patient--not together but--successively within a time interval of less than 20'. Hence the data appeared as "pairwise" observations for any of the three scales above. The results of the analysis, arising from a rather strict statistical reasoning, can be summarized as follows: (1) The rank correlation coefficient r(s) between: (i) RLS85 and GCS sum score, (ii) RLS85 and E2CS(M), was found to be at a satisfactory level meaning that all three scales indicate almost the same "ranking order of severity". (2) Reliability was compared by taking into account as to what extent the two observers agreed on RLS85 and--simultaneously--disagreed on the other scale. The "sign" test was applied and as a result RLS85 proved to be more reliable than; (i) GCS (EMY profile), (ii) GCS sum score, and (iii) E2CS(M), in all the above mentioned at a high level of significance. (3) Apart from the test above, some values of the index kappa (kappa) of interobserver agreement were calculated. Those corresponding to RLS85 are considerably higher. In particular the overall value based on 74 pairwise assessments amounted to kappa = 0.733 associated with a standard error sigma(kappa) = 0.061. This was a satisfactory result regarding the features of RLS85. (4) As far as coverage is concerned, again--by the "sign" test--the predominance of RLS85 versus GCS (EMY profile) was accepted.

Enterococcal infections in a Greek intensive care unit: a 5-y study.

In this study we determined the incidence, resistance pattern, and mortality rate associated with infection caused by Enterococcus faecalis and Enterococcus faecium among patients in a multidisciplinary intensive care unit (ICU). A total of 111 patients with E. faecalis and 60 with E. faecium infections were identified during a 5-y period (1992-96). We observed an increase in the incidence of enterococcal infections (from 5.46 to 8.46 per 1000 patients-days, p = 0.0112), due mainly to the increased incidence of E. faecium (from 0.45 to 4.06 per 1000 patients-days, p = 0.002). Blood was the most common site of enterococcus isolation. E. faecium was more resistant to antibiotics than E. faecalis, but no vancomycin resistant enterococcus was isolated. Patients with E. faecium infection had a significantly higher mortality than patients with E. faecalis infection (66% vs. 41.5%, p = 0.0035 for infection from any site and 85.7 vs. 47.7%, p = 0.012 for bacteremic patients). r 4n- D I .- .- - .. . .

Pulmonary lactate release in patients with acute lung injury is not attributable to lung tissue hypoxia.

OBJECTIVE: To determine whether pulmonary lactate production in patients with acute lung injury is attributable to lung tissue hypoxia. DESIGN: Prospective, controlled, clinical study. SETTING: A multidisciplinary university intensive care unit in a general hospital. PATIENTS: Seventy consecutive critically ill patients requiring mechanical ventilation and invasive hemodynamic monitoring. Of these patients, 18 had no acute lung injury (no ALI); 33 had acute lung injury (ALI) (Lung Injury Score [LIS] < or =2.5); and 19 had acute respiratory distress syndrome (ARDS) (LIS >2.5). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After hemodynamic measurements, lactate and pyruvate concentrations were assessed in simultaneously drawn arterial (a) and mixed venous (v) blood samples. Pulmonary lactate release was calculated as the product of transpulmonary a-v lactate difference (L[a-v]) times the cardiac index. Two indices of anaerobic metabolism of the lung, i.e., the transpulmonary a-v difference of lactate pyruvate ratio (L/P[a-v]) and excess lactate formation across the lungs (XL), were calculated. L(a-v) and pulmonary lactate release were higher in patients with ARDS than in the other groups (p<.001), and they were also higher in patients with ALI compared with patients with no ALI (p<.001). In patients with ALI and ARDS (n = 52), pulmonary lactate release correlated significantly with LIS (r2 = .14, p<.01) and venous admixture (r2 = .13, p<.01). When all patients were lumped together (n = 70), pulmonary lactate release directly correlated with LIS (r2 = .30, p<.001), venous admixture (r2 = .26, p<.001), and P(A-a)O2 (r2 = .14, p<.01). Neither L/P(a-v) nor XL was significantly different among the three groups. CONCLUSION: The lungs of patients with ALI produce lactate that is proportional to the severity of lung injury. This lactate production does not seem to be attributable to lung tissue hypoxia.

Aspergillus bronchitis causing atelectasis and acute respiratory failure in an immunocompromised patient.

Aspergillus tracheobronchitis is an uncommon clinical form of invasive aspergillosis with fungal infection limited entirely or predominantly to the tracheobronchial tree. We report a case of Aspergillus fumigatus bronchitis, diagnosed by fiberoptic bronchoscopy, with fungal growth completely occluding the left main bronchus leading to lung collapse and acute respiratory failure in a 60-year-old male with erythroleukemia and profound granulocytopenia.