IntroductionElevated plasma B-type natriuretic peptide (BNP) levels in patients with critical sepsis (severe sepsis and septic shock) may indicate septic cardiomyopathy. However, multiple heterogeneous conditions may also be involved in increased BNP level. In addition, the prognostic value of BNP in sepsis remains debatable. In this study, we sought to discover potential independent determinants of BNP elevation in critical sepsis. The prognostic value of BNP was also evaluated.MethodsIn this observational study, we enrolled mechanically ventilated, critically septic patients requiring hemodynamic monitoring through a pulmonary artery catheter. All clinical, laboratory and survival data were prospectively collected. Plasma BNP concentrations were measured daily for five consecutive days. Septic cardiomyopathy was assessed on day 1 on the basis of left and right ventricular ejection fractions (EF) derived from echocardiography and thermodilution, respectively. Mortality was recorded at day 28.ResultsA total of 42 patients with severe sepsis (N = 12) and septic shock (N = 30) were ultimately enrolled. Daily BNP levels were significantly elevated in septic shock patients compared with those with severe sepsis (P ≤0.002). Critical illness severity (assessed by Acute Physiology and Chronic Health Evaluation II and maximum Sequential Organ Failure Assessment scores), and peak noradrenaline dose on day 1 were independent determinants of BNP elevation (P <0.05). Biventricular EFs were inversely correlated with longitudinal BNP measurements (P <0.05), but not independently. Pulmonary capillary wedge pressures (PCWP) and volume expansion showed no correlation with BNP. In septic shock, increased central venous pressure (CVP) and CVP/PCWP ratio were independently associated with early BNP values (P <0.05).Twenty-eight-day mortality was 47.6% (20 of 42 patients). Daily BNP values poorly predicted outcome; BNP on day 1 > 800 pg/ml (the best cutoff point) fairly predicted mortality, with a sensitivity%, specificity% and area under the curve values of 65, 64 and 0.70, respectively (95% confidence interval = 0.54 to 0.86; P = 0.03). Plasma BNP levels declined faster in survivors than in nonsurvivors in both critical sepsis and septic shock (P ≤0.002). In septic shock, a BNP/CVP ratio >126 pg/mmHg/ml on day 2 and inability to reduce BNP <500 pg/ml implied increased mortality (P ≤0.036).ConclusionsThe severity of critical illness, rather than septic cardiomyopathy, is probably the major determinant of BNP elevation in patients with critical sepsis. Daily BNP values are of limited prognostic value in predicting 28-day mortality; however, fast BNP decline over time and a decrease in BNP <500 pg/ml may imply a favorable outcome.

bColistin pharmacokinetics were prospectively studied after intravenous administration of colistin methanesulphonate in critically ill patients without central nervous system infection (controls, n ‫؍‬ 5) and in patients with external ventricular drain-associated ventriculitis after intravenous administration (EVDViv, n ‫؍‬ 3) or combined intravenous/intraventricular administration (EVDVcomb, n ‫؍‬ 4). Cerebrospinal fluid (CSF)/serum colistin concentration ratios were higher in EVDViv than in control patients (11% versus 7%, P < 0.05) and in EVDVcomb compared to all other patients (P < 0.0001). CSF colistin concentrations above the MIC of 0.5 g/ml were achieved only in EVDVcomb patients. Previous studies have suggested that the level of antibiotics in the ventricular cerebrospinal fluid (CSF) is important for the outcome of external ventricular drainage (EVD)-related ventriculitis (1-3). The presence of multiresistant bacteria and the poor penetration of many drugs through the blood-brain barrier have imposed the use of intrathecal therapies (4).Today, colistin, administered as its prodrug colistin methanesulphonate (CMS), is one of the few antibiotics available for treatment of infections by multidrug-resistant Gram-negative organisms. However, intravenous (i.v.) administration is reported to have a relatively poor CSF distribution and clinical outcomes vary (5-7). Data with respect to the efficacy of intraventricular polymyxins, as an add-on therapy, combined with systemic antibiotics are sparse and mainly observational (5, 8).We aimed to determine the effect of intravenous and combined intravenous/intraventricular CMS administration on colistin concentrations in the CSF and serum in critically ill patients with or without central nervous system (CNS) infection.This prospective case-controlled randomized study was conducted in a tertiary hospital, during a 12-month period between 2011 and 2012. Inclusion criteria were as follows: age Ͼ 18 years, diagnosis of EVD-related ventriculitis caused by Gram-negative bacteria, controlled intracranial pressure (Ͻ20 mm Hg) for 24 h prior to the study, no renal failure, and no allergy to colistin. Patients with EVD on i.v. CMS treatment for infections by Gramnegative bacteria other than CNS infections were included in the study as controls. The study was approved by the Hospital Ethics and Research Committee and performed in accordance with good clinical practice guidelines.Control patients received 3,000,000 IU (240 mg) CMS (approximately 90 mg colistin base activity [CBA]) i.v. every 8 h. Patients with EVD-associated ventriculitis caused by Gram-negative bacteria (diagnosed on the basis of clinical grounds plus positive CSF cultures or CSF inflammation, including pleocytosis and a reduced CSF/serum glucose ratio) were randomized to receive the same i.v. dose (EVDViv group), or the i.v. dose combined with 125,000 IU (10 mg) CMS (ϳ3.75 CBA) administered intraventricularly, once daily (EVDVcomb). A 2-ml volume of 0.9% NaCl (volume of catheter lumen) was instilled via the ca...

Data on the effectiveness of ceftazidime-avibactam (CAZ-AVI) in critically ill, mechanically ventilated patients are limited. The present retrospective observational cohort study, which was conducted in two general intensive care units (ICUs) in central Greece, compared critically ill, mechanically ventilated patients suffering from carbapenem-resistant Enterobacteriaceae (CRE) infections receiving CAZ-AVI to patients who received appropriate available antibiotic therapy. Clinical and microbiological outcomes and safety issues were evaluated. A secondary analysis in patients with bloodstream infections (BSIs) was conducted. Forty-one patients that received CAZ-AVI (the CAZ-AVI group) were compared to 36 patients that received antibiotics other than CAZ-AVI (the control group). There was a significant improvement in the Sequential Organ Failure Assessment (SOFA) score on days 4 and 10 in the CAZ-AVI group compared to that in the control group (P = 0.006, and P = 0.003, respectively). Microbiological eradication was accomplished in 33/35 (94.3%) patients in the CAZ-AVI group and 21/31 (67.7%) patients in the control group (P = 0.021), and clinical cure was observed in 33/41 (80.5%) versus 19/36 (52.8%) patients (P = 0.010), respectively. The results were similar in the BSI subgroups for both outcomes (P = 0.038 and P = 0.014, respectively). The 28-day survival was 85.4% in the CAZ-AVI group and 61.1% in the control group (log-rank test = 0.035), while there were 2 and 12 relapses in the CAZ-AVI and control groups, respectively (P = 0.042). A CAZ-AVI-containing regime was an independent predictor of survival and clinical cure (odds ratio [OR] = 5.575 and P = 0.012 and OR = 5.125 and P = 0.004, respectively), as was illness severity. No significant side effects were recorded. In conclusion, a CAZ-AVI-containing regime was more effective than other available antibiotic agents for the treatment of CRE infections in the high-risk, mechanically ventilated ICU population evaluated.